-
Molecular Autism Jan 2024Numerous interventions for irritability in autism spectrum disorder (ASD) have been investigated. We aimed to appraise the magnitude of pharmacological and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Numerous interventions for irritability in autism spectrum disorder (ASD) have been investigated. We aimed to appraise the magnitude of pharmacological and non-pharmacological interventions for irritability in ASD without any restrictions in terms of eligible interventions.
METHODS
We systematically searched PubMed/MEDLINE, Scopus, and Web of Science until April 15, 2023. We included randomized controlled trials (RCTs) with a parallel design that examined the efficacy of interventions for the treatment of irritability in patients of any age with ASD without any restrictions in terms of eligible interventions. We performed a random-effects meta-analysis by pooling effect sizes as Hedges' g. We classified assessed interventions as follows: pharmacological monotherapy, risperidone plus adjuvant therapy versus risperidone monotherapy, non-pharmacological intervention, and dietary intervention. We utilized the Cochrane tool to evaluate the risk of bias in each study and the GRADE approach to assess the certainty of evidence for each meta-analyzed intervention.
RESULTS
Out of 5640 references, we identified 60 eligible articles with 45 different kinds of interventions, including 3531 participants, of which 80.9% were males (mean age [SD] = 8.79 [3.85]). For pharmacological monotherapy, risperidone (Hedges' g - 0.857, 95% CI - 1.263 to - 0.451, certainty of evidence: high) and aripiprazole (Hedges' g - 0.559, 95% CI - 0.767 to - 0.351, certainty of evidence: high) outperformed placebo. Among the non-pharmacological interventions, parent training (Hedges' g - 0.893, 95% CI - 1.184 to - 0.602, certainty of evidence: moderate) showed a significant result. None of the meta-analyzed interventions yielded significant effects among risperidone + adjuvant therapy and dietary supplementation. However, several novel molecules in augmentation to risperidone outperformed risperidone monotherapy, yet from one RCT each.
LIMITATIONS
First, various tools have been utilized to measure the irritability in ASD, which may contribute to the heterogeneity of the outcomes. Second, meta-analyses for each intervention included only a small number of studies and participants.
CONCLUSIONS
Only risperidone, aripiprazole among pharmacological interventions, and parent training among non-pharmacological interventions can be recommended for irritability in ASD. As an augmentation to risperidone, several novel treatments show promising effects, but further RCTs are needed to replicate findings. Trial registration PROSPERO, CRD42021243965.
Topics: Male; Humans; Female; GRADE Approach; Aripiprazole; Risperidone; Autism Spectrum Disorder
PubMed: 38263251
DOI: 10.1186/s13229-024-00585-6 -
BMC Psychiatry Jan 2024The utilization of once-monthly paliperidone palmitate (PP1M) in schizophrenia treatment has increased due to its enhanced adherence and convenience. However, there is...
BACKGROUND
The utilization of once-monthly paliperidone palmitate (PP1M) in schizophrenia treatment has increased due to its enhanced adherence and convenience. However, there is limited evidence on patient characteristics that may influence treatment outcomes when switching from oral antipsychotics (OAPs) to PP1M therapy. This systematic review aims to identify such patient characteristics and explore potential beneficial factors to aid healthcare professionals in clinical practice.
METHODS
A systematic literature search was conducted in the PubMed, Embase, and Cochrane Library databases up to July 19, 2022. Studies related to patients with schizophrenia who had been previously treated with OAPs and switched to PP1M were identified and included. Outcomes included the Positive and Negative Syndrome Scale (PANSS) total score, the clinical Global Impressions - Severity (CGI-S) score, the Personal and Social Performance (PSP) total score, and hospitalisation rate. Data were independently extracted and analysed. The results were presented through a narrative synthesis.
RESULTS
Eleven studies with a total of 4150 patients were included, identifying nine potential characteristics. The most commonly reported characteristics was patient's prior treatment with OAPs, followed by the stage of disease, duration of illness (DI), ethnicity, reason for switching to PP1M, history of hospitalisation, time of start injection of PP1M, the PANSS and PSP total score at baseline. Patients in the acute stage, with a shorter DI, a less than 1-week time interval to PP1M injection, and a lower PANSS total score at baseline may have a trend on providing better improvements on PANSS total score. Acute stage and shorter DI also showed potential trends in reducing CGI-S score. Early initiation of PP1M, switching for reasons other than lack of efficacy, and a higher PSP score at baseline exhibited potential trends towards better PSP total score improvements.
CONCLUSION
Our findings may suggest that patients in acute stage, with a shorter duration of illness, with early initiation of PP1M injection, and lower PANSS or PSP scores may trend towards better clinical results when transitioning to PP1M from OAPs. Further research is necessary to validate these potential associations and identify any unexplored characteristics. Such investigations are crucial for providing comprehensive clinical recommendations and informing treatment strategies in this context.
Topics: Humans; Antipsychotic Agents; Paliperidone Palmitate; Schizophrenia; Administration, Oral; Treatment Outcome
PubMed: 38243208
DOI: 10.1186/s12888-024-05508-6 -
Psychopharmacology Feb 2024Dopamine antagonists induce dopamine receptor supersensitivity. This may manifest in late-appearing movement disorders (tardive dyskinesia (TD). VMAT-2 inhibitors reduce... (Meta-Analysis)
Meta-Analysis Review
RATIONALE
Dopamine antagonists induce dopamine receptor supersensitivity. This may manifest in late-appearing movement disorders (tardive dyskinesia (TD). VMAT-2 inhibitors reduce dopaminergic transmission but have limited activity at postsynaptic receptors and so may have antipsychotic activity with lower risk of tardive dyskinesia.
METHODS
We conducted a systematic database search from inception to September 2022 for articles describing the use of VMAT-2 inhibitors in psychosis. Inclusion criteria were as follows: Population: adults diagnosed with psychosis or schizophrenia; Intervention: treatment with tetrabenazine, deutetrabenazine or valbenazine; Comparison: comparison with placebo or/and antipsychotic drug; Outcomes: with efficacy outcomes (e.g. Brief Psychiatric Rating Scale (BPRS) change or clinician assessment) and adverse effects ratings (e.g. rating scale or clinician assessment or dropouts); and Studies: in randomised controlled trials and non-randomised studies.
RESULTS
We identified 4892 records relating to VMAT-2 inhibitor use of which 5 (173 participants) met our a priori meta-analysis inclusion criteria. VMAT-2 inhibitors were more effective than placebo for the outcome 'slight improvement' (risk ratio (RR) = 1.77 (95% CI 1.03, 3.04)) but not for 'moderate improvement' (RR 2.81 (95% CI 0.27, 29.17). VMAT-2 inhibitors were as effective as active comparators on both measures for-'slight improvement' (RR 1.05 (95% CI 0.6, 1.81)) and 'moderate improvement' (RR 1.11 (95% CI 0.51, 2.42). Antipsychotic efficacy was also suggested by a narrative review of 37 studies excluded from the meta-analysis.
CONCLUSIONS
VMAT-2 inhibitors may have antipsychotic activity and may offer promise for treatment of psychosis with the potential for a reduced risk of TD.
Topics: Adult; Humans; Antipsychotic Agents; Psychotic Disorders; Schizophrenia; Tardive Dyskinesia; Tetrabenazine; Vesicular Monoamine Transport Proteins
PubMed: 38238580
DOI: 10.1007/s00213-023-06488-3 -
Neuropsychopharmacology Reports Mar 2024This systematic review and frequentist network meta-analysis used random-effects models is conducted to determine whether there are differences in the efficacy,... (Meta-Analysis)
Meta-Analysis
AIM
This systematic review and frequentist network meta-analysis used random-effects models is conducted to determine whether there are differences in the efficacy, acceptability, tolerability, and safety profiles of brexpiprazole (BRE) and aripiprazole (ARI) for Japanese with major depressive disorder (MDD) who were inadequately responsive to antidepressants.
METHODS
Outcome measures were scores on the Montgomery Åsberg Depression Rating Scale (primary), the Clinical Global Impression severity scale, and social functioning scale; the non-response rate; the non-remission rate; all-cause discontinuation; discontinuation due to adverse events (DAE); at least one adverse event (1AE); serious adverse event, akathisia; tremor; weight gain.
RESULTS
A literature search identified three double-blind, randomized, placebo-controlled trials. These comprised one BRE study (with a 1 mg/day [BRE1] and a 2 mg/day [BRE2]) and two ARI studies (with a 3 mg/day arm and a flexible-dose arm[within the dosage range approved in Japan]) (n = 1736). Both BRE and ARI demonstrated better efficacy than the placebo. BRE but not ARI had a higher DAE than the placebo. ARI but not BRE had a higher 1AE than the placebo. BRE and ARI had a higher risk of akathisia and weight gain than the placebo. There were no significant differences between BRE and ARI for any of the outcomes. Although BRE1 had good efficacy, it carried risk of weight gain. Although BRE2 also had efficacy, it carried risks of DAE, akathisia, and weight gain. However, the risk of akathisia in BRE2 was reduced by an initial dose of 0.5 mg/day rather than 1.0 mg/day.
CONCLUSIONS
Overall BRE showed similar utility to ARI and a good risk-benefit balance.
Topics: Humans; Aripiprazole; Depressive Disorder, Major; Japan; Psychomotor Agitation; Network Meta-Analysis; Weight Gain; Randomized Controlled Trials as Topic; Thiophenes; Quinolones
PubMed: 38219278
DOI: 10.1002/npr2.12414 -
BMC Gastroenterology Oct 2023Since the previous network meta-analysis assessing the efficacy of prokinetics for functional dyspepsia (FD), there have been a number of new studies and cinitapride is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Since the previous network meta-analysis assessing the efficacy of prokinetics for functional dyspepsia (FD), there have been a number of new studies and cinitapride is a new prokinetic agent for FD. This updated meta-analysis aimed to explore the efficacy and safety of prokinetics for FD.
METHODS
An updated study search in Pubmed, EMBASE, Cochrane Library and Web of Science was conducted in literatures published from July 2015 to March 2023. Randomized controlled trials investigating the use of prokinetics in adult FD patients were included. The primary outcome was the total efficacy rate and the secondary outcome was adverse events. A Bayesian network meta-analysis was performed using R software.
RESULTS
A total of 28 studies were included. Network meta-analysis showed that metoclopramide had a higher total efficacy rate than mosapride (OR: 3.53, 95%CI: 1.70-7.47), domperidone (OR: 2.29, 95%CI: 1.16-4.63), itopride(OR: 2.77, 95%CI: 1.41-5.59), acotiamide(OR: 2.63, OR: 1.33-5.36), and placebo(OR: 5.68, 95%CI: 2.98-11.10), however similar to cinitapride (OR: 1.62, 95%CI: 0.75-3.53). Cinitapride had a higher total efficacy rate than mosapride (OR: 2.18, 95%CI: 1.16-4.14) and placebo (OR: 3.52, 95%CI: 2.01-6.24). Cinitapride had lower risk of total adverse events than domperidone. There was no difference in the risk of drug-related adverse events between the prokinetics.
CONCLUSIONS
Metoclopramide and cinitapride may have a better efficacy than other prokinetics in the treatment of FD, and cinitapride may have a lower risk of total adverse events. Further studies using uniform definitions or validated tools to measure the total efficacy rate are needed.
Topics: Adult; Humans; Dyspepsia; Domperidone; Metoclopramide; Network Meta-Analysis; Bayes Theorem; Randomized Controlled Trials as Topic
PubMed: 37907846
DOI: 10.1186/s12876-023-03014-9 -
Current Psychiatry Reports Nov 2023Despite clear evidence that sex differences largely impact the efficacy and tolerability of antipsychotic medication, current treatment guidelines for schizophrenia... (Review)
Review
PURPOSE OF REVIEW
Despite clear evidence that sex differences largely impact the efficacy and tolerability of antipsychotic medication, current treatment guidelines for schizophrenia spectrum disorders (SSD) do not differentiate between men and women. This review summarizes the available evidence on strategies that may improve pharmacotherapy for women and provides evidence-based recommendations to optimize treatment for women with schizophrenia.
RECENT FINDINGS
We systematically searched PubMed and Embase for peer-reviewed studies on three topics: (1) sex differences in dose-adjusted antipsychotic serum concentrations, (2) hormonal augmentation therapy with estrogen and estrogen-like compounds to improve symptom severity, and (3) strategies to reduce antipsychotic-induced hyperprolactinemia. Based on three database studies and one RCT, we found higher dose-adjusted concentrations in women compared to men for most antipsychotics. For quetiapine, higher concentrations were specifically found in older women. Based on two recent meta-analyses, both estrogen and raloxifene improved overall symptomatology. Most consistent findings were found for raloxifene augmentation in postmenopausal women. No studies evaluated the effects of estrogenic contraceptives on symptoms. Based on two meta-analyses and one RCT, adjunctive aripiprazole was the best-studied and safest strategy for lowering antipsychotic-induced hyperprolactinemia. Evidence-based recommendations for female-specific pharmacotherapy for SSD consist of (1) female-specific dosing for antipsychotics (guided by therapeutic drug monitoring), (2) hormonal replacement with raloxifene in postmenopausal women, and (3) aripiprazole addition as best evidenced option in case of antipsychotic-induced hyperprolactinemia. Combining these strategies could reduce side effects and improve outcome of women with SSD, which should be confirmed in future longitudinal RCTs.
Topics: Female; Humans; Male; Aged; Antipsychotic Agents; Schizophrenia; Aripiprazole; Hyperprolactinemia; Raloxifene Hydrochloride; Estrogens
PubMed: 37864676
DOI: 10.1007/s11920-023-01460-6 -
BMC Psychiatry Oct 2023We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of blonanserin and risperidone for the treatment of schizophrenia and to provide... (Meta-Analysis)
Meta-Analysis
BACKGROUND
We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of blonanserin and risperidone for the treatment of schizophrenia and to provide reliable pharmacotherapeutic evidence for in the clinical treatment of schizophrenia.
METHODS
We systematically searched the PubMed, Cochrane Library, Embase, Chinese Biomedical Literature Database (CBM), and China National Knowledge Infrastructure (CNKI) databases for head-to-head randomized controlled trials that compared blonanserin with risperidone for the treatment of schizophrenia. We extracted the following data: author, year, country, diagnostic criteria, sample size, course of treatment, dosage and outcomes. Our main endpoint was the changes in the Positive and Negative Syndrome Scale (PANSS) total scores. Meta-analysis of the included data was conducted by RevMan 5.3 software. We used the GRADE criteria to evaluate the certainty of the evidence.
RESULTS
A total of 411 studies were initially; 8 trials were eligible and were included in our analysis (N = 1386 participants). Regarding efficacy, there was no difference in changes in the PANSS total scores between the two groups (P > 0.05). In terms of safety, compared to risperidone, the incidence of serum prolactin increases and weight gain in the blonanserin group was lower (P<0.05), but the incidence of extrapyramidal symptoms (EPS) was higher (P<0.05).
CONCLUSION
The efficacy of blonanserin is similar to that of risperidone, but it is unclear whether blonanserin is more effective than risperidone at improving cognitive and social function. More high-quality studies are needed to verify the efficacy and safety of blonanserin in the future.
Topics: Humans; Risperidone; Schizophrenia; Antipsychotic Agents; Randomized Controlled Trials as Topic
PubMed: 37821875
DOI: 10.1186/s12888-023-05240-7 -
Medicine Sep 2023Atypical antipsychotic (AAP) augmentation is an alternative strategy for patients with major depressive disorder (MDD) who had an inadequate response to antidepressant... (Meta-Analysis)
Meta-Analysis
Comparative efficacy and safety of 4 atypical antipsychotics augmentation treatment for major depressive disorder in adults: A systematic review and network meta-analysis.
BACKGROUND
Atypical antipsychotic (AAP) augmentation is an alternative strategy for patients with major depressive disorder (MDD) who had an inadequate response to antidepressant therapy (ADT). We aimed to compare and rank the efficacy and safety of 4 AAPs in the adjuvant treatment of MDD.
METHODS
We searched randomized controlled trials (RCTs) published and unpublished from the date of databases and clinical trial websites inception to April 30, 2023. The evidence risk of bias (RoB) and certainty are assessed using the Cochrane bias risk tool and grading of recommendations assessment, development, and evaluation (GRADE) framework, respectively. Using network meta-analysis, we estimated summary risk ratios (RRs) or standardized mean difference (SMD) based on the random effects model.
RESULTS
56 eligible studies comprising 11448 participants were included. In terms of primary efficacy outcome, compared with placebo (PBO), all AAPs had significant efficacy (SMD = -0.40; 95% CI, -0.68 to -0.12 for quetiapine (QTP); -0.35, -0.59 to -0.11 for olanzapine (OLA); -0.28, -0.47 to -0.09 for aripiprazole (ARI) and -0.25, -0.42 to -0.07 for brexpiprazole (BRE), respectively). In terms of acceptability, no significant difference was found, either agents versus agents or agents versus PBO. In terms of tolerability, compared with the PBO, QTP (RR = 0.24; 95% CI,0.11-0.53), OLA (0.30,0.10-0.55), ARI (0.39,0.22-0.69), and BRE (0.37,0.18-0.75) were significantly less well tolerated. 8 (14.2%) of 56 trials were assessed as low RoB, 38 (67.9%) trials had moderate RoB, and 10 (17.9%) had high RoB; By the GRADE, the certainty of most evidence was low or very low.
CONCLUSION
Adjuvant AAPs had significant efficacy compared with PBO, but treatment decisions must be made to balance the risks and benefits.
Topics: Adult; Humans; Depressive Disorder, Major; Antipsychotic Agents; Network Meta-Analysis; Quetiapine Fumarate; Aripiprazole; Olanzapine; Adjuvants, Immunologic; Adjuvants, Pharmaceutic
PubMed: 37746943
DOI: 10.1097/MD.0000000000034670 -
Cureus Aug 2023Calcium channel blocker poisoning is one of the most common poisonings encountered which presents with life-threatening complications. However, there is no unified... (Review)
Review
Calcium channel blocker poisoning is one of the most common poisonings encountered which presents with life-threatening complications. However, there is no unified approach for treating these patients in the existing literature. This study aimed to assess the effects of different treatment modalities used in calcium channel blocker poisoning, as reported by previous studies. The primary outcomes studied were mortality and hemodynamic parameters after treatment. The secondary outcomes were the length of hospital stay, length of intensive care unit stay, duration of vasopressor use, functional outcomes, and serum calcium channel blocker concentrations. A thorough literature search was performed through Ovid, PubMed, Cochrane Library, and Google Scholar from January 2014 to December 31, 2022, to identify all studies analyzing the effects of the treatment of calcium channel blocker poisoning on the desired outcomes. Two reviewers reviewed 607 published articles from January 2014 to December 2022 to identify studies analyzing the effects of the treatment of calcium channel blocker poisoning on desired outcomes. In this review, 18 case reports, one case series, and one cohort study were included. Most patients were treated with an injection of calcium gluconate or calcium chloride. The use of calcium along with dopamine and norepinephrine was found to have lower mortality rates. A few patients were also treated with injection atropine for bradycardia. High-dose insulin therapy was used in 14 patients, of whom two did not survive. In the cohort study, 66 calcium channel blocker toxicity patients were included. These patients were treated with high-dose insulin therapy. A total of 11 patients with calcium channel blocker toxicity succumbed. Although it was found to be associated with improved hemodynamic parameters and lower mortality, side effects such as hypokalemia and hypoglycemia were noted. Intravenous lipid emulsion therapy (administered to eight patients), extracorporeal life support (used in three patients with refractory shock or cardiac arrest), injection glucagon, methylene blue, albumin infusion, and terlipressin were associated with a lower mortality rate as well as improvement in hemodynamic parameters. None of the case reports provided any information on end-organ damage on long-term follow-up.
PubMed: 37664357
DOI: 10.7759/cureus.42854 -
Critical Care (London, England) Aug 2023Haloperidol is frequently used in critically ill patients with delirium, but evidence for its effects has been sparse and inconclusive. By including recent trials, we... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Haloperidol is frequently used in critically ill patients with delirium, but evidence for its effects has been sparse and inconclusive. By including recent trials, we updated a systematic review assessing effects of haloperidol on mortality and serious adverse events in critically ill patients with delirium.
METHODS
This is an updated systematic review with meta-analysis and trial sequential analysis of randomised clinical trials investigating haloperidol versus placebo or any comparator in critically ill patients with delirium. We adhered to the Cochrane handbook, the PRISMA guidelines and the grading of recommendations assessment, development and evaluation statements. The primary outcomes were all-cause mortality and proportion of patients with one or more serious adverse events or reactions (SAEs/SARs). Secondary outcomes were days alive without delirium or coma, delirium severity, cognitive function and health-related quality of life.
RESULTS
We included 11 RCTs with 15 comparisons (n = 2200); five were placebo-controlled. The relative risk for mortality with haloperidol versus placebo was 0.89; 96.7% CI 0.77 to 1.03; I = 0% (moderate-certainty evidence) and for proportion of patients experiencing SAEs/SARs 0.94; 96.7% CI 0.81 to 1.10; I = 18% (low-certainty evidence). We found no difference in days alive without delirium or coma (moderate-certainty evidence). We found sparse data for other secondary outcomes and other comparators than placebo.
CONCLUSIONS
Haloperidol may reduce mortality and likely result in little to no change in the occurrence of SAEs/SARs compared with placebo in critically ill patients with delirium. However, the results were not statistically significant and more trial data are needed to provide higher certainty for the effects of haloperidol in these patients.
TRIAL REGISTRATION
CRD42017081133, date of registration 28 November 2017.
Topics: Humans; Haloperidol; Coma; Critical Illness; Quality of Life; Delirium; Randomized Controlled Trials as Topic
PubMed: 37633991
DOI: 10.1186/s13054-023-04621-4