Dose-Response Meta-Analysis of Antipsychotic Drugs for Acute Schizophrenia

Abstract

The dose-response relationships of antipsychotic drugs for schizophrenia are not well defined, but such information would be important for decision making by clinicians. The authors sought to fill this gap by conducting dose-response meta-analyses.Methods: A search of multiple electronic databases (through November 2018) was conducted for all placebo-controlled dose-finding studies for 20 second-generation antipsychotic drugs and haloperidol (oral and long-acting injectable, LAI) in people with acute schizophrenia symptoms. Dose-response curves were constructed with random-effects dose-response meta-analyses and a spline model. The outcome measure was total score reduction from baseline on the Positive and Negative Syndrome Scale or the Brief Psychiatric Rating Scale. The authors identified 95% effective doses, explored whether higher or lower doses than the currently licensed ones might be more appropriate, and derived dose equivalencies from the 95% effective doses.Results: Sixty-eight studies met the inclusion criteria. The 95% effective doses and the doses equivalent to 1 mg of oral risperidone, respectively, were as follows: amisulpride for patients with positive symptoms, 537 mg/day and 85.8 mg; aripiprazole, 11.5 mg/day and 1.8 mg; aripiprazole LAI (lauroxil), 463 mg every 4 weeks and 264 mg; asenapine, 15.0 mg/day and 2.4 mg; brexpiprazole, 3.36 mg/day and 0.54 mg; haloperidol, 6.3 mg/day and 1.01 mg; iloperidone, 20.13 mg/day and 3.2 mg; lurasidone, 147 mg/day and 23.5 mg; olanzapine, 15.2 mg/day and 2.4 mg; olanzapine LAI, 277 mg every 2 weeks and 3.2 mg; paliperidone, 13.4 mg/day and 2.1 mg; paliperidone LAI, 120 mg every 4 weeks and 1.53 mg; quetiapine, 482 mg/day and 77 mg; risperidone, 6.3 mg/day and 1 mg; risperidone LAI, 36.6 mg every 2 weeks and 0.42 mg; sertindole, 22.5 mg/day and 3.6 mg; and ziprasidone, 186 mg/day and 30 mg. For amisulpride and olanzapine, specific data for patients with predominant negative symptoms were available. The authors have made available on their web site a spreadsheet with this method and other updated methods that can be used to estimate dose equivalencies in practice.

Efficacy, tolerability, and safety of lurasidone for acute schizophrenia: A systematic review and network meta‐analysis of phase 3 trials in Japan

“…Although there was no significant difference in the primary outcome between LUR40 and LUR80, the effect size of LUR40 seems to be larger than that of LUR80. Dose‐response meta‐analysis of antipsychotic drugs for acute schizophrenia showed that the 95% effective dose of lurasidone was 147 mg/d 17 . Further studies are needed to investigate why LUR’s efficacy did not increase dose dependently in Japanese patients (eg, pharmacogenetics on drug response and drug metabolism).…”

A network meta-analysis of the dose–response effects of lurasidone on acute schizophrenia

“…Despite the uses of different statistical techniques and datasets, the dose-response relationships of lurasidone for overall psychotic symptoms found in a previous meta-analysis and this study were relatively similar 13 . Leucht and colleagues (2020) conducted their meta-analysis using a multivariate statistical technique to plot both metaanalysis estimates and their 95% CIs 41 .…”

Theta-Burst Stimulation for Auditory-Verbal Hallucination in Very-Late-Onset Schizophrenia-Like Psychosis—A Functional Magnetic Resonance Imaging Case Study

“…Impaired connectivity of the auditory-related neural circuitry leads to altered self-monitoring, and misinterpretation of own thoughts as external voices (12,13). Considering their similar psychopathology and responsiveness to the antipsychotic treatment (4,14), we speculate that AVH in both mental conditions might be caused by disturbances in a common pathophysiological pathway, despite obviously distinct etiological origins of SZ and VLOSLP.…”