sample case study for bipolar 1 disorder

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CASE STUDY Gary (bipolar disorder)

Case study details.

Gary is a 19-year-old who withdrew from college after experiencing a manic episode during which he was brought to the attention of the Campus Police (“I took the responsibility to pull multiple fire alarms in my dorm to ensure that they worked, given the life or death nature of fires”). He had changed his major from engineering to philosophy and increasingly had reduced his sleep, spending long hours engaging his friends in conversations about the nature of reality. He had been convinced about the importance of his ideas, stating frequently that he was more learned and advanced than all his professors. He told others that he was on the verge of revolutionizing his new field, and he grew increasingly irritable and intolerant of any who disagreed with him. He also increased a number of high-risk behaviors – drinking and engaging in sexual relations in a way that was unlike his previous history.  At the present time, he has returned home and his been placed on a mood stabilizer (after a period of time on an antipsychotic), and his psychiatrist is requesting adjunctive psychotherapy for his bipolar disorder.  The patient’s parents are somewhat shocked by the diagnosis, but they acknowledge that Gary had early problems with anxiety during pre-adolescence, followed by some periods of withdrawal and depression during his adolescence.  His parents are eager to be involved in treatment, if appropriate.

• Alcohol Use
• Elevated Mood
• Impulsivity
• Irritability
• Mania/Hypomania
• Mood Cycles
• Risky Behaviors

Diagnoses and Related Treatments

1. bipolar disorder.

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Real Life Bipolar Disorder: A Case Study of Susan

Bipolar disorder is a complex and often misunderstood mental health condition that affects millions of individuals worldwide. For those living with bipolar disorder, the highs and lows of life can be dizzying, as they navigate through periods of intense mania and debilitating depression. To truly grasp the impact of this disorder, it’s crucial to explore real-life experiences and the stories of those who have dealt firsthand with its challenges.

In this article, we delve into the fascinating case study of Susan, a woman whose life has been profoundly shaped by her bipolar disorder diagnosis. By examining Susan’s journey, we aim to shed light on the realities of living with this condition and the strategies employed to manage and treat it effectively.

But before we plunge deeper into Susan’s story, let’s first gain a comprehensive understanding of bipolar disorder itself. We’ll explore the formal definition, the prevalence of the condition, and its impact on both individuals and society as a whole. This groundwork will set the stage for a more insightful exploration of Susan’s experience and provide valuable context for the subsequent sections of this article.

Bipolar disorder is more than just mood swings; it is a condition that can significantly disrupt an individual’s life, relationships, and overall well-being. By studying a real-life case like Susan’s, we can gain a personal insight into the multifaceted challenges faced by those with bipolar disorder and the importance of effective treatment and support systems. In doing so, we hope to foster empathy, inspire early diagnosis, and contribute to the advancement of knowledge about bipolar disorder’s complexities.

The Case of Susan: A Real Life Experience with Bipolar Disorder

Susan’s story provides a compelling illustration of the impact that bipolar disorder can have on an individual’s life. Understanding her background, symptoms, and the effects of the disorder on her daily life can provide valuable insights into the challenges faced by those with bipolar disorder.

Background Information on Susan

Susan, a thirty-eight-year-old woman, was diagnosed with bipolar disorder at the age of twenty-five. Her early experiences with the disorder were characterized by periods of extreme highs and lows, often resulting in strained relationships and an inability to maintain steady employment. Susan’s episodes of mania frequently led to impulsive decision-making, excessive spending sprees, and risky behaviors. On the other hand, her depressive episodes left her feeling hopeless, fatigued, and unmotivated.

Symptoms and Diagnosis of Bipolar Disorder in Susan

To receive an accurate diagnosis, Susan underwent a thorough examination by mental health professionals. The criteria for diagnosing bipolar disorder include significant and persistent mood swings, alternating between periods of mania and depression. Susan exhibited classic symptoms of bipolar disorder, such as elevated mood, increased energy, racing thoughts, decreased need for sleep, and reckless behavior during her manic episodes. These episodes were interspersed with periods of deep sadness, loss of interest in activities, and changes in appetite and sleep patterns during depressive phases.

Effects of Bipolar Disorder on Susan’s Daily Life

Living with bipolar disorder presents unique challenges for Susan. The unpredictable shifts in her mood and energy levels significantly impact her ability to function in both personal and professional spheres. During manic phases, Susan experiences heightened productivity, creativity, and confidence, often leading her to take on excessive responsibilities and projects. However, these periods are eventually followed by crashes into depressive episodes, leaving her unable to complete tasks, maintain relationships, or even perform routine self-care. The constant fluctuations in her emotional state make it difficult for Susan to establish a sense of stability and predictability in her life.

Susan’s struggle with bipolar disorder is not uncommon. Many individuals with this condition face similar obstacles in their daily lives, attempting to manage the debilitating highs and lows while striving for a sense of normalcy. By understanding the real-life implications of bipolar disorder, we can more effectively tailor our support systems and treatment options to address the needs of individuals like Susan. In the next section, we will explore the various approaches to treating and managing bipolar disorder, providing potential strategies for improving the quality of life for those living with this condition.

Treatment and Management of Bipolar Disorder in Susan

Managing bipolar disorder requires a multifaceted approach that combines psychopharmacological interventions, psychotherapy, counseling, and lifestyle modifications. Susan’s journey towards finding effective treatment and management strategies highlights the importance of a comprehensive and tailored approach.

Psychopharmacological Interventions

Pharmacological interventions play a crucial role in stabilizing mood and managing symptoms associated with bipolar disorder. Susan’s treatment plan involved medications such as mood stabilizers, antipsychotics, and antidepressants. These medications aim to regulate the neurotransmitters in the brain associated with mood regulation. Susan and her healthcare provider closely monitored her medication regimen and made adjustments as needed to achieve symptom control.

Psychotherapy and Counseling

Psychotherapy and counseling provide individuals with bipolar disorder a safe space to explore their thoughts, emotions, and behaviors. Susan engaged in cognitive-behavioral therapy (CBT), which helped her identify and challenge negative thought patterns and develop healthy coping mechanisms. Additionally, psychoeducation in the form of group therapy or support groups allowed Susan to connect with others facing similar challenges, fostering a sense of community and reducing feelings of isolation.

Lifestyle Modifications and Self-Care Strategies

In addition to medical interventions and therapy, lifestyle modifications and self-care strategies play a vital role in managing bipolar disorder. Susan found that maintaining a stable routine, including regular sleep patterns, exercise, and a balanced diet, helped regulate her mood. Avoiding excessive stressors and implementing stress management techniques, such as mindfulness meditation or relaxation exercises, also supported her overall well-being. Engaging in activities she enjoyed, nurturing her social connections, and setting realistic goals further enhanced her quality of life.

Striving for stability and managing bipolar disorder is an ongoing process. What works for one individual may not be effective for another. It is crucial for individuals with bipolar disorder to work closely with their healthcare providers and engage in open communication about treatment options and progress. Fine-tuning the combination of psychopharmacological interventions, therapy, and self-care strategies is essential to optimize symptom control and maintain stability.

Understanding the complexity of treatment and management helps foster empathy for individuals like Susan, who face the daily challenges associated with bipolar disorder. It underscores the importance of early diagnosis, accessible mental health care, and ongoing support systems to enhance the lives of individuals living with this condition. In the following section, we will explore the various support systems available to individuals with bipolar disorder, including family support, peer support groups, and the professional resources that contribute to their well-being.

Support Systems for Individuals with Bipolar Disorder

Navigating the challenges of bipolar disorder requires a strong support system that encompasses various sources of assistance. From family support to peer support groups and professional resources, these networks play a significant role in helping individuals manage their condition effectively.

Family Support

Family support is vital for individuals with bipolar disorder. Understanding and empathetic family members can provide emotional support, monitor medication adherence, and help identify potential triggers or warning signs of relapse. In Susan’s case, her family played a crucial role in her recovery journey, providing a stable and nurturing environment. Education about bipolar disorder within the family helps foster empathy, reduces stigma, and promotes open communication.

Peer Support Groups

Peer support groups provide individuals with bipolar disorder an opportunity to connect with others who share similar experiences. Sharing personal stories, strategies for coping, and offering mutual support can be empowering and validating. In these groups, individuals like Susan can find solace in knowing that they are not alone in their struggles. Peer support groups may meet in-person or virtually, allowing for easier access to support regardless of physical proximity.

Professional Support and Resources

Professional support is crucial in the management of bipolar disorder. Mental health professionals, such as psychiatrists, psychologists, and therapists, provide expertise and guidance in developing comprehensive treatment plans. Regular therapy sessions allow individuals like Susan to explore emotional challenges and develop healthy coping mechanisms. Psychiatrists closely monitor medication effectiveness and make necessary adjustments. Additionally, case managers or social workers can assist with navigating the healthcare system, accessing resources, and connect individuals with other community services.

Beyond direct professional support, there are resources and organizations dedicated to bipolar disorder education, advocacy, and support. Online forums, websites, and helplines provide information, guidance, and a sense of community. These platforms allow individuals to access information at any time and connect with others who understand their unique experiences.

Support systems for bipolar disorder are crucial in empowering individuals and enabling them to lead fulfilling lives. They contribute to reducing stigma, providing emotional support, and ensuring access to resources and education. Through these support systems, individuals with bipolar disorder can gain self-confidence, develop effective coping strategies, and improve their overall well-being.

In the next section, we explore the significance of case studies in understanding bipolar disorder and how they contribute to advancing research and knowledge in the field. Specifically, we will examine how Susan’s case study serves as a valuable contribution to furthering our understanding of this complex disorder.

The Importance of Case Studies in Understanding Bipolar Disorder

Case studies play a vital role in advancing our understanding of bipolar disorder and its complexities. They offer valuable insights into individual experiences, treatment outcomes, and the overall impact of the condition on individuals and society. Susan’s case study, in particular, provides a unique perspective that contributes to broader research and knowledge in the field.

How Case Studies Contribute to Research

Case studies provide an in-depth examination of specific individuals and their experiences with bipolar disorder. They allow researchers and healthcare professionals to observe patterns, identify commonalities, and gain valuable insights into the factors that influence symptom presentation, treatment response, and prognosis. By analyzing various case studies, researchers can generate hypotheses and refine treatment approaches to optimize outcomes for individuals with bipolar disorder.

Case studies are particularly helpful in documenting rare or atypical presentations of bipolar disorder. They shed light on lesser-known subtypes, such as rapid-cycling bipolar disorder or mixed episodes, contributing to a more comprehensive understanding of the condition. Case studies also provide opportunities for clinicians and researchers to discuss unique challenges and discover innovative interventions to improve treatment outcomes.

Susan’s Case Study in the Context of ATI Bipolar Disorder

Susan’s case study is an example of how individual experiences can inform the development of Assessment Technologies Institute (ATI) for bipolar disorder. By examining her journey, researchers can analyze treatment approaches, evaluate the effectiveness of various interventions, and develop evidence-based guidelines for managing bipolar disorder.

Susan’s case study provides rich information about the impact of medication, psychotherapy, and lifestyle modifications on symptom control and overall well-being. It offers valuable insights into the benefits and limitations of specific interventions, highlighting the importance of personalized treatment plans tailored to individual needs. Additionally, Susan’s case study can contribute to ongoing discussions about the role of support systems and the integration of peer support groups in managing and enhancing the lives of individuals with bipolar disorder.

The detailed documentation of Susan’s experiences serves as a powerful tool for healthcare providers, researchers, and individuals living with bipolar disorder. It highlights the complexities and challenges associated with the condition while fostering empathy and understanding among various stakeholders.

Case studies, such as Susan’s, play a crucial role in enhancing our understanding of bipolar disorder. They provide insights into individual experiences, treatment approaches, and the impact of the condition on individuals and society. Through these case studies, we can cultivate empathy for individuals with bipolar disorder, advocate for early diagnosis and effective treatment, and contribute to advancements in research and knowledge.

By illuminating the realities of living with bipolar disorder, we acknowledge the need for accessible mental health care, support systems, and evidence-based interventions. Susan’s case study exemplifies the importance of a comprehensive approach to managing bipolar disorder, integrating psychopharmacological interventions, psychotherapy, counseling, and lifestyle modifications.

Moving forward, it is essential to continue studying cases like Susan’s and explore the diverse experiences within the bipolar disorder population. By doing so, we can foster empathy, encourage early intervention and personalized treatment, and contribute to advancements in understanding bipolar disorder, ultimately improving the lives of individuals affected by this complex condition.

Empathy and Understanding for Individuals with Bipolar Disorder

Developing empathy and understanding for individuals with bipolar disorder is crucial in fostering a supportive and inclusive society. By recognizing the unique challenges they face and the complexity of their experiences, we can better advocate for their needs and provide the necessary resources and support.

It is important to understand that bipolar disorder is not simply a matter of mood swings or being “moody.” It is a chronic and often debilitating mental health condition that affects individuals in profound ways. The extreme highs of mania and the lows of depression can disrupt relationships, employment, and overall quality of life. Developing empathy means acknowledging that these struggles are real and offering support and understanding to those navigating them.

Encouraging Early Diagnosis and Effective Treatment

Early diagnosis and effective treatment are key factors in managing bipolar disorder and reducing the impact of its symptoms. Encouraging individuals to seek help and reducing the stigma associated with mental illness are crucial steps toward achieving early diagnosis. Increased awareness campaigns and education can empower individuals to recognize the signs and symptoms of bipolar disorder in themselves or their loved ones, facilitating timely intervention.

Once diagnosed, providing access to quality mental health care and ensuring individuals receive appropriate treatment is essential. Bipolar disorder often requires a combination of pharmacological interventions, psychotherapy, and lifestyle modifications. By advocating for comprehensive treatment plans and promoting ongoing care, we can help individuals with bipolar disorder achieve symptom control and improve their overall well-being.

The Role of Case Studies in Advancing Knowledge about Bipolar Disorder

Case studies, like Susan’s, play a significant role in advancing knowledge about bipolar disorder. They provide unique insights into individual experiences, treatment outcomes, and the wider impact of the condition. Researchers and healthcare providers can learn from these individual cases, developing evidence-based guidelines and refining treatment approaches.

Additionally, case studies contribute to reducing stigma by providing personal narratives that humanize the disorder. They showcase the challenges faced by individuals with bipolar disorder and highlight the importance of support systems, empathy, and understanding. By sharing these stories, we can help dispel misconceptions and promote a more compassionate approach toward mental health as a whole.

In conclusion, developing empathy and understanding for individuals with bipolar disorder is essential. By recognizing the complexity of their experiences, advocating for early diagnosis and effective treatment, and valuing the insights provided by case studies, we can create a society that supports and uplifts those with bipolar disorder. It is through empathy and education that we can reduce stigma, promote accessible mental health care, and improve the lives of those affected by this condition.In conclusion, gaining a comprehensive understanding of bipolar disorder is crucial in order to support individuals affected by this complex mental health condition. Through the real-life case study of Susan, we have explored the numerous facets of bipolar disorder, including its background, symptoms, and effects on daily life. Susan’s journey serves as a powerful reminder of the challenges individuals face in managing the highs and lows of bipolar disorder and emphasizes the importance of effective treatment and support systems.

We have examined the various approaches to treating and managing bipolar disorder, including psychopharmacological interventions, psychotherapy, and lifestyle modifications. Understanding the role of these treatments and the need for personalized care can significantly improve the quality of life for individuals like Susan.

Support systems also play a crucial role in helping those with bipolar disorder navigate the complexities of the condition. From family support to peer support groups and access to professional resources, fostering a strong network of assistance can provide the necessary emotional support, education, and guidance needed for individuals to effectively manage their symptoms.

Furthermore, case studies, such as Susan’s, contribute to advancing our knowledge about bipolar disorder. By delving into individual experiences, researchers gain valuable insights into treatment outcomes, prognosis, and the impact of the condition on individuals and society as a whole. These case studies foster empathy, reduce stigma, and contribute to the development of evidence-based guidelines and interventions that can improve the lives of individuals with bipolar disorder.

In fostering empathy and promoting early diagnosis, effective treatment, and ongoing support, we create a society that actively embraces and supports individuals with bipolar disorder. By encouraging understanding, reducing stigma, and prioritizing mental health care, we can ensure that those affected by bipolar disorder receive the support and resources necessary to lead fulfilling and meaningful lives. Through empathy, education, and continued research, we can work towards a future where individuals with bipolar disorder are understood, valued, and empowered to thrive.

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5 Psychiatric Treatment of Bipolar Disorder: The Case of Janice

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Chapter 5 covers the psychiatric treatment of bipolar disorder, including a case history, key principles, assessment strategy, differential diagnosis, case formulation, treatment planning, nonspecific factors in treatment, potential treatment obstacles, ethical considerations, common mistakes to avoid in treatment, and relapse prevention.

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The challenges of living with bipolar disorder: a qualitative study of the implications for health care and research

• Eva F. Maassen   ORCID: orcid.org/0000-0003-0211-0994 1 , 2 ,
• Barbara J. Regeer 1 ,
• Eline J. Regeer 2 ,
• Joske F. G. Bunders 1 &
• Ralph W. Kupka 2 , 3  

International Journal of Bipolar Disorders volume  6 , Article number:  23 ( 2018 ) Cite this article

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In mental health care, clinical practice is often based on the best available research evidence. However, research findings are difficult to apply to clinical practice, resulting in an implementation gap. To bridge the gap between research and clinical practice, patients’ perspectives should be used in health care and research. This study aimed to understand the challenges people with bipolar disorder (BD) experience and examine what these challenges imply for health care and research needs.

Two qualitative studies were used, one to formulate research needs and another to formulate healthcare needs. In both studies focus group discussions were conducted with patients to explore their challenges in living with BD and associated needs, focusing on the themes diagnosis, treatment and recovery.

Patients’ needs are clustered in ‘disorder-specific’ and ‘generic’ needs. Specific needs concern preventing late or incorrect diagnosis, support in search for individualized treatment and supporting clinical, functional, social and personal recovery. Generic needs concern health professionals, communication and the healthcare system.

Patients with BD address disorder-specific and generic healthcare and research needs. This indicates that disorder-specific treatment guidelines address only in part the needs of patients in everyday clinical practice.

Bipolar disorder (BD) is a major mood disorder characterized by recurrent episodes of depression and (hypo)mania (Goodwin and Jamison 2007 ). According to the Diagnostic and Statistical Manual 5 (DSM-5), the two main subtypes are BD-I (manic episodes, often combined with depression) and BD-II (hypomanic episodes, combined with depression) (APA 2014 ). The estimated lifetime prevalence of BD is 1.3% in the Dutch adult population (de Graaf et al. 2012 ), and BD is associated with high direct (health expenditure) and indirect (e.g. unemployment) costs (Fajutrao et al. 2009 ; Michalak et al. 2012 ), making it an important public health issue. In addition to the economic impact on society, BD has a tremendous impact on patients and their caregivers (Granek et al. 2016 ; Rusner et al. 2009 ). Even between mood episodes, BD is often associated with functional impairment (Van Der Voort et al. 2015 ; Strejilevich et al. 2013 ), such as occupational or psychosocial impairment (Huxley and Baldessarini 2007 ; MacQueen et al. 2001 ; Yasuyama et al. 2017 ). Apart from symptomatic recovery, treatment can help to overcome these impairments and so improve the person’s quality of life (IsHak et al. 2012 ).

Evidence Based Medicine (EBM), introduced in the early 1990s, is a prominent paradigm in modern (mental) health care. It strives to deliver health care based on the best available research evidence, integrated with individual clinical expertise (Sackett et al. 1996 ). EBM was introduced as a new paradigm to ‘de - emphasize intuition’ and ‘ unsystematic clinical experience’ (Guyatt et al. 1992 ) (p. 2420). Despite its popularity in principle (Barratt 2008 ), EBM has also been criticized. One such criticism is the ignorance of patients’ preferences and healthcare needs (Bensing 2000 ). A second criticism relates to the difficulty of adopting evidence-based treatment options in clinical practice (Bensing 2000 ), due to the fact that research outcomes measured in ‘the gold standard’ randomized-controlled trials (RCTs) seldom correspond to the outcomes clinical practice seeks and are not responsive to patients’ needs (Newnham and Page 2010 ). Moreover, EBM provides an overview on population level instead of individual level (Darlenski et al. 2010 ). Thus, adopting research evidence in clinical practice entails difficulties, resulting in an implementation gap.

To bridge the gap between research and clinical practice, it is argued that patients’ perspectives should be used in both health care and research. Patients have experiential knowledge about their illness, living with it in their personal context and their care needs (Tait 2005 ). This is valuable for both clinical practice and research as their knowledge complements that of health professionals and researchers (Tait 2005 ; Broerse et al. 2010 ; Caron-Flinterman et al. 2005 ). This source of knowledge can be used in the process of translating evidence into clinical practice (Schrevel 2015 ). Moreover, patient participation can enhance the clinical relevance of and support for research and the outcomes in practice (Abma and Broerse 2010 ). Hence, it is argued that these perspectives should be explicated and integrated into clinical guidelines, clinical practice, and research (Misak 2010 ; Rycroft-Malone et al. 2004 ).

Given the advantages of including patients’ perspectives, patients are increasingly involved in healthcare services (Bagchus et al. 2014 ; Larsson et al. 2007 ), healthcare quality (e.g. guideline development) (Pittens et al. 2013 ) and health-related research (e.g. agenda setting, research design) (Broerse et al. 2010 ; Boote et al. 2010 ; Elberse et al. 2012 ; Teunissen et al. 2011 ). However, patients’ perspectives on health care and on research are often studied separately. We argue that to be able to provide care focused on the patients and their needs, care and research must closely interact.

We hypothesize that the challenges BD patients experience and the associated care and research needs are interwoven, and that combining them would provide a more comprehensive understanding. We hypothesize that this more comprehensive understanding would help to close the gap between clinical practice and research. For this reason, this study aims to understand the challenges people with BD experience and examine what these challenges imply for healthcare and research needs.

To understand the challenges and needs of people with BD, we undertook two qualitative studies. The first aimed to formulate a research agenda for BD from a patient’s perspective, by gaining insights into their challenges and research needs. A second study yielded an understanding of the care needs from a patient’s perspective. In this article, the results of these two studies are combined in order to investigate the relationship between research needs and care needs. Challenges are defined as ‘difficulties patients face, due to having BD’. Care needs are defined as that what patients ‘desire to receive from healthcare services to improve overall health’ (Asadi-Lari et al. 2004 ) (p. 2). Research needs are defined as that what patients ‘desire to receive from research to improve overall health’.

Study on research needs

In this study, mixed-methods were used to formulate research needs from a patient’s perspective. First six focus group discussions (FGDs) with 35 patients were conducted to formulate challenges in living with BD and hopes for the future, and to formulate research needs arising from these difficulties and aspirations. These research needs were validated in a larger sample (n = 219) by means of a questionnaire. We have reported this study in detail elsewhere (Maassen et al. 2018 ).

Study on care needs

This study was part of a nationwide Dutch project to generate a practical guideline for BD: a translation of the existing clinical guideline to clinical practice, resulting in a standard of care that patients with BD could expect. The practical guideline (Netwerk Kwaliteitsontwikkeling GGZ 2017 ) was written by a taskforce comprising health professionals, patients. In addition to the involvement of three BD patients in the taskforce, a systematic qualitative study was conducted to gain insight into the needs of a broader group of patients.

Participants and data collection

To formulate the care needs of people with BD, seven FGDs were conducted, with a total of 56 participants, including patients (n = 49) and caregivers (n = 9); some participants were both patient and caregiver. The inclusion criteria for patients were having been diagnosed with BD, aged 18 years or older and euthymic at time of the FGDs. Inclusion criteria for caregivers were caring for someone with BD and aged 18 years or older. To recruit participants, a maximum variation sampling strategy was used to collect a broad range of care needs (Kuper et al. 2008 ). First, all outpatient clinics specialized in BD affiliated with the Dutch Foundation for Bipolar Disorder (Dutch: Kenniscentrum Bipolaire Stoornissen) were contacted by means of an announcement at regular meetings and by email if they were interested to participate. From these outpatient clinics, patients were recruited by means of flyers and posters. Second, patients were recruited at a quarterly meeting of the Dutch patient and caregiver association for bipolar disorder. The FGDs were conducted between March and May 2016.

The FGDs were designed to address challenges experienced in BD health care and areas of improvement for health care for people with BD. The FGDs were structured by means of a guide and each session was facilitated by two moderators. The leading moderator was either BJR or EFM, having both extensive experience with FGD’s from previous studies. The first FGD explored a broad range of needs. The subsequent six FGDs aimed to gain a deeper understanding of these care needs, and were structured according to the outline of the practical guideline (Netwerk Kwaliteitsontwikkeling GGZ 2017 ). Three chapters were of particular interest: diagnosis, treatment and recovery. These themes were discussed in the FGDs, two in each session, all themes three times in total. Moreover, questions on specific aspects of care formulated by the members of the workgroup were posed. The sessions took 90–120 min. The FGDs were audiotaped and transcribed verbatim. A summary of the FGDs was sent to the participants for a member check.

Data analysis

To analyze the data on challenges and needs, a framework for thematic analysis to identify, analyze and report patterns (themes) in qualitative data sets by Braun and Clarke ( 2006 ) was used. First, we familiarized ourselves with the data by carefully reading the transcripts. Second, open coding was used to derive initial codes from the data. These codes were provided to quotes that reflected a certain challenge or care need. Third, we searched for patterns within the codes reflecting challenges and within those reflecting needs. For both challenges and needs, similar or overlapping codes were clustered into themes. Subsequently, all needs were categorized as ‘specific’ or ‘generic’. The former are specific to BD and the latter are relevant for a broad range of psychiatric illnesses. Finally, a causal analysis provided a clear understanding of how challenges related to each other and how they related to the described needs.

To analyze the data on needs regarding recovery, four domains were distinguished, namely clinical, functional, social and personal recovery (Lloyd et al. 2008 ; van der Stel 2015 ). Clinical recovery refers to symptomatic remission; functional recovery concerns recovery of functioning that is impaired due to the disorder, particularly in the domain of executive functions; social recovery concerns the improvement of the patient’s position in society; personal recovery concerns the ability of the patient to give meaning to what had happened and to get a grip on their own life. The analyses were discussed between BR and EM. The qualitative software program MAX QDA 11.1.2 was used (MaxQDA).

Ethical considerations

According to the Medical Ethical Committee of VU University Medical Center, the Medical Research Involving Human Subjects Act does not apply to the current study. All participants gave written or verbal informed consent regarding the aim of the study and for audiotaping and its use for analysis and scientific publications. Participation was voluntary and participants could withdraw from the study at any time. Anonymity was ensured.

This section is in three parts. The first presents the participants’ characteristics. The second presents the challenges BD patients face, derived from both studies, and the disorder-specific care and research needs associated with these challenges. The third part describes the generic care needs that patients formulated.

Characteristics of the participants

In the study on care needs, 56 patients and caregivers participated. The mean age of the participants was 52 years (24–75), of whom 67.8% were women. The groups varied from four to sixteen participants, and all groups included men and women. Of all participants 87.5% was diagnosed with BD, of whom 48.9% was diagnosed with BD I. 3.5% was both caregivers and diagnosed with BD. Of 4 patients the age was missing, and from 6 patients the bipolar subtype.

Despite the fact that participants acknowledge the inevitable diagnostic difficulties of a complex disorder like BD, in both studies they describe a range of challenges in different phases of the diagnostic process (Fig.  1 ). Patients explained that the general practitioner (GP) and society in general did not recognize early-warning signs and mood swings were not well interpreted, resulting in late or incorrect diagnosis. Patients formulated a need for more research on what early-warning signs could be and on how to improve GPs’ knowledge about BD. Formulated care needs were associated with GPs using this knowledge to recognize early-warning signs in individual patients. One participant explained that certain symptoms must be noticed and placed in the right context:

Challenges with diagnosis (squares) including relating research needs (white circles) and care needs (grey circles). (1): mentioned in study on research needs; (2): mentioned in study on care needs. Dotted lines: division of challenges into sub challenges. Arrows: causal relation between challenges

I call it, ‘testing overflow of ideas’. [….] When it happens for the first time you yourself do not recognize it. Someone else close to you or the health professional, who is often not involved yet, must signal it. (FG6)

Moreover, these challenges are associated with the need to pay attention to family history and to use a multidisciplinary approach to diagnosis to benefit from multiple perspectives. The untimely recognition of early symptoms also results in another challenge: inadequate referral to the right specialized health professional. After referral, people often face a waiting list, again causing delay in the diagnostic process. These challenges result in the need for research on optimal referral systems and the care need for timely referral. One participant described her process after the GP decided to refer her:

But, yes, at that moment the communication wasn’t good at all. Because the general practitioner said: ‘she urgently has to be seen by someone’. Subsequently, three weeks went by, until I finally arrived at depression [department]. And at that department they said: ‘well, you are in the wrong place, you need to go to bipolar [department ]’. (FG1)

The challenge of being misdiagnosed is associated with the need to be able to ask for a second opinion and to have a timely and thorough diagnosis. On the one hand, it is important for patients that health professionals quickly understand what is going on, on the other hand that health professionals take the time to thoroughly investigate the symptoms by making several appointments.

From both studies, two main challenges related to the treatment of BD were derived (Fig.  2 ). The first is finding appropriate and satisfactory treatment. Participants explained that it is difficult to find the right medication and dosage that is effective and has acceptable side-effects. One participant illustrates:

Challenges with treatment (squares) including relating research needs (white circles) and care needs (grey circles). (1): mentioned in study on research needs; (2): mentioned in study on care needs. Dotted lines: division of challenges into sub challenges. Arrows: causal relation between challenges

I think, at one point, we have to choose, either overweight or depressed. (FG1)

Some participants said that they struggle with having to use medication indefinitely, including the associated medical checks. The difficult search for the right pharmacological treatment results in the need for research on long-term side-effects, on the mechanism of action of medicine and on the development of better targeted medication with fewer adverse side-effects. In care, patients would appreciate all the known information on the side-effects and intended effects. One participant explained the importance of being properly informed about medication:

I don’t read anything [about medication], because then I wouldn’t dare taking it. But I do think, when you explain it well, the advantages, the disadvantages, the treatment, the idea behind it, that would help a lot in compliance. (FG1)

A second aspect is the challenge of finding non-pharmacological therapies that fit patients’ needs. They said they and the health professionals often do not know which non-pharmacological therapies are available and effective:

But we found the carefarm ourselves Footnote 1 [….]. You have to search for yourself completely. Yes, I actually hoped that that would be presented to you, like: ‘this would be something for you’. (FG3)

Participants mentioned a variety of non-pharmacological therapies they found useful, namely cognitive behavior therapy (CBT), EMDR, running therapy, social-rhythm training, light therapy, mindfulness, psychotherapy, psychoeducation, and training in living with mood swings. They formulated the care need to receive an overview of all available treatment options in order to find a treatment best suited to their needs. They would appreciate research on the effectiveness of non-pharmacological treatments.

A third aspect within this challenge is finding the right balance between non-pharmacological and pharmacological treatment. Participants differed in their opinion about the need for medication. Whereas some participants stated that they need medication to function, others pointed out that they found non-pharmacological treatments effective, resulting in less or no medication use. They explained that the preferred balance can also change over time, depending on their mood. However, they experience a dominant focus on pharmacological treatment by the health professionals. To address this challenge, patients need support in searching for an appropriate balance.

Next to the challenge of finding appropriate and satisfactory treatment, a second treatment-related challenge is hospitalization. Participants often had a traumatic experience, due to seclusion, the authoritarian attitudes of clinical staff, and not involving their family. Patients therefore found it important to try preventing being hospitalized, for example by means of home treatment, which some participants experienced positively. Despite the challenges relating to hospitalization, participants did acknowledge that in some cases it cannot be avoided, in which case they urged for close family involvement, open communication and being treated by their own psychiatrist. Still, in the study on research needs, hospitalization did not emerge as an important research theme.

In both studies, participants described challenges in all four domains of recovery: clinical, functional, social and personal (Fig.  3 ). In relation to clinical recovery, participants struggled with the symptoms of mood episodes, the psychosis and the fear of a future episode. In contrast, some participants mentioned that they sometimes miss the hypomanic state they had experienced previously due to effective medical treatment. In the domain of functional recovery, participants contended with having to function below their educational level due to residual symptoms, such as cognitive problems, due to the importance of preventing stress in order to reduce the risk of a new episode, and because of low energy levels. This leads to the care need that health professionals should pay attention to the level of functioning of their patients.

Challenges with recovery (squares) including relating research needs (white circles) and care needs (grey circles). (1): mentioned in study on research needs; (2): mentioned in study on care needs. Dotted lines: division of challenges into sub challenges. Arrows: causal relation between challenges

In the domain of social recovery, participants described challenges with maintaining friendships, due to stigma, being unpredictable and with deciding when to disclose the disorder. The latter resulted in the care need for tips on disclosure. Moreover, patients experienced challenges with reintegration to work, due to colleagues’ lack of understanding, problems with functioning during an episode, the complicating policy of the (Dutch) Employee Insurance Agency Footnote 2 in relation to the fluctuating course of BD and the negative impact of stress. These challenges are associated with the care need that health professionals should pay attention to work and the need for research on how to improve the Social Security Agency’s policy.

For their personal recovery, participants struggled with acceptance of the disorder, due to shame, stigma, having to live by structured rules and disciplines, and the chronic nature of BD. This results in care needs for grief counselling and attention to acceptance and the need for research on the impact of being diagnosed with BD. Limited understanding within society also causes problems with acceptance, corresponding with the care need for education for caregivers and for research on how to increase social acceptance. Another challenge in personal recovery was discovering what recovery means and what constitute meaningful daily activities. Patients appreciated the support of health professionals in this area. One participant described the difficult search for the meaning of recovery:

I have been looking to recover towards the situation [before diagnosis] for a long time; that I could do what I always did and what I liked. But then I was confronted with the fact that I shouldn’t expect that to happen, or only with a lot of effort. (…) Then you start thinking, now what? A compromise. I don’t want to call that recovery, but it is a recovered, partly accepted, situation. But it is not recovery as I expected it to be. (FG5)

In general, participants considered frequent contact with a nurse or psychiatrist supportive, to help them monitor their mood and help them find (efficient) self-management strategies. Most participants appreciated the involvement of caregivers in the treatment and contact with peers.

Generic care needs

We have described BD-specific needs, but patients mentioned also mentioned several generic care needs. The latter are clustered into three categories. The first concerns the health professionals . Participants stressed the importance of a good health professional, who carefully listens, takes time, and makes them feel understood, resulting in a sense of connection. Furthermore, a good health professional treats beyond the guideline, and focuses on the needs of the individual patient. When there is no sense of connection, it should be possible to change to another health professional. The second category concerns communication between the patient and the health professional . Health professionals should communicate in an open, honest and clear way both in the early diagnostic phase and during treatment. Open communication facilitates individualized care, in which the patient is involved in decision making. In addition, participants wanted to be treated as a person, not as a patient, and according to a strength-based approach. The third category concerns needs at the level of the healthcare system . Participants struggled with the availability of the health professionals and preferred access to good care 24/7 and being able to contact their health professional quickly when necessary. Currently, according to the participants, the care system is not geared to the mood swings of BD, because patients often faced waiting lists before they could see a health professional.

Is adequate treatment also having a number from a mental health institution you can always call when you are in need, that you can go there? And not that you can go in three weeks, but on a really short notice. So at least a phone call. (FG3)

Participants were often frustrated by the limited collaboration between health professionals, within their own team, between departments of the organization, and between different organizations, including complementary health professionals. They would appreciate being able to merge their conventional and complementary treatment, with greater collaboration among the different health professionals. Furthermore, they would like continuity of health professionals as this improves both the diagnostic phase and treatment, and because that health professional gets to know the patient.

We hypothesized that research and care needs of patients are closely intertwined and that understanding these, by explicating patients’ perspectives, could contribute to closing the gap between research and care. Therefore, this study aimed to understand the challenges patients with BD face and examine what these imply for both healthcare and research. In the study on needs for research and in the study on care needs, patients formulated challenges relating to receiving the correct diagnosis, finding the right treatment, including the proper balance between non-pharmacological and pharmacological treatment, and to their individual search for clinical, functional, social and personal recovery. The formulated needs in both studies clearly reflected these challenges, leading to closely corresponding needs. Another important finding of our study is that patients not only formulate disorder-specific needs, but also many generic needs.

The needs found in our study are in line with the current literature on the needs of patients with BD, namely for more non-pharmacological treatment (Malmström et al. 2016 ; Nestsiarovich et al. 2017 ), timely recognition of early-warning signs and self-management strategies to prevent a new episode (Goossens et al. 2014 ), better information on treatment and treatment alternatives (Malmström et al. 2016 ; Neogi et al. 2016 ) and coping with grief (Goossens et al. 2014 ). Moreover, the need for frequent contact with health professionals, being listened to, receiving enough time, shared decision-making on pharmacological treatment, involving caregivers (Malmström et al. 2016 ; Fisher et al. 2017 ; Skelly et al. 2013 ), and the urge for better access to health care and continuity of health professionals (Nestsiarovich et al. 2017 ; Skelly et al. 2013 ) are confirmed by the literature. Our study added to this set of literature by providing insights in patients’ needs in the diagnostic process and illustrating the interrelation between research needs and care needs from a patient’s perspective.

The generic healthcare needs patients addressed in this study are clustered into three categories: the health professional , communication between the patient and the health professional and the health system. These categories all fit in a model of patient-centered care (PCC) by Maassen et al. ( 2016 ) In their review, patients’ perspectives on good care are compared with academic perspectives of PCC and a model of PCC is created comprising four dimensions: patient, health professional, patient – professional interaction and healthcare organization. All the generic needs formulated in this study fit into these four dimensions. The need to be treated as a person with strengths fits the dimension ‘patient’, and the need for a good health professional who carefully listens, takes time and makes them feel understood, resulting in a good connection with the professional, fits the dimension ‘health professional’ of this model. Furthermore, patients in this study stressed the importance of open communication in order to provide individualized care, which fits the dimension of ‘patient–professional interaction’. The urge for better access to health care, geared to patients’ mood swings and the need for better collaboration between health professionals and continuity of health professionals fits the dimension of ‘health care organization’ of the model. This study confirms the findings from the review and contributes to the literature stressing the importance of a patient-centered care approach (Mills et al. 2014 ; Scholl et al. 2014 ).

In the prevailing healthcare paradigm, EBM, the best available evidence should guide treatment of patients (Sackett et al. 1996 ; Darlenski et al. 2010 ). This evidence is translated into clinical and practical guidelines, which thus facilitate EBM and could be used as a decision-making tool in clinical practice (Skelly et al. 2013 ). For many psychiatric disorders, treatment is based on such disorder - specific clinical and practical guidelines. However, this disease-focused healthcare system has contributed to its fragmented nature Stange ( 2009 ) argues that this fragmented care system has expanded without the corresponding ability to integrate and personalize accordingly. We argue that acknowledging that disorder - specific clinical and practical guidelines address only parts of the care needs is of major importance, since otherwise important aspects of the patients’ needs will be ignored. Because there is an increasing acknowledgement that health care should be responsive to the needs of patients and should change from being disease-focused towards being patient-focused (Mead and Bower 2000 ; Sidani and Fox 2014 ), currently in the Netherlands generic practical guidelines are written on specific care themes (e.g. co-morbidity, side-effects, daily activity and participation). These generic practical guidelines address some of the generic needs formulated by the patients in our study. We argue that in addition to disorder-specific guidelines, these generic practical guidelines should increasingly be integrated into clinical practice, while health professionals should continuously be sensitive to other emerging needs. We believe that an integration of a disorder-centered and a patient-centered focus is essential to address all needs a patient.

Strengths, limitations and future research

This study has several strengths. First, it contributes to the literature on the challenges and needs of patients with BD. Second, the study is conducted from a patient’s perspective. Moreover, addressing this aim by conducting two separate studies enabled us to triangulate the data.

This study also has several limitations. First, this study reflects the challenges, care needs and research needs of Dutch patient with BD and caregivers. Despite the fact that a maximum variation sampling strategy was used to derive a broad range of challenges and needs throughout the Netherlands, the Dutch setting of the study may limit the transferability to other countries. To understand the overlap and differences between countries, similar research should be conducted in other contexts. Second, given the design of the study, we could not differentiate between patients and caregivers since they participated together in the FGDs. More patients than caregivers participated in the study. For a more in-depth understanding of the challenges and needs faced by caregivers, in future research separate FGDs should be conducted. Third, due to the fixed outline of the practical guideline used to conduct the FGDs, only the healthcare needs for diagnosis, treatment and recovery of BD are studied. Despite the fact that these themes might cover a broad range of health care, it could have resulted in overlooking certain needs in related areas of well-being. Therefore, future research should focus on needs outside of these themes in order to provide a complete set of healthcare needs.

Patients and their caregivers face many challenges in living with BD. Our study contributes to the literature on care and research needs from a patient perspective. Needs specific for BD are preventing late or incorrect diagnosis, support in search for individualized treatment, and supporting clinical, functional, social and personal recovery. Generic healthcare needs concern health professionals, communication and the healthcare system. This explication of both disorder-specific and generic needs indicates that clinical practice guidelines should address and integrate both in order to be responsive to the needs of patients and their caregivers.

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Authors’ contributions

EFM designed the study, contributed to the data collection, managed the analysis and wrote the first draft of the manuscript. BJR designed the study and contributed to the data collection, data analysis, and writing of the manuscript. JFGB contributed to the study design and critical revision of the manuscript. EJR contributed to the study conception and critical revision of the manuscript. RWK contributed to the study design, acquisition of data, and critical revision of the manuscript. All authors contributed to the final manuscript. All authors read and approved the final manuscript.

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Maassen, E.F., Regeer, B.J., Regeer, E.J. et al. The challenges of living with bipolar disorder: a qualitative study of the implications for health care and research. Int J Bipolar Disord 6 , 23 (2018). https://doi.org/10.1186/s40345-018-0131-y

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Language: English | French

First Manic Episode in an 11 Year-old Girl

Don quang tran.

1 Centre Hospitalier Universitaire de Sherbrooke, University of Sherbrooke, Department of Psychiatry, Sherbrooke, Quebec

Vincent Beaudry

Yves lajoie.

We present the case of an 11 year-old girl admitted to the Centre hospitalier universitaire de Sherbrooke for a first manic episode.

Differential diagnoses of adjustment disorder, attention-deficit/hyperactivity disorder, oppositional defiant disorder, and conduct disorder were considered but eliminated.

No organic etiology was detected. Her condition rapidly remitted with aripiprazole 3mg. After her discharge, she suffered a relapse due to instability of her living conditions and was rehospitalized.

Conclusion:

Mania is a difficult diagnosis in youths due to its nonspecific symptoms, rare prepubertal occurrence, and diagnostic complexity. Despite ongoing research, there is little conclusive information on the impact of psychosocial stressors on the evolution of early-onset bipolar disorder.

Résumé

Nous présentons le cas d’une fillette de 11 ans hospitalisée au Centre hospitalier universitaire de Sherbrooke pour un premier épisode de manie.

Méthode:

Les diagnostics différentiels du trouble d’adaptation, du trouble de déficit de l’attention avec hyperactivité, du trouble oppositionnel avec provocation et du trouble des conduites ont été envisagés mais rejetés.

Résultats:

Aucune étiologie organique n’a été détectée. La rémission de son affection a été rapide avec 3 mg d’aripiprazole. Après son congé, elle a souffert d’une rechute attribuable à l’instabilité de ses conditions de vie et a été réhospitalisée.

La manie est un diagnostic difficile chez les adolescents en raison de ses symptômes non spécifiques, d’une rare occurrence pré-pubère, et de la complexité diagnostique. Malgré la recherche en cours, il y a peu d’information concluante sur l’effet des stresseurs psychologiques sur l’évolution du trouble bipolaire d’apparition précoce.

“Ansa” is an eleven year-old girl who lives with Mrs. J, her mother; her parents have been divorced for years, and she has little contact with her father. Ansa’s early childhood history was marked by her mother’s numerous unstable relationships which led to the mother and daughter moving many times before Ansa was seven. Ansa was unknown to any child psychiatry service. From age six to eight, Ansa was on methylphenidate for suspected attention-deficit/hyperactivity disorder (ADHD); there were no beneficial effects, and the medication was discontinued. Otherwise, Ansa’s past psychiatric history is negative. She has never had physical illnesses, has never taken drugs, alcohol, or medication. Family history is positive for Mrs. J’s borderline personality disorder and her uncle’s possible but unconfirmed diagnosis of bipolar disorder.

Ansa was admitted to our service for grandiosity, agitation, and distractibility that had appeared in the last two days. She had no sleep, spending the nights cleaning her room. She had excessive projects, including becoming a rock star. These symptoms rendered her totally unable to attend school and even take care of her basic needs, such as hygiene. There were no recent stressors. The mental status examination showed a child unable to remain seated (spending the whole interview moving from object to object), an irritable and labile affect, logorrhea, accelerated speech, and flight of thoughts. She expressed countless projects although there was no delusional grandiosity. She denied hallucinations and suicidal ideations. Baseline metabolic tests were negative, including complete blood count, electrolytes, thyroid levels, and urinalysis. A physical evaluation by the pediatrician yielded no significant findings. An electroencephalogram and brain magnetic resonance imaging (MRI) were negative. Ansa was diagnosed with acute manic episode with no identifiable organic etiology but with a possible biological vulnerability for emotional dysregulation, given the mother’s borderline personality disorder.

After no improvement with quetiapine 12.5mg and olanzapine 5mg trials, Ansa was given aripiprazole 5mg. With the medication and strong presence of nurses and psychoeducators, her condition was stabilized in less than five days. Due to sedation, aripiprazole was lowered to 2mg, resulting in a manic relapse. Aripiprazole was increased to 3mg, and the manic symptoms quickly resolved, again in less than five days. The hospitalisation lasted one month in order to monitor Ansa’s symptoms and level of functioning during progressive returns to school. They were ultimately successful, and Ansa was discharged.

The following week, despite compliance to medication, Ansa suffered a relapse of the identical symptoms and was readmitted. This coincided perfectly with turbulent changes in her environment. Indeed, Ansa and her mother had just moved in with family friends: there were frequent unexpected visits from various acquaintances, accompanied by daily verbal violence. Mrs. J admitted to her fragile emotional state and that Ansa would usually internalize her mother’s feelings. Since no other cause was identified, the manic relapse was attributed mainly to the unstable environment with a child in a symbiotic relationship with her mother, who suffers from borderline personality disorder but whose parental capacities were considered preserved. Given the apparently clear temporal relationship of the symptomatic relapse with the stressors, an adjustment disorder was considered as part of the differential diagnosis. However, the clinical presentation – especially the mental status examination as previously described – clearly corresponded to the severity of a mood disorder. In addition, the patient’s personal and longitudinal history revealed no signs of conduct disorder or oppositional defiant disorder. The relapse also heightened the prior hypothesis of Ansa’s biological vulnerability to emotional dysregulation.

No pharmacological change was made and with the presence of the multidisciplinary team, Ansa’s condition remitted in four days. The total hospital stay lasted three weeks in order to once again observe Ansa’s evolution during progressive returns to school, which were successful. Ansa was then discharged with a follow-up by a social worker and psychiatrist. After a year of follow-up, she is doing well, and the family situation remains stable.

Early-onset Bipolar Disorder

Studies have shown that bipolar disorder usually begins with an index episode of depression: positive family history ( Pavuluri, Birmaher, & Naylor, 2005 ), clinical severity, psychotic symptoms, and psychomotor retardation are well documented predictors of bipolarity. Approximately 20% of youths with a first major depressive episode will develop a manic episode. Prodromal symptoms of bipolar disorder – hyperactivity, anxiety, dysphoria – have been identified but remain nonspecific (American Academy of Child and Adolescent Psychiatry – AACAP, 2007 ). Ansa’s case illustrates this diagnostic complexity since prodromal symptoms must be taken in the context of environmental instability.

Early-onset bipolar disorder is often considered atypical because of the fluctuating course of symptoms and lack of clear episodes, which defines the classic phenotype ( AACAP, 2007 ). Some authors have introduced the concept of “broad phenotype” of bipolar disorder for youths with extreme irritability, explosiveness, mood variability, and functional impairment. In bipolar disorder literature, one particularity for the pediatric population is the introduction of the concepts of “ultrarapid cycling” (hours to days) and “ultradian cycling” (minutes to hours). Geller et al. (2000) described a prepubertal and early adolescent bipolar disorder (PEA-BP) phenotype which includes both types of cycles.

Although continuity between this “juvenile mania” and adult bipolar disorder has not been established ( Duffy, 2007 ), the prevalence of bipolar disorder diagnoses in children and adolescents is increasing dramatically, with a fortyfold increase in 1993–2004 in the USA ( AACAP, 2007 ). The prevalence of the classic phenotype in prepubertal children is unknown but is considered rare. Ansa represents our service’s earliest manic episode and one of the few prepubertal cases.

The rate of comorbidity between juvenile bipolar disorder and ADHD has been previously described as high in numerous studies. However, a recent review by Anne Duffy (2012) stated that ADHD is not a reliable predictor for the development of juvenile bipolar disorder. The strong overlap of symptoms between the two conditions (distractibility, hyperactivity, talkativeness) raises questions about diagnostic specificity. Thus, DSM-V work groups for bipolar disorder have proposed specifying in the “B” criteria of (hypo)mania that symptoms must absolutely represent a change from baseline ( American Psychiatric Association, 2012b ). This proposal could help reduce the double-counting of symptoms towards ADHD and bipolarity. “Disruptive Mood Dysregulation Disorder” is a proposed additional diagnosis to target youths suffering from sustained irritability ( American Psychiatric Association, 2012a ; Margulies, Weintraub, Basile, Grover, & Carlson 2012 ).

In our opinion, the debate on early-onset bipolar disorder remains important. The AACAP states in its most recent practice parameters that “caution must be taken before applying this diagnosis in preschool children” ( AACAP, 2007 ). The stigma of psychiatric diagnoses and the consequences of mislabeling juveniles should not be minimized. Iatrogenic risks must be weighed against risks of inappropriately treating ill juveniles especially since mood stabilizers are associated with potential serious adverse effects ( Parens & Johnston, 2010 ). Nonetheless, a recent meta-analysis concluded in the efficacy and safety of antipsychotics in early-onset bipolar disorder, leading to the US Food and Drug Administration’s approval of several antipsychotics in juveniles, including aripiprazole ( Liu et al., 2011 ).

Ansa’s case is striking in her fragility to psychosocial stressors and quick improvement with environmental stability and medication. There is little conclusive information on the impact of the environment on the evolution of early-onset bipolar disorder. This is a crucial point since the therapeutic approach might have to target better psychosocial follow-ups with the entire family rather than focus on individual treatments. Ultimately, these issues illustrate the need for more scientific research to better identify and treat patients with bipolar disorder.

The patient and parent have both given written consent to the publication of this paper following an explanation of the procedure. Patient anonymity has been protected.

Acknowledgements/Conflicts of Interest

The authors have no financial relationships to disclose.

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Case Scenario 1: Patient With Bipolar 1 Disorder Reports New Onset Movements

In this custom video series, experts share overall impressions of a female patient with bipolar 1 disorder who develops new onset movements suggesting tardive dyskinesia and the rationale for intervening with VMAT2 therapy.

EP: 1 . Case Scenario 1: Patient With Bipolar 1 Disorder Reports New Onset Movements

EP: 2 . Case Scenario 2: Patient With Tardive Dyskinesia Prescribed a VMAT2 Inhibitor

EP: 3 . Screening for Tardive Dyskinesia and Intervening With VMAT2 Inhibitors

Ep: 4 . assessing severity of tardive dyskinesia, ep: 5 . managing patients on antipsychotic therapy, ep: 6 . anticholinergic medications and impaired cognition, ep: 7 . vmat2 inhibitors for tardive dyskinesia, ep: 8 . treating tardive dyskinesia with a vmat2 inhibitor, ep: 9 . prevention and early detection of tardive dyskinesia.

EP: 10 . Expert Perspectives on Recognition and Management of Tardive Dyskinesia

Leslie L. Citrome, MD, MPH: Welcome to this Psychiatric Times Case-Based Psych Perspectives, expert perspectives on recognition and management of tardive dyskinesia. I am Dr. Leslie Citrome, clinical professor of Psychiatry and Behavioral Sciences at New York Medical College in Valhalla, New York. And joining me is Dr. Rose Mary Xavier, research scientist and psychiatric nurse practitioner with the University of North Carolina at Chapel Hill. Welcome.

Rose Mary Xavier, PhD, MS, RN, PMHNP-BC: Thank you. I am happy to be here.

Leslie L. Citrome, MD, MPH: I am happy to have this conversation here. It is very clinically relevant to our audience. The goal of our discussion today is to provide an overview of tardive dyskinesia, as well as offer insights into the management of this detrimental disease. Let’s start by reviewing a couple of case scenarios and try to figure this out. The first one is a patient with bipolar 1 disorder who reports new onset of movements. This is a 54-year-old woman who received a diagnosis of bipolar 1 disorder at the age of 32, after requiring hospitalization for an acute manic episode. She was started on lithium at that time. She relapsed at age 41 with a florid manic episode requiring psychiatric hospitalization, resulting in an atypical antipsychotic being added to her regimen. She presents for routine follow-up. Her only concern relates to feedback received from her husband. About 6 months ago, her husband began observing constant movement of both her hands while watching television in the living room. He had not seen these types of movements by her before, and they seemed to be increasing in degree. He also frequently asked her if she was chewing gum or if she had something in her eye. This case tells us something about a woman exposed to a dopamine receptor blocking agent, that is an antipsychotic, who develops abnormal movements after some delay. It did not happen right away, but over time they became noticeable. Dr. Xavier, what is your overall impression?

Rose Mary Xavier, PhD, MS, RN, PMHNP-BC: My impression of this case is focusing on the use of antipsychotic medications for treatment of mood disorders, or disorders other than a primary psychotic disorder. When, just reading through this case, there are several things that stand out. Now she is a 54-year-old female. When we look at the risk factors for development of tardive dyskinesia, there are several things that stand out from the studies that have been published. We know that female sex and that the duration of treatment with antipsychotic medications increase the risk for developing tardive dyskinesia. So here we have a 54-year-old female. She has been diagnosed with bipolar disorder. Even though she was started on treatment with lithium, she relapsed at the age of 41 when an atypical antipsychotic medication was added. That is a 13-year history of treatment with antipsychotic medications. And just thinking about, going back to the training period in recent times, we also think about old generation medications, so the first-generation medications would cause tardive dyskinesia. We do not often hear about atypical antipsychotics, but we have data coming in that show that just because a patient is on an atypical medication, it does not diminish the risk for TD [tardive dyskinesia]. The next thing that comes to us is the type of movements that this patient has had. When you look at the case history, we know it has been about 6 months. She has constant movement of both the hands which is increasing in degree progressively, and she has chewing gum type of moments, as well as there is something in her eyes. So talk about the blepharospasm that could occur with TD. She has 4 different types of moments that have been progressively increasing. So it’s a very interesting case, and I look forward to hearing what your thoughts are.

Leslie L. Citrome, MD, MPH: Well, you have highlighted the important points here. She has had a multi-year exposure to an atypical antipsychotic. Atypical antipsychotics today still block postsynaptic dopamine receptors, and we know that is a key ingredient in perhaps the causation of tardive dyskinesia. And her movements, which appeared over time, are delayed. So tardive dyskinesia, tardive delayed dyskinesia, abnormal movement. It all makes sense that that is what we are going to be thinking about in terms of a drug induced movement disorder with her. And I think you pointed out a very important aspect about our treatments today. Although we use atypical antipsychotics, most of the time, they still incur a risk for tardive dyskinesia. They are better in terms of other drug induced movement disorders dramatically, and we do not see as much drug induced Parkinsonism. For example, that rhythmic tremor that appears right after you start an antipsychotic with the shuffling gait or the rigidity, we see a lot less of that. But there is still this liability for tardive dyskinesia. Epidemiological studies tell us that perhaps the prevalence is a little lower with atypical antipsychotics, but it is certainly not zero. My concern with her though is that she is deriving significant benefit from her regimen currently. It is keeping her stable, euthymic. It is preventing the recurrence of mania, which is really devastating for her. It required hospitalization for example. And we know it is very disruptive to functioning. She needs her medicine. And one of the things we cannot really do is stop the antipsychotic. This is what has kept her stable. We need to look at interventions that will allow us to continue her ongoing treatment for her underlying psychiatric disorder. The option in my mind would be something like a VMAT2 [vesicular monoamine transporter type 2] inhibitor, of which two are approved by the FDA [Food and Drug Administration] for the treatment of tardive dyskinesia, which are added to a person's ongoing regimen. If the patient feels secure with their current long-standing regimen, and I'm comfortable with continuing it, and there is a real concern about relapse, that would be my option. And this ties in with our next case where we are going to talk about a patient with tardive dyskinesia who is prescribed a VMAT2 inhibitor.

Transcript edited for clarity.

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Nursing Case Study for Bipolar Disorder

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Kelli is a 20-year-old patient brought to the ER after being reported by neighbors in her apartment complex for disruptive behavior. Law enforcement and emergency medical services were called, and, as a team, decided she needed a higher level of medical care.

The patient says she is” on a break from art college” but works at a local restaurant as a server and occasionally cleans houses as well. She has also sold her paintings and drawings in the past as well. She denies taking any medication. She also says, “I don’t understand why I am here. I was working on my art projects, and I guess I played my music too loud or something. I said I’d come here so I would not be arrested.”

What are some questions that should be included in the initial assessment?

• Ask about drug and alcohol consumption and previous episodes. Make sure she does not intend to harm herself or others. Check to see why the patient does not understand coming to a medical treatment facility (make sure she is lucid). Ask about trauma or accidents.

What interventions do you anticipate being ordered by the provider?

• Obtain old medical charts (there may be a pattern). Screen for drugs and alcohol. Assess for trauma (especially head injury, so neuro checks). Complete a thorough medical history to rule out medical reasons for behavior. Conduct a medical examination including labs (eg. thyroid-stimulating hormone, complete blood count, chemistries)

Kelli’s drug and alcohol tests are negative. Her roommate is now at the bedside and asks to speak to staff privately. She expresses concern that Kelli can be emotional at times as well as going days without sleep then not being able to get out of bed. The nurse returns to further evaluate the patient.

With this new information, what might the nurse ask Kelli?

• Ask about “periods of unusually intense emotion, changes in sleep patterns and activity levels, and uncharacteristic behavior—often without recognizing their likely harmful or undesirable effects” (from NIH). Dig deeper to find if these “episodes” last for long or short periods. Specifically, ask about extreme highs and lows, change in appetite, racing thoughts vs concentration difficulty, risky behaviors (eg gambling, extreme shopping sprees, sexual promiscuity), anxiety, excessive talking, thoughts of death/dying.

Kelli admits to being able to stay awake for what seems like entire weekends without being tired, but that is when she says her creativity is best. When she was attending college and living in the dorms, she says she had lots of friends but worried about what she calls “all the partying.” This is because she liked to “hook up” with strangers because it was fun, but she worries about possible sexually transmitted infections now that she is older. She says she was extremely popular, and her talent was at its peak. But there are times she could not pay attention in class or even get out of bed, so she dropped out of school. Sometimes, she cannot even touch her art supplies, but says she is probably the “most talented artist around.”

What signs and symptoms indicate Kelli may have bipolar disorder?

• Sleep disturbances, cycling between being creative and not being able to concentrate, sexual promiscuity, feelings of grandiosity, loss of pleasure of usual activities

Are there risk factors for this condition?

• The exact cause of bipolar disorder is not clear. The problem may be related to an imbalance of chemicals in the brain such as norepinephrine, serotonin, or dopamine. These chemicals allow cells to communicate with each other and play an essential role in all brain functions, including movement, sensation, memory, and emotions.
• Approximately one to three percent of people worldwide have bipolar disorder. People with a family history of bipolar disorder are at increased risk of developing the condition. Most people develop the first symptoms of bipolar disorder between age 15 to 30 years.

Kelli’s medical records have arrived, and the provider advises nursing staff she has a history of being brought to the ER for similar episodes. The provider says, “This patient is a schizophrenic. We don’t have time for this.”

What is the best response to the provider’s statement?

• As the patient’s advocate, the nurse should advise the provider this is inappropriate. First, it is a disparaging remark. Second, if he means schizophrenic, that is not accurate and as an ER physician should refer the patient for further psychiatric screening and evaluation.
• It is never wrong to stand up to providers or colleagues, but it should be done respectfully and NOT in front of the patient when at all possible.

What should the nurse screen Kelli for at this point?

• Suicidal ideations include whether she has a plan or has attempted suicide in the past. Suicide screening is an ongoing process and not just a few questions at admission. Per UpToDate, “A review estimated that approximately 10 to 15 percent of bipolar patients die by suicide and many studies indicate that the rate of suicide deaths in patients is greater than the rate in the general population.”

How can the nurse address Kelli’s question about help?

• Something like (from uptodate), “Treatment of mania focuses on managing symptoms and keeping you safe. In the early phase of mania (called the acute phase), you may be psychotic (having false, fixed beliefs or hearing voices or seeing things others cannot see or hear). You may not be able to make good decisions and you may be at risk of hurting yourself or others. You may need to be treated in a hospital temporarily, until your medicine begins to work.”
• Also, “Once the worst symptoms of mania or depression are under control, treatment focuses on preventing a recurrence. People who have suffered a manic episode are often advised to continue taking medicine(s) to control bipolar disorder. Although medicines are the treatment of choice for bipolar disorder, counseling and talk therapy also have an important role in treatment. This is especially true after an acute episode has passed. Psychotherapy may include individual counseling as well as education, marital and family therapy, or treatment of alcohol and/or drug abuse. Therapy can help you to stick with your medicine, which can decrease the risk of relapse and the need for hospitalization.”

Kelli is amenable to being held for the state’s required psychological hold. She says she wants to be able to live her life as “normally” as possible. She asks about medications that may be available to help.

What patient education about medications should the nurse provide at this time?

• While it is beyond the scope of the RN to prescribe medications, generalized education on pharmaceutical options is acceptable. Saying something like, “Treatments with medications is recommended for people with bipolar disorder, and studies show starting it early and maintaining it is best.” Point out there may be multiple medications needed and they may need to be changed and/or adjusted for her individual responses.

The nurse knows which medications may be prescribed for long-term management of this condition?

• Mood stabilizers (examples: lithium, valproic acid, divalproex sodium, carbamazepine,and lamotrigine). Antipsychotics. [examples: olanzapine (Zyprexa), risperidone (Risperdal), quetiapine (Seroquel), aripiprazole (Abilify), ziprasidone (Geodon), lurasidone (Latuda) or asenapine (Saphris)] Antidepressants or antidepressant-antipsychotic combo like Symbyax combines the antidepressant fluoxetine and the antipsychotic olanzapine Anti-anxiety medications (example: benzodiazepines)

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Book contents

• Case Studies in Communication Disorders
• Copyright page
• Section A Speech disorders
• Section B Language disorders
• Section C Fluency disorders
• Section D Voice disorders
• Section E Hearing disorders
• Section F Psychiatric disorders
• Case study 45 Girl aged 8 years with selective mutism
• Case study 46 Two boys with attention deficit hyperactivity disorder
• Case study 47 Man aged 26 years with schizophrenia
• Case study 48 Woman aged 24 years with bipolar disorder

Case study 48 - Woman aged 24 years with bipolar disorder

from Section F - Psychiatric disorders

Published online by Cambridge University Press:  09 November 2016

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• Woman aged 24 years with bipolar disorder
• Louise Cummings , Nottingham Trent University
• Book: Case Studies in Communication Disorders
• Online publication: 09 November 2016
• Chapter DOI: https://doi.org/10.1017/CBO9781316651100.055

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Improving quality of life in bipolar disorders with an immersive virtual reality remediation training randomized controlled trial (rct).

1. Introduction

2.1. study design, 2.2. sample, 2.3. experimental and control interventions, 2.4. instrument, 2.5. statistical analysis, 4. discussion, 4.1. limitations, 4.2. implications for research, 5. conclusions, supplementary materials, author contributions, institutional review board statement, informed consent statement, data availability statement, conflicts of interest.

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Primavera, D.; Migliaccio, G.M.; Garau, V.; Orrù, G.; Scano, A.; Perra, A.; Pinna, S.; Tusconi, M.; Carta, M.G.; Sancassiani, F. Improving Quality of Life in Bipolar Disorders with an Immersive Virtual Reality Remediation Training Randomized Controlled Trial (RCT). J. Clin. Med. 2024 , 13 , 3886. https://doi.org/10.3390/jcm13133886

Primavera D, Migliaccio GM, Garau V, Orrù G, Scano A, Perra A, Pinna S, Tusconi M, Carta MG, Sancassiani F. Improving Quality of Life in Bipolar Disorders with an Immersive Virtual Reality Remediation Training Randomized Controlled Trial (RCT). Journal of Clinical Medicine . 2024; 13(13):3886. https://doi.org/10.3390/jcm13133886

Primavera, Diego, Gian Mario Migliaccio, Valentino Garau, Germano Orrù, Alessandra Scano, Alessandra Perra, Samantha Pinna, Massimo Tusconi, Mauro Giovanni Carta, and Federica Sancassiani. 2024. "Improving Quality of Life in Bipolar Disorders with an Immersive Virtual Reality Remediation Training Randomized Controlled Trial (RCT)" Journal of Clinical Medicine 13, no. 13: 3886. https://doi.org/10.3390/jcm13133886

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Research on clinical aspects of bipolar disorder: A review of Indian studies

Affiliations.

• 1 Department of Psychiatry, Postgraduate Institute of Medical Educations and Research, Chandigarh, India.
• 2 Department of Psychiatry, All India Institute of Medical Sciences, Kalyani, West Bengal, India.
• 3 Consultant Psychiatrist, ASHA Hospital, Hyderabad, Telangana, India.
• 4 Department of Psychiatry, Government Medical College and Hospital, Nagpur, Maharashtra, India.
• PMID: 38919568
• PMCID: PMC11195747
• DOI: 10.4103/indianjpsychiatry.indianjpsychiatry_698_23

Background: Bipolar disorder is one of the severe mental disorders that are associated with significant morbidity of the patients. Despite advancements in our understanding about the disorder, it remains a challenging proposition to treat bipolar disorder, largely since the prophylactic treatment of the disorder requires assessment of complex clinical algorithms. The revisions of the classificatory systems have also changed the conceptualization of the disorder. In this background, we conducted a review of the Indian studies conducted on the clinical aspects of bipolar disorder.

Methods: A narrative review was conducted with focus on the literature published from India. The databases searched included PubMed, Scopus, and Google Scholar, and articles published over the last 15 years by Indian authors were included for this review.

Results: In our review, we could access a substantial volume of research published from India. We could identify studies that catered to most of the relevant themes in bipolar disorder including epidemiology, etiology, comorbidities, stigma, disability, clinical course, cognitive profile, pathways to care, and recovery.

Conclusion: The research trajectory was in line with the research conducted elsewhere in the world. However, certain dissimilarities in terms of focus could also be observed. The possible reason behind this deviation could be the difference in clinical need and unique challenges faced in the management and rehabilitation of patients in bipolar disorder in Indian scenario.

Keywords: Bipolar disorder; India; clinical research; etiopathogenesis; neurobiology.

Copyright: © 2024 Indian Journal of Psychiatry.

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Conflict of interest statement

There are no conflicts of interest.

Infographic summarizing salient features of…

Infographic summarizing salient features of Indian research on bipolar disorder over the last…

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• Introduction
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ADHD indicates attention-deficit/hyperactivity disorder; CVD, cardiovascular disease.

a Controls were derived from the same base cohort as the cases; thus, a case with a later date of CVD diagnosis could potentially serve as a control for another case in the study.

Crude odds ratios (ORs) were based on cases and controls matched on age, sex, and calendar time. Adjusted ORs (AORs) were based on cases and controls matched on age, sex, and calendar time and adjusted for country of birth, educational level, somatic comorbidities (type 2 diabetes, obesity, dyslipidemia, and sleep disorders), and psychiatric comorbidities (anxiety disorders, autism spectrum disorder, bipolar disorder, conduct disorder, depressive disorder, eating disorders, intellectual disability, personality disorders, schizophrenia, and substance use disorders).

The solid lines represent the adjusted odds ratios, and the shaded areas represent the 95% CIs. In restricted cubic splines analysis, knots were placed at the 10th, 50th, and 90th percentiles of ADHD medication use.

eTable 1. International Classification of Diseases (ICD) Codes from the Swedish National Inpatient Register

eTable 2. Type of Cardiovascular Disease in Cases

eTable 3. Risk of CVD Associated With ADHD Medication Use Across Different Average Defined Daily Doses

eTable 4. Risk of CVD Associated With Cumulative Duration of Use of Different Types of ADHD Medications

eTable 5. Sensitivity Analyses of CVD Risk Associated With Cumulative Use of ADHD Medications, Based On Different Cohort, Exposure, and Outcome Definitions

eFigure. Risk of CVD Associated With Cumulative Use of ADHD Medications, Stratified by Sex

Data Sharing Statement

• Long-Term ADHD Medications and Cardiovascular Disease Risk JAMA Medical News in Brief December 26, 2023 Emily Harris
• Long-Term Cardiovascular Effects of Medications for ADHD—Balancing Benefits and Risks of Treatment JAMA Psychiatry Editorial February 1, 2024 Samuele Cortese, MD, PhD; Cristiano Fava, MD, PhD

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Zhang L , Li L , Andell P, et al. Attention-Deficit/Hyperactivity Disorder Medications and Long-Term Risk of Cardiovascular Diseases. JAMA Psychiatry. 2024;81(2):178–187. doi:10.1001/jamapsychiatry.2023.4294

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Attention-Deficit/Hyperactivity Disorder Medications and Long-Term Risk of Cardiovascular Diseases

• 1 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
• 2 Unit of Cardiology, Heart and Vascular Division, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
• 3 School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
• 4 Department of Applied Health Science, School of Public Health, Indiana University, Bloomington
• 5 Department of Psychological and Brain Sciences, Indiana University, Bloomington
• Editorial Long-Term Cardiovascular Effects of Medications for ADHD—Balancing Benefits and Risks of Treatment Samuele Cortese, MD, PhD; Cristiano Fava, MD, PhD JAMA Psychiatry
• Medical News in Brief Long-Term ADHD Medications and Cardiovascular Disease Risk Emily Harris JAMA

Question   Is long-term use of attention-deficit/hyperactivity disorder (ADHD) medication associated with an increased risk of cardiovascular disease (CVD)?

Findings   In this case-control study of 278 027 individuals in Sweden aged 6 to 64 years who had an incident ADHD diagnosis or ADHD medication dispensation, longer cumulative duration of ADHD medication use was associated with an increased risk of CVD, particularly hypertension and arterial disease, compared with nonuse.

Meaning   Findings of this study suggest that long-term exposure to ADHD medications was associated with an increased risk of CVD; therefore, the potential risks and benefits of long-term ADHD medication use should be carefully weighed.

Importance   Use of attention-deficit/hyperactivity disorder (ADHD) medications has increased substantially over the past decades. However, the potential risk of cardiovascular disease (CVD) associated with long-term ADHD medication use remains unclear.

Objective   To assess the association between long-term use of ADHD medication and the risk of CVD.

Design, Setting, and Participants   This case-control study included individuals in Sweden aged 6 to 64 years who received an incident diagnosis of ADHD or ADHD medication dispensation between January 1, 2007, and December 31, 2020. Data on ADHD and CVD diagnoses and ADHD medication dispensation were obtained from the Swedish National Inpatient Register and the Swedish Prescribed Drug Register, respectively. Cases included individuals with ADHD and an incident CVD diagnosis (ischemic heart diseases, cerebrovascular diseases, hypertension, heart failure, arrhythmias, thromboembolic disease, arterial disease, and other forms of heart disease). Incidence density sampling was used to match cases with up to 5 controls without CVD based on age, sex, and calendar time. Cases and controls had the same duration of follow-up.

Exposure   Cumulative duration of ADHD medication use up to 14 years.

Main Outcomes and Measures   The primary outcome was incident CVD. The association between CVD and cumulative duration of ADHD medication use was measured using adjusted odds ratios (AORs) with 95% CIs.

Results   Of 278 027 individuals with ADHD aged 6 to 64 years, 10 388 with CVD were identified (median [IQR] age, 34.6 [20.0-45.7] years; 6154 males [59.2%]) and matched with 51 672 control participants without CVD (median [IQR] age, 34.6 [19.8-45.6] years; 30 601 males [59.2%]). Median (IQR) follow-up time in both groups was 4.1 (1.9-6.8) years. Longer cumulative duration of ADHD medication use was associated with an increased risk of CVD compared with nonuse (0 to ≤1 year: AOR, 0.99 [95% CI, 0.93-1.06]; 1 to ≤2 years: AOR, 1.09 [95% CI, 1.01-1.18]; 2 to ≤3 years: AOR, 1.15 [95% CI, 1.05-1.25]; 3 to ≤5 years: AOR, 1.27 [95% CI, 1.17-1.39]; and >5 years: AOR, 1.23 [95% CI, 1.12-1.36]). Longer cumulative ADHD medication use was associated with an increased risk of hypertension (eg, 3 to ≤5 years: AOR, 1.72 [95% CI, 1.51-1.97] and >5 years: AOR, 1.80 [95% CI, 1.55-2.08]) and arterial disease (eg, 3 to ≤5 years: AOR, 1.65 [95% CI, 1.11-2.45] and >5 years: AOR, 1.49 [95% CI, 0.96-2.32]). Across the 14-year follow-up, each 1-year increase of ADHD medication use was associated with a 4% increased risk of CVD (AOR, 1.04 [95% CI, 1.03-1.05]), with a larger increase in risk in the first 3 years of cumulative use (AOR, 1.08 [95% CI, 1.04-1.11]) and stable risk over the remaining follow-up. Similar patterns were observed in children and youth (aged <25 years) and adults (aged ≥25 years).

Conclusions and Relevance   This case-control study found that long-term exposure to ADHD medications was associated with an increased risk of CVDs, especially hypertension and arterial disease. These findings highlight the importance of carefully weighing potential benefits and risks when making treatment decisions about long-term ADHD medication use. Clinicians should regularly and consistently monitor cardiovascular signs and symptoms throughout the course of treatment.

Attention-deficit/hyperactivity disorder (ADHD) is a common psychiatric disorder characterized by developmentally inappropriate inattentiveness, impulsivity, and hyperactivity. 1 , 2 Pharmacological therapy, including both stimulants and nonstimulants, is recommended as the first-line treatment for ADHD in many countries. 1 , 3 The use of ADHD medication has increased greatly in both children and adults during the past decades. 4 Although the effectiveness of ADHD medications has been demonstrated in randomized clinical trials (RCTs) and other studies, 5 , 6 concerns remain regarding their potential cardiovascular safety. 7 Meta-analyses of RCTs have reported increases in heart rate and blood pressure associated with both stimulant and nonstimulant ADHD medications. 5 , 7 - 9

As RCTs typically evaluate short-term effects (average treatment duration of 75 days), 7 it remains uncertain whether and to what extent the increases in blood pressure and heart rate associated with ADHD medication lead to clinically significant cardiovascular disease (CVD) over time. Longitudinal observational studies 10 - 12 examining the association between ADHD medication use and serious cardiovascular outcomes have emerged in recent years, but the findings have been mixed. A meta-analysis 13 of observational studies found no statistically significant association between ADHD medication and risk of CVD. However, the possibility of a modest risk increase cannot be ruled out due to several methodological limitations in these studies, including confounding by indication, immortal time bias, and prevalent user bias. Additionally, most of these studies had an average follow-up time of no more than 2 years. 13 , 14 Thus, evidence regarding the long-term cardiovascular risk of ADHD medication use is still lacking.

Examining the long-term cardiovascular risk associated with ADHD medicine use is clinically important given that individuals with a diagnosis of ADHD, regardless of whether they receive treatment, face an elevated risk of CVD. 15 Additionally, a substantial proportion of young individuals with ADHD continues to have impairing symptoms in adulthood, 16 necessitating prolonged use of ADHD medication. Notably, studies have indicated a rising trend in the long-term use of ADHD medications, with approximately half of individuals using ADHD medication for over 5 years. 17 Furthermore, evidence is lacking regarding how cardiovascular risk may vary based on factors such as type of CVD, type of ADHD medication, age, and sex. 13 Therefore, there is a need for long-term follow-up studies to address these knowledge gaps and provide a more comprehensive understanding of the cardiovascular risks associated with ADHD medication use. This information is also crucial from a public health perspective, particularly due to the increasing number of individuals receiving ADHD medications worldwide. 4

This study aimed to assess the association between cumulative use of ADHD medication up to 14 years and the risk of CVD by using nationwide health registers in Sweden. We hypothesized that longer cumulative use of ADHD medication would be associated with increased CVD risk. In addition, we aimed to examine whether the associations differ across types of ADHD medication, types of CVD, sex, and age groups.

We used data from several Swedish nationwide registers linked through unique personal identification numbers. 18 Diagnoses were obtained from the National Inpatient Register, 19 which contains data on inpatient diagnoses since 1973 and outpatient diagnoses since 2001. Information on prescribed medications was retrieved from the Swedish Prescribed Drug Register, which contains all dispensed medications in Sweden since July 2005 and includes information on drug identity based on the Anatomical Therapeutic Chemical (ATC) classification, 20 dispensing dates, and free-text medication prescriptions. Socioeconomic factors were obtained from the Longitudinal Integrated Database for Health Insurance and Labour Market studies. 21 Information on death was retrieved from the Swedish Cause of Death Register, 22 which contains information on all deaths since 1952. The study was approved by the Swedish Ethical Review Authority. Informed patient consent is not required for register-based studies in Sweden. The study followed the Reporting of Studies Conducted Using Observational Routinely Collected Health Data–Pharmacoepidemiological Research ( RECORD-PE ) guideline. 23

We conducted a nested case-control study of all individuals residing in Sweden aged 6 to 64 years who received an incident diagnosis of ADHD or ADHD medication dispensation 15 between January 1, 2007, and December 31, 2020. The diagnosis of ADHD ( International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ ICD-10 ] code F90) was identified from the National Inpatient Register. Incident ADHD medication dispensation was identified from the Swedish Prescribed Drug Register and was defined as a dispensation after at least 18 months without any ADHD medication dispensation. 24 Baseline (ie, cohort entry) was defined as the date of incident ADHD diagnosis or ADHD medication dispensation, whichever came first. Individuals with ADHD medication prescriptions for indications other than ADHD 25 and individuals who emigrated, died, or had a history of CVD before baseline were excluded from the study. The cohort was followed until the case index date (ie, the date of CVD diagnosis), death, migration, or the study end date (December 31, 2020), whichever came first.

Within the study cohort, we identified cases as individuals with an incident diagnosis of any CVD (including ischemic heart diseases, cerebrovascular diseases, hypertension, heart failure, arrhythmias, thromboembolic disease, arterial disease, and other forms of heart disease; eTable 1 in Supplement 1 ) during follow-up. For each case, the date of their CVD diagnosis was assigned as the index date. Using incidence density sampling, 26 up to 5 controls without CVD were randomly selected for each case from the base cohort of individuals with ADHD. The matching criteria included age, sex, and calendar time, ensuring that cases and controls had the same duration of follow-up from baseline to index date. Controls were eligible for inclusion if they were alive, living in Sweden, and free of CVD at the time when their matched case received a diagnosis of CVD, with the index date set as the date of CVD diagnosis of the matched case ( Figure 1 ). Controls were derived from the same base cohort as the cases. Thus, a case with a later date of CVD diagnosis could potentially serve as a control for another case in the study. 26

The main exposure was cumulative duration of ADHD medication use, which included all ADHD medications approved in Sweden during the study period, including stimulants (methylphenidate [ATC code N06BA04], amphetamine [ATC code N06BA01], dexamphetamine [ATC code N06BA02], and lisdexamfetamine [ATC code N06BA12]) as well as nonstimulants (atomoxetine [ATC code N06BA09] and guanfacine [ATC code C02AC02]). Duration of ADHD medication use was derived from a validated algorithm that estimates treatment duration from free text in prescription records. 25 The cumulative duration of ADHD medication use was calculated by summing all days covered by ADHD medication between baseline and 3 months prior to the index date. The last 3 months before the index date were excluded to reduce reverse causation, as clinicians’ perception of potential cardiovascular risks may influence ADHD medication prescription. This time window was chosen because routine psychiatric practice in Sweden limits a prescription to a maximum 3 months at a time. 27 Individuals with follow-up of less than 3 months were excluded.

We conducted conditional logistic regression analyses to estimate odds ratios (ORs) for the associations between cumulative durations of ADHD medication use and incident CVD. Crude ORs were adjusted for all matching variables (age, sex, and calendar time) by design. Adjusted ORs (AORs) were additionally controlled for country of birth (Sweden vs other), highest educational level (primary or lower secondary, upper secondary, postsecondary or postgraduate, or unknown; individuals aged <16 years were included as a separate category), and diagnoses of somatic (type 2 diabetes, obesity, dyslipidemia, and sleep disorders) and psychiatric comorbidities (anxiety disorders, autism spectrum disorder, bipolar disorder, conduct disorder, depressive disorder, eating disorders, intellectual disability, personality disorders, schizophrenia, and substance use disorders; eTable 1 in Supplement 1 ) before baseline. The association between cumulative ADHD medication use and incident CVD was assessed using both continuous and categorical measures (no ADHD medication use, 0 to ≤1, 1 to ≤2, 2 to ≤3, 3 to ≤5, and >5 years). To capture potential nonlinear associations, we used restricted cubic splines to examine ADHD medication use as a continuous measure throughout follow-up. 28 The associations were examined in the full sample and stratified by age at baseline, that is, children or youth (<25 years old) and adults (≥25 years old). Furthermore, to evaluate the association with dosage of ADHD medication, we estimated the risk of CVD associated with each 1-year increase in use of ADHD medication across different dosage groups categorized by the average defined daily dose (DDD; for instance, 1 DDD of methylphenidate equals 30 mg) during follow-up. 29

In subgroup analyses, we examined the associations between ADHD medication use and specific CVDs, including arrhythmias, arterial disease, cerebrovascular disease, heart failure, hypertension, ischemic heart disease, and thromboembolic disease (eTable 1 in Supplement 1 ). Additionally, we investigated the associations with CVD risk for the most commonly prescribed ADHD medications in Sweden, ie, methylphenidate, lisdexamfetamine, and atomoxetine, while adjusting for other ADHD medication use. We also examined sex-specific associations.

To further examine the robustness of our findings, we conducted 4 sensitivity analyses. First, we restricted the sample to ever users of ADHD medication to reduce unmeasured confounding between ADHD medication users and nonusers. Second, we assessed ADHD medication exposure over the entire follow-up period without excluding the 3 months prior to the index date. Third, to capture fatal cardiovascular events, we additionally included death by CVD in the outcome definition. Finally, we constructed a conditional logistic regression model that adjusted for propensity scores of ADHD medication use. Data management was performed using SAS, version 9.4 (SAS Institute Inc) and all analyses were performed using R, version 4.2.3 (R Foundation for Statistical Computing).

The study cohort consisted of 278 027 individuals with ADHD aged 6 to 64 years. The incidence rate of CVD was 7.34 per 1000 person-years. After applying exclusion criteria and matching, the analysis included 10 388 cases (median [IQR] age at baseline, 34.6 (20.0-45.7) years; 6154 males [59.2%] and 4234 females [40.8%]) and 51 672 matched controls (median [IQR] age at baseline, 34.6 [19.8-45.6] years; 30 601 males [59.2%] and 21 071 females [40.8%]) ( Figure 1 and Table 1 ). Median (IQR) follow-up in both groups was 4.1 (1.9-6.8) years. Among the controls, 3363 had received a CVD diagnosis after their index dates. The most common types of CVD in cases were hypertension (4210 cases [40.5%]) and arrhythmias (1310 cases [12.6%]; eTable 2 in Supplement 1 ). Table 1 presents the sociodemographic information and somatic and psychiatric comorbidities in cases and controls. In general, cases had higher rates of somatic and psychiatric comorbidities and a lower level of educational attainment compared with controls.

A similar proportion of cases (83.9%) and controls (83.5%) used ADHD medication during follow-up, with methylphenidate being the most commonly dispensed type, followed by atomoxetine and lisdexamfetamine. Longer cumulative duration of ADHD medication use was associated with an increased risk of CVD compared with nonuse (0 to ≤1 year: AOR, 0.99 [95% CI, 0.93-1.06]; 1 to ≤2 years: AOR, 1.09 [95% CI, 1.01-1.18]; 2 to ≤3 years: AOR, 1.15 [95% CI, 1.05-1.25]; 3 to ≤5 years: AOR, 1.27 [95% CI, 1.17-1.39]; and >5 years: AOR, 1.23 [95% CI, 1.12-1.36]) ( Figure 2 ). The restricted cubic spline model suggested a nonlinear association, with the AORs increasing rapidly for the first 3 cumulative years of ADHD medication use and then becoming stable thereafter ( Figure 3 ). Throughout the entire follow-up, each 1-year increase in the use of ADHD medication was associated with a 4% increased risk of CVD (AOR, 1.04 [95% CI, 1.03-1.05]), and the corresponding increase for the first 3 years was 8% (AOR, 1.08 [95% CI, 1.04-1.11]). We observed similar results when examining children or youth and adults separately ( Figure 2 ). The restricted cubic spline model suggested a similar nonlinear association, with higher AORs in children or youth than in adults, but the 95% CIs largely overlapped ( Figure 3 ). Furthermore, similar associations were observed for females and males (eFigure in Supplement 1 ). The dosage analysis showed that the risk of CVD associated with each 1 year of ADHD medication use increased with higher average DDDs. The risk was found to be statistically significant only among individuals with a mean dose of at least 1.5 times the DDD (eTable 3 in Supplement 1 ). For example, among individuals with a mean DDD of 1.5 to 2 or less (eg, for methylphenidate, 45 to ≤60 mg), each 1-year increase in ADHD medication use was associated with a 4% increased risk of CVD (AOR, 1.04 [95% CI, 1.02-1.05]). Among individuals with a mean DDD >2 (eg, for methylphenidate >60 mg), each 1-year increase in ADHD medication use was associated with 5% increased risk of CVD (AOR, 1.05 [95% CI, 1.03-1.06]).

When examining the risk for specific CVDs, we found that long-term use of ADHD medication (compared with no use) was associated with an increased risk of hypertension (AOR, 1.72 [95% CI, 1.51-1.97] for 3 to ≤5 years; AOR, 1.80 [95% CI 1.55-2.08] for >5 years) ( Table 2 ), as well as arterial disease (AOR, 1.65 [95% CI, 1.11-2.45] for 3 to ≤5 years; AOR, 1.49 [95% CI 0.96-2.32] for >5 years). However, we did not observe any statistically significant increased risk for arrhythmias, heart failure, ischemic heart disease, thromboembolic disease, or cerebrovascular disease ( Table 2 ). Furthermore, long-term use of methylphenidate (compared with no use) was associated with an increased risk of CVD (AOR, 1.20 [95% CI, 1.10-1.31] for 3 to ≤5 years; AOR, 1.19 [95% CI, 1.08-1.31]) for >5 years; eTable 4 in Supplement 1 ). Compared with no use, lisdexamfetamine was also associated with an elevated risk of CVD (AOR, 1.23 [95% CI, 1.05-1.44] for 2 to ≤3 years; AOR, 1.17 [95% CI, 0.98-1.40] for >3 years), while the AOR for atomoxetine use was significant only for the first year of use (1.07 [95% CI 1.01-1.13]; eTable 4 in Supplement 1 ).

In sensitivity analyses, we observed a similar pattern of estimates when the analysis was restricted to ever users of ADHD medications. Significantly increased risk of CVD was found when comparing ADHD medication use for 1 year or less with use for 3 to 5 or less years (AOR, 1.28 (95% CI, 1.18-1.38) or for use for more than 5 years (AOR, 1.24 [95% CI, 1.13-1.36]) (eTable 5 in Supplement 1 ). When assessing ADHD medication use across the entire follow-up period, and compared with no use, the pattern of estimates was similar to the main analysis (3 to ≤5 years: AOR, 1.28 [95% CI, 1.18-1.39]; >5 years: AOR, 1.25 [95% CI, 1.14-1.37]) (eTable 5 in Supplement 1 ). The analysis that included cardiovascular death as a combined outcome also had results similar to the main analysis. Moreover, when adjusting for propensity scores of ADHD medication use, the findings remained consistent (eTable 5 in Supplement 1 ).

This large, nested case-control study found an increased risk of incident CVD associated with long-term ADHD medication use, and the risk increased with increasing duration of ADHD medication use. This association was statistically significant both for children and youth and for adults, as well as for females and males. The primary contributors to the association between long-term ADHD medication use and CVD risk was an increased risk of hypertension and arterial disease. Increased risk was also associated with stimulant medication use.

We found individuals with long-term ADHD medication use had an increased risk of incident CVD in a dose-response manner in the first 3 years of cumulative ADHD medication use. To our knowledge, few previous studies have investigated the association between long-term ADHD medication use and the risk of CVD with follow-up of more than 2 years. 13 The only 2 prior studies with long-term follow-up (median, 9.5 and 7.9 years 30 , 31 ) found an average 2-fold and 3-fold increased risk of CVD with ADHD medication use compared with nonuse during the study period, yet 1 of the studies 30 included only children, and participants in the other study 31 were not the general population of individuals with ADHD (including those with ADHD and long QT syndrome). Furthermore, both studies were subject to prevalent user bias. Results from the current study suggest that the CVD risk associated with ADHD medication use (23% increased risk for >5 years of ADHD medication use compared with nonuse) is lower than previously reported. 30 , 31 Furthermore, we observed that the increased risk stabilized after the first several years of medication use and persisted throughout the 14-year follow-up period.

The association between ADHD medication use and CVD was significant for hypertension and arterial disease, while no significant association was observed with other types of cardiovascular events. To our knowledge, only 1 previous study 12 has examined the association between ADHD medication use and clinically diagnosed hypertension, and it found an increased risk, although the increase was not statistically significant. Furthermore, increased blood pressure associated with ADHD medication use has been well documented. 7 , 9 One study 32 found that blood pressure was mainly elevated during the daytime, suggesting that the cardiovascular system may recover at night. However, the cross-sectional nature of that study cannot preclude a long-term risk of clinically diagnosed hypertension associated with ADHD medication use. We also identified an increased risk for arterial disease. To date, no previous study has explored the association between ADHD medication use and arterial disease. A few studies have reported that ADHD medication may be associated with changes in serum lipid profiles, but the results were not consistent. 33 , 34 Further research is needed on the potential implications of ADHD medications for individuals’ lipid profiles. We did not observe any association between ADHD medication use and the risk of arrhythmias. A recent systematic review of observational studies of ADHD medication use reported an elevated risk of arrhythmias, but the finding was not statistically significant. 13 A review of RCTs also found that the use of stimulants was associated with an average increase in heart rate of 5.7 beats/min, 9 but no evidence of prolonged QT interval or tachycardia was found based on electrocardiograms. 7 Additionally, it is worth noting that some individuals receiving ADHD medications might be prescribed antiarrhythmic β-blockers to alleviate palpitation symptoms, thus potentially attenuating an association between ADHD medications and arrhythmias. Nevertheless, the absence of an association between ADHD medication use and clinically diagnosed arrhythmias in the present study does not rule out an increased risk for mild arrhythmias or subclinical symptoms, as palpitations and sinus tachycardia are not routinely coded as arrhythmia diagnoses. Further research is necessary to replicate our findings.

Regarding types of ADHD medication, findings of the present study suggest that increasing cumulative durations of methylphenidate and lisdexamfetamine use were associated with incident CVD, while the associations for atomoxetine were statistically significant only for the first year of use. Previous RCTs have reported increased blood pressure and heart rate with methylphenidate, lisdexamfetamine, and atomoxetine, 5 , 35 , 36 but the mechanisms behind these adverse effects are still a topic of debate; there might be differences in cardiovascular adverse effects in stimulants vs nonstimulants. 37

We found that the association between cumulative duration of ADHD medication use and CVD was similar in females and males. Previous investigations exploring sex-specific association found higher point estimates in females, although the differences were not statistically significant. 13 Research has indicated that females diagnosed with ADHD may demonstrate different comorbidity patterns and potentially have different responses to stimulant medications compared with males. 38 - 40 Therefore, additional studies are needed to explore and better understand the potential sex-specific differences in cardiovascular responses to ADHD medications.

A strength of this study is that data on ADHD medication prescriptions and CVD diagnoses were recorded prospectively, so the results were not affected by recall bias. The findings should, however, be interpreted in the context of several limitations. First, our approach for identification of patients with CVD was based on recorded diagnoses and there could be under ascertainment of cardiovascular diagnoses in the registers used. This means that some controls may have had undiagnosed CVD that did not yet require medical care, which would tend to underestimate associations between ADHD medication use and CVD. Second, exposure misclassification may have occurred if patients did not take their medication as prescribed. This misclassification, if nondifferential, would tend to reduce ORs such that the estimates we observed were conservative. Third, while we accounted for a wide range of potential confounding variables, considering the observational nature of the study and the possibility of residual confounding, we could not prove causality. It is possible that the association observed might have been affected by time-varying confounders. For example, other psychotropic medications and lifestyle factors could have affected both ADHD medication use and the occurrence of cardiovascular events. 41 , 42 Confounding by ADHD severity is also a potential factor to consider, as individuals with more severe ADHD symptoms may have more comorbidities and a less healthy lifestyle, which could affect the risk of CVD. Fourth, the study did not examine the risk of CVD among individuals with preexisting CVD. Individuals with preexisting CVD represent a distinct clinical group that requires careful monitoring; thus, evaluating the risk among them necessitates a different study design that carefully considers the potential impact of prior knowledge and periodic monitoring. Finally, the results by type of ADHD medication and type of CVD need to be replicated by studies with larger sample sizes.

The results of this population-based case-control study with a longitudinal follow-up of 14 years suggested that long-term use of ADHD medication was associated with an increased risk of CVD, especially hypertension and arterial disease, and the risk was higher for stimulant medications. These findings highlight the importance of carefully weighing potential benefits and risks when making treatment decisions on long-term ADHD medication use. Clinicians should be vigilant in monitoring patients, particularly among those receiving higher doses, and consistently assess signs and symptoms of CVD throughout the course of treatment. Monitoring becomes even more crucial considering the increasing number of individuals engaging in long-term use of ADHD medication.

Accepted for Publication: August 29, 2023.

Published Online: November 22, 2023. doi:10.1001/jamapsychiatry.2023.4294

Open Access: This is an open access article distributed under the terms of the CC-BY License . © 2023 Zhang L et al. JAMA Psychiatry .

Corresponding Authors: Zheng Chang, PhD ( [email protected] ) and Le Zhang, PhD ( [email protected] ), Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Nobels väg 12A, 171 65 Stockholm, Sweden.

Author Contributions: Dr Zhang and Prof Chang had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Zhang, Johnell, Larsson, Chang.

Acquisition, analysis, or interpretation of data: Zhang, Li, Andell, Garcia-Argibay, Quinn, D'Onofrio, Brikell, Kuja-Halkola, Lichtenstein, Johnell, Chang.

Drafting of the manuscript: Zhang.

Critical review of the manuscript for important intellectual content: All authors.

Statistical analysis: Zhang, Li.

Obtained funding: Larsson, Chang.

Administrative, technical, or material support: Garcia-Argibay, D'Onofrio, Kuja-Halkola, Lichtenstein, Chang.

Supervision: Andell, Lichtenstein, Johnell, Larsson, Chang.

Conflict of Interest Disclosures: Dr Larsson reported receiving grants from Takeda Pharmaceuticals and personal fees from Takeda Pharmaceuticals, Evolan, and Medici Medical Ltd outside the submitted work. No other disclosures were reported.

Funding/Support: This study was supported by grants from the Swedish Research Council for Health, Working Life, and Welfare (2019-01172 and 2022-01111) (Dr Chang) and the European Union’s Horizon 2020 research and innovation program under grant agreement 965381 (Dr Larsson).

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Data Sharing Statement: See Supplement 2 .

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Beyond therapeutic potential: a systematic investigation of ketamine misuse in patients with depressive disorders

• Open access
• Published: 01 July 2024
• Volume 4 , article number  23 , ( 2024 )

Cite this article

You have full access to this open access article

• Keshav Juneja 1 ,
• Sabah Afroze 2 ,
• Zeel Goti 3 ,
• Sweta Sahu   ORCID: orcid.org/0000-0003-2555-2584 4 ,
• Shivani Asawa 3 ,
• Hamsa Priya Bhuchakra 5 &
• Balaganesh Natarajan 6  

Ketamine, a pharmacological agent that acts as an antagonist of the N-methyl-D-aspartate (NMDA) receptor, has garnered considerable interest because of its notable and expeditious antidepressant properties observed in individuals diagnosed with major depressive disorder (MDD) who exhibit resistance to conventional therapeutic interventions. A comprehensive and rigorous systematic review was undertaken to evaluate the prevalence of ketamine abuse undergoing ketamine treatment for depressive disorders. A comprehensive search was conducted across the electronic databases to identify pertinent studies published between 2021 and 2023. The present investigation incorporated a comprehensive range of studies encompassing the abuse or misuse of ketamine, including case reports, observational studies, and clinical trials. Data extraction and quality assessment were conducted in accordance with predetermined criteria. The findings of this systematic review demonstrate the importance of monitoring and addressing ketamine abuse in patients receiving ketamine treatment for depressive disorders like MDD. The wide range of reported prevalence rates highlights the need for standardized criteria and measures for defining and assessing ketamine abuse. This study presents a significant contribution to the field by introducing a novel screening questionnaire and assessment algorithm designed to identify and evaluate ketamine misuse among major depressive disorder (MDD) patients undergoing ketamine treatment. This innovative tool holds the potential to enhance clinical practice by providing healthcare professionals with a standardized approach to promptly detect and address ketamine misuse. The integration of this screening tool into routine care protocols can facilitate more effective monitoring and management of ketamine misuse in this population, ultimately leading to improved patient outcomes and safety.

Avoid common mistakes on your manuscript.

1 Introduction

Several studies have shown that ketamine has strong and rapid antidepressant effects in patients with major depressive disorder (MDD) [ 1 , 2 ]. Ketamine is becoming a popular therapy because it quickly relieves symptoms of depression. However, besides its therapeutic advantages, ketamine misuse is a potential problem in this population [ 3 ]. Ketamine misuse refers to the inappropriate or non-medical use of ketamine, where individuals use the substance outside legitimate medical purposes or in doses or frequencies other than prescribed. Misuse can include using ketamine to achieve a high for recreational purposes or in ways not intended by healthcare professionals [ 4 ]. Ketamine misuse can lead to various negative consequences, including addiction and cognitive impairment. Healthcare professionals should closely monitor ketamine administration to ensure its appropriate use and minimize the risk of abuse. Ongoing research aims to develop alternative treatments with similar rapid antidepressant effects but without the potential for misuse associated with ketamine.

Ketamine abuse can result in various negative outcomes, particularly when used at higher dosages. Ketamine abuse represents a more severe form of misuse, characterized by recurrent and problematic use despite negative consequences. This includes patterns of ketamine use that lead to significant impairments in daily functioning, psychological dependence, and potential physical harm [ 5 ]. Memory deficiencies and concentration issues are among the cognitive impairments linked to persistent ketamine misuse, according to recent research [ 4 ]. Ketamine use over an extended period has also been associated with the emergence of psychiatric conditions such as depersonalization-derealization disorder and hallucinogen persistent perception disorder (HPPD) [ 5 ]. These results underline the importance of thoroughly monitoring and treating the potential dangers of ketamine use in patients with MDD.

The psychotomimetic properties of ketamine have increased its potential for abuse. Ketamine is appealing for recreational use because it can cause dissociation and psychedelic experiences [ 6 ]. However, this also raises the possibility of abuse and complicates the treatment of patients with MDD. The possibility of abuse has been made much more likely by ketamine's accessibility outside medical settings. The illegal use of ketamine has increased, especially among young adults and those looking to treat their depressive symptoms [ 7 ]. The potential for misuse in this population is worsened by the simplicity of ketamine administration. Furthermore, ketamine abuse can occur when it diverts from its intended medicinal purposes. Since there is a chance that ketamine will be abused, it is typically only delivered in therapeutic settings under close supervision. There have been cases of people attempting to obtain ketamine from medical sources for purposes other than those for which it was prescribed [ 8 ]. Such a diversion jeopardizes patient safety and highlights the necessity for strict ketamine use supervision and regulation.

Healthcare providers must be attentive to monitoring patients' use of ketamine because of the risk of abuse and addiction. To protect patients' well-being, a recent study routinely checked for indicators of abuse and dependence while undergoing ketamine treatment [ 9 ]. By implementing these measures, healthcare providers can maintain a comprehensive approach to patient care and help mitigate the potential negative consequences of ketamine use. The implementation thorough screening methods and monitoring systems can make it easier to identify abuse early and enable the necessary actions. In conclusion, ketamine abuse among individuals utilizing ketamine for this purpose cannot be ignored, even though ketamine is a promising drug for successful treatment of MDD. According to recent studies, the risk of abuse is influenced by cognitive deficits, psychotomimetic effects, availability outside medical settings, and diversion from medical use. Healthcare practitioners should prioritize monitoring and regulating ketamine use to reduce the risk of misuse among MDD patients [ 10 , 11 ].

2 Methodology

2.1 search strategy.

This study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, which are used extensively to conduct effective research [ 10 ]. The literature-based search for this article was conducted on scientific databases such as the National Library of Medicine (Pubmed), Medline-Ovid, Cochrane Central Register of Controlled Trials (CENTRAL) of Cochrane Library along with Pubmed Central (PMC), and Google Scholar with the utilization of the following medical subject heading (MeSH) such as ‘Ketamine Abuse’, ‘Ketamine misuse in bipolar disorder’, ‘ketamine in major depressive disorder’, ‘bipolar depressive disorder’, ‘unipolar depressive disorder’, and ‘treatment-resistant disorder’ along with many more.

2.2 Inclusion criteria

The Studies included in our search focused on ketamine usage among patients with psychiatric disorders, particularly major depressive disorder or bipolar disorder.

Only studies published between 2012 and 2023 were considered, with a preference for those available in English.

2.3 Exclusion criteria

Studies not available in English or lacking full-text accessibility were excluded.

Studies did not include the ketamine use or those published before 2012 were also excluded.

2.4 Eligibility & extraction

The titles and abstracts were initially screened to assess study eligibility based on the criteria outlined above. English-language articles were preferred, and randomized controlled trials were preferred. Review articles, case series, and case reports were also included. Eligible articles underwent a thorough full-text review and analysis, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines (Fig.  1 ).

PRISMA diagram for studies selection, eligibility, and data extraction

2.5 Quality assessment using Newcastle Ottawa Scale (NOS)

The quality of included studies was assessed using the Newcastle Ottawa Scale (NOS), a widely recognized tool for evaluating the methodological quality of non-randomized studies in systematic reviews and meta-analyses [ 11 ]. The NOS assesses studies based on three main criteria: selection of study groups, comparability of groups, and ascertainment of the exposure or outcome of interest.

Each study was independently evaluated by two authors to determine its quality rating on the NOS. Discrepancies in ratings were resolved through consensus or consultation with a third author. Studies were categorized into two quality levels based on the NOS score:

Excellent: studies with a high methodological quality and minimal risk of bias across all evaluated criteria.

Fair: studies with some limitations in methodological quality but still providing valuable information.

The NOS findings for each included study are summarized in (Table  1 ), highlighting key quality indicators such as selection of study participants, comparability of study groups, and outcome assessment.

The papers selected for the study were reviewed, and (Table  2 ) provides the details of data extracted from the research articles. Studies have indicated that ketamine usage is positively correlated with reducing the symptoms of depressive episodes and decreasing suicidal scoring or ideation, primarily MADRS score.

4 Discussion

The ketamine derivative of phenylene is used as a rapid-acting intravenous drug along with its sustained antidepressant effect on the human body, mainly in depressive disorders, both major and minor. It is known to positively affect depression and suicidal ideation in patients [ 12 ].

4.1 Clinical applications of ketamine

Ketamine has been used in the treatment of several psychiatric conditions, such as major depressive disorder (MDD), treatment-resistant depression (TRD), bipolar disorder (BD), and post-traumatic stress disorder (PTSD). Subanesthetic dosages of ketamine elicit prompt antidepressant and antisuicidal effects in individuals diagnosed with Major Depressive Disorder (MDD), Treatment-Resistant Depression (TRD), and Bipolar Disorder (BD). The FDA granted approval for the use of esketamine nasal spray (Spravato ® ) for the treatment of treatment-resistant depression (TRD). Although ketamine shows potential as a treatment for various diseases, its psychoactive side effects have hindered its widespread use. This finding highlights the need to thoroughly understand the potential for addiction [ 13 ].

However, its misuse can lead to non-specific clinical symptoms ranging in the extent of symptom appearance, which can be mild or chronic. Some signs include biliary dilation, abnormality in liver function, hydronephrosis, and cholangitis in some cases. It was suggested that after a thorough investigation of ketamine usage during depressive disorders, it might result in an elevated response and remission ratio with a reduction in rating scale scores over placebo or midazolam [ 12 ].

4.2 Therapeutic effects of ketamine in depressive disorders

Antidepressants and anti-suicidal drugs are prescribed to them owing to the fact that a significant portion of their life is spent in depression and pessimistic thoughts. Major depressive disorder, specifically treatment-resistant depression, whose etiology is not known, was reviewed for the purpose of this study. The ventral prefrontal cortex (PFC) and striatum, the primary reward circuits of the brain were observed, and proposed that ketamine elevates the functional connectivity of the frontal striatal circuit of TRD.

The ventral prefrontal cortex (PFC) and striatum, the primary reward circuits of the brain were observed, and proposed that ketamine elevates the functional connectivity of the frontal striatal circuit of TRD. Ketamine usage was correlated with sustained improvement in patients with TRD, along with stability of frontal striatal connections in their brains.

4.3 Clinical presentation, diagnosis, and management of Major Depressive Disorder (MDD)

The study group belonged to the age category of adults, mainly 18 years or older. The studies by Dean et al. [ 12 ] and Hassan et al. [ 14 ] consisted of larger sample sizes of 5299 and 664, respectively. Larger cohorts indicate reliable results and validity of inferences. The studies included were predominantly control trials with placebo or other factors controlled to ensure the gold standard of research utilized to derive this outcome.

Major depressive disorders are reported to be the ones with a lack of energy and persistently pessimistic behavior, along with complaints of anhedonia, agitation, and sleep issues [ 12 , 15 ]. Suicidal thoughts are also holding prominence in major depressive disorder [ 16 ]. Antidepressants, along with other psychological and pharmacological therapeutic methodologies, are used to overcome depression and remission among patients with MDD. The constant use of medications causes resistance to the treatment of depression. In contrast, first line of antidepressants, such as NMDAR antagonists, are not always beneficial to the patient. If two or more antidepressant medications do not provide aid to patients with depression, their depression is marked as treatment-resistant depression with electroconvulsive therapy or other severe measures to be used for ease of symptoms. Such treatments are available to make patients with MDD feel better, along with the urge to increase their quality of life by the team of professionals adept at handling such cases [ 17 ].

Bipolar disorder, along with MDD, is among the classes of psychiatric diseases requiring constant care and management, as a significant portion of a patient's life is spent in depression and the urge to fight it. Treatment resistance and failure are significantly higher in patients with bipolar disorder than in those with other types of MDD [ 12 ]. We utilized patients with bipolar disorder in many studies alongside other psychiatric disorders, such as unipolar disorder. The diagnostic criteria used vary among patients within MDD. Some studies utilized the DSM-IV, DSM-V, ICD-10, and many different scales to diagnose bipolar, unipolar, or major depressive disorders among individuals [ 17 ].

4.4 Ketamine use in MDD

Ketamine has garnered significant attention for its remarkable efficacy in treating MDD, especially treatment-resistant depression (TRD). Numerous clinical trials and meta-analyses have demonstrated the rapid onset of antidepressant effects, often within hours to days of administration. For instance, a meta-analysis pooled data from several randomized controlled trials (RCTs) and reported a significant reduction in depressive symptoms within 24 h of ketamine infusion [ 18 ]. Zarate et al. [ 19 ] showed sustained antidepressant effects lasting up to several weeks post-treatment [ 19 ].

While ketamine's efficacy is promising, its use in MDD necessitates careful consideration of safety and tolerability. Short-term adverse effects commonly include dissociation, transient increase in blood pressure, and cognitive impairment. Long-term concerns such as the potential for abuse and cognitive decline also warrant attention. To mitigate risks, clinicians implement dose optimization strategies and closely monitor patients during and after ketamine administration [ 20 ].

Patient selection criteria for ketamine therapy typically include a diagnosis of MDD, failure to respond to conventional antidepressant treatments, and absence of contraindications such as psychosis or unstable medical conditions. Dosing regimens vary, but often involve intravenous infusion of ketamine at subanesthetic doses, with treatment frequency ranging from weekly to monthly. However, the emergence of alternative administration routes, such as intranasal ketamine, offers flexibility in treatment delivery and may improve patient adherence. Daly et al. [ 21 ] compared intravenous and intranasal ketamine and found comparable efficacy and tolerability between the two routes [ 21 ].

Ongoing research seeks to optimize ketamine's therapeutic potential in MDD and address unresolved issues. Novel formulations, including esketamine nasal spray, represent an advancement in treatment delivery and have received regulatory approval for TRD. Combination therapies involving ketamine and traditional antidepressants or psychotherapy are being investigated to enhance treatment outcomes and prolong remission. However, challenges persist, such as determining optimal maintenance strategies to sustain antidepressant effects and identifying reliable predictors of treatment response. Collaborative efforts between clinicians, researchers, and pharmaceutical companies are crucial for advancing ketamine-based therapies and improving outcomes for individuals with MDD.

4.5 Ketamine effect on the brain

Ketamine operates primarily at the molecular level as an antagonist of the N-methyl-D-aspartate (NMDA) receptor. This interaction disrupts glutamatergic neurotransmission, leading to downstream effects on neural signaling and circuitry in the brain. By blocking NMDA receptors, ketamine alters the balance between excitatory and inhibitory neurotransmission, which is crucial for various cognitive and emotional processes [ 22 ]. One of the most intriguing aspects of ketamine's mechanism is its potential to enhance neuroplasticity and promote synaptic connectivity. This phenomenon is particularly relevant for the observed antidepressant effects. Studies have suggested that ketamine administration can stimulate the growth of new synaptic connections and facilitate the remodeling of existing neural circuits. These changes may underlie the rapid and sustained improvements in mood observed after ketamine treatment.

Research has highlighted the effect of ketamine on key brain regions involved in mood regulation, including the prefrontal cortex, hippocampus, and amygdala. A study by Reed et al. [ 23 ] used functional magnetic resonance imaging (fMRI) to demonstrate that ketamine administration led to increased activation in the prefrontal cortex, a region associated with emotional regulation and cognitive control [ 23 ]. Another study by Rawat et al. [ 24 ] utilized structural MRI to show that ketamine induced rapid and transient increases in hippocampal volume, suggesting a potential role in promoting neurogenesis and synaptic plasticity [ 24 ]. Scheidegger et al. [ 25 ] found that ketamine administration reduced amygdala hyperactivity, a common feature of mood disorders, and restored normal fear responses [ 25 ].

In addition to its actions on NMDA receptors, ketamine modulates various neurotransmitter systems, including glutamate, gamma-aminobutyric acid (GABA), and monoamines such as serotonin and dopamine. Ketamine's effects on these neurotransmitters play a crucial role in shaping its therapeutic profile and may contribute to its efficacy in treating mood disorders. A study by Aleksandrova et al. [ 26 ] demonstrated that ketamine's rapid antidepressant effects were dependent on its ability to increase glutamate release and activate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors [ 26 ].

Ketamine exerts its effects on the brain through a multifaceted mechanism involving NMDA receptor antagonism, modulation of neurotransmitter systems, and promotion of neuroplasticity. Understanding these neurobiological mechanisms is essential for elucidating ketamine's therapeutic potential and developing novel treatments for mood disorders.

4.6 Assessment of ketamine treatment efficacy, and clinical outcomes

The studies utilized MADRS scoring primarily to determine the effect of ketamine by assessing and recording the scores before and after treatment for optimal comparison and analysis. One study showed that a few dosages, such as three intakes of ketamine therapy, reported a positive improvement in the severity of depressive episodes along with an improvement in PHQ-9 and GAD-7 scores in half of the patients. Scores improved by up to 60% in patients who completed the six ketamine therapy courses recommended clinically. The anxiety category with moderate to severe category patients showed a reduction in anxiety after three dosages with GAD-7 score improvement and a 50% reduction in scores compared to the scores at baseline of the study [ 14 ].

Bryant et al. [ 27 ] characterized a group of six elderly patients who had received short and long-term maintenance phases of ketamine infusions. Five of six patients demonstrated a significant reaction, indicating the promising effects of ketamine infusion [ 28 ].

4.7 Analogues of ketamine

Analogues Analogs of ketamine represent a diverse array of compounds that share structural similarities or pharmacological properties with ketamine etsketamine (S)-ketamine and R enantiomer (R)-ketamine (arketamine), two notable analogs of ketamine. Esketamine is the S-enantiomer of ketamine, a dissociative anesthetic agent originally developed in the 1960s. It is a non-competitive NMDA receptor antagonist that blocks the action of N-methyl-D-aspartate (NMDA) receptors in the brain. Arketamine is the R-enantiomer of ketamine. Similar to esketamine, it is a non-competitive NMDA receptor antagonist. Although esketamine has been developed and approved for the treatment of depression, its potential therapeutic effects are still being investigated [ 29 ].

Esketamine has garnered attention for its rapid and robust antidepressant effects, leading to FDA approval for the treatment of Major Depressive Disorder (MDD). Conversely, arketamine, an enantiomer of ketamine, has also demonstrated promising effects in MDD treatment. In an open-label pilot trial, seven participants with Treatment-Resistant Depression (TRD) who received only one intravenous infusion provided data on arketamine. Administration of 0.5 mg/kg arketamine resulted in a decrease in the Montgomery-Asberg Depression Rating Scale (MADRS) scores with minimal signs of dissociation. This distinction between esketamine (S)-ketamine and arketamine is essential, as both enantiomers may offer unique therapeutic benefits and safety profiles in the treatment of MDD [ 28 ]. Wei et al. asserted that NMDAR is frequently involved in the mechanism by which antidepressants function with arketamine. However, the principal biochemical mechanism by which ketamine functions to treat depression is not known [ 30 ].

4.8 Ketamine in electroconvulsive therapy

Electroconvulsive therapy (ECT), the most effective treatment for depressive disorders, and ketamine were compared. There is an abundance of interest in the findings of a glutamate-modulating pharmaceutical that reduced depression-related symptoms and enabled patients to recuperate within hours of receiving a single IV Subanesthetic dosage, so they compared it to electroconvulsive therapy to investigate the reliability of ketamine effect in MDD or TRD. Among patients receiving ECT, 63% of patients remitted and felt better, whereas 45% of ketamine-treated patients remitted, indicating that the remission rate was higher in the ECT group with 47/94(61%) patients remitted, and 44/97 (45%) remitted in ketamine-treated group (chi 2  = 4.5, P = 0.034, 95% CI [1.1%, 29]) [ 31 ].

4.9 Ketamine in pediatric usage

Ketamine is widely used as a pediatric anesthetic drug during medical procedures. Repeated exposure to subanesthetic doses of ketamine can result in extensive neuronal degeneration in the developing nervous system of neonates [ 32 ]. However, it is unknown whether this might cause cognitive impairment in the adult brain. NMDA receptors in the central nervous system play a role in myelination, which is essential for the development of neurons and optimal cognitive functioning [ 33 ]. However, it is unclear whether ketamine exposure during brain development can inhibit myelination and subsequently impair cognitive function in adults. This issue should be researched to address concerns regarding the use of ketamine in pediatric anesthesia.

The findings of this study demonstrated that ketamine, prenatal exposure to the experimental setting, or both enhanced MBP transcription in the mPFC of adult female rats. Ketamine was also shown to cause more MBP expression, which renders it a safe medication for pediatric anesthesia [ 34 ].

4.10 Misuse of ketamine

The efficacy of ketamine as an antidepressant medication has been questioned, while adverse outcomes of ketamine treatment in depressed individuals, particularly long-term consequences, remain only partially understood. Acute and temporary side effects are frequent, and include alterations in cognition, hypertension, anxiety, dissociation, and vertigo. Additionally, there are cases of hepatocellular and urinary intoxication among recreational drug users and patients receiving recurrent high dosages of medications for pain [ 31 ].

4.11 Ketamine misuse mechanism

Ketamine, a rapid-acting antidepressant, is sustained for up to 7 days in patients with TRD and suicidal patients. Its use was done sparingly for managing TRD and MDD or both, but due to abuse, addiction, and side effects, it has been minimized [ 15 ]. The formation of subcortical areas, such as the nucleus accumbens, which is linked to addiction behaviors, is influenced by the disruption of glutamate neurotransmission, which is connected to ketamine addiction. Additionally, studies have demonstrated that NMDA receptor-targeting glutamatergic drugs have distinct antidepressant qualities that effectively reduce suicidal thoughts [ 35 ]. γ-Aminobutyric acid (GABA), serotonin, dopamine, opioids, sigma, and cholinergic receptors are some of the additional low-affinity pharmaceutical targets of ketamine, in addition to voltage-gated sodium levels and hyperpolarization-activated cyclic nucleotide-gated channels [ 36 ]. This may result in various outcomes resulting from acute to long-term ketamine usage. For instance, GABA is the primary inhibiting neurotransmitter in the human brain, and optimal communication between neurons and cognitive performance depends on a healthy equilibrium between inhibitory and excitatory synaptic transmissions. Convulsions in the brain were the patient's primary symptoms, potentially due to insufficient inhibitory effects such as GABA. However, the functional significance of the impact of ketamine on GABA receptors is unknown [ 37 ]. According to a recent study [ 38 ], the effect of GluN2B-NMDARs on GABA neurons causes a single sub-anesthetic dose of ketamine to have an immediate and long-lasting antidepressant effect. This suggests that ketamine may not act directly on other receptors (aside from NMDA receptors) but may also have secondary effects. The medication dosage used for abuse is the same as or even higher than the amount used for therapy, which is usually 1–2 mg/kg body weight. Furthermore, extended-period ketamine users might exhibit a decrease in frontal gray matter volume on MRI [ 39 ]. Consequently, it was anticipated that researchers would identify cerebral atrophy on CT scans in patients with long-term ketamine abuse. AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid) receptors are linked to ketamine damage. Additionally, a study found that atypical protein tau phosphorylation at specific locations mediates alterations in membrane AMPA receptors and synaptic functioning caused by ketamine. There is a correlation between addictive substances and alterations in brain volume as reported by Liu et al. [ 15 ].

4.12 Consideration of risks and side effects

While ketamine demonstrates significant therapeutic potential in the treatment of depressive disorders, it is not without risks, particularly when used inappropriately or excessively. Understanding and acknowledging these potential adverse effects is crucial for informed decision making in clinical practice.

Prolonged or excessive use of ketamine has been associated with a range of adverse effects on hepatic, urinary, and neurological functioning. Studies have documented hepatic dysfunction, urinary tract abnormalities, and neurological impairments among individuals misusing ketamine [ 15 ].

Long-term misuse of ketamine has raised concerns regarding its potential to induce brain atrophy and neurological damage. Chronic ketamine abuse has been linked to structural alterations in the brain, including reductions in gray matter volume and disruptions in neural connectivity [ 17 ]. Studies have reported significant brain atrophy and neurological dysfunction in individuals with a history of prolonged ketamine misuse, highlighting the need for caution and vigilance in its use [ 40 ].

4.13 Safe intake

Ketamine usage using the prescribed method and design is advised to avoid the adverse effects of ketamine usage. The potential benefits of ketamine in TRD are of significant importance, which can pave the way for the substantial use of ketamine in major depressive disorders, such as unipolar and bipolar depression.

The absence of sufficient data about the addictive potential of ketamine as a psychiatric treatment does not deter its usage when deemed necessary. However, prudence is required, akin to benzodiazepines and stimulants. Medical practitioners should exercise caution when prescribing ketamine while remaining attentive to potential emerging data that could alter the balance between risks and benefits.

4.14 Limitations

The lack of extensive data with the availability of cohort data on this subject limits the study with the recommendation of further observational and cohort studies along with randomized control trials. The combined effect of other drugs with ketamine should also be observed, and enantiomers with decreased risk of addiction or brain atrophy should be developed to increase the quality of life of patients with major depressive disorder who spend a significant amount of time fighting the internal battle of mental health, which is of prime importance.

Our systematic review acknowledges several potential biases that could affect the interpretation of our findings. First, publication bias may have affected our results, as studies with statistically significant or positive outcomes were more likely to be published, potentially skewing our synthesis of evidence. Selection bias could have affected the generalizability of our findings. Although we aimed to include a wide range of studies, certain populations or types of studies may have been disproportionately included in our review. We conducted a comprehensive search using predefined criteria to minimize bias in study selection. The quality and characteristics of the included studies could influence the overall conclusions of our systematic review.

While our review provides valuable insights into ketamine misuse in major depressive disorder patients with MDD, readers should interpret the findings within the context of these acknowledged biases. Future research should address these biases through more rigorous study designs and transparent reporting practices.

4.15 Future implications

The correlation between the ketamine abuse and depressive disorders is a multifaceted problem that necessitates inventive approaches to enhance timely identification, tailored treatment strategies, and overall psychological welfare. Progress in technology, including artificial intelligence and machine learning, has the potential to transform the screening procedures for depressive illnesses. Predictive algorithms can examine behavioral patterns, social media activity, and biomarkers to detect the initial indications of depression. The integration of wearable gadgets and smartphone applications has the potential to provide real-time data, leading to more precise treatment. Pharmacological precision medicine can provide guidance for the proper use of ketamine in a closely supervised setting, thereby reducing the likelihood of its misuse. Telemedicine and remote monitoring have the potential to improve the availability of mental health services, making it easier to identify individuals who are at risk of misusing ketamine or experiencing symptoms of depression at an early stage. Integrated care models have the potential to facilitate a more cohesive approach to mental health care by dismantling barriers between primary care, mental health services, and drug misuse. Ethical considerations are vital, as it is essential to strike a balance between technological development and individual privacy. Prudent supervision and guidelines are necessary for ethical administration of ketamine in the management of depressive disorders. By adopting these advancements, we come closer to a more thorough and efficient strategy for dealing with the intricate relationship between ketamine abuse, depressive conditions, and overall psychological welfare. The tools available for the diagnosis of such abuse can also be utilized, as shown in Table  3 and Fig.  2 .

Assessment of patients for ketamine abuse

5 Conclusion

Ketamine has demonstrated potent and expeditious antidepressant properties in individuals diagnosed with depressive disorders such as Major Depressive Disorder (MDD). However, overuse of ketamine can lead to undesirable outcomes such as addiction and cognitive damage. Healthcare practitioners should diligently oversee the administration of ketamine to guarantee its proper utilization and mitigate the potential for misuse. The abuse of ketamine can lead to a range of adverse consequences, such as cognitive impairment, mental disorders, and physiological ailments. Prolonging and excessive use of ketamine can cause adverse hepatic and urinary effects along with the risk of brain atrophy. The implementation of comprehensive screening procedures and monitoring systems is crucial for promptly detecting instances of abuse and taking appropriate measures. Notwithstanding its potential advantages, ketamine abuse must not be disregarded, and stringent oversight and control are important. This study introduces a valuable contribution to the field through a novel screening questionnaire and assessment algorithm tailored for individuals with MDD undergoing ketamine treatment, offering healthcare professionals a standardized tool to promptly detect and address ketamine misuse. Integrating this innovative approach into routine care protocols enhances monitoring, mitigates risks, and underscores the importance of stringent oversight and control in addressing the complex issue of ketamine abuse in this population.

Data availability

No datasets were generated or analysed during the current study.

Abbreviations

• Major depressive disorder

Hallucinogen persistent perception disorder

Preferred reporting items for systematic reviews and meta-analysis

Newcastle Ottawa scale

Unipolar major depressive disorder

Research diagnostic criteria

Diagnostic and statistical manual of mental disorders

International classification of diseases

Hamilton depression rating scale

Montgomery–Åsberg depression rating scale

Treatment-resistant bipolar disease

Bipolar disease

Post traumatic stress disorder

Treatment-resistant depression

Hypertension

Emotionally instable personality disorder

Pre-frontal cortex

N-methyl D-aspartate receptor

Patient Health Questionnaire-9

α- Amino-3 hydroxy- 5-methyl -4 isoxazolepropionic acid

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Contributions

In this systematic review titled "Beyond Therapeutic Potential: A Systematic Investigation of Ketamine Misuse in Major Depressive Disorder Patients," the collaborative efforts of the authors are outlined as follows: K. J. conceived and designed the study, acquired data, conducted analysis, and interpreted results. Drafted and critically revised the manuscript for important intellectual content. S.A. contributed substantially to the acquisition, analysis, and interpretation of data. Participated in drafting and revising the manuscript for intellectual content. Z. G. provided expertise in the systematic review process, including study design, data extraction, and critical appraisal. Contributed to drafting and revising the manuscript. S.S. is involved in the analysis and interpretation of data. Provided critical feedback during the manuscript drafting and revising process. S.A. contributed to the acquisition and interpretation of data. Participated in drafting and revising the manuscript for important intellectual content. B.H. made a substantial contribution to the study conception, design, and interpretation of results. Participated in the critical revision of the manuscript. B.N. involved in the acquisition and analysis of data. Provided critical feedback during the drafting and revising of the manuscript. All authors have read and approved the final version of the manuscript. Each author takes public responsibility for the content and agrees to be accountable for all aspects of the work, ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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Correspondence to Sweta Sahu .

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Juneja, K., Afroze, S., Goti, Z. et al. Beyond therapeutic potential: a systematic investigation of ketamine misuse in patients with depressive disorders. Discov Ment Health 4 , 23 (2024). https://doi.org/10.1007/s44192-024-00077-2

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Received : 13 February 2024

Accepted : 17 June 2024

Published : 01 July 2024

DOI : https://doi.org/10.1007/s44192-024-00077-2

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