Effectiveness of Antipsychotic Drugs in Patients With Chronic Schizophrenia

N Engl J Med. 2005 Sep 22;353(12):1209-23. doi: 10.1056/NEJMoa051688. Epub 2005 Sep 19.

Abstract

Background: The relative effectiveness of second-generation (atypical) antipsychotic drugs as compared with that of older agents has been incompletely addressed, though newer agents are currently used far more commonly. We compared a first-generation antipsychotic, perphenazine, with several newer drugs in a double-blind study.

Methods: A total of 1493 patients with schizophrenia were recruited at 57 U.S. sites and randomly assigned to receive olanzapine (7.5 to 30 mg per day), perphenazine (8 to 32 mg per day), quetiapine (200 to 800 mg per day), or risperidone (1.5 to 6.0 mg per day) for up to 18 months. Ziprasidone (40 to 160 mg per day) was included after its approval by the Food and Drug Administration. The primary aim was to delineate differences in the overall effectiveness of these five treatments.

Results: Overall, 74 percent of patients discontinued the study medication before 18 months (1061 of the 1432 patients who received at least one dose): 64 percent of those assigned to olanzapine, 75 percent of those assigned to perphenazine, 82 percent of those assigned to quetiapine, 74 percent of those assigned to risperidone, and 79 percent of those assigned to ziprasidone. The time to the discontinuation of treatment for any cause was significantly longer in the olanzapine group than in the quetiapine (P<0.001) or risperidone (P=0.002) group, but not in the perphenazine (P=0.021) or ziprasidone (P=0.028) group. The times to discontinuation because of intolerable side effects were similar among the groups, but the rates differed (P=0.04); olanzapine was associated with more discontinuation for weight gain or metabolic effects, and perphenazine was associated with more discontinuation for extrapyramidal effects.

Conclusions: The majority of patients in each group discontinued their assigned treatment owing to inefficacy or intolerable side effects or for other reasons. Olanzapine was the most effective in terms of the rates of discontinuation, and the efficacy of the conventional antipsychotic agent perphenazine appeared similar to that of quetiapine, risperidone, and ziprasidone. Olanzapine was associated with greater weight gain and increases in measures of glucose and lipid metabolism.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / therapeutic use*
  • Benzodiazepines / adverse effects
  • Benzodiazepines / therapeutic use
  • Chronic Disease
  • Dibenzothiazepines / adverse effects
  • Dibenzothiazepines / therapeutic use
  • Double-Blind Method
  • Female
  • Humans
  • Lipids / blood
  • Male
  • Olanzapine
  • Patient Compliance
  • Perphenazine / adverse effects
  • Perphenazine / therapeutic use
  • Piperazines / adverse effects
  • Piperazines / therapeutic use
  • Proportional Hazards Models
  • Quetiapine Fumarate
  • Risperidone / adverse effects
  • Risperidone / therapeutic use
  • Schizophrenia / blood
  • Schizophrenia / drug therapy*
  • Thiazoles / adverse effects
  • Thiazoles / therapeutic use
  • Treatment Outcome
  • Weight Gain / drug effects

Substances

  • Antipsychotic Agents
  • Dibenzothiazepines
  • Lipids
  • Piperazines
  • Thiazoles
  • Benzodiazepines
  • Quetiapine Fumarate
  • ziprasidone
  • Perphenazine
  • Risperidone
  • Olanzapine