Acetaminophen as Adjuvant to Risperidone in Chronic Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Objective: Although the pathogenesis of schizophrenia is still uncertain, a variety of predisposing mechanisms have been implicated including inflammatory cascades. The present study was conducted to investigate the effectiveness of acetaminophen as a cyclooxygenase inhibitor in treating patients with schizophrenia. Method: A double-blind clinical trial was performed on 52 patients with chronic schizophrenia. Patients received risperidone (up to 6 mg/day) plus either acetaminophen (975mg/day) or placebo. Psychotic symptoms were assessed by the Positive and Negative Syndrome Scale (PANSS) at the onset of the trial, and at 2, 4, 6, and 8 weeks post therapy. Results: Compared to the placebo group, the acetaminophen group showed no significant difference in any subtypes of PANSS. Moreover, the side effect profiles of the 2treatment regimens were not significantly different. Conclusion: Acetaminophen adjuvant to risperidone showed no significant effect in ameliorating symptoms of schizophrenia. TRIAL REGISTRATION: The trial was registered at the Iranian Registry of Clinical Trials (registration number: IRCT201410251556N67).

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.

Riluzole in augmentation of fluvoxamine for moderate to severe obsessive-compulsive disorder: Randomized, double-blind, placebo-controlled study.

AIM: The aim of the present randomized, double-blind, placebo-controlled, 8-week trial was to assess the efficacy and tolerability of riluzole augmentation of fluvoxamine in treatment of patients with moderate to severe obsessive-compulsive disorder. METHODS: Patients were randomized into two parallel groups to receive fluvoxamine plus placebo or fluvoxamine plus riluzole (50 mg twice daily). All patients, regardless of their treatment group, received fluvoxamine at 100 mg/day for the initial 4 weeks of the study followed by 200 mg/day of fluvoxamine for the rest of the trial course. A total of 50 patients (25 in each group) were evaluated for response to treatment using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) at baseline and at weeks 4, 8 and 10. Side-effects were recorded using predesigned checklists in each visit. Repeated-measure analysis of variance showed a significant effect for time × treatment interaction in the Y-BOCS total score and a significant effect for time × treatment interaction in the Y-BOCS Compulsive subscale score between the two groups. RESULTS: Repeated-measure analysis of variance showed a significant effect for time × treatment interaction (Greenhouse-Geisser corrected: F = 4.07, d.f. = 1.22, P = 0.04) in the Y-BOCS total score and a significant effect for time × treatment interaction (Greenhouse-Geisser corrected: F = 4.45, d.f. = 1.33, P = 0.028) in the Y-BOCS Compulsive subscale score between the two groups. Riluzole augmentation therapy demonstrated higher, partial or complete treatment response according to the Y-BOCS total scores. CONCLUSION: Riluzole may be of clinical use as an adjuvant agent to fluvoxamine in treatment of moderate to severe obsessive-compulsive disorder.

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.

Riluzole combination therapy for moderate-to-severe major depressive disorder: A randomized, double-blind, placebo-controlled trial.

Recent evidences suggest that glutamatergic dysregulation implicated in neural plasticity and cellular resilience may contribute to the pathophysiology of Major Depressive Disorder (MDD). Riluzole, which exerts its effect by targeting glutamate neurotransmission, has shown antidepressant effect in recent preclinical, observational and open label studies. This study aimed to assess the efficacy and tolerability of riluzole in patients with MDD. Sixty-four inpatients with diagnosis of moderate to severe major depressive disorder participated in a parallel, randomized, controlled trial, and sixty patients underwent 6 weeks treatment with either riluzole (50 mg/bid) plus citalopram (40 mg/day) or placebo plus citalopram (40 mg/day). All participants were inpatients for the whole duration of the study. Patients were assessed using Hamilton depression rating scale (HDRS) at baseline and weeks 2, 4 and 6. The primary outcome measure was to assess the efficacy of riluzole compared to placebo in improving the depressive symptoms. General linear model repeated measures demonstrated significant effect for time × treatment interaction on HDRS [F (1.86, 107.82) = 8.63, p < 0.001]. Significantly greater improvement was observed in HDRS scores in the riluzole group compared to the placebo group from baseline HDRS score at weeks 2, 4 and 6 (p < 0.001, p = 0.001, p = 0.002, respectively). Significantly greater response with greater speed to treatment was observed in the riluzole group than the placebo group. No serious adverse event occurred. This study showed a favorable safety and efficacy profile in patients with major depressive disorder. Larger controlled studies with longer treatment periods are needed to investigate long term safety, efficacy and optimal dosing.