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Not All Antipsychotics Created Equal: Analysis Reveals Important Differences

Science Update

Person writing prescription for medication

An analysis of studies on antipsychotics reveals multiple differences among the newer, second-generation antipsychotics as well as the older medications, and suggests the current classification system blurs important differences, rendering it unhelpful. The analysis, partially funded by NIMH, was published online December 5, 2008, in The Lancet.

Stefan Leucht, M.D., of Technische Universität München in Munich, Germany, and colleagues looked at 150 studies from all parts of the world with a total of 21,533 participants. By examining these double-blind studies, they were able to compare nine second-generation—also called atypical—antipsychotics with first-generation antipsychotics. They examined symptom reduction; quality of life; side effects such as movement disorders, weight gain and sedation (sleepiness); and other factors.

Four atypical antipsychotics—amisulpride (Solian), clozapine (Clozaril), olanzapine (Zyprexa) and risperidone (Risperdal)—were found to be more effective in treating overall symptoms of schizophrenia than first-generation medications. The other five studied—aripiprazole (Abilify), quetiapine (Seroquel), sertindole (Serdolect), ziprasidone (Geodon), and zotepine (Nipolept)—were found to be as effective as first-generation medications in treating symptoms of the disease.

Other findings include the following:

  • Although quality of life was not reported in most studies, the few that did report it indicated that only amisulpride, clozapine and sertindole improved patients’ quality of life more than first-generation medications.
  • All nine atypical antipsychotics caused fewer movement disorders than the first- generation medication haloperidol, which is highly potent. However, when compared with low-potency, first-generation medications such as chlorpromazine and thioridazine, studies showed that only a few atypical medications (clozapine, olanzapine, and risperidone) caused fewer movement disorders, but the low-potency drugs also tended to induce weight gain and sedation like the atypicals. Few studies compared mid-potency first-generation medications, such as perphenazine and sulpiride, to atypicals with regard to movement disorders.
  • Amisulpride, clozapine, olanzapine, quetiapine, risperidone, sertindole and zotepine were associated with statistically significantly more weight gain than haloperidol. The researchers found no significant differences in weight gain between the atypicals and the lower-potency, first-generation drugs.
  • Clozapine, quetiapine and zotepine were significantly more sedating than haloperidol, while aripiprazole was significantly less sedating than haloperidol.

The researchers conclude that antipsychotics are a heterogeneous group that defies generalization. Leucht and colleagues recommend that clinicians use the data in this report to determine individualized treatment plans for their patients with schizophrenia, keeping in mind effectiveness, side effects and cost of the various antipsychotic medications.


Leucht S, Corves C, Arbter D, Engel RR, Li C, Davis JM. Second-generation versus first-generation antipsychotic drugs for schizophrenia: a meta-analysis . The Lancet. Online ahead of print Dec. 5, 2008.