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Schizophrenia Research Jun 2024Antipsychotic polypharmacy (APP) is frequent but evidence-based guidelines on reducing APP to antipsychotic monotherapy (APM) are sparse. We aimed to systematically...
BACKGROUND
Antipsychotic polypharmacy (APP) is frequent but evidence-based guidelines on reducing APP to antipsychotic monotherapy (APM) are sparse. We aimed to systematically review clinical interventions randomizing patients to reducing APP to APM versus continuing APP.
METHODS
Systematic literature review searching Medline and Embase (latest search January 10, 2024) for randomized clinical trials (RCTs) studying interventions comparing individuals randomized to reduction of APP to APM with individuals continuing on APP. Two independent reviewers performed the literature screening, data extraction, and risk of bias assessment (RoB2). We performed random effects meta-analyses on the main outcome all-cause discontinuation/"acceptability" of the treatment strategy and secondary outcomes change in psychopathology, functional level, and side effects.
RESULTS
The search identified 4672 hits, whereof 8 trials (N = 1204, 6 patient-level RCTs and 2 cluster-RCTs) were included, primarily in patients with schizophrenia. All trials were associated with high risk of bias. Compared to APP continuation, reduction to APM was associated with no significant change in all-cause discontinuation (studies = 6, n = 455, RR = 1.48, 95%CI = 0.74-2.95, I = 78 %) or inefficacy-related discontinuation (studies = 5, n = 351, RR = 1.60, 95%CI = 0.46-5.55, I = 70 %). Patients randomized to APM showed a trend towards greater reduction in psychopathology (studies = 5, n = 244, SMD = -0.24, 95%CI = -0.49, 0.02, I = 0 %) but no difference in functional level nor side effects. The cluster-RCTs found that interventions at the departmental level can result in lower rates of APP.
CONCLUSION
Although switching patients from APP to APM can be a viable approach, too few RCTs exist on this important topic. Clinicians need to evaluate potential benefits and risks of APP and APM on an individual basis.
PROSPERO REGISTRATION
CRD42022329955.
PubMed: 38908279
DOI: 10.1016/j.schres.2024.06.001 -
European Neuropsychopharmacology : the... Jun 2020Iron homeostasis may be implicated in the pathophysiology of antipsychotic-related akathisia. We performed a systematic review in six databases from database inception... (Meta-Analysis)
Meta-Analysis
Iron homeostasis may be implicated in the pathophysiology of antipsychotic-related akathisia. We performed a systematic review in six databases from database inception until 03/2020, conducting a meta-analysis of studies investigating iron metabolism in antipsychotic-treated patients with versus without akathisia. Using a fixed- and a random-effects model, standardized mean difference (SMD) was estimated for levels of iron, ferritin, transferrin and total iron-binding capacity. Meta-regression analyses included sex, age, illness duration and antipsychotic treatment and dose. Subgroup analyses included chronic vs. acute akathisia and different diagnoses. Study quality was assessed using the Newcastle-Ottawa scale. In 10 studies (n = 395), compared to non-akathisia patients (n = 213), iron levels were lower in patients with akathisia (n = 182; fixed-effect model: SMD=-0.49, 95%CI=-0.28,-0.70, p<0.001; random-effects model: SMD=-0.55, 95%CI=-0.14,-0.96, p = 0.008). For secondary outcomes, differences were significant regarding lower ferritin levels in patients with akathisia in the fixed-effect model (SMD=-0.32, 95%CI=-0.08,-0.55, p = 0.007), but not in the random-effects model (SMD=-0.29, 95%CI=0.20,-0.79, p = 0.24). None of the moderators/mediators had a significant effect on the group difference of iron levels. Subgroup analyses reported lower iron levels in both patients with chronic and acute akathisia vs. patients without. Iron levels for schizophrenia patients were lower in the fixed-effect model (SMD=-0.55, 95%CI=-0.23, -0.86, p<0.001), while a trend was observed in the random-effects model (SMD=-0.52, 95%CI=-0.07, -1.12, p = 0.08). The studies' quality was overall poor, with one exception. This meta-analysis suggests lower iron levels in akathisia patients, while ferritin differences were significant only in the fixed-effect model. Further data are required to promote the understanding of related pathways.
Topics: Akathisia, Drug-Induced; Antipsychotic Agents; Cross-Sectional Studies; Homeostasis; Humans; Iron; Observational Studies as Topic; Risk Factors; Treatment Outcome
PubMed: 32444336
DOI: 10.1016/j.euroneuro.2020.04.001 -
Clinical Psychology Review Jun 2020Cognitive biases, which are tendencies to systematically process, select and remember certain information (e.g., jumping to conclusions), are exacerbated in... (Meta-Analysis)
Meta-Analysis
Cognitive biases, which are tendencies to systematically process, select and remember certain information (e.g., jumping to conclusions), are exacerbated in schizophrenia and associated with delusions. Here we review and quantitatively assess psychological interventions targeting cognitive biases (e.g., metacognitive training, reasoning training, Maudsley review training programme) to evaluate their efficacy in improving cognitive biases, positive symptoms, and insight. Overall, thirty-two studies, including 15 distinct interventions and 2738 participants, were identified through a comprehensive keyword database search. Meta-analytic effect sizes were calculated and heterogeneity, publication bias, and subgroup analyses (study bias, active/passive intervention) were conducted. We observed significant small to moderate beneficial effects of cognitive interventions on cognitive biases (Hedges' g = 0.27; 95% CI = [0.13-0.41]; z = 3.77; p < .001), positive symptoms (Hedges' g = 0.30; 95% CI = [0.13-0.48]; z = 3.44, p < .005), and insight (Hedges' g = 0.35; 95% CI = [0.15-0.56]; z = 3.37,p < .005). Interestingly, studies with high risk of bias or passive control condition did not differ significantly from those with low risk or active control condition, respectively. Thus, cognitive biases are malleable via psychological interventions, which also exert, either directly or indirectly through reduced cognitive biases, beneficial effects on positive symptoms and insight.
Topics: Cognitive Behavioral Therapy; Humans; Outcome Assessment, Health Care; Psychosocial Intervention; Schizophrenia; Thinking
PubMed: 32361339
DOI: 10.1016/j.cpr.2020.101854 -
European Neuropsychopharmacology : the... Jan 2022Bipolar disorder (BD) might be associated with higher infection rates of coronavirus disease (COVID-19) which in turn could result in worsening the clinical course and...
Bipolar disorder (BD) might be associated with higher infection rates of coronavirus disease (COVID-19) which in turn could result in worsening the clinical course and outcome. This may be due to a high prevalence of somatic comorbidities and an increased risk of delays in and poorer treatment of somatic disease in patients with severe mental illness in general. Vaccination is the most important public health intervention to tackle the ongoing pandemic. We undertook a systematic review regarding the data on vaccinations in individuals with BD. Proportion of prevalence rates, efficacy and specific side effects of vaccinations and in individuals with BD were searched. Results show that only five studies have investigated vaccinations in individuals with BD, which substantially limits the interpretation of overall findings. Studies on antibody production after vaccinations in BD are very limited and results are inconsistent. Also, the evidence-based science on side effects of vaccinations in individuals with BD so far is poor.
Topics: Bipolar Disorder; COVID-19; Communicable Disease Control; Communicable Diseases; Humans; Pandemics; SARS-CoV-2; Vaccines
PubMed: 34607722
DOI: 10.1016/j.euroneuro.2021.09.001 -
The Lancet. Psychiatry Jun 2021Dose reduction of antipsychotic maintenance treatment in individuals with schizophrenia could be desirable to minimise adverse effects, but evidence for this strategy is... (Comparative Study)
Comparative Study Meta-Analysis
Standard versus reduced dose of antipsychotics for relapse prevention in multi-episode schizophrenia: a systematic review and meta-analysis of randomised controlled trials.
BACKGROUND
Dose reduction of antipsychotic maintenance treatment in individuals with schizophrenia could be desirable to minimise adverse effects, but evidence for this strategy is unclear. We aimed to compare risks and benefits of reduced versus standard doses of antipsychotics.
METHODS
We searched Embase, Medline, PsycINFO, and the Cochrane Library from database inception until June 17, 2020, for randomised trials in adults with schizophrenia or schizoaffective disorder lasting at least 24 weeks, including individuals clinically stable at baseline, and comparing at least two doses of the same antipsychotic, excluding trials in first-episode psychosis or treatment-resistant schizophrenia. We compared low-dose (within 50-99% of the lower limit of the standard dose) and very-low dose (less than 50% of the lower limit) with standard dose, defined as doses higher than the lower limit of the treatment dose recommended by the International Consensus Study. Data from published reports on number of participants, treatment, sex, age, number of events, and changes in psychopathology scores were extracted independently by at least two authors. Investigators or sponsors were contacted by email to obtain missing information regarding outcomes. Co-primary outcomes were relapse and all-cause discontinuation. Study-level data were meta-analysed using random-effects models, calculating risk ratios (RRs) for dichotomous data, and Hedges' g for continuous data. The protocol was registered with OSF registries.
FINDINGS
7853 references were identified in the database search and one additional reference from a manual review of relevant studies. 5744 abstracts were assessed for eligibility, and 101 references were assessed for full-text review. Of these, 79 were excluded for a variety of reasons, resulting in 22 studies being included in the meta-analysis, reporting on 24 trials and 3282 individuals. Study participants had a median age of 38 years (IQR 36-40) with 2166 (65·9%) males and 1116 (34·0%) females. Compared with standard dose, low dose increased the risk of relapse by 44% (16 trials, 1920 participants; RR 1·44, 95% CI 1·10-1·87; p=0·0076; I=46%) and the risk of all-cause discontinuation by 12% (16 trials, 1932 participants; RR 1·12, 1·03-1·22; p=0·0085; I=0%). Very low dose increased the risk of relapse by 72% (13 trials, 2058 participants; RR 1·72, 95% CI 1·29-2·29; p=0·0002; I=70%) and all-cause discontinuation by 31% (11 trials, 1866 participants; RR 1·31, 1·11-1·54; p=0·0011; I=63%). Compared with low dose, very low dose did not significantly increase the risk of relapse (five trials, 686 participants; RR 1·31, 95% CI 0·96-1·79; p=0·092; I=51%) or all-cause discontinuation (five trials 686 participants; RR 1·11, 95% CI 0·95-1·30; p=0·18; I=43%). Subgroup analyses comparing double-blind versus open-label studies, first-generation versus second-generation antipsychotics, and oral versus long-acting injectable antipsychotics were consistent with the overall results. Most studies were classified as having some concerns in the risk of bias assessment, which was mainly caused by absence of publicly available study registrations.
INTERPRETATION
During maintenance treatment in multi-episode schizophrenia, antipsychotic doses should probably not be reduced below the standard dose range recommended for acute stabilisation, because reducing the dose further is associated with an increased risk of both relapse and all-cause discontinuation.
FUNDING
None.
Topics: Adult; Antipsychotic Agents; Dose-Response Relationship, Drug; Humans; Randomized Controlled Trials as Topic; Recurrence; Schizophrenia; Secondary Prevention; Treatment Outcome
PubMed: 34023019
DOI: 10.1016/S2215-0366(21)00078-X -
Revista Brasileira de Psiquiatria (Sao... 2021Electrical and magnetic brain stimulation techniques present distinct mechanisms and efficacy in the acute treatment of depression. This was an umbrella review of...
Appraising the effectiveness of electrical and magnetic brain stimulation techniques in acute major depressive episodes: an umbrella review of meta-analyses of randomized controlled trials.
Electrical and magnetic brain stimulation techniques present distinct mechanisms and efficacy in the acute treatment of depression. This was an umbrella review of meta-analyses of randomized controlled trials of brain stimulation techniques for managing acute major depressive episodes. A systematic review was performed in the PubMed/MEDLINE databases from inception until March 2020. We included the English language meta-analysis with the most randomized controlled trials on the effects of any brain stimulation technique vs. control in adults with an acute depressive episode. Continuous and dichotomous outcomes were assessed. A Measurement Tool to Assess Systematic Reviews-2 was applied and the credibility of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation framework. Seven meta-analyses were included (5,615 patients), providing evidence for different modalities of brain stimulation techniques. Three meta-analyses were evaluated as having high methodological quality, three as moderate, and one as low. The highest quality of evidence was found for high frequency-repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation, and bilateral rTMS. There is strong clinical research evidence to guide future clinical use of some techniques. Our results confirm the heterogeneity of the effects across these techniques, indicating that different mechanisms of action lead to different efficacy profiles.
Topics: Adult; Brain; Depression; Depressive Disorder, Major; Humans; Magnetic Phenomena; Meta-Analysis as Topic; Randomized Controlled Trials as Topic; Transcranial Direct Current Stimulation
PubMed: 33111776
DOI: 10.1590/1516-4446-2020-1169 -
The Mental Health Clinician Aug 2023
PubMed: 37860589
DOI: 10.9740/mhc.2023.08.196