Long-term efficacy of antipsychotic drugs in initially acutely ill adults with schizophrenia: systematic review and network meta-analysis

Stefan Leucht; Johannes Schneider-Thoma; Angelika Burschinski; Natalie Peter; Dongfang Wang; Shimeng Dong; Maximilian Huhn; Adriani Nikolakopoulou; Georgia Salanti; John M Davis

doi:10.1002/wps.21089

Long-term efficacy of antipsychotic drugs in initially acutely ill adults with schizophrenia: systematic review and network meta-analysis

World Psychiatry. 2023 Jun;22(2):315-324. doi: 10.1002/wps.21089.

Authors

Affiliations

¹ Department of Psychiatry and Psychotherapy, School of Medicine, Technical University of Munich, Klinikum rechts der Isar, Munich, Germany.
² Department of Psychiatry and Psychotherapy, Sozialstiftung Bamberg, Klinikum Bamberg, Bamberg, Germany.
³ Institute of Medical Biometry and Statistics, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany.
⁴ Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
⁵ Psychiatric Institute, University of Illinois at Chicago, Chicago, IL, USA.
⁶ Maryland Psychiatric Research Center, Baltimore, MD, USA.

Abstract

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.

Keywords: Antipsychotics; all-cause discontinuation; long-term efficacy; negative symptoms; olanzapine; positive symptoms; schizophrenia; weight gain.