Clonidine normalizes levels of P50 gating in patients with schizophrenia on stable medication

Schizophr Bull. 2014 Sep;40(5):1022-9. doi: 10.1093/schbul/sbt144. Epub 2013 Oct 8.


Background: Sensory gating deficits are among the core features of schizophrenia. Recently, we reported significantly increased sensorimotor gating following additional administration of single dosages of clonidine to the treatment of stably medicated patients with schizophrenia who, in spite of their medication, showed gating deficits. In the current study, we investigated whether this result is generalizable to filtering of sensory information as a whole, by examining clonidine's effect on P50 suppression in the same group of patients.

Methods: In a double-blind, placebo-controlled, randomized yet balanced cross-over design, 20 male schizophrenia patients on stable medication were assessed in a psychophysiological test battery, including a sensory gating paradigm on 5 occasions: once after oral administration of placebo and after single doses of 25, 50, 75, and 150 µg of clonidine. Their results were compared with 20 age-matched healthy male volunteers, who received no treatment.

Results: Patients showed significantly reduced levels of P50 suppression in the placebo session compared with controls. All dosages of clonidine significantly diminished these deficits to such levels that they no longer differed significantly from the healthy controls (except the highest dose).

Conclusions: This is the first study to show that even a single low dose of clonidine administered to stably medicated patients with schizophrenia not only significantly increases their levels of P50 suppression but also normalizes them. The results indicate that α2-noradrenergic agonists are capable of normalizing levels of P50 gating, which has a potentially high clinical relevance for the medical treatment of schizophrenia.

Keywords: P50 suppression; chronic schizophrenia; clonidine; noradrenaline.

Publication types

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

MeSH terms

  • Adrenergic alpha-2 Receptor Agonists / administration & dosage
  • Adrenergic alpha-2 Receptor Agonists / pharmacology*
  • Adult
  • Clonidine / administration & dosage
  • Clonidine / pharmacology*
  • Cross-Over Studies
  • Double-Blind Method
  • Electroencephalography
  • Evoked Potentials / drug effects*
  • Humans
  • Male
  • Middle Aged
  • Schizophrenia / drug therapy*
  • Schizophrenia / physiopathology
  • Sensory Gating / drug effects*
  • Treatment Outcome


  • Adrenergic alpha-2 Receptor Agonists
  • Clonidine