Clinical Psychopharmacology and Neuroscience Papers in Press available online.

Pharmacological augmentation strategies for partial or non-responders to clozapine in patients with schizophrenia: A Bayesian network meta-analysis of randomized controlled trials
All India Institute of Medical Sciences, Bhubaneswar, India
Clozapine is the only approved drug for treatment-resistant schizophrenia, but the response to the drug is often inadequate. Augmentation with other antipsychotics, anticonvulsants, and antidepressants is recommended for such patients, but there is a lack of evidence regarding the most effective therapy. This network meta-analysis was conducted to evaluate the efficacy of pharmacological agents used in the augmentation strategies in patients who were partial/non-responders to clozapine. Relevant data were extracted from 29 randomized controlled trials through searches of electronic databases (MEDLINE/PubMed, Embase, Cochrane, clinical trial registries). PRISMA guidelines were followed for the extraction, management, analysis, and reporting of the data. The outcome measure in this study was a reduction in symptom severity according to total PANSS/BPRS and was reported as the standardized mean difference with a 95% credible interval. Bayesian network meta-analysis with random effects model and uninformative priors was conducted, and the ranking probability of each intervention was done. Meta-regression was done to assess the effect of duration on the reduction in symptom severity scores. Mirtazapine [−5.2 (95%CrI: −7.7, −2.7)] and memantine [−2.1 (95%CrI: −4.0, −0.19)] were more efficacious than placebo for augmentation of clozapine in partial/non-responders and were the most effective adjunctive agents as per SUCRA scores. Both drugs did not cause a significant increase in frequency of adverse events compared to placebo. There was a significant effect of duration on the reduction in symptom severity. There was no evident publication bias. Mirtazapine and memantine may prove beneficial for augmentation of clozapine in non/partial responders to monotherapy.
Accepted Manuscript [Submitted on 2023-07-17, Accepted on 2023-10-19]