Majority of long-acting injectable and oral antipsychotics are similar in efficacy for schizophrenia maintenance therapy

1. There was no evidence of superiority among the different antipsychotics.

2. Choice of antipsychotic regimen for schizophrenia maintenance should be guided by side effect profiles.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Schizophrenia is a common, chronic, and debilitating psychiatric condition. While antipsychotics are often used as first-line treatment for patients with schizophrenia, they are often associated with notable adverse effects. This systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to evaluate the safety and efficacy of 32 oral and long-acting injectable antipsychotics for maintenance treatment of adults with schizophrenia. The primary outcome was the proportion of patients with symptom relapse, while key secondary outcomes included patients readmitted to hospital, those in remission, and those discharged. According to study results, most antipsychotics had a lower risk of relapse compared to placebo. However, there was no major difference in efficacy between the types of antipsychotics. Significant differences in side effects such as weight gain, sedation, Parkinsonism, and QTc interval prolongation were noted and varied depending on the antipsychotic. This study was strengthened by the inclusion of a broad array of antipsychotics; however, it did not compare the effect of route of administration (long-acting injectable vs. oral) on symptom relapse.

Click to read the study in The Lancet

Relevant Reading: A Non–D2-Receptor-Binding Drug for the Treatment of Schizophrenia

In-depth [systematic review and meta-analysis]: An initial search of Cochrane and PubMed obtained 4157 references. Included were randomized controlled trials (RCTs) assessing the effect of antipsychotics on adults with stable schizophrenia or schizoaffective disorder, while articles showing resistance to antipsychotics were excluded. In total, 501 references (comprising 127 RCTs with 18 152 patients) were included in the analysis. The primary outcome of symptom relapse was lower in the antipsychotic group (risk ratio [RR] < 1.00) compared to placebo. With respect to symptom relapse, zuclopenthixol LAI (RR 0.07, 95% credible interval [CrI] 0.00-0.34) and paliperidone PO (RR 0.20, 95% CrI 0.05-0.41) were most effective, while lurasidone PO (RR 0.63, 95% CrI 0.25-1.02) and cariprazine PO (0.65, 0.16-1.14) were least effective. There was no evidence of superiority among the various antipsychotics. Overall, findings from this study suggest that use of antipsychotic is superior to placebo for management of schizophrenia. However, given that there is no consensus on which antipsychotic is most effective, its use should be guided mainly by patient tolerance to side effects.

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