OBJECTIVES: Pharmacotherapy can reduce or prevent symptom relapse among schizophrenics, thereby providing long-term benefits. Relapse is common following noncompliance or discontinuation of antipsychotic medication, and dissatisfaction with medication may lead to noncompliance resulting in symptom relapse and increased healthcare expenditures. We assessed how schizophrenic patients view the use of antipsychotics. METHODS: The Drug Attitude Inventory (DAI), comprised of 10 "yes/no" questions about efficacy, side effects and satisfaction, was used to characterize patients' attitudes and subjective responses to antipsychotic treatment. The DAI was administered to subjects with chronic or subchronic schizophrenia or schizoaffective disorder in a forty-week, double-blind, randomized, parallel-group, flexible-dose study of two regimens of ziprasidone (80 to 120 mg QD or 40 to 80 BID) and one regimen of haloperidol (5 to 20 mg daily). A score was calculated as the sum of the responses to all questionnaire items, and the subsets of six subjective and four attitudinal questions. A categorical linear model was used to analyze the marginal probabilities of favorable responses to the questions. RESULTS: For total, subjective and attitudinal items, DAI scores at baseline were comparable between treatment groups. Overall item response significantly favored ziprasidone at week 40 (p=0.0016; 7/10 questions showed a higher percentage of positive responses for ziprasidone, and the magnitude of differences per question ranged from +14.2% to -3.7%). This difference was primarily due to positive responses to the subjective questions (p=0.0006; 4/6 questions showed a higher percentage of positive responses for ziprasidone, and the magnitude of differences per question ranged from +14.2% to -3.2%). CONCLUSIONS: Patients in the ziprasidone groups had a significantly more positive attitude regarding their medication than those in the haloperidol group over 40 weeks of treatment. These findings have implications for greater patient compliance with ziprasidone treatment, which may lead to decreases in relapse rates, hospitalizations, and other healthcare resource use.