Efficacy and extrapyramidal side-effects of the new antipsychotics olanzapine, quetiapine, risperidone, and sertindole compared to conventional antipsychotics and placebo. A meta-analysis of randomized controlled trials

Schizophr Res. 1999 Jan 4;35(1):51-68. doi: 10.1016/s0920-9964(98)00105-4.


The objective of this meta-analysis is to summarize the efficacy and tolerability of the new antipsychotics risperidone, olanzapine, sertindole and quetiapine in schizophrenia compared to placebo and conventional antipsychotics. The main results are: (1) All of the 4 new drugs are more effective than placebo, but the magnitude of the effect is only moderate [mean effect size, r, of all antipsychotics vs. placebo = 0.25, with a 95% confidence interval (CI) = 0.22-0.28, n = 2477]. (2) According to the studies published to date, sertindole and quetiapine are as effective as haloperidol, and risperidone and olanzapine are slightly more effective than haloperidol in the treatment of global schizophrenic symptomatology. (3) With respect to negative symptoms, all new antipsychotics are more effective than placebo. However, contrary to widespread opinion, so is the 'conventional' antipsychotic haloperidol. Risperidone and olanzapine are slightly superior, sertindole is as effective and--according to the only study fully published to date--quetiapine is even slightly less effective than haloperidol in this regard. (4) All new antipsychotics are associated with less frequent use of antiparkinson medication than haloperidol, with risperidone appearing to have a slightly less favourable EPS-profile than the other new antipsychotics. The methodological limitations of this review, the generalizability of the results and expectations from future research are discussed.

Publication types

  • Comparative Study
  • Meta-Analysis

MeSH terms

  • Antipsychotic Agents / adverse effects*
  • Basal Ganglia Diseases / chemically induced*
  • Basal Ganglia Diseases / diagnosis
  • Benzodiazepines
  • Dibenzothiazepines / adverse effects*
  • Double-Blind Method
  • Haloperidol / therapeutic use
  • Humans
  • Imidazoles / adverse effects*
  • Indoles / adverse effects*
  • Olanzapine
  • Pirenzepine / adverse effects
  • Pirenzepine / analogs & derivatives*
  • Quetiapine Fumarate
  • Randomized Controlled Trials as Topic
  • Risperidone / adverse effects*
  • Schizophrenia / drug therapy*


  • Antipsychotic Agents
  • Dibenzothiazepines
  • Imidazoles
  • Indoles
  • Benzodiazepines
  • Quetiapine Fumarate
  • Pirenzepine
  • sertindole
  • Haloperidol
  • Risperidone
  • Olanzapine