Findings in previous studies investigating the beneficial effect of risperidone and olanzapine versus typical antipsychotics on quality of life (QOL) are controversial since they did not adjust for various factors contributing to QOL. To test this assumption in a naturalistic cross-sectional design, we evaluated general and domain-specific QOL scores for baseline data of schizophrenia outpatients stabilized on atypical (N = 78, risperidone or olanzapine) and typical (N = 55) agents. Self-report and observer-rated QOL outcomes of both risperidone and olanzapine with typical antipsychotic therapy were compared across demographic, illness-related, and treatment-related factors using analysis of variance, multivariate analysis of variance, and correlation analysis. No significant differences were found in QOL outcomes of risperidone-treated and olanzapine-treated patients. Both self-report and rater-observed QOL measures indicated superiority of atypical over typical antipsychotic agents after adjusting for daily doses, duration of treatment, subjective tolerability, and adjuvant antidepressants. Lower daily doses and longer antipsychotic treatment were associated with better QOL. Self-report and observer-rated QOL scores correlated positively (r = 0.64, P < 0.001). Gender, marital status, age, education, living arrangement and employment status, age of onset, illness duration, symptom severity, emotional distress, subtypes of schizophrenia, and side effects did not affect QOL outcomes in either group. Risperidone and olanzapine revealed an advantage over typical agents in terms of QOL. Findings suggest that when calculating the beneficial effects of atypical antipsychotic therapy on QOL outcomes, daily doses, duration of treatment, and subjective tolerability may be intervening variables and should be adjusted accordingly to clearly appreciate benefits of atypical antipsychotics.

In routine practice, subjective response to antipsychotics is becoming a critical outcome measure among schizophrenia patients. This study sought to compare subjective response to atypical (risperidone and olanzapine) and typical antipsychotic drugs. Using a naturalistic cross-sectional design, we examined subjective response to antipsychotics (satisfaction with medication and subjective tolerability), psychopathology, side effects, emotional distress, and awareness in schizophrenia patients stabilized on atypical (n = 78) and typical (n = 55) drugs. Analysis of variance and multiple regression analysis were applied. We found that atypical drugs were superior to typical antipsychotics in both measures of subjective response, which were positively correlated (r = 0.52, P < 0.001). Poor subjective response was associated with severity of emotional distress, negative, and activation symptoms in the atypical group and with extrapyramidal side effects and positive symptoms in the typical group. Awareness of treatment is a positive factor that accounted for 20% and 34% of variation in the subjective responses to atypical and typical antipsychotic drugs, respectively. Demographic variables, age of onset, illness duration, and adjunctive drugs did not relate significantly to subjective response to antipsychotic drugs. Thus, atypical drugs are characterized by better subjective response compared with typical antipsychotics; their determinants differed considerably. Satisfaction with medication together with subjective tolerability needs to be considered in clinical trials.