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JAMA Psychiatry Feb 2021Several psychotherapy protocols have been evaluated as adjuncts to pharmacotherapy for patients with bipolar disorder, but little is known about their comparative... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Several psychotherapy protocols have been evaluated as adjuncts to pharmacotherapy for patients with bipolar disorder, but little is known about their comparative effectiveness.
OBJECTIVE
To use systematic review and network meta-analysis to compare the association of using manualized psychotherapies and therapy components with reducing recurrences and stabilizing symptoms in patients with bipolar disorder.
DATA SOURCES
Major bibliographic databases (MEDLINE, PsychInfo, and Cochrane Library of Systematic Reviews) and trial registries were searched from inception to June 1, 2019, for randomized clinical trials of psychotherapy for bipolar disorder.
STUDY SELECTION
Of 3255 abstracts, 39 randomized clinical trials were identified that compared pharmacotherapy plus manualized psychotherapy (cognitive behavioral therapy, family or conjoint therapy, interpersonal therapy, or psychoeducational therapy) with pharmacotherapy plus a control intervention (eg, supportive therapy or treatment as usual) for patients with bipolar disorder.
DATA EXTRACTION AND SYNTHESIS
Binary outcomes (recurrence and study retention) were compared across treatments using odds ratios (ORs). For depression or mania severity scores, data were pooled and compared across treatments using standardized mean differences (SMDs) (Hedges-adjusted g using weighted pooled SDs). In component network meta-analyses, the incremental effectiveness of 13 specific therapy components was examined.
MAIN OUTCOMES AND MEASURES
The primary outcome was illness recurrence. Secondary outcomes were depressive and manic symptoms at 12 months and acceptability of treatment (study retention).
RESULTS
A total of 39 randomized clinical trials with 3863 participants (2247 of 3693 [60.8%] with data on sex were female; mean [SD] age, 36.5 [8.2] years) were identified. Across 20 two-group trials that provided usable information, manualized treatments were associated with lower recurrence rates than control treatments (OR, 0.56; 95% CI, 0.43-0.74). Psychoeducation with guided practice of illness management skills in a family or group format was associated with reducing recurrences vs the same strategies in an individual format (OR, 0.12; 95% CI, 0.02-0.94). Cognitive behavioral therapy (SMD, -0.32; 95% CI, -0.64 to -0.01) and, with less certainty, family or conjoint therapy (SMD, -0.46; 95% CI, -1.01 to 0.08) and interpersonal therapy (SMD, -0.46; 95% CI, -1.07 to 0.15) were associated with stabilizing depressive symptoms compared with treatment as usual. Higher study retention was associated with family or conjoint therapy (OR, 0.46; 95% CI, 0.26-0.82) and brief psychoeducation (OR, 0.44; 95% CI, 0.23-0.85) compared with standard psychoeducation.
CONCLUSIONS AND RELEVANCE
This study suggests that outpatients with bipolar disorder may benefit from skills-based psychosocial interventions combined with pharmacotherapy. Conclusions are tempered by heterogeneity in populations, treatment duration, and follow-up.
Topics: Adult; Bipolar Disorder; Female; Humans; Male; Middle Aged; Network Meta-Analysis; Psychotherapy
PubMed: 33052390
DOI: 10.1001/jamapsychiatry.2020.2993 -
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 -
Medicina (Kaunas, Lithuania) Jun 2021Childhood onset bipolar disorder (CO-BD) presents a panoply of difficulties associated with early recognition and treatment. CO-BD is associated with a variety of... (Review)
Review
Childhood onset bipolar disorder (CO-BD) presents a panoply of difficulties associated with early recognition and treatment. CO-BD is associated with a variety of precursors and comorbidities that have been inadequately studied, so treatment remains obscure. The earlier the onset, the longer is the delay to first treatment, and both early onset and treatment delay are associated with more depressive episodes and a poor prognosis in adulthood. Ultra-rapid and ultradian cycling, consistent with a diagnosis of BP-NOS, are highly prevalent in the youngest children and take long periods of time and complex treatment regimens to achieve euthymia. Lithium and atypical antipsychotics are effective in mania, but treatment of depression remains obscure, with the exception of lurasidone, for children ages 10-17. Treatment of the common comorbid anxiety disorders, oppositional defiant disorders, pathological habits, and substance abuse are all poorly studied and are off-label. Cognitive dysfunction after a first manic hospitalization improves over the next year only on the condition that no further episodes occur. Yet comprehensive expert treatment after an initial manic hospitalization results in many fewer relapses than traditional treatment as usual, emphasizing the need for combined pharmacological, psychosocial, and psycho-educational approaches to this difficult and highly recurrent illness.
Topics: Adolescent; Adult; Antipsychotic Agents; Bipolar Disorder; Child; Comorbidity; Humans; Lithium; Substance-Related Disorders
PubMed: 34207966
DOI: 10.3390/medicina57060601 -
Canadian Journal of Psychiatry. Revue... May 2023Given the increasing acceptability and legalization of cannabis in some jurisdictions, clinicians need to improve their understanding of the effect of cannabis use on... (Review)
Review
Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force Report: A Systematic Review and Recommendations of Cannabis use in Bipolar Disorder and Major Depressive Disorder.
BACKGROUND
Given the increasing acceptability and legalization of cannabis in some jurisdictions, clinicians need to improve their understanding of the effect of cannabis use on mood disorders.
OBJECTIVE
The purpose of this task force report is to examine the association between cannabis use and incidence, presentation, course and treatment of bipolar disorder and major depressive disorder, and the treatment of comorbid cannabis use disorder.
METHODS
We conducted a systematic literature review using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, searching PubMed, Embase, PsycINFO, CINAHL and Cochrane Central Register of Controlled Trials from inception to October 2020 focusing on cannabis use and bipolar disorder or major depressive disorder, and treatment of comorbid cannabis use disorder. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach was used to evaluate the quality of evidence and clinical considerations were integrated to generate Canadian Network for Mood and Anxiety Treatments recommendations.
RESULTS
Of 12,691 publications, 56 met the criteria: 23 on bipolar disorder, 21 on major depressive disorder, 11 on both diagnoses and 1 on treatment of comorbid cannabis use disorder and major depressive disorder. Of 2,479,640 participants, 12,502 were comparison participants, 73,891 had bipolar disorder and 408,223 major depressive disorder without cannabis use. Of those with cannabis use, 2,761 had bipolar disorder and 5,044 major depressive disorder. The lifetime prevalence of cannabis use was 52%-71% and 6%-50% in bipolar disorder and major depressive disorder, respectively. Cannabis use was associated with worsening course and symptoms of both mood disorders, with more consistent associations in bipolar disorder than major depressive disorder: increased severity of depressive, manic and psychotic symptoms in bipolar disorder and depressive symptoms in major depressive disorder. Cannabis use was associated with increased suicidality and decreased functioning in both bipolar disorder and major depressive disorder. Treatment of comorbid cannabis use disorder and major depressive disorder did not show significant results.
CONCLUSION
The data indicate that cannabis use is associated with worsened course and functioning of bipolar disorder and major depressive disorder. Future studies should include more accurate determinations of type, amount and frequency of cannabis use and select comparison groups which allow to control for underlying common factors.
Topics: Humans; Bipolar Disorder; Depressive Disorder, Major; Cannabis; Marijuana Abuse; Canada; Anxiety; Substance-Related Disorders
PubMed: 35711159
DOI: 10.1177/07067437221099769 -
Journal of Affective Disorders Aug 2022Rapid cycling is a phase of bipolar disorder with increased episode frequencies. It is a severe and disabling condition that often poses a major challenge to the... (Review)
Review
OBJECTIVES
Rapid cycling is a phase of bipolar disorder with increased episode frequencies. It is a severe and disabling condition that often poses a major challenge to the clinician. The aim of this paper is to give an overview of the evidence-based treatment options for rapid cycling.
METHODS
A systematic search on Pubmed, Embase and Cochrane databases from inception until December 2021 was conducted according to the PRISMA guidelines. An additional search on clinicaltrials.gov was done. References of retrieved papers and key reviews were hand-searched. Randomized controlled trials including at least 10 patients with bipolar disorder, rapid cycling, reporting an objective outcome measure were selected.
RESULTS
Our search, initially revealing 1330 articles, resulted in 16 papers about treatment of an acute mood episode, relapse prevention or both. Lithium, anticonvulsants, second generation antipsychotics, antidepressants and thyroid hormone were assessed as treatment options in the presented data. Evidence supporting the use of aripiprazole, olanzapine, quetiapine, valproate and lamotrigine for treatment of rapid cycling bipolar disorder was found.
LIMITATIONS
Small sample sizes, different index episodes and variety of outcome measures.
CONCLUSION
Evidence regarding treatment of rapid cycling remains scarce. Evidence supports the use of aripiprazole, olanzapine, and valproate for acute manic or mixed episodes, quetiapine for acute depressive episodes and aripiprazole and lamotrigine for relapse prevention. Given the paucity of available evidence, and the burden that accompanies rapid cycling, future research is warranted.
Topics: Anticonvulsants; Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Humans; Lamotrigine; Olanzapine; Quetiapine Fumarate; Valproic Acid
PubMed: 35545157
DOI: 10.1016/j.jad.2022.05.017 -
International Journal of Molecular... Feb 2022Bipolar disorder (BD) is characterized by mood changes, including recurrent manic, hypomanic, and depressive episodes, which may involve mixed symptoms. Despite the... (Review)
Review
Bipolar disorder (BD) is characterized by mood changes, including recurrent manic, hypomanic, and depressive episodes, which may involve mixed symptoms. Despite the progress in neurobiological research, the pathophysiology of BD has not been extensively described to date. Progress in the understanding of the neurobiology driving BD could help facilitate the discovery of therapeutic targets and biomarkers for its early detection. Oxidative stress (OS), which damages biomolecules and causes mitochondrial and dopamine system dysfunctions, is a persistent finding in patients with BD. Inflammation and immune dysfunction might also play a role in BD pathophysiology. Specific nutrient supplements (nutraceuticals) may target neurobiological pathways suggested to be perturbed in BD, such as inflammation, mitochondrial dysfunction, and OS. Consequently, nutraceuticals may be used in the adjunctive treatment of BD. This paper summarizes the possible roles of OS, mitochondrial dysfunction, and immune system dysregulation in the onset of BD. It then discusses OS-mitigating strategies that may serve as therapeutic interventions for BD. It also analyzes the relationship between diet and BD as well as the use of nutritional interventions in the treatment of BD. In addition, it addresses the use of lithium therapy; novel antipsychotic agents, including clozapine, olanzapine, risperidone, cariprazine, and quetiapine; and anti-inflammatory agents to treat BD. Furthermore, it reviews the efficacy of the most used therapies for BD, such as cognitive-behavioral therapy, bright light therapy, imagery-focused cognitive therapy, and electroconvulsive therapy. A better understanding of the roles of OS, mitochondrial dysfunction, and inflammation in the pathogenesis of bipolar disorder, along with a stronger elucidation of the therapeutic functions of antioxidants, antipsychotics, anti-inflammatory agents, lithium therapy, and light therapies, may lead to improved strategies for the treatment and prevention of bipolar disorder.
Topics: Antipsychotic Agents; Bipolar Disorder; Cognitive Behavioral Therapy; Combined Modality Therapy; Dietary Supplements; Dopamine; Humans; Mitochondria; Oxidative Stress; Treatment Outcome
PubMed: 35163764
DOI: 10.3390/ijms23031844 -
Acta Psychiatrica Scandinavica Sep 2020In this paper, we aimed at reviewing evidence-based treatment options for bipolar mania and proposed tentative evidence-based clinical suggestions regarding the... (Review)
Review
OBJECTIVE
In this paper, we aimed at reviewing evidence-based treatment options for bipolar mania and proposed tentative evidence-based clinical suggestions regarding the management of a manic episode, especially regarding the choice of the proper mood stabilizer and antipsychotic medication.
METHOD
A narrative review was undertaken addressing 'treatment of bipolar mania'. Findings have been synthesized and incorporated with clinical experience into a model to support different treatment choices.
RESULTS
To date, there is solid evidence supporting the use of several medications, such as lithium, divalproex, and carbamazepine, and antipsychotics, such as chlorpromazine, haloperidol, risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, inhaled loxapine, asenapine, and cariprazine in acute mania, and some evidence supporting the use of clozapine or electroconvulsive therapy in treatment-refractory cases. However, in clinical practice, when making decisions about treatment, personalized treatment is needed, according to the different clinical presentations and more complex clinical situations within the manic episode and considering a long-term view and with the objective of not only a symptomatic but also functional recovery. After remission from acute mania, psychoeducation strategies are useful to ensure adherence.
DISCUSSION
Despite the evidence forefficacy of many currently available treatments for mania, the majority of RCTs provide little direction for the clinician as to what steps might be optimal in different presentations of mania as well as in the presence of specific patient characteristics. Manic episodes should be managed on a personalized basis considering the clinical course and patient criteria and with the expectation of maintaining that treatment in the long-term.
Topics: Antipsychotic Agents; Bipolar Disorder; Clozapine; Humans; Mania; Olanzapine
PubMed: 33460070
DOI: 10.1111/acps.13209 -
Psychiatria Polska Dec 2022Bipolar affective disorder (BPAD) is a chronic mental disorder, characterised by mood swings, alternating between depression and manic or hypomanic episodes.... (Review)
Review
Bipolar affective disorder (BPAD) is a chronic mental disorder, characterised by mood swings, alternating between depression and manic or hypomanic episodes. Unfortunately, in some patients pharmacological treatment does not bring satisfactory results, and a certain group of patients shows resistance to treatment. Therefore, other treatment methods are sought after, including a change in diet. The most promising nutrition model is the ketogenic diet. In the presented case study of a male patient, thanks to the introduction of the ketogenic diet, full remission of the disease was achieved, doses of lamotrigine were reduced and quetiapine was completely discontinued. Previously, neither lamotrigine monotherapy nor combined treatment with quetiapine achieved euthymia. The effects of the diet may be related to, among others, the influence on ionic channels and increase in blood acidity (similarly to mood stabilisers), increase in gamma-aminobutyric acid (GABA) concentration, modulation of GABAA receptors and blocking of AMPA receptors by medium-chain fatty acids. The ketogenic diet influences glutamate metabolism and nerve cell metabolism, which uses ketone bodies as energy sources. Ketosis can also stimulate the biogenesis of mitochondria, improve brain metabolism, act as a neuroprotective factor, as well as increase glutathione synthesis and reduce oxidative stress. However, there is a need for carefully planned studies, with an appropriate representative group, to verify the potential benefits and risks of introducing the ketogenic diet in patients with BPAD.
Topics: Humans; Male; Bipolar Disorder; Lamotrigine; Diet, Ketogenic; Quetiapine Fumarate; Mood Disorders; Anticonvulsants
PubMed: 37098202
DOI: 10.12740/PP/OnlineFirst/136356 -
JAMA Psychiatry May 2020Behavioral high-risk phenotypes predict the onset of bipolar disorder among youths who have parents with bipolar disorder. Few studies have examined whether early... (Comparative Study)
Comparative Study Randomized Controlled Trial
IMPORTANCE
Behavioral high-risk phenotypes predict the onset of bipolar disorder among youths who have parents with bipolar disorder. Few studies have examined whether early intervention delays new mood episodes in high-risk youths.
OBJECTIVE
To determine whether family-focused therapy (FFT) for high-risk youths is more effective than standard psychoeducation in hastening recovery and delaying emergence of mood episodes during the 1 to 4 years after an active period of mood symptoms.
DESIGN, SETTINGS, AND PARTICIPANTS
This multisite randomized clinical trial included referred youths (aged 9-17 years) with major depressive disorder or unspecified (subthreshold) bipolar disorder, active mood symptoms, and at least 1 first- or second-degree relative with bipolar disorder I or II. Recruitment started from October 6, 2011, and ended on September 15, 2016. Independent evaluators interviewed participants every 4 to 6 months to measure symptoms for up to 4 years. Data analysis was performed from March 13 to November 3, 2019.
INTERVENTIONS
High-risk youths and parents were randomly allocated to FFT (12 sessions in 4 months of psychoeducation, communication training, and problem-solving skills training; n = 61) or enhanced care (6 sessions in 4 months of family and individual psychoeducation; n = 66). Youths could receive medication management in either condition.
MAIN OUTCOMES AND MEASURES
The coprimary outcomes, derived using weekly psychiatric status ratings, were time to recovery from prerandomization symptoms and time to a prospectively observed mood (depressive, manic, or hypomanic) episode after recovery. Secondary outcomes were time to conversion to bipolar disorder I or II and longitudinal symptom trajectories.
RESULTS
All 127 participants (82 [64.6%] female; mean [SD] age, 13.2 [2.6] years) were followed up for a median of 98 weeks (range, 0-255 weeks). No differences were detected between treatments in time to recovery from pretreatment symptoms. High-risk youths in the FFT group had longer intervals from recovery to the emergence of the next mood episode (χ2 = 5.44; P = .02; hazard ratio, 0.55; 95% CI, 0.48-0.92;), and from randomization to the next mood episode (χ2 = 4.44; P = .03; hazard ratio, 0.59; 95% CI, 0.35-0.97) than youths in enhanced care. Specifically, FFT was associated with longer intervals to depressive episodes (log-rank χ2 = 6.24; P = .01; hazard ratio, 0.53; 95% CI, 0.31-0.88) but did not differ from enhanced care in time to manic or hypomanic episodes, conversions to bipolar disorder, or symptom trajectories.
CONCLUSIONS AND RELEVANCE
Family skills-training for youths at high risk for bipolar disorder is associated with longer times between mood episodes. Clarifying the relationship between changes in family functioning and changes in the course of high-risk syndromes merits future investigation.
TRIAL REGISTRATION
ClinicalTrials.gov identifier: NCT01483391.
Topics: Adolescent; Bipolar Disorder; Child; Disease Progression; Family Therapy; Female; Humans; Male; Mood Disorders; Psychotropic Drugs; Treatment Outcome
PubMed: 31940011
DOI: 10.1001/jamapsychiatry.2019.4520 -
Fortschritte Der Neurologie-Psychiatrie Apr 2022Bipolar affective disorder (short: bipolar disorder) describe a group of affective disorders characterised by depressive as well as manic/hypomanic episodes. The article...
Bipolar affective disorder (short: bipolar disorder) describe a group of affective disorders characterised by depressive as well as manic/hypomanic episodes. The article deals with the diagnostic and therapeutic challenges of bipolar II disorder.
Topics: Bipolar Disorder; Humans; Mood Disorders
PubMed: 35443282
DOI: 10.1055/a-1680-7187