Effects of antipsychotics on prepulse inhibition of the startle response in drug-naïve schizophrenic patients

Biol Psychiatry. 2002 Nov 1;52(9):863-73. doi: 10.1016/s0006-3223(02)01409-9.


Background: Disturbances in sensorimotor gating measured by prepulse inhibition of the startle response (PPI) have frequently been reported in medicated and unmedicated schizophrenia spectrum patients and in their relatives, suggesting that the deficit represents a stable vulnerability marker for schizophrenia. Clinical data on the effects of antipsychotics on PPI disturbances are scarce, but from preclinical studies, antipsychotics have been shown to influence PPI. To differentiate pathogenetic mechanisms from drug related effects, longitudinal clinical studies on the effect of antipsychotic treatment on PPI in drug-naive first-episode schizophrenic patients are needed.

Methods: First-episode schizophrenic patients never previously medicated with antipsychotics were examined at inclusion and after 3 months of treatment with the atypical antipsychotic compound, risperidone, or the typical drug, zuclopenthixol. Healthy controls were used as a comparison group.

Results: The results confirm deficits in PPI in drug-naive first-episode patients. No effect of antipsychotic treatment on PPI dysfunction was observed in any of the treatment groups.

Conclusions: The data are the first to show the possible effect of treatment with antipsychotic drugs on PPI disturbances in a longitudinal study of drug-naive schizophrenic patients. The data do not support any influence of treatment with antipsychotic drugs on sensorimotor gating deficits. Instead, the results point to the impairment in PPI as a stable vulnerability indicator.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antipsychotic Agents / pharmacology
  • Antipsychotic Agents / therapeutic use*
  • Clopenthixol / pharmacology
  • Clopenthixol / therapeutic use*
  • Female
  • Follow-Up Studies
  • Habituation, Psychophysiologic
  • Humans
  • Longitudinal Studies
  • Male
  • Neural Inhibition / physiology*
  • Reflex, Startle / drug effects*
  • Risperidone / pharmacology
  • Risperidone / therapeutic use*
  • Schizophrenia / drug therapy*
  • Schizophrenia / physiopathology*


  • Antipsychotic Agents
  • Clopenthixol
  • Risperidone