Piracetam in the treatment of schizophrenia: implications for the glutamate hypothesis of schizophrenia

J Clin Pharm Ther. 1999 Oct;24(5):369-74. doi: 10.1046/j.1365-2710.1999.00238.x.


Objective: There is a growing interest in investigating the role of glutamate receptors in the pathophysiology of schizophrenia. Indeed, the hyperdopaminergic theory of schizophrenia can explain only the positive symptoms of schizophrenia, whereas the glutamate hypothesis may provide a more comprehensive view of the illness. We undertook a trial to investigate whether the combination of haloperidol with piracetam, a nootropic agent which modulates the glutamate receptor positively was more effective than haloperidol alone.

Methods: Thirty patients who met the DSM IV criteria for schizophrenia completed the study. Patients were allocated in a random fashion, 14 to haloperidol 30 mg/day plus piracetam 3200 mg/day and 16 to haloperidol 30 mg/day plus placebo.

Results: Although both protocols significantly decreased the score of the positive symptoms, the negative symptoms, the general psychopathological symptoms and the total score of PANSS scale over the trial period, the combination of haloperidol and piracetam showed a significant superiority over haloperidol alone in the treatment of schizophrenic patients.

Conclusion: Piracetam, a member of the nootropic class of drugs and a positive modulator of glutamate receptor, may be of therapeutic benefit in treating schizophrenic patients in combination with typical neuroleptics. However, a larger study to confirm our results is warranted

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Analysis of Variance
  • Antipsychotic Agents / therapeutic use
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Haloperidol / therapeutic use
  • Humans
  • Male
  • Nootropic Agents / therapeutic use*
  • Piracetam / therapeutic use*
  • Placebos
  • Psychiatric Status Rating Scales
  • Receptors, AMPA / physiology*
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Schizophrenia / drug therapy*
  • Schizophrenia / physiopathology


  • Antipsychotic Agents
  • Nootropic Agents
  • Placebos
  • Receptors, AMPA
  • Receptors, N-Methyl-D-Aspartate
  • Haloperidol
  • Piracetam