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Antipsychotics differ more in their adverse events than in their efficacy

Differences in adverse events were more marked than differences in efficacy when comparing 32 different antipsychotics, according to findings from a large network meta-analysis published in The Lancet.

Although the results showed that all antipsychotic medications reduced overall symptoms more than placebo, antipsychotics often scored worse for adverse event outcomes, with different profiles.

“A clear understanding of the relative risks and benefits is essential for informed decision making,” Maximilian Huhn, MD, from the department of psychiatry and psychotherapy, Technical University of Munich School of Medicine, and colleagues wrote. “According to WHO, many drugs are available that vary considerably in their affinity to different synaptic receptors, leading to possible diverging efficacy and safety profiles.”

Huhn and colleagues conducted a network meta-analysis of placebo-controlled and head-to-head randomized controlled trials to compare and rank 32 antipsychotic medications.

Researchers searched online clinical databases for randomized controlled trials in adults with acute symptoms of schizophrenia or related disorders to study the change in overall symptoms, measured via standardized rating scales, as well as efficacy and safety outcomes. They also used Confidence in Network Meta-Analysis (CINeMA) to determine confidence in the evidence.

Overall, 402 studies encompassing data on more than 53,000 participants was included in analyses.

Based on effect size estimates, Huhn and colleagues reported that all antipsychotics decreased overall symptoms more than placebo; standardized mean differences (SMDs) ranged from –0.89 (95% credible interval [CrI], –1.08 to –0.71) for clozapine to –0.03 (95% CrI, –0.59 to 0.52) for levomepromazine. Antipsychotics also had lower all-cause discontinuation rates than placebo; risk ratios ranged from 0.52 (95% CrI, 0.12-0.95) for clopenthixol to 1.15 (95% CrI, 0.36-1.47) for pimozide.

However, analysis revealed that antipsychotics caused significantly more weight gain than placebo, with mean differences ranging from –0.16 kg (95% CrI, –0.73 to 0.4) for ziprasidone to 3.21 kg (95% CrI, 2.1-4.31) for zotepine. Also, antipsychotic treatment resulted in greater prolactin elevation (from –77.05 ng/mL [95% CrI, –120.23 to –33.54] for clozapine to 48.51 ng/mL [95% CrI, 43.52-53.51] for paliperidone) and in greater QTc prolongation (from –2.21 ms [95% CrI, –4.54 to 0.15] for lurasidone to 23.90 ms [95% CrI, 20.56-27.33] for sertindole) than placebo.

“Because so many antipsychotic options are available, our results should help health care providers find the most suitable drug for the individual patient, balancing side-effect profiles and the efficacy of different drugs,” Huhn and colleagues wrote.

“We believe that efficacy differences between compounds exist, but the fact that their measurement is based on subjective rating scales is problematic. The development of objective efficacy measures would render interpretation easier,” they continued. “Clinicians must remember that reported results are averages and that response and side-effects might vary considerably in individual patients.” – by Savannah Demko

Disclosures: Huhn reports honoraria from Janssen and Lundbeck. Please see the study for all other authors’ relevant financial disclosures.