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Journal of Child and Adolescent... Dec 2022Pediatric bipolar disorder (PBD) is a severe psychiatric illness diagnosed before the age of 18, which is associated with extreme shifts in mood characterized by manic... (Review)
Review
Pediatric bipolar disorder (PBD) is a severe psychiatric illness diagnosed before the age of 18, which is associated with extreme shifts in mood characterized by manic and depressive episodes. In 2005, AACAP published algorithms to guide pharmacological treatment of manic/mixed episodes associated with PBD. At that time, lithium was the only Food and Drug Administration (FDA)-approved treatment for pediatric bipolar manic/mixed episodes. The goal of this article is to review evidence that has emerged since the AACAP algorithm in 2005. Literature searches were conducted through PubMed and limited to studies published between 2005 and 2021, using keywords that focused on randomized controlled trials (RCTs) for available psychopharmacological medications. In addition, the authors conducted in-depth searches for articles providing evidence for agents included in the 2005 AACAP algorithm. Since the publication of the AACAP algorithm in 2005, multiple RCTs have been conducted in PBD, leading to FDA approval of five medications (aripiprazole, asenapine, olanzapine, quetiapine, and risperidone) for the treatment of manic/mixed episodes and two medications (lurasidone and olanzapine-fluoxetine combination) for the treatment of depressed episodes. Divalproex sodium and oxcarbazepine were studied in pediatric RCTs and failed to separate from placebo. We offer an update to the 2005 AACAP algorithms for the treatment of pediatric bipolar mixed/manic episodes and added an evidence-based algorithm for the treatment of depression in PBD. In addition to treatment algorithms, we review current evidence for efficacy of agents proposed in the AACAP algorithm and provide tables summarizing medication side effects and efficacy.
Topics: Humans; Child; Bipolar Disorder; Antipsychotic Agents; Mania; Olanzapine; Algorithms
PubMed: 36472471
DOI: 10.1089/cap.2022.0035 -
Lancet (London, England) Dec 2020Bipolar disorders are a complex group of severe and chronic disorders that includes bipolar I disorder, defined by the presence of a syndromal, manic episode, and... (Review)
Review
Bipolar disorders are a complex group of severe and chronic disorders that includes bipolar I disorder, defined by the presence of a syndromal, manic episode, and bipolar II disorder, defined by the presence of a syndromal, hypomanic episode and a major depressive episode. Bipolar disorders substantially reduce psychosocial functioning and are associated with a loss of approximately 10-20 potential years of life. The mortality gap between populations with bipolar disorders and the general population is principally a result of excess deaths from cardiovascular disease and suicide. Bipolar disorder has a high heritability (approximately 70%). Bipolar disorders share genetic risk alleles with other mental and medical disorders. Bipolar I has a closer genetic association with schizophrenia relative to bipolar II, which has a closer genetic association with major depressive disorder. Although the pathogenesis of bipolar disorders is unknown, implicated processes include disturbances in neuronal-glial plasticity, monoaminergic signalling, inflammatory homoeostasis, cellular metabolic pathways, and mitochondrial function. The high prevalence of childhood maltreatment in people with bipolar disorders and the association between childhood maltreatment and a more complex presentation of bipolar disorder (eg, one including suicidality) highlight the role of adverse environmental exposures on the presentation of bipolar disorders. Although mania defines bipolar I disorder, depressive episodes and symptoms dominate the longitudinal course of, and disproportionately account for morbidity and mortality in, bipolar disorders. Lithium is the gold standard mood-stabilising agent for the treatment of people with bipolar disorders, and has antimanic, antidepressant, and anti-suicide effects. Although antipsychotics are effective in treating mania, few antipsychotics have proven to be effective in bipolar depression. Divalproex and carbamazepine are effective in the treatment of acute mania and lamotrigine is effective at treating and preventing bipolar depression. Antidepressants are widely prescribed for bipolar disorders despite a paucity of compelling evidence for their short-term or long-term efficacy. Moreover, antidepressant prescription in bipolar disorder is associated, in many cases, with mood destabilisation, especially during maintenance treatment. Unfortunately, effective pharmacological treatments for bipolar disorders are not universally available, particularly in low-income and middle-income countries. Targeting medical and psychiatric comorbidity, integrating adjunctive psychosocial treatments, and involving caregivers have been shown to improve health outcomes for people with bipolar disorders. The aim of this Seminar, which is intended mainly for primary care physicians, is to provide an overview of diagnostic, pathogenetic, and treatment considerations in bipolar disorders. Towards the foregoing aim, we review and synthesise evidence on the epidemiology, mechanisms, screening, and treatment of bipolar disorders.
Topics: Adolescent; Adult; Anticonvulsants; Antidepressive Agents; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Carbamazepine; Cardiovascular Diseases; Child; Child Abuse; Comorbidity; Depressive Disorder, Major; Environmental Exposure; Humans; Lamotrigine; Lithium; Mania; Suicide; Valproic Acid; Young Adult; Suicide Prevention
PubMed: 33278937
DOI: 10.1016/S0140-6736(20)31544-0 -
Translational Psychiatry Jan 2022Mania, the diagnostic hallmark of bipolar disorder, is an episodic disturbance of mood, sleep, behavior, and perception. Improved understanding of the neurobiology of... (Review)
Review
Mania, the diagnostic hallmark of bipolar disorder, is an episodic disturbance of mood, sleep, behavior, and perception. Improved understanding of the neurobiology of mania is expected to allow for novel avenues to address current challenges in its diagnosis and treatment. Previous research focusing on the impairment of functional neuronal circuits and brain networks has resulted in heterogenous findings, possibly due to a focus on bipolar disorder and its several phases, rather than on the unique context of mania. Here we present a comprehensive overview of the evidence regarding the functional neuroanatomy of mania. Our interpretation of the best available evidence is consistent with a convergent model of lateralized circuit dysfunction in mania, with hypoactivity of the ventral prefrontal cortex in the right hemisphere, and hyperactivity of the amygdala, basal ganglia, and anterior cingulate cortex in the left hemisphere of the brain. Clarification of dysfunctional neuroanatomic substrates of mania may contribute not only to improve understanding of the neurobiology of bipolar disorder overall, but also highlights potential avenues for new circuit-based therapeutic approaches in the treatment of mania.
Topics: Amygdala; Bipolar Disorder; Humans; Magnetic Resonance Imaging; Mania; Neuroanatomy
PubMed: 35075120
DOI: 10.1038/s41398-022-01786-4 -
Neuroscience and Biobehavioral Reviews Mar 2021Bipolar disorder is a mental health disorder characterized by extreme shifts in mood, high suicide rate, sleep problems, and dysfunction of psychological traits like... (Review)
Review
Bipolar disorder is a mental health disorder characterized by extreme shifts in mood, high suicide rate, sleep problems, and dysfunction of psychological traits like self-esteem (feeling inferior when depressed and superior when manic). Bipolar disorder is rare among populations that have not adopted contemporary Western lifestyles, which supports the hypothesis that bipolar disorder results from a mismatch between Homo sapiens's evolutionary and current environments. Recent studies have connected bipolar disorder with low-grade inflammation, the malfunctioning of the internal clock, and the resulting sleep disturbances. Stress is often a triggering factor for mania and sleep problems, but stress also causes low-grade inflammation. Since inflammation desynchronizes the internal clock, chronic stress and inflammation are the primary biological mechanisms behind bipolar disorder. Chronic stress and inflammation are driven by contemporary Western lifestyles, including stressful social environments, unhealthy dietary patterns, limited physical activity, and obesity. The treatment of bipolar disorder should focus on reducing stress, stress sensitivity, and inflammation by lifestyle changes rather than just temporarily alleviating symptoms with psychopharmacological interventions.
Topics: Affect; Biological Evolution; Bipolar Disorder; Humans; Sleep Wake Disorders; Suicide
PubMed: 33421542
DOI: 10.1016/j.neubiorev.2020.12.031 -
The Journal of Neuropsychiatry and... 2022The aim of this study was to assess the perception of speech in adverse acoustic conditions during manic and depressive episodes of mood disorders.
OBJECTIVE
The aim of this study was to assess the perception of speech in adverse acoustic conditions during manic and depressive episodes of mood disorders.
METHODS
Forty-three patients with bipolar disorder (mania, N=20; depression, N=23) and 32 patients with unipolar depression were included for analyses. Thirty-five participants served as the control group. The study of speech understanding was carried out using the Polish Sentence Matrix Test, allowing for the determination of the speech reception threshold (SRT). The test was performed in the clinical groups both during an acute episode and remission; during remission, patients underwent audiometric evaluation.
RESULTS
Compared with control subjects, patients with mood disorders had worse speech understanding (higher SRT), regardless of the episode or remission. A manic episode in the course of bipolar disorder was not associated with worse speech understanding compared with remission of mania. However, an episode of depression in the course of both bipolar disorder and unipolar depression was associated with worse speech understanding compared with remission of depression. In bipolar depression, this correlated with age, duration of the disorder, number of episodes, and number of hospitalizations, as well as in remission with age and duration of illness. In unipolar depression, poor speech understanding was more severe in individuals with hearing impairment.
CONCLUSIONS
These findings revealed that patients with mood disorders had impaired speech understanding, even while in remission, and manic episodes in the course of bipolar disorder were not associated with impaired speech understanding compared with mania remission.
Topics: Bipolar Disorder; Depressive Disorder; Humans; Mania; Mood Disorders; Speech
PubMed: 35414193
DOI: 10.1176/appi.neuropsych.21050125 -
European Child & Adolescent Psychiatry Feb 2013The publication of the DSM-5 is nearing, yet a debate continues about the boundaries of bipolar disorder (BP) in children and adolescents. This article focuses on two... (Review)
Review
The publication of the DSM-5 is nearing, yet a debate continues about the boundaries of bipolar disorder (BP) in children and adolescents. This article focuses on two key components of this debate that are often treated under the collective term mood dysregulation: the first is chronic irritability (and the proposed DSM-5 category of disruptive mood dysregulation disorder) and the other concerns short episodes of mania-like symptoms. We update our previous review [Stringaris in Eur Child Adolesc Psychiatry 20(2):61-66, 2011] and also present relevant neurobiological evidence. Most findings so far suggests that chronic, severe irritability is not a developmental presentation of mania. The diagnostic status of brief duration hypomania is less clear, with some evidence in support of its clinical relevance to BP. We end with recommendations for future research to inform classification and treatment.
Topics: Adolescent; Adolescent Psychiatry; Affect; Bipolar Disorder; Child; Child Psychiatry; Diagnostic and Statistical Manual of Mental Disorders; Humans; Irritable Mood
PubMed: 23229139
DOI: 10.1007/s00787-012-0355-9 -
The New England Journal of Medicine Aug 2023Antidepressants are used to treat acute depression in patients with bipolar I disorder, but their effect as maintenance treatment after the remission of depression has... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Antidepressants are used to treat acute depression in patients with bipolar I disorder, but their effect as maintenance treatment after the remission of depression has not been well studied.
METHODS
We conducted a multisite, double-blind, randomized, placebo-controlled trial of maintenance of treatment with adjunctive escitalopram or bupropion XL as compared with discontinuation of antidepressant therapy in patients with bipolar I disorder who had recently had remission of a depressive episode. Patients were randomly assigned in a 1:1 ratio to continue treatment with antidepressants for 52 weeks after remission or to switch to placebo at 8 weeks. The primary outcome, assessed in a time-to-event analysis, was any mood episode, as defined by scores on scales measuring symptoms of hypomania or mania, depression, suicidality, and mood-episode severity; additional treatment or hospitalization for mood symptoms; or attempted or completed suicide. Key secondary outcomes included the time to an episode of mania or hypomania or depression.
RESULTS
Of 209 patients with bipolar I disorder who participated in an open-label treatment phase, 150 who had remission of depression were enrolled in the double-blind phase in addition to 27 patients who were enrolled directly. A total of 90 patients were assigned to continue treatment with the prescribed antidepressant for 52 weeks (52-week group) and 87 were assigned to switch to placebo at 8 weeks (8-week group). The trial was stopped before full recruitment was reached owing to slow recruitment and funding limitations. At 52 weeks, 28 of the patients in the 52-week group (31%) and 40 in the 8-week group (46%) had a primary-outcome event. The hazard ratio for time to any mood episode in the 52-week group relative to the 8-week group was 0.68 (95% confidence interval [CI], 0.43 to 1.10; P = 0.12 by log-rank test). A total of 11 patients in the 52-week group (12%) as compared with 5 patients in the 8-week group (6%) had mania or hypomania (hazard ratio, 2.28; 95% CI, 0.86 to 6.08), and 15 patients (17%) as compared with 35 patients (40%) had recurrence of depression (hazard ratio, 0.43; 95% CI, 0.25 to 0.75). The incidence of adverse events was similar in the two groups.
CONCLUSIONS
In a trial involving patients with bipolar I disorder and a recently remitted depressive episode, adjunctive treatment with escitalopram or bupropion XL that continued for 52 weeks did not show a significant benefit as compared with treatment for 8 weeks in preventing relapse of any mood episode. The trial was stopped early owing to slow recruitment and funding limitations. (Funded by the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00958633.).
Topics: Humans; Bipolar Disorder; Mania; Bupropion; Depression; Escitalopram; Canada; Neoplasm Recurrence, Local; Antidepressive Agents; Double-Blind Method; Treatment Outcome
PubMed: 37530824
DOI: 10.1056/NEJMoa2300184 -
Asian Journal of Psychiatry Jul 2022Mood-incongruent psychosis during bipolar disorder has been associated with poor outcomes. However, it remains unknown whether this is secondary to persistent affective...
BACKGROUND
Mood-incongruent psychosis during bipolar disorder has been associated with poor outcomes. However, it remains unknown whether this is secondary to persistent affective or psychotic symptoms or both.
METHOD
Sixty-eight patients with bipolar disorder between the ages of 16 and 45 were recruited during their first psychiatric hospitalization for mania. These patients were evaluated using structured and semi-structured clinical interview then followed longitudinally. Outcomes during the first twenty-four months of follow-up were compared between patients with mood-incongruent psychosis and those without (i.e., patients with mood-congruent psychosis or no psychosis) during the index manic episode. Specifically, ratings of the percent of weeks during follow-up with the duration of mood incongruent psychotic symptom, any psychotic symptom, affective syndromes, and scores of global outcomes were compared.
RESULTS
Comparing the 24-month follow-up results between the two groups, patients with mood incongruent psychotic symptoms had a lower global functional rating scale, efficacy index, while the duration of mood incongruent psychotic symptom, any psychotic symptom, and complete affective symptom showed statistically significant differences between the two groups. There were also statistically significant differences between the two groups in the duration of mood stabilizers, and antidepressants use, typical antipsychotics, and atypical antipsychotics. Partial correlation analysis reveals the scores of the global assessment of functioning scale (GAF) after 24 months showed a significant negative correlation with the length of time of incongruent psychotic symptoms. Still, the correlation was intermediate (correlation coefficients less than 0.5,r = -0.471, P < 0.001).
CONCLUSION
Mood-incongruent psychosis that occurs during the first manic episode appears to predict an increased likelihood of persistent psychotic symptoms during the subsequent twenty-four months. This persistence of psychosis is associated with a worse overall course of illness than patients without mood-incongruent psychosis.
LIMITATIONS
These results apply to a relatively short outcome period, and the sample size is relatively small.
Topics: Adolescent; Adult; Antipsychotic Agents; Bipolar Disorder; Follow-Up Studies; Humans; Mania; Middle Aged; Psychotic Disorders; Young Adult
PubMed: 35468481
DOI: 10.1016/j.ajp.2022.103118 -
Therapeutische Umschau. Revue... Jun 2009Within recent years the diagnostic concept of bipolar disorders has profoundly changed. The original view of one manic-depressive illness has become more and more a... (Review)
Review
Within recent years the diagnostic concept of bipolar disorders has profoundly changed. The original view of one manic-depressive illness has become more and more a spectrum disorder ranging from personality traits to the full clinical feature of manic-depressive illness. Therefore, prevalence has increased in the general population. However, for differential treatment approaches with mood stabilisers the clinical distinction between bipolar I and bipolar II disorders becomes more and more relevant and, importantly, rapid cycling is a critical criterion for a differential indication of mood stabilisers. In acute treatment the psychopathological features such as euphoric versus dysphoric mania, the severity and the frequency of episodes play an important role for the choice of the mood stabiliser. According to international guidelines Lithium and Valproat are first-line treatment options. In addition, Lamotrigin has become a first-line treatment in special issues such as long-term treatment of bipolar depression. Carbamazepin, however, has lost its first-line place due to the evidence-based data situation and due to the side-effect profile. Within recent years the atypical anti-psychotics were investigated in bipolar disorder. Meanwhile, most of them have an indication for the treatment of acute mania, some of them for bipolar depression. Some studies also point to an efficacy in long-term prophylactic treatment. In summary, the psychopharmacological indications for the differential use of mood stabilisers are becoming more and more complex, therefore clear guidelines are needed.
Topics: Acute Disease; Affect; Algorithms; Anticonvulsants; Antimanic Agents; Bipolar Disorder; Drug Therapy, Combination; Humans; Practice Guidelines as Topic; Secondary Prevention
PubMed: 19496037
DOI: 10.1024/0040-5930.66.6.413 -
JAMA Psychiatry Jan 2024Antidepressants are increasingly prescribed to pediatric patients with unipolar depression, but little is known about the risk of treatment-emergent mania. Previous...
IMPORTANCE
Antidepressants are increasingly prescribed to pediatric patients with unipolar depression, but little is known about the risk of treatment-emergent mania. Previous research suggests pediatric patients may be particularly vulnerable to this adverse outcome.
OBJECTIVE
To estimate whether pediatric patients treated with antidepressants have an increased incidence of mania/hypomania compared with patients not treated with antidepressants and to identify patient characteristics associated with the risk of mania/hypomania.
DESIGN, SETTING, AND PARTICIPANTS
In a cohort study applying the target trial emulation framework, nationwide inpatient and outpatient care in Sweden from July 1, 2006, to December 31, 2019, was evaluated. Follow-up was conducted for 12 and 52 weeks after treatment initiation, with administrative follow-up ending December 31, 2020. Data were analyzed between May 1, 2022, and June 28, 2023. Individuals aged 4 to 17 years with a diagnosis of depression, but without a prior diagnosis of mania/hypomania, bipolar disorder, or psychosis or treatment with mood stabilizer (lithium, valproate, or carbamazepine), prescriptions were included.
EXPOSURES
The treatment group included patients who initiated any antidepressant medication within 90 days of diagnosis. The control group included patients who did not initiate antidepressants within 90 days.
MAIN OUTCOMES AND MEASURES
Diagnosis of mania/hypomania or initiation of mood stabilizer therapy. Incidences were estimated with Kaplan-Meier estimator, and inverse probability of treatment weighting was used to adjust for group differences at baseline.
RESULTS
The cohort included 43 677 patients (28 885 [66%] girls); 24 573 in the treatment group and 19 104 in the control group. The median age was 15 (IQR, 14-16) years. The outcome occurred in 96 individuals by 12 weeks and in 291 by 52 weeks. The cumulative incidence of mania was 0.26% (95% CI, 0.19%-0.33%) in the treatment group and 0.20% (95% CI, 0.13%-0.27%) in the control group at 12 weeks, with a risk difference of 0.06% (95% CI, -0.04% to 0.16%). At 52 weeks, the cumulative incidence was 0.79% (95% CI, 0.68%-0.91%) in the treatment group and 0.52% (95% CI, 0.40%-0.63%) in the control group (risk difference, 0.28%; 95% CI, 0.12%-0.44%). Hospitalizations, parental bipolar disorder, and use of antipsychotics and antiepileptics were the most important predictors of mania/hypomania by 12 weeks.
CONCLUSION
This cohort study found no evidence of treatment-emergent mania/hypomania by 12 weeks in children and adolescents. This corresponds to the time frame for antidepressants to exert their psychotropic effect. A small risk difference was found only with longer follow-up. Certain patient characteristics were associated with mania/hypomania, which warrants clinical attention.
Topics: Female; Humans; Adolescent; Child; Male; Mania; Cohort Studies; Depression; Antidepressive Agents; Depressive Disorder; Antipsychotic Agents
PubMed: 37755835
DOI: 10.1001/jamapsychiatry.2023.3555