New generation antipsychotics versus low-potency conventional antipsychotics: a systematic review and meta-analysis

Area of Science:

• Psychiatry
• Pharmacology
• Clinical Trials

Background:

• Newer atypical antipsychotics are believed to have fewer extrapyramidal side-effects (EPS) than conventional antipsychotics.
• Previous comparisons may be biased by the use of high-potency comparator drugs like haloperidol.

Purpose of the Study:

• To determine if new generation antipsychotics cause fewer EPS compared to low-potency conventional antipsychotics.
• To evaluate the comparative efficacy and safety of atypical versus conventional antipsychotics.

Main Methods:

• Meta-analysis of 31 randomized controlled trials involving 2320 participants.
• Inclusion of studies meeting Cochrane Collaboration Handbook quality criteria A or B, assessed by the Jadad scale.
• Primary outcome: incidence of at least one EPS. Effect size measured by risk differences and 95% confidence intervals (CIs).

Main Results:

• Clozapine was the only new generation antipsychotic significantly associated with fewer EPS (RD=-0.15, 95% CI -0.26 to -0.4) and higher efficacy compared to low-potency conventional drugs.
• Olanzapine showed a borderline significant reduction in EPS (RD=-0.15, 95% CI -0.31 to -0.01).
• Low-potency conventional antipsychotics at doses below 600 mg/day of chlorpromazine equivalent did not show a higher risk of EPS than new generation drugs. New generation drugs as a group were moderately more efficacious.

Conclusions:

• Optimal doses of low-potency conventional antipsychotics may have a similar risk of EPS as new generation drugs.
• The potential efficacy advantages of new generation antipsychotics should be considered in clinical treatment decisions.
• Further research is needed for amisulpride, quetiapine, risperidone, ziprasidone, and sertindole in comparison to low-potency agents.