Modafinil improves antipsychotic-induced parkinsonism but not excessive daytime sleepiness, psychiatric symptoms or cognition in schizophrenia and schizoaffective disorder: a randomized, double-blind, placebo-controlled study.

OBJECTIVE: To examine the efficacy and safety of modafinil on parkinsonism and excessive daytime sleepiness (EDS), as well as on negative symptoms and cognitive abilities in patients with schizophrenia or schizoaffective disorder (DSM-IV criteria) in a randomized double-blind placebo-controlled 8-week study. METHODS: Twenty-four male patients, who were aged 20-63 years and on stable dose of second generation antipsychotic medications and with a negative symptom score of ≥ 20 on the Positive and Negative Syndrome Scale (PANSS), were randomized into either the modafinil (n=12) or placebo (n=12) group. The modafinil group received flexible does of modafinil 50-200mg/day. Primary measurements were the Simpson-Angus Scale (SAS) for extrapyramidal side effects (EPS), the Epworth Sleepiness Scale (ESS), the PANSS and a neuropsychological (NP) test battery. Data were collected on Days 0, 14, 28, 42 and 56 for rating scales, and on Days 0, 28 and 56 for NP tests. RESULTS: Mixed model analyses showed a significant group-x-time interaction for total SAS scores (P<0.006), with scores decreasing in the modafinil group but remaining the same in the placebo group. There were no significant group-x-time interactions for scores of ESS (total), PANSS (total, positive and negative), and NP tests (composite and domains) (all P's>0.5). No significant adverse events were observed. CONCLUSION: The data suggest that modafinil was a safe adjunctive treatment which improved parkinsonian symptoms and signs in patients with schizophrenia or schizoaffective disorder. Further studies in larger samples and with longer study time are needed to test/confirm the beneficial effects of modafinil on motor function.

Metabolic syndrome: relative risk associated with post-traumatic stress disorder (PTSD) severity and antipsychotic medication use.

BACKGROUND: In recent years, numerous lines of converging evidence have revealed an association between post-traumatic stress disorder (PTSD) and impaired physical health outcomes, including cardiovascular disease and metabolic syndrome. Although these findings have been interpreted as indicating a direct association of PTSD with metabolic syndrome and obesity, previous studies have not addressed the important confound of antipsychotic drug usage in this population. Second generation antipsychotic medications themselves are associated with metabolic syndrome and obesity, and it is unclear whether the common utilization of these drugs in PTSD may account for some if not all of the observed metabolic problems. OBJECTIVE: The present study examined the relative contributions of PTSD severity and use of antipsychotic medications to risk of metabolic syndrome among veterans. METHOD: Cross-sectional clinical data, including five factors representing metabolic syndrome, psychiatric diagnoses, and medications were gathered from 253 veterans enrolling in mental health services. We used a logistic regression model to measure the relative association of antipsychotic medication use and PTSD severity on risk of metabolic syndrome. RESULTS: We found that antipsychotic medication usage was not uniquely associated with elevated risk of metabolic syndrome (Wald = 0.30, ns) when PTSD severity and other sociodemographic, psychiatric, and behavioral variables were accounted for. Furthermore, PTSD severity continued to be a significant and unique predictor of risk for metabolic syndrome (Wald = 4.04, p < 0.05). CONCLUSIONS: These findings suggest that chronic and moderately severe PTSD, independent of antipsychotic medications, is associated with increased risk of metabolic syndrome.