Mechanism of the antipsychotic effect in the treatment of acute schizophrenia

Lancet. 1978 Apr 22;1(8069):848-51. doi: 10.1016/s0140-6736(78)90193-9.


In a double-blind trial in which 45 patients with acute schizophrenia took part the alpha-isomer of flupenthixol (which blocks the dopamine receptor) was found to be significantly more effective than both beta-flupenthixol (which does not) and placebo. The drug effect was confined to the "positive" symptoms--delusions, hallucinations, and though disorder--and appeared only in the 3rd and 4th weeks of the trial. It was as great in patients with evidence of deterioration (Feighner-positive patients) as in patients without deterioration and was less in patients who had affective disturbance in addition to schizophrenia symptoms. The findings are consistent with the hypothesis that dopamine-receptor blockade is the only requirement for antipsychotic activity and suggest that the antipsychotic effect occurs in patients with typically schizophrenic illnesses but may be limited to positive symptoms.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Chlorpromazine / administration & dosage
  • Chlorpromazine / therapeutic use
  • Clinical Trials as Topic
  • Drug Evaluation
  • Drug Therapy, Combination
  • Female
  • Flupenthixol / administration & dosage
  • Flupenthixol / pharmacology*
  • Flupenthixol / therapeutic use
  • Humans
  • Isomerism
  • Male
  • Placebos
  • Receptors, Dopamine / drug effects
  • Research Design
  • Schizophrenia / drug therapy*
  • Thioxanthenes / pharmacology*


  • Placebos
  • Receptors, Dopamine
  • Thioxanthenes
  • Flupenthixol
  • Chlorpromazine