Study Distinguishes Schizophrenia Drug Effects Among Patients

Maximilian Huhn, PhD

While antipsychotic drugs are considered the preferred treatment for schizophrenia, it is unclear which agent should ultimately be used to treat the disorder.

A team of investigators—led by Maximilian Huhn, PhD, of the Department of Psychiatry and Psychotherapy, School of Medicine, Technical University of Munich—are hoping to provide a baseline guide outlining the risks and rewards after completing a network meta-analysis of placebo-controlled and head-to-head randomized controlled trials, comparing 32 antipsychotics including clozapine, levomepromazine, amisulpride, brexpiprazole, flupentixol, and sulpiride.

The investigators searched several databases for the study and also identified randomized controlled trials for adults with acute schizophrenia symptoms or other related disorders. In total, they identified 402 studies that included data from 53,463 participants.

They found that effect size estimates indicate that all antipsychotics reduced symptoms more than placebo. The standardized mean differences ranged from -0.89 for clozapine to -0.03 for levomepromazine.

The standardized mean differences compared with placebo for reduction of positive symptoms ranged from -0.69 for amisulpride to -0.17 for brexpiprazole. For negative symptoms, it varied from -0.62 for clozapine to -0.10 for flupentixol and from -0.90 for sulpiride to 0.04 for flupentixol for depressive symptoms.

Risk ratios compared with placebo for all-cause discontinuation ranged from 0.52 for clopenthixol to 1.15 for pimozide, and from 0.92 for pimozide to 10.20 for zuclopenthixol for sedation. For use of anti-Parkinson medication, it ranged from 0.46 for clozapine to 6.14 for pimozide.

Conclusions for the primary outcome did not significantly change after investigators adjusted for possible effect moderators or in sensitive analysis, such as when they excluded the placebo-controlled studies.

Excluded from the study, however, were studies of patients with treatment resistance, first episode, predominant negative or depressive symptoms, concomitant medical illnesses, and relapse-prevention studies.

At the study’s conclusion, investigators found a change in overall symptoms measured with standardized rating scales, and extracted data for 8 efficacy and safety outcomes each.

The differences in the results were explored in meta-regressions and sensitivity analysis, where effect size measures were standardized mean differences, mean differences and risk ratios with 95% confidence intervals, assessed by Confidence in Network Meta-Analysis (CINeMA).

“There are some efficacy differences between antipsychotics, but most of them are gradual rather than discrete,” investigators wrote. “Differences in side-effects are more marked. These findings will aid clinicians in balancing risks versus benefits of those drugs available in their countries.”

Huhn was previously part of a group that focused on cognitive behavioral therapy as a treatment for schizophrenia, presenting the first ever meta-analysis examining the response rates of patients with schizophrenia and positive symptoms to cognitive behavioral therapy.

Similar to the current study, investigators combed through several databases for randomized controlled trials on psychological interventions of schizophrenia, including patients with positive symptoms and studies on cognitive behavioral therapy.

The findings indicate that adding cognitive behavioral therapy to pharmacotherapy brings about a minimal improvement in overall symptoms among 44.5% of its recipients.

Coupled with his most recent findings, Huhn and colleagues have given peers a more concise guide for optimized schizophrenia care.

The study, “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,” was published online in The Lancet.