Comparative efficacy and tolerability of 32 oral antipsychotics for the acute treatment of adults with multi-episode schizophrenia: a systematic review and network meta-analysis

Schizophrenia is one of the most common, burdensome, and costly psychiatric disorders in adults worldwide. Antipsychotic drugs are its treatment of choice, but there is controversy about which agent should be used. We aimed to compare and rank antipsychotics by quantifying information from randomise...

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Bibliographic Details
Published in:The Lancet (British edition) 2019-09, Vol.394 (10202), p.939-951
Main Authors: Huhn, Maximilian, Nikolakopoulou, Adriani, Schneider-Thoma, Johannes, Krause, Marc, Samara, Myrto, Peter, Natalie, Arndt, Thomas, Bäckers, Lio, Rothe, Philipp, Cipriani, Andrea, Davis, John, Salanti, Georgia, Leucht, Stefan
Format: Article
Language:English
Subjects:
Administration, Oral
Adults
Antipsychotic Agents - administration & dosage
Antipsychotic Agents - adverse effects
Antipsychotic Agents - therapeutic use
Antipsychotics
Balances (scales)
Biomedical research
Clinical decision making
Clinical trials
Clozapine
Comparative Effectiveness Research - methods
Confidence
Control methods
Decision making
Disorders
Drug dosages
Drugs
Effectiveness
Emotional behavior
Evidence-based medicine
Flupenthixol
Health services
Humans
Illnesses
Medical research
Mental depression
Mental disorders
Meta-analysis
Moderators
Patients
Prolactin
Prolongation
Psychotropic drugs
Quality of life
Randomization
Randomized Controlled Trials as Topic
Schizophrenia
Schizophrenia - drug therapy
Sensitivity analysis
Side effects
Signs and symptoms
Statistical analysis
Sulpiride
Systematic review
Treatment Outcome
Ziprasidone
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Summary:Schizophrenia is one of the most common, burdensome, and costly psychiatric disorders in adults worldwide. Antipsychotic drugs are its treatment of choice, but there is controversy about which agent should be used. We aimed to compare and rank antipsychotics by quantifying information from randomised controlled trials. We did a network meta-analysis of placebo-controlled and head-to-head randomised controlled trials and compared 32 antipsychotics. We searched Embase, MEDLINE, PsycINFO, PubMed, BIOSIS, Cochrane Central Register of Controlled Trials (CENTRAL), WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov from database inception to Jan 8, 2019. Two authors independently selected studies and extracted data. We included randomised controlled trials in adults with acute symptoms of schizophrenia or related disorders. We excluded studies in patients with treatment resistance, first episode, predominant negative or depressive symptoms, concomitant medical illnesses, and relapse-prevention studies. Our primary outcome was change in overall symptoms measured with standardised rating scales. We also extracted data for eight efficacy and eight safety outcomes. Differences in the findings of the studies were explored in metaregressions and sensitivity analyses. Effect size measures were standardised mean differences, mean differences, or risk ratios with 95% credible intervals (CrIs). Confidence in the evidence was assessed using CINeMA (Confidence in Network Meta-Analysis). The study protocol is registered with PROSPERO, number CRD42014014919. We identified 54 417 citations and included 402 studies with data for 53 463 participants. Effect size estimates suggested all antipsychotics reduced overall symptoms more than placebo (although not statistically significant for six drugs), with standardised mean differences ranging from −0·89 (95% CrI −1·08 to −0·71) for clozapine to −0·03 (−0·59 to 0·52) for levomepromazine (40 815 participants). Standardised mean differences compared with placebo for reduction of positive symptoms (31 179 participants) varied from −0·69 (95% CrI −0·86 to −0·52) for amisulpride to −0·17 (−0·31 to −0·04) for brexpiprazole, for negative symptoms (32 015 participants) from −0·62 (−0·84 to −0·39; clozapine) to −0·10 (−0·45 to 0·25; flupentixol), for depressive symptoms (19 683 participants) from −0·90 (−1·36 to −0·44; sulpiride) to 0·04 (−0·39 to 0·47; flupentixol). Risk ratios compared with placebo for all-cause dis
ISSN:0140-6736
1474-547X
DOI:10.1016/S0140-6736(19)31135-3