Effects of risperidone and haloperidol on superoxide dismutase and nitric oxide in schizophrenia

Neuropharmacology. 2012 Apr;62(5-6):1928-34. doi: 10.1016/j.neuropharm.2011.12.014. Epub 2011 Dec 30.


Oxidative stress may be involved in the pathophysiology of schizophrenia. No double-blind study has compared the effects of typical and atypical antipsychotics on both antioxidant enzyme activity and nitric oxide (NO) levels in schizophrenic patients. Seventy-eight inpatients with chronic schizophrenia were randomly assigned to 12 weeks of treatment with 6 mg/day of risperidone or 20 mg/day of haloperidol using a double-blind design. Clinical efficacy was determined using the Positive and Negative Syndrome Scale. Blood superoxide dismutase (SOD) and plasma NO levels were measured in patients and 30 normal controls. Our results showed that following a 2-week washout period, levels of SOD and NO were significantly increased in patients with schizophrenia compared to normal controls. Both risperidone and haloperidol equivalently reduced the elevated blood SOD levels in schizophrenia, but neither medication reduced the elevated plasma NO levels in schizophrenia. Low blood SOD levels at baseline predicted greater symptom improvement during treatment, and greater change in SOD was correlated with greater symptom improvement. These results suggest that both typical and atypical antipsychotic drugs may at least partially normalize abnormal free radical metabolism in schizophrenia, and some free radical parameters at baseline may predict antipsychotic responses of schizophrenic patients.

Publication types

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

MeSH terms

  • Adult
  • Antipsychotic Agents / pharmacology*
  • Antipsychotic Agents / therapeutic use
  • Double-Blind Method
  • Female
  • Haloperidol / pharmacology*
  • Haloperidol / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Nitric Oxide / blood*
  • Oxidative Stress / drug effects
  • Risperidone / pharmacology*
  • Risperidone / therapeutic use
  • Schizophrenia / blood*
  • Schizophrenia / drug therapy
  • Superoxide Dismutase / blood*


  • Antipsychotic Agents
  • Nitric Oxide
  • Superoxide Dismutase
  • Haloperidol
  • Risperidone