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European Neuropsychopharmacology : the... Jan 2022The aim of the study was to systematically review the hard evidence alone, concerning lithium efficacy separately for the phases and clinical facets of Bipolar disorder... (Review)
Review
The aim of the study was to systematically review the hard evidence alone, concerning lithium efficacy separately for the phases and clinical facets of Bipolar disorder (BD). The PRISMA method was followed to search the MEDLINE for Randomized Controlled trials, Post-hoc analyses and Meta-analyses and review papers up to August 1st 2020, with the combination of the words 'bipolar', 'manic', 'mania', 'manic depression' and 'manic depressive' and 'randomized'. Trials and meta-analyses concerning the use of lithium either as monotherapy or in combination with other agents in adults were identified concerning acute mania (Ν=64), acute bipolar depression (Ν=78), the maintenance treatment (Ν=73) and the treatment of other issues (N = 93). Treatment guidelines were also identified. Lithium is efficacious for the treatment of acute mania including concomitant psychotic symptoms. In acute bipolar depression it is efficacious only in combination with specific agents. For the maintenance phase, it is efficacious as monotherapy mainly in the prevention of manic while its efficacy for the prevention of depressive episodes is unclear. Its combinations increase its therapeutic value. It is equaly efficacious in rapid and non-rapid cycling patients, in concomitant obsessive-compulsive symptoms, alcohol and substance abuse, the neurocognitive deficit, suicidal ideation and fatigue The current systematic review provided support for the usefulness of lithium against a broad spectrum of clinical issues in Bipolar disorder. Its efficacy is comparable to that of more recently developed agents.
Topics: Adult; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Humans; Lithium; Lithium Compounds; Mania; Randomized Controlled Trials as Topic
PubMed: 34980362
DOI: 10.1016/j.euroneuro.2021.10.003 -
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 -
Molecular Psychiatry Apr 2022The emerging understanding of gut microbiota as 'metabolic machinery' influencing many aspects of physiology has gained substantial attention in the field of psychiatry.... (Review)
Review
The emerging understanding of gut microbiota as 'metabolic machinery' influencing many aspects of physiology has gained substantial attention in the field of psychiatry. This is largely due to the many overlapping pathophysiological mechanisms associated with both the potential functionality of the gut microbiota and the biological mechanisms thought to be underpinning mental disorders. In this systematic review, we synthesised the current literature investigating differences in gut microbiota composition in people with the major psychiatric disorders, major depressive disorder (MDD), bipolar disorder (BD) and schizophrenia (SZ), compared to 'healthy' controls. We also explored gut microbiota composition across disorders in an attempt to elucidate potential commonalities in the microbial signatures associated with these mental disorders. Following the PRISMA guidelines, databases were searched from inception through to December 2021. We identified 44 studies (including a total of 2510 psychiatric cases and 2407 controls) that met inclusion criteria, of which 24 investigated gut microbiota composition in MDD, seven investigated gut microbiota composition in BD, and 15 investigated gut microbiota composition in SZ. Our syntheses provide no strong evidence for a difference in the number or distribution (α-diversity) of bacteria in those with a mental disorder compared to controls. However, studies were relatively consistent in reporting differences in overall community composition (β-diversity) in people with and without mental disorders. Our syntheses also identified specific bacterial taxa commonly associated with mental disorders, including lower levels of bacterial genera that produce short-chain fatty acids (e.g. butyrate), higher levels of lactic acid-producing bacteria, and higher levels of bacteria associated with glutamate and GABA metabolism. We also observed substantial heterogeneity across studies with regards to methodologies and reporting. Further prospective and experimental research using new tools and robust guidelines hold promise for improving our understanding of the role of the gut microbiota in mental and brain health and the development of interventions based on modification of gut microbiota.
Topics: Bipolar Disorder; Brain; Depressive Disorder, Major; Gastrointestinal Microbiome; Humans; Schizophrenia
PubMed: 35194166
DOI: 10.1038/s41380-022-01456-3 -
Acta Psychiatrica Scandinavica Oct 2022Rapid cycling is a common and disabling phenomenon in individuals with bipolar disorders. In the absence of a recent literature examination, this systematic review and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Rapid cycling is a common and disabling phenomenon in individuals with bipolar disorders. In the absence of a recent literature examination, this systematic review and meta-analysis aimed to synthesise the evidence of efficacy, acceptability and tolerability of treatments for individuals with rapid cycling bipolar disorder (RCBD).
METHOD
A systematic search was conducted to identify randomised controlled trials assigning participants with RCBD to pharmacological and/or non-pharmacological interventions. Study inclusion and data extraction were undertaken by two reviewers independently. The primary outcome was continuous within-subject RCBD illness severity before and after treatment. Pre-post random effects meta-analyses were conducted for each outcome/intervention arm studied, generating a standardised effect size (hedge's g) and 95% confidence interval (CI).
RESULTS
A total of 34 articles describing 30 studies were included. A total of 16 separate pharmacological treatments were examined in contrast to 1 psychological therapy study. Only quetiapine and lamotrigine were assessed in >5 studies. By assessing 95% CI overlap of within-subject efficacy effects compared to placebo, the only interventions suggesting significant depression benefits (placebo g = 0.60) were olanzapine (with/without fluoxetine; g = 1.01), citalopram (g = 1.10) and venlafaxine (g = 2.48). For mania, benefits were indicated for quetiapine (g = 1.01), olanzapine (g = 1.19) and aripiprazole (g = 1.09), versus placebo (g = 0.33). Most of these effect sizes were from only one trial per treatment. Heterogeneity between studies was variable, and 20% were rated to have a high risk of bias.
CONCLUSIONS
While many interventions appeared efficacious, there was a lack of robust evidence for most treatments. Given the limited and heterogeneous evidence base, the optimal treatment strategies for people with RCBD are yet to be established.
Topics: Aripiprazole; Bipolar Disorder; Citalopram; Fluoxetine; Humans; Lamotrigine; Olanzapine; Quetiapine Fumarate; Venlafaxine Hydrochloride
PubMed: 35778967
DOI: 10.1111/acps.13471 -
Journal of Affective Disorders Jan 2021Ketamine appears to have a therapeutic role in certain mental disorders, most notably depression. However, the comparative performance of different formulations of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Ketamine appears to have a therapeutic role in certain mental disorders, most notably depression. However, the comparative performance of different formulations of ketamine is less clear.
OBJECTIVES
This study aimed to assess the comparative efficacy and tolerability of racemic and esketamine for the treatment of unipolar and bipolar major depression.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
We searched PubMed, MEDLINE, Embase, PsycINFO, the Cochrane Central Register of Controlled Clinical Trials, and the Cochrane Database of Systematic Reviews for relevant studies published since database inception and December 17, 2019.
STUDY ELIGIBILITY CRITERIA
We considered randomized controlled trials examining racemic or esketamine for the treatment of unipolar or bipolar major depression.
OUTCOMES
Primary outcomes were response and remission from depression, change in depression severity, suicidality, retention in treatment, drop-outs, and drop-outs due to adverse events.
ANALYSIS
Evidence from randomized controlled trials was synthesized as rate ratios (RRs) for treatment response, disorder remission, adverse events, and withdrawals and as standardized mean differences (SMDs) for change in symptoms, via random-effects meta-analyses.
FINDINGS
24 trials representing 1877 participants were pooled. Racemic ketamine relative to esketamine demonstrated greater overall response (RR = 3.01 vs. RR = 1.38) and remission rates (RR = 3.70 vs. RR = 1.47), as well as lower dropouts (RR = 0.76 vs. RR = 1.37).
CONCLUSIONS
Intravenous ketamine appears to be more efficacious than intranasal esketamine for the treatment of depression.
Topics: Antidepressive Agents; Depression; Depressive Disorder, Major; Humans; Ketamine
PubMed: 33022440
DOI: 10.1016/j.jad.2020.09.071 -
Molecular Psychiatry Mar 2022The gabapentinoids, gabapentin, and pregabalin, target the αδ subunits of voltage-gated calcium channels. Initially licensed for pain and seizures, they have become... (Meta-Analysis)
Meta-Analysis
The gabapentinoids, gabapentin, and pregabalin, target the αδ subunits of voltage-gated calcium channels. Initially licensed for pain and seizures, they have become widely prescribed drugs. Many of these uses are off-label for psychiatric indications, and there is increasing concern about their safety, so it is particularly important to have good evidence to justify this usage. We conducted a systematic review and meta-analysis of the evidence for three of their common psychiatric uses: bipolar disorder, anxiety, and insomnia. Fifty-five double-blind randomised controlled trials (RCTs) and 15 open-label studies were identified. For bipolar disorder, four double-blind RCTs investigating gabapentin, and no double-blind RCTs investigating pregabalin, were identified. A quantitative synthesis could not be performed due to heterogeneity in the study population, design and outcome measures. Across the anxiety spectrum, a consistent but not universal effect in favour of gabapentinoids compared to placebo was seen (standardised mean difference [SMD] ranging between -2.25 and -0.25). Notably, pregabalin (SMD -0.55, 95% CI -0.92 to -0.18) and gabapentin (SMD -0.92, 95% CI -1.32 to -0.52) were more effective than placebo in reducing preoperative anxiety. In insomnia, results were inconclusive. We conclude that there is moderate evidence of the efficacy of gabapentinoids in anxiety states, but minimal evidence in bipolar disorder and insomnia and they should be used for these disorders only with strong justification. This recommendation applies despite the attractive pharmacological and genetic rationale for targeting voltage-gated calcium channels.
Topics: Amines; Anxiety; Bipolar Disorder; Calcium Channels; Cyclohexanecarboxylic Acids; Gabapentin; Humans; Pregabalin; Randomized Controlled Trials as Topic; Sleep Initiation and Maintenance Disorders; gamma-Aminobutyric Acid
PubMed: 34819636
DOI: 10.1038/s41380-021-01386-6 -
European Neuropsychopharmacology : the... Jan 2022Uncertainty remains regarding the relative efficacy of maintenance pharmacotherapy for bipolar disorder (BD), and available data require updating. The present systematic... (Meta-Analysis)
Meta-Analysis Review
Uncertainty remains regarding the relative efficacy of maintenance pharmacotherapy for bipolar disorder (BD), and available data require updating. The present systematic review and meta-analysis aims to consolidate the evidence from the highest quality randomized controlled trials (RCTs) published up to July 2021, overcoming the limitations of earlier reviews. The PubMed and the Cochrane Central Register of Controlled Trials were searched for double-blind RCTs involving lithium, mood stabilizing anticonvulsants (MSAs), antipsychotics, antidepressants, and other treatments. Rates of new mood episodes with test vs. reference treatments (placebo or alternative active agent) were compared by random-effects meta-analysis. Polarity index was calculated for each treatment type. Eligible trials involved ≥6 months of maintenance follow up. Of 2,158 identified reports, 22 met study eligibility criteria, and involved 7,773 subjects stabilized for 1-12 weeks and followed-up for 24-104 weeks. Psychotropic monotherapy overall (including lithium, MSAs, and second generation antipsychotics (SGA) was more effective in preventing new BD episodes than placebo (odds ratio, OR=0.42; 95% confidence interval, CI 0.34-0.51, p<0.00001). Significantly lower risk of new BD episodes was observed with the following individual drugs: aripiprazole, asenapine, lithium, olanzapine, quetiapine, and risperidone long-acting (ORs varied 0.19-0.46). Adding aripiprazole, divalproex, quetiapine, or olanzapine/risperidone to lithium or an MSA was more effective compared with lithium or MSA monotherapy (OR=0.37; 95%CI 0.25-0.55, p<0.00001). Active treatment favored prevention of mania over depression. The key limitations were "responder-enriched" design in most trials and high outcomes heterogeneity. PROSPERO registration number is CRD42020162663.
Topics: Adult; Anticonvulsants; Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Humans; Lithium; Olanzapine; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone
PubMed: 34489127
DOI: 10.1016/j.euroneuro.2021.08.264 -
Journal of Clinical Psychopharmacology Aug 2016Antipsychotics are the drugs prescribed to treat psychotic disorders; however, patients often fail to adhere to their treatment, and this has a severe negative effect on... (Review)
Review
Antipsychotics are the drugs prescribed to treat psychotic disorders; however, patients often fail to adhere to their treatment, and this has a severe negative effect on prognosis in these kinds of illnesses. Among the wide range of risk factors for treatment nonadherence, this systematic review covers those that are most important from the point of view of clinicians and patients and proposes guidelines for addressing them. Analyzing 38 studies conducted in a total of 51,796 patients, including patients with schizophrenia spectrum disorders and bipolar disorder, we found that younger age, substance abuse, poor insight, cognitive impairments, low level of education, minority ethnicity, poor therapeutic alliance, experience of barriers to care, high intensity of delusional symptoms and suspiciousness, and low socioeconomic status are the main risk factors for medication nonadherence in both types of disorder. In the future, prospective studies should be conducted on the use of personalized patient-tailored treatments, taking into account risk factors that may affect each individual, to assess the ability of such approaches to improve adherence and hence prognosis in these patients.
Topics: Antipsychotic Agents; Bipolar Disorder; Humans; Medication Adherence; Schizophrenia
PubMed: 27307187
DOI: 10.1097/JCP.0000000000000523 -
European Neuropsychopharmacology : the... Apr 2019Long-Acting Injectable Antipsychotics (LAIs) are used to overcome non-compliance in psychoses, mainly schizophrenia spectrum disorders. We aimed to summarize available... (Review)
Review
Long-Acting Injectable Antipsychotics (LAIs) are used to overcome non-compliance in psychoses, mainly schizophrenia spectrum disorders. We aimed to summarize available evidence of studies comparing the efficacy of LAIs to placebo or oral medications for Bipolar Disorder (BD) and/or Schizoaffective Disorder (SAD). We searched six databases from inception to 28-March-2018, using the strategy: long-acting antipsychotics AND (bipolar disorder OR schizoaffective disorder OR mania OR manic OR bipolar depression). We included peer-reviewed double-blind comparisons of LAIs for any clinical outcome occurrence in BD, or open mirror studies with same prospective as retrospective assessment periods. We excluded studies reporting on mixed schizophrenia/SAD populations without reporting results separately. The pooled records amounted to 642. After duplicate removal and inclusion/exclusion criteria application, we included 15 studies, 6 double-blind and 9 open, 13 assessing BD and 2 SAD. Depot neuroleptics prevented manic, but not depressive recurrences and may worsen depressive symptoms. Risperidone long-acting injectable was found to be effective in protecting from any mood/manic symptom compared to placebo, but not from depressive recurrences. Add-on or monotherapy paliperidone palmitate in SAD patients protected from psychotic, depressive, and manic symptoms. In patients with BD-I with a manic episode at study enrolment, aripiprazole monohydrate significantly delayed time to recurrence of manic episodes without inducing depressive episodes. LAIs are effective and well-tolerated maintenance treatments for BD and SAD. They showed better efficacy in preventing mania than depression. LAIs may be first-line for BD-I and SAD patients with a manic predominant polarity and with non-adherence problems.
Topics: Antipsychotic Agents; Bipolar Disorder; Delayed-Action Preparations; Humans; Injections, Intramuscular; Psychotic Disorders; Recurrence
PubMed: 30770235
DOI: 10.1016/j.euroneuro.2019.02.003 -
International Journal of Environmental... Sep 2021Adherence to prescribed medication regimes improves outcomes for patients with severe mental illness such as schizophrenia or bipolar disorders. The aim of this... (Meta-Analysis)
Meta-Analysis Review
Adherence to prescribed medication regimes improves outcomes for patients with severe mental illness such as schizophrenia or bipolar disorders. The aim of this systematic review and meta-analysis was to compare the effectiveness among interventions to improve medication adherence in patients with schizophrenia or bipolar disorders. Literature published in the last decade was searched for interventions studies to improve adherence in patients with schizophrenia or a bipolar disorder. Interventions were categorised on the basis of type, and the context and effectiveness of the interventions were described. Two review authors independently extracted and assessed data, following criteria outlined by the Cochrane Handbook for Systematic Reviews of Interventions. The GRADEPro (McMaster University, 2020, Ontario, Canada) was used for assessing the quality of the evidence. Twenty-three publications met the selection criteria. Different types of interventions aiming to improve adherence were tested: educational, behavioural, family-based, technological, or a combination of previous types. Meta-analysis could be performed for 10 interventions. When considered separately by subgroups on the basis of intervention type, no significant differences were found in adherence among interventions ( = 0.29; I = 19.9%). This review concluded that successful interventions used a combination of behavioural and educational approaches that seem easy to implement in daily practice.
Topics: Bipolar Disorder; Humans; Medication Adherence; Ontario; Schizophrenia
PubMed: 34639510
DOI: 10.3390/ijerph181910213