Neurocognitive effects of ziprasidone and related factors in patients with chronic schizophrenia undergoing usual care: a 12-month, open-label, flexible-dose, naturalistic observational trial

Clin Neuropharmacol. 2008 Jul-Aug;31(4):204-20. doi: 10.1097/WNF.0b013e3181572781.


Objective: Two questions were addressed in the present report: whether cognitive improvement would occur during 12-month ziprasidone treatment and whether the changes in cognitive functioning are dependent of changes in the illness-related variables.

Methods: Seventy schizophrenia patients with persistent symptoms or troublesome side effects were assigned to a 12-month, open-label, flexible-dosage (40-160 mg/d) trial. Outcome measures were taken at baseline, 6, and 12 months and included the Mindstreams Computerized Cognitive Battery, the Wisconsin Card Sorting Test, the Clinical Global Impression Scale, the Positive and Negative Syndrome Scale, and the Extrapyramidal Symptom Rating Scale.

Results: Baseline performance was impaired across all cognitive tasks on average without significant differences between 32 completers and 38 discontinued patients. At the end of the study, significant improvement in performance of executive functions, attention, and information processing domains among ziprasidone-completed patients was observed. The effect sizes for these changes were moderate (0.61). Improvement in the executive performances was associated with a reduction in the severity of positive, activation, and dysphoric mood symptoms but was unrelated to the ziprasidone daily dose, Clinical Global Impression Scale and Extrapyramidal Symptom Rating Scale scores, and concomitantly prescribed antidepressants, anxiolytics, mood stabilizers, or antiparkinson drugs.

Conclusions: Ziprasidone had a long-term neurocognitive effect among patients with chronic schizophrenia undergoing the usual care. This effect tended to increase over time and was associated, at least partly, with changes in symptoms, but not with changes in the severity of illness, side effects, the ziprasidone daily dose, and concomitant medicines.

Publication types

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

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Antipsychotic Agents / therapeutic use*
  • Chronic Disease
  • Cognition / drug effects*
  • Cognition / physiology
  • Cognition Disorders / drug therapy*
  • Cognition Disorders / etiology
  • Cognition Disorders / physiopathology
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Male
  • Middle Aged
  • Piperazines / therapeutic use*
  • Psychiatric Status Rating Scales
  • Schizophrenia / complications
  • Schizophrenia / drug therapy*
  • Schizophrenia / physiopathology
  • Schizophrenic Psychology
  • Severity of Illness Index
  • Thiazoles / therapeutic use*


  • Antipsychotic Agents
  • Piperazines
  • Thiazoles
  • ziprasidone