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Molecular Psychiatry Aug 2023Antipsychotic drugs differ in their propensity to cause extrapyramidal side-effects (EPS), but their dose-effects are unclear. Therefore, we conducted a systematic... (Meta-Analysis)
Meta-Analysis
Antipsychotic drugs differ in their propensity to cause extrapyramidal side-effects (EPS), but their dose-effects are unclear. Therefore, we conducted a systematic review and dose-response meta-analysis. We searched multiple electronic databases up to 20.02.2023 for fixed-dose studies investigating 16 second-generation antipsychotics and haloperidol (all formulations and administration routes) in adults with acute exacerbations of schizophrenia. The primary outcome was the number of participants receiving antiparkinsonian medication, and if not available, the number of participants with extrapyramidal side-effects (EPS) and the mean scores of EPS rating scales were used as proxies. The effect-size was odds ratio (ORs) compared with placebo. One-stage random-effects dose-response meta-analyses with restricted cubic splines were conducted to estimate the dose-response curves. We also examined the relationship between dopamine D receptor (DR) occupancy and ORs by estimating occupancies from administrated doses. We included data from 110 studies with 382 dose arms (37193 participants). Most studies were short-term with median duration of 6 weeks (range 3-26 weeks). Almost all antipsychotics were associated with dose-dependent EPS with varied degrees and the maximum ORs ranged from OR = 1.57 95%CI [0.97, 2.56] for aripiprazole to OR = 7.56 95%CI [3.16, 18.08] for haloperidol at 30 mg/d. Exceptions were quetiapine and sertindole with negligible risks across all doses. There was very low quality of findings for cariprazine, iloperidone, and zotepine, and no data for clozapine. The DR occupancy curves showed that the risk increased substantially when DR occupancy exceeded 75-85%, except for DR partial agonists that had smaller ORs albeit high DR occupancies. In conclusion, we found that the risk of EPS increases with rising doses and differs substantially in magnitude among antipsychotics, yet exceptions were quetiapine and sertindole with negligible risks. Our data provided additional insights into the current DR therapeutic window for EPS.
Topics: Adult; Humans; Antipsychotic Agents; Quetiapine Fumarate; Haloperidol; Clozapine; Receptors, Dopamine D2; Drug-Related Side Effects and Adverse Reactions
PubMed: 37537284
DOI: 10.1038/s41380-023-02203-y -
Schizophrenia Bulletin Jan 2024Long-acting injectable antipsychotic drugs (LAIs) are mainly used for relapse prevention but could also be advantageous for acutely ill patients with schizophrenia. (Meta-Analysis)
Meta-Analysis
Long-Acting Injectable Second-Generation Antipsychotics vs Placebo and Their Oral Formulations in Acute Schizophrenia: A Systematic Review and Meta-Analysis of Randomized-Controlled-Trials.
BACKGROUND AND HYPOTHESIS
Long-acting injectable antipsychotic drugs (LAIs) are mainly used for relapse prevention but could also be advantageous for acutely ill patients with schizophrenia.
STUDY DESIGN
We conducted a systematic review and meta-analysis of randomized-controlled-trials (RCTs) comparing the second-generation long-acting injectable antipsychotics (SGA-LAIs) olanzapine, risperidone, paliperidone, and aripiprazole with placebo or their oral counterparts in acutely ill patients with schizophrenia. We analyzed 23 efficacy and tolerability outcomes, with the primary outcome being overall symptoms of schizophrenia. The results were obtained through random effects, pairwise meta-analyses, and subgroup tests. The study quality was assessed using the Cochrane-Risk-of-Bias-Tool version-1.
STUDY RESULTS
Sixty-six studies with 16 457 participants were included in the analysis. Eleven studies compared second-generation long-acting injectable antipsychotics (SGA-LAIs) with a placebo, 54 compared second-generation oral antipsychotics (SGA-orals) with a placebo, and one compared an SGA-LAI (aripiprazole) with its oral formulation. All 4 SGA-LAIs reduced overall symptoms more than placebo, with mean standardized differences of -0.66 (95% CI: -0.90; -0.43) for olanzapine, -0.64 (-0.80; -0.48) for aripiprazole, -0.62 (-0.76; -0.48) for risperidone and -0.42 (-0.53; -0.31) for paliperidone. The side-effect profiles of the LAIs corresponded to the patterns known from the oral formulations. In subgroup tests compared to placebo, some side effects were less pronounced under LAIs than under their oral formulations.
CONCLUSIONS
SGA-LAIs effectively treat acute schizophrenia. Some side effects may be less frequent than under oral drugs, but due to the indirect nature of the comparisons, this finding must be confirmed by RCTs comparing LAIs and orals head-to-head.
Topics: Humans; Antipsychotic Agents; Paliperidone Palmitate; Aripiprazole; Olanzapine; Risperidone; Delayed-Action Preparations; Schizophrenia
PubMed: 37350486
DOI: 10.1093/schbul/sbad089 -
Tijdschrift Voor Psychiatrie 2023Metformin is the most investigated pharmacological treatment of antipsychotics-induced weight gain (AIWG). Based on a systematic literature review, the first guideline...
BACKGROUND
Metformin is the most investigated pharmacological treatment of antipsychotics-induced weight gain (AIWG). Based on a systematic literature review, the first guideline for the treatment of AIWG with metformin was recently published.
AIM
To present a step-by-step plan, based on recent literature and clinical experience to monitor, prevent, and treat AIWG.
METHOD
Literature search to give specific advice on the choice of antipsychotic medication, stop, dose reduction or switch of antipsychotic, screening, non-pharmacological and pharmacological interventions to prevent and treat AIWG.
RESULTS
Especially in the first year of antipsychotic treatment timely detection of AIWG through regular monitoring is pivotal. The best way to treat AIWG is to prevent its emergence by choosing an antipsychotic with a favourable metabolic profile. Secondly, by titration of antipsychotic medication to the lowest dose possible. Achieving a healthy lifestyle shows a limited beneficial effect on AIWG. Drug-induced weight loss can be attained by the addition of metformin, topiramate, or aripiprazole. Topiramate and aripiprazole can improve positive and negative residual symptoms of schizophrenia. The evidence on liraglutide is scarce. All augmentation strategies may cause side effects. Besides, in case of nonresponse augmentation therapy should be stopped to prevent unnecessary polypharmacy.
CONCLUSION
In the revision of the Dutch multidisciplinary guideline for schizophrenia, the detection, prevention, and treatment of AIWG deserves more attention.
Topics: Humans; Antipsychotic Agents; Aripiprazole; Topiramate; Weight Gain; Metformin
PubMed: 37323046
DOI: No ID Found -
World Psychiatry : Official Journal of... Jun 2023Most acute phase antipsychotic drug trials in schizophrenia last only a few weeks, but patients must usually take these drugs much longer. We examined the long-term...
Most acute phase antipsychotic drug trials in schizophrenia last only a few weeks, but patients must usually take these drugs much longer. We examined the long-term efficacy of antipsychotic drugs in acutely ill patients using network meta-analysis. We searched the Cochrane Schizophrenia Group register up to March 6, 2022 for randomized, blinded trials of at least 6-month duration on all second-generation and 18 first-generation antipsychotics. The primary outcome was change in overall symptoms of schizophrenia; secondary outcomes were all-cause discontinuation; change in positive, negative and depressive symptoms; quality of life, social functioning, weight gain, antiparkinson medication use, akathisia, serum prolactin level, QTc prolongation, and sedation. Confidence in the results was assessed by the CINeMA (Confidence in Network Meta-Analysis) framework. We included 45 studies with 11,238 participants. In terms of overall symptoms, olanzapine was on average more efficacious than ziprasidone (standardized mean difference, SMD=0.37, 95% CI: 0.26-0.49), asenapine (SMD=0.33, 95% CI: 0.21-0.45), iloperidone (SMD=0.32, 95% CI: 0.15-0.49), paliperidone (SMD=0.28, 95% CI: 0.11-0.44), haloperidol (SMD=0.27, 95% CI: 0.14-0.39), quetiapine (SMD=0.25, 95% CI: 0.12-0.38), aripiprazole (SMD=0.16, 95% CI: 0.04-0.28) and risperidone (SMD=0.12, 95% CI: 0.03-0.21). The 95% CIs for olanzapine versus aripiprazole and risperidone included the possibility of trivial effects. The differences between olanzapine and lurasidone, amisulpride, perphenazine, clozapine and zotepine were either small or uncertain. These results were robust in sensitivity analyses and in line with other efficacy outcomes and all-cause discontinuation. Concerning weight gain, the impact of olanzapine was higher than all other antipsychotics, with a mean difference ranging from -4.58 kg (95% CI: -5.33 to -3.83) compared to ziprasidone to -2.30 kg (95% CI: -3.35 to -1.25) compared to amisulpride. Our data suggest that olanzapine is more efficacious than a number of other antipsychotic drugs in the longer term, but its efficacy must be weighed against its side effect profile.
PubMed: 37159349
DOI: 10.1002/wps.21089 -
PloS One 2023Second-generation antipsychotics (SGAs) are frequently prescribed for the treatment of resistant anorexia nervosa. However, few clinical trials have been conducted so...
INTRODUCTION
Second-generation antipsychotics (SGAs) are frequently prescribed for the treatment of resistant anorexia nervosa. However, few clinical trials have been conducted so far and no pharmacological treatment has yet been approved by the Food and Drug Administration. The aim of this paper is to conduct a systematic scoping review exploring the effectiveness and safety of atypical antipsychotics in anorexia nervosa (AN).
METHOD
We conducted a systematic scoping review of the effectiveness and tolerability of SGAs in the management of AN. We included articles published from January 1, 2000, through September 12, 2022 from the PubMed and PsycInfo databases and a complementary manual search. We selected articles about adolescents and adults treated for AN by four SGAs (risperidone, quetiapine, aripiprazole or olanzapine). This work complies with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for scoping reviews (PRIMA-ScR) and was registered in the Open Science Framework (OSF) repository.
RESULTS
This review included 55 articles: 48 assessing the effectiveness of SGAs in AN and 7 focusing only on their tolerability and safety. Olanzapine is the treatment most frequently prescribed and studied with 7 randomized double-blind controlled trials. Other atypical antipsychotics have been evaluated much less often, such as aripiprazole (no randomized trials), quetiapine (two randomized controlled trials), and risperidone (one randomized controlled trial). These treatments are well tolerated with mild and transient adverse effects in this population at particular somatic risk.
DISCUSSION
Limitations prevent the studies both from reaching conclusive, reliable, robust, and reproducible results and from concluding whether or not SGAs are effective in anorexia nervosa. Nonetheless, they continue to be regularly prescribed in clinical practice. International guidelines suggest that olanzapine and aripiprazole can be interesting in severe or first-line resistant clinical situations.
Topics: Adult; Adolescent; Humans; Antipsychotic Agents; Olanzapine; Risperidone; Aripiprazole; Quetiapine Fumarate; Anorexia Nervosa; Benzodiazepines; Randomized Controlled Trials as Topic
PubMed: 36928656
DOI: 10.1371/journal.pone.0278189 -
PharmacoEconomics Jun 2023Various treatment approaches are available for depression. Given the scarcity of healthcare resources, it is important to optimise treatment availability in an efficient...
BACKGROUND
Various treatment approaches are available for depression. Given the scarcity of healthcare resources, it is important to optimise treatment availability in an efficient manner. Economic evaluations can inform the optimal allocation of healthcare resources. However, there is currently no review synthesising what is known about the cost effectiveness of treatments for depression in low- and middle-income countries (LMICs).
METHODS
This review identified articles from six database searches: APA PsycINFO, CINAHL Complete, Cochrane Library, EconLit, Embase and MEDLINE Complete. Trial- and model-based economic evaluations published between 1 January 2000 and 3 December 2022 were included. The quality of health economic studies (QHES) instrument was used to assess the quality of the included papers.
RESULTS
This review comprised 22 articles, with most studies (N = 17) focusing exclusively on the adult population. Even though evidence regarding the cost effectiveness of antidepressants for treating various forms of depression was inconsistent; an atypical antipsychotic (aripiprazole) was frequently reported to be cost effective for treatment-resistant depression. Task shifting (aka task sharing) to lay health workers or non-specialist health care providers appeared to be a cost-effective approach for treating depression in LMICs.
CONCLUSIONS
Overall, this review found mixed evidence on the cost effectiveness of depression treatment choices among LMICs, with some indication that task sharing with lay health workers may be cost effective. Future research will be needed to fill the gaps around the cost effectiveness of depression treatments in younger people and beyond healthcare facilities.
Topics: Adult; Humans; Depression; Cost-Effectiveness Analysis; Developing Countries; Antidepressive Agents; Cost-Benefit Analysis
PubMed: 36894798
DOI: 10.1007/s40273-023-01257-8 -
BMJ Mental Health Feb 2023Are antipsychotic dose equivalents between acute mania and schizophrenia the same? (Meta-Analysis)
Meta-Analysis
QUESTION
Are antipsychotic dose equivalents between acute mania and schizophrenia the same?
STUDY SELECTION AND ANALYSIS
Six databases were systematically searched (from inception to 17 September 2022) to identify blinded randomised controlled trials (RCTs) that used a flexible-dose oral antipsychotic drug for patients with acute mania. The mean and SD of the effective dose and the pre-post changes in manic symptoms were extracted. A network meta-analysis (NMA) under a frequentist framework was performed to examine the comparative efficacy between the antipsychotics. A classic mean dose method (sample size weighted) was used to calculate each antipsychotic dose equivalent to 1 mg/day olanzapine for acute mania. The antipsychotic dose equivalents of acute mania were compared with published data for schizophrenia.
FINDINGS
We included 42 RCTs which enrolled 11 396 participants with acute mania. The NMA showed that risperidone was superior to olanzapine (reported standardised mean difference: -022, 95% CI -0.41 to -0.02), while brexpiprazole was inferior to olanzapine (standardised mean difference: 0.36, 95% CI 0.08 to 0.64). The dose equivalents to olanzapine (with SD) were 0.68 (0.23) for haloperidol, 0.32 (0.07) for risperidone, 0.60 (0.11) for paliperidone, 8.00 (1.41) for ziprasidone, 41.46 (5.98) for quetiapine, 1.65 (0.32) for aripiprazole, 1.23 (0.20) for asenapine, 0.53 (0.14) for cariprazine and 0.22 (0.03) for brexpiprazole. Compared with the olanzapine dose equivalents for schizophrenia, those of acute mania were higher for quetiapine (p<0.001, 28.5%) and aripiprazole (p<0.001, 17.0%), but lower for haloperidol (p<0.001, -8.1%) and risperidone (p<0.001, -15.8%).
CONCLUSIONS
Antipsychotic drugs have been considered first-line treatment for acute mania, warranting specific dose equivalence for scientific and clinical purposes.
Topics: Humans; Antipsychotic Agents; Olanzapine; Risperidone; Aripiprazole; Quetiapine Fumarate; Haloperidol; Bipolar Disorder; Mania; Schizophrenia; Randomized Controlled Trials as Topic
PubMed: 36789916
DOI: 10.1136/bmjment-2022-300546 -
Revista Brasileira de Psiquiatria (Sao... May 2023To summarize evidence-based pharmacological treatments and provide guidance on clinical interventions for adult patients with obsessive-compulsive disorder (OCD).
Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders guidelines for the treatment of adult obsessive-compulsive disorder. Part I: pharmacological treatment.
OBJECTIVES
To summarize evidence-based pharmacological treatments and provide guidance on clinical interventions for adult patients with obsessive-compulsive disorder (OCD).
METHODS
The American Psychiatric Association (APA) guidelines for the treatment of OCD (2013) were updated with a systematic review assessing the efficacy of pharmacological treatments for adult OCD, comprising monotherapy with selective serotonin reuptake inhibitors (SSRIs), clomipramine, serotonin and norepinephrine reuptake inhibitors (SNRIs), and augmentation strategies with clomipramine, antipsychotics, and glutamate-modulating agents. We searched for the literature published from 2013-2020 in five databases, considering the design of the study, primary outcome measures, types of publication, and language. Selected articles had their quality assessed with validated tools. Treatment recommendations were classified according to levels of evidence developed by the American College of Cardiology and the American Heart Association (ACC/AHA).
RESULTS
We examined 57 new studies to update the 2013 APA guidelines. High-quality evidence supports SSRIs for first-line pharmacological treatment of OCD. Moreover, augmentation of SSRIs with antipsychotics (risperidone, aripiprazole) is the most evidence-based pharmacological intervention for SSRI-resistant OCD.
CONCLUSION
SSRIs, in the highest recommended or tolerable doses for 8-12 weeks, remain the first-line treatment for adult OCD. Optimal augmentation strategies for SSRI-resistant OCD include low doses of risperidone or aripiprazole. Pharmacological treatments considered ineffective or potentially harmful, such as monotherapy with antipsychotics or augmentation with ketamine, lamotrigine, or N-acetylcysteine, have also been detailed.
Topics: Humans; Adult; Antipsychotic Agents; Selective Serotonin Reuptake Inhibitors; Clomipramine; Aripiprazole; Risperidone; Brazil; Treatment Outcome; Obsessive-Compulsive Disorder
PubMed: 36749887
DOI: 10.47626/1516-4446-2022-2891 -
Paediatric Drugs Mar 2023Long-acting injectable antipsychotics (LAIAs) are an efficacious and well-tolerated treatment in adults with schizophrenia spectrum disorders (SSD). However, there is...
BACKGROUND
Long-acting injectable antipsychotics (LAIAs) are an efficacious and well-tolerated treatment in adults with schizophrenia spectrum disorders (SSD). However, there is less evidence for their use in children and adolescents.
OBJECTIVES
The aim of this systematic review was to summarize findings regarding the effectiveness and side effects of LAIA in children and adolescents with SSD.
METHODS
Four databases (Web of Science, PubMed, MEDES, and Dialnet) were systematically searched for articles published between inception and 12 March, 2022, with the following inclusion criteria: (1) original articles or case reports; (2) providing data on efficacy/effectiveness or safety/tolerability of LAIA treatment in children and adolescents diagnosed with SSD (schizophrenia, schizoaffective disorder, schizophreniform disorder, non-affective psychotic disorder); (3) mean age of samples ≤ 18 years; and (4) written in English or Spanish. Exclusion criteria were review articles, clinical guides, expert consensus as well as posters or oral communication in conferences. The risk of bias was assessed using the ROBIS tool.
RESULTS
From 847 articles found, 13 met the inclusion criteria. These included seven single case reports or case series, four retrospective chart reviews, a 24-week open-label trial, and one observational prospective study, covering a total of 119 adolescents (aged 12-17 years) with SSD. Almost all the articles described data on second-generation LAIA (53 patients on risperidone [once every other week], 33 on paliperidone palmitate [once monthly], 10 on aripiprazole [once monthly], and two on olanzapine pamoate [once monthly]). Twenty-one patients were reported to be only on first-generation LAIAs. Non-adherence was the main reason for starting an LAIA. In all of the studies, the use of LAIAs was associated with improvement in the patients' symptoms.
CONCLUSIONS
There are few studies assessing the use of LAIAs in adolescents with SSD. Overall, these treatments have suggested good effectiveness and acceptable safety and tolerability. However, we found no studies examining their use in children aged < 12 years. The problems and benefits linked to this type of antipsychotic formulation in the child and adolescent population require further study, ideally with prospective, controlled designs.
Topics: Adult; Adolescent; Child; Humans; Antipsychotic Agents; Schizophrenia; Prospective Studies; Retrospective Studies; Risperidone; Delayed-Action Preparations; Paliperidone Palmitate
PubMed: 36662369
DOI: 10.1007/s40272-023-00558-x -
Frontiers in Aging Neuroscience 2022Depressive symptoms play an essential role in cognition decline, while the benefit and acceptability of treatments for depressive symptoms in cognitive impairment are...
BACKGROUND
Depressive symptoms play an essential role in cognition decline, while the benefit and acceptability of treatments for depressive symptoms in cognitive impairment are still unknown.
OBJECTIVE
To comprehensively evaluate the comparative efficacy and acceptability of treatments for depressive symptoms in cognitive impairment based on the quantitative Bayesian network meta-analysis method (NMA).
METHOD
We searched MEDLINE, Embase, the Cochrane Library, CINAHL, and PsycINFO from inception until August 2022 to identify randomized clinical trials (RCTs) evaluating treatments for depressive symptoms in cognitive impairment. Efficacy was evaluated by the Cornell Scale for Depression in Dementia (CSDD), the Hamilton Depression Rating Scale (HDRS), and the Geriatric Depression Scale (GDS) for depression; the Neuropsychiatric Inventory (NPI) and the Cohen-Mansfeld Agitation Inventory (CMAI) for behavior; and the Mini-Mental State Examination (MMSE) for cognition. Safety was evaluated by total adverse events (AEs), serious AEs, diarrhea, headache, and nausea.
RESULTS
In this study, 13,043 participants from 107 RCTs were included, involving 28 treatments and the discontinuation of antidepressants. On CSDD, aerobic exercise (MD -4.51, 95%CrI -8.60 to -0.37), aripiprazole (MD -1.85, 95%CrI -3.66 to -0.02), behavioral training (MD -1.14, 95%CrI -2.04 to -0.34), electrical current stimulation (MD -3.30, 95%CrI -5.94 to -0.73), massage (MD -12.67, 95%CrI -14.71 to -10.59), music therapy (MD -2.63, 95%CrI -4.72 to -0.58), and reminiscence therapy (MD -2.34, 95%CrI -3.51 to -1.25) significantly outperformed the placebo. On MMSE, cognitive stimulation therapy (MD 1.42, 95%CrI 0.49 to 2.39), electrical current stimulation (MD 4.08, 95%CrI 1.07 to 7.11), and reminiscence therapy (MD 1.31, 95%CrI 0.04 to 2.91) significantly outperformed the placebo. Additionally, no treatments showed a significantly higher risk than the placebo.
CONCLUSION
Our NMAs indicated that non-pharmacological interventions were more efficacious and safe than pharmacological treatments for reducing depressive symptoms as well as improving cognitive impairment. Electrical current stimulation, aerobic exercise, and reminiscence therapy could be first recommended considering their beneficial performance on both depression and cognition. Hence, non-pharmacological treatments deserve more attention and extensive application and should at least be considered as an alternative or assistance in clinical settings.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021239621, identifier: CRD42021239621.
PubMed: 36578447
DOI: 10.3389/fnagi.2022.1037414