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Background: While neurosteroids exert multiple effects in the central nervous system, their associations with neurocognitive deficits in schizophrenia are not yet fully understood. The purpose of this study was to identify the contribution of circulating levels of dehydroepiandrosterone (DHEA), its sulfate (DHEAS), androstenedione, and cortisol to neurocognitive deficits through DHEA administration in schizophrenia., Methods: Data regarding cognitive function, symptom severity, daily doses, side effects of antipsychotic agents and blood levels of DHEA, DHEAS, androstenedione and cortisol were collected among 55 schizophrenia patients in a double-blind, randomized, placebo-controlled, crossover trial with DHEA at three intervals: upon study entry, after 6weeks of DHEA administration (200mg/d), and after 6weeks of a placebo period. Multiple regression analysis was applied for predicting sustained attention, memory, and executive function scores across three examinations controlling for clinical, treatment and background covariates., Results: Findings indicated that circulating DHEAS and androstenedione levels are shown as positive predictors of cognitive functioning, while DHEA level as negative predictor. Overall, blood neurosteroid levels and their molar ratios accounted for 16.5% of the total variance in sustained attention, 8-13% in visual memory tasks, and about 12% in executive functions. In addition, effects of symptoms, illness duration, daily doses of antipsychotic agents, side effects, education, and age of onset accounted for variability in cognitive functioning in schizophrenia., Conclusions: The present study suggests that alterations in circulating levels of neurosteroids and their molar ratios may reflect pathophysiological processes, which, at least partially, underlie cognitive dysfunction in schizophrenia., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Objective: Health related quality of life (HRQL) has become an important outcome measure in the treatment of psychiatric disorders. This long-term observational study examined ziprasidone-induced improvement in satisfaction with HRQL in schizophrenia patients treated under real-world conditions., Method: Seventy schizophrenia patients with persistent symptoms or troublesome side effects were assigned to a 12-month, open-label, flexible-dose (40-160 mg/d), large-scale, naturalistic trial. Outcome measures were taken at baseline, 6, and 12 months, and included the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), severity of symptoms, distress, and side effects., Results: Thirty-two patients fully completed the study protocol. Patients reported poorer general HRQL compared with healthy subjects. At the end of the study, significant improvement in general activity, and satisfaction with life was observed. The effect sizes for these changes were moderate (0.55, and 0.72, respectively). After Bonferroni correction for multiple comparisons improvement in satisfaction with general activity remained significant. No significant changes were noted in other Q-LES-Q dimensions. Improvement in general activity was associated with a reduction in the severity of symptoms and emotional distress, but was unrelated to the ziprasidone daily dose, side effect scores, and concomitantly prescribed antidepressants, anxiolytics, mood stabilizers, or antiparkinson drugs., Conclusion: This study indicates that ziprasidone treatment resulted in the improvement of the satisfaction with general activity that tended to increase over time, from month 6 onwards. This effect was associated with reduction in the severity of clinical symptoms, and emotional distress.

Objective: This is a first report from a long-term study aimed to evaluate efficacy, safety, tolerability, cognitive functioning, and quality of life outcomes during ziprasidone treatment of chronic schizophrenia patients in the "real-world"., Method: Seventy clinically unstable schizophrenia patients with persistent symptoms or troublesome side effects were assigned to a 12-month, open-label, flexible-dose (40-160 mg/day), large-scale, naturalistic trial. Outcome measures were taken at baseline, 6, and 12 months, and included the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression (CGI-S) scale, the Global Assessment of Functioning Scale (GAF) scores, treatment-emergent adverse events, body weight, and drug attitude., Results: Thirty-two patients fully completed the study protocol. A discontinuation of treatment for any cause occurred in 54.3% of patients; the mean time until discontinuation was 4.4 +/- 2.7 months. A discontinuation due to lack of clinical efficacy was more predominantly linked to patient perception (25.7%) than to physicians' conclusions alone (8.6%), adverse events (11.4%), and other reasons (8.6%). After controlling daily dose of ziprasidone, concomitant medications and sex, ANCOVA revealed improvement in PANSS factors, and global functioning among patients who had completed the study. Improvement in PANSS and GAF dimensions was evident at a 6-month visit, and it continued until the endpoint. When a cutoff of 20% improvement of PANSS total scores was used, the response rate among completers was 43.8%. Most common side effects were: fatigue, sleep disturbances, and headache. Ziprasidone did not appear to be linked to weight gain., Conclusion: This study suggests that ziprasidone may be beneficial for long-term treatment of schizophrenia patients in terms of severity of symptoms, and general functioning. Ziprasidone is well tolerated during the long-term treatment of chronic schizophrenia patients undergoing usual care.

Objective: This study examined specific predictors of the efficacy of risperidone (RP), olanzapine (OL) and first-generation antipsychotic agents (FGAs), the role of confounding factors, and concomitant agents such as antidepressants, anxiolytics, and mood stabilizers in the treatment of health related quality of life (HRQL) impairment of schizophrenia patients., Method: This was a community-based, open label, parallel group naturalistic study of 124 schizophrenia outpatients who received either RP, OL, FGA, or combined agents (CA). Evaluations were performed at baseline and 12 months later. They included the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), the Positive and Negative Syndrome Scale (PANSS), the Distress Scale for Adverse Symptoms, and inventories for the assessment of distress severity, subjective tolerability, and self-efficacy., Results: OL was found to be superior to RP, FGAs and CA in terms of quality of life. FGAs revealed greater therapeutic benefit than RP, which was more beneficial than combined therapy. Improvement in Q-LES-Q was revealed in patients who received antidepressants and anxiolytics, but not mood stabilizers, or anti-Parkinson drugs. This effect was independent of treatment groups and gender. Regression models revealed that changes in emotional distress and side effects were common predictors for HRQL changes across treatment groups. Specific predictors of HRQL efficacy included self-efficacy for OL, negative and positive symptoms for RP, dysphoric mood and positive symptoms, daily doses and self-efficacy for FGA treated patients., Conclusion: These findings suggest that OL is beneficial in the treatment of HRQL impairment in schizophrenia compared with RP, FGAs and CA. Special attention should be paid to specific predictors of HRQL efficacy for each antipsychotic agent, and to concomitant treatment with antidepressants and anxiolytics.