Cilostazol adjunctive therapy in treatment of negative symptoms in chronic schizophrenia: Randomized, double-blind, placebo-controlled study.

OBJECTIVE: To evaluate the efficacy and safety of cilostazol, a selective inhibitor of phosphodiesterase III, as an adjunctive to risperidone in alleviating the negative symptoms of schizophrenia. METHODS: Eighty-four in-patients with diagnosis of chronic schizophrenia participated in a randomized, placebo-controlled trial and underwent 8 weeks of treatment with either cilostazol (50 mg twice a day) or placebo as an adjuvant to risperidone. Participants were assessed using the positive and negative syndrome scale (PANSS) at baseline and at weeks 2, 4, 6, and 8. The primary outcome measure of the trial was to evaluate the efficacy of cilostazol compared to placebo in improving the PANSS negative subscale score. RESULT: General linear model repeated measures demonstrated significant effect for time × treatment interaction on negative subscale scores (p < .001) and PANSS total (p = .006) but did not demonstrate significant effect on the PANSS positive (p = .37) and general (p = .06) subscales. Frequency of adverse events was not significantly different between the 2 treatment groups. No serious adverse event was observed. CONCLUSION: An 8-week course of treatment with cilostazol as an adjunct to risperidone showed a favorable safety and efficacy profile in patients with schizophrenia.

The effects of pioglitazone adjuvant therapy on negative symptoms of patients with chronic schizophrenia: a double-blind and placebo-controlled trial.

OBJECTIVE: The evident central role of inflammation, oxidative stress, and metabolic derangement in pathophysiology of negative symptoms of schizophrenia has opened new insights into probable pharmacological options for these symptoms. Pioglitazone is an antidiabetic agent with anti-inflammatory and antioxidant properties. In this study, we evaluated the efficacy of pioglitazone as an adjunct to risperidone for reduction of negative symptoms in schizophrenia. METHODS: In this randomized, double-blind, placebo-controlled trial, 40 patients with chronic schizophrenia and a minimum score of 20 on the negative subscale of Positive and Negative Syndrome Scale (PANSS) were randomly allocated to receive risperidone plus either pioglitazone (30 mg/day) or placebo for 8 weeks. Patients' symptoms and adverse events were rated at baseline and weeks 2, 4, 6, and 8. The difference between the two groups in decline of PANSS negative subscale scores was considered as the primary outcome of this study. RESULTS: At the study endpoint, patients in the pioglitazone group showed significantly more improvement in PANSS negative subscale scores (p < 0.001) as well as PANSS total scores (p = 0.01) compared with the placebo group. CONCLUSION: These findings suggest the probable efficacy of pioglitazone as an augmentation therapy in reducing the negative symptoms of schizophrenia.