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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., (Copyright © 2016 John Wiley & Sons, Ltd.)

The objective of this study was to assess the efficacy and tolerability of minocycline add-on to risperidone in treatment of negative symptoms of patients with chronic schizophrenia. In a randomized double-blind placebo-controlled study, 40 patients with chronic schizophrenia who were stabilized on risperidone for a minimum duration of eight weeks were recruited. The patients were randomly assigned to minocycline (titrated up to 200 mg/day) or placebo in addition to risperidone (maximum dose of 6 mg/day) for eight weeks. Positive and Negative Syndrome Scale (PANSS), Hamilton Depression Rating Scale, and Extrapyramidal Syndrome Rating Scale were used. Thirty-eight patients completed the study. Significant time × treatment interaction for negative [F(2.254,85.638)=59.046, P<0.001] general psychopathology [F(1.703,64.700)=6.819, P=0.001], and positive subscales [F(1.655,62.878)=5.193, P=0.012] as well as total PANSS scores [F(1.677,63.720)=28.420, P<0.001] were observed. The strongest predictors for change in negative symptoms were the treatment group (β=-0.94, t=-10.59, P<0.001) followed by the change in PANSS positive subscale (β=-0.185, t=-2.075, P=0.045). Side effect profiles of the two treatment regimens were not significantly different. Minocycline seems to be an efficacious and tolerable short-term add-on to risperidone for treatment of negative and general psychopathology symptoms of schizophrenia., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Objectives: Despite the burden of negative symptoms on quality of life in schizophrenic patients, no completely effective treatment has been developed to address such symptoms yet. Abnormalities in oxidative stress pathways have been recently demonstrated to be involved in the pathophysiology of schizophrenia, and a growing interest in antioxidant agents is emerging for targeting negative symptoms of schizophrenia. N-Acetylcysteine (NAC) is a potent antioxidant with neuroprotective properties. This study aimed to evaluate the possible effects of NAC as an adjunct to risperidone in treating negative symptoms of schizophrenia., Materials and Methods: In this randomized, double-blind, placebo-controlled, parallel-group study, 42 patients with chronic schizophrenia and a score of 20 or greater on the negative subscale of positive and negative syndrome scale (PANSS) were enrolled in the active phase of their illness. The participants were equally randomized to receive NAC (up to 2 g/d) or placebo, in addition to risperidone (up to 6 mg/d) for 8 weeks. The participants were rated using PANSS every 2 weeks, and the decrease of PANSS negative subscale score was considered as our primary outcome., Results: By the study end point, NAC-treated patients showed significantly greater improvement in the PANSS total (P = 0.006) and negative subscale (P < 0.001) scores than that in the placebo group, but this difference was not significant for positive and general psychopathology subscales. There was no significant difference between the 2 groups in the frequency of adverse effects., Conclusions: NAC add-on therapy showed to be a safe and effective augmentative strategy for alleviating negative symptoms of schizophrenia.

Impaired activity of the purinergic system is a plausible common factor that could be responsible for many aspects of schizophrenia. Based on purinegic hypothesis of schizophrenia, pharmacological treatments enhancing adenosine activity could be effective treatment in schizophrenia. Propentofylline is a novel xantine derivative which is being developed for treatment of degenerative and vascular dementia. It enhances extracellular adenosine level via inhibition of adenosine uptake. The purpose of the present investigation was to assess the efficacy of propentofylline as an adjuvant agent in the treatment of chronic schizophrenia in an 8-week double blind and placebo controlled trial. Eligible participants in this study were 50 patients with chronic schizophrenia. All patients were inpatients and were in the active phase of the illness, and met DSM-IV-TR criteria for schizophrenia. Patients were allocated in a random fashion, 25 to risperidone 6 mg/day plus propentofylline 900 mg/day (300 mg TDS) and 25 to risperidone 6 mg/day plus placebo. The principal measure of the outcome was Positive and Negative Syndrome Scale (PANSS). Although both protocols significantly decreased the score of the positive, negative and general psychopathological symptoms over the trial period, the combination of risperidone and propentofylline showed a significant superiority over risperidone alone in the treatment of positive symptoms, general psychopathology symptoms as well as PANSS total scores. The means Extrapyramidal Symptoms Rating Scale for the placebo group were higher than in the propentofylline group over the trial. However, the differences were not significant. The present study indicates propentofylline as a potential adjunctive treatment strategy for chronic schizophrenia. Nevertheless, results of larger controlled trials are needed, before recommendation for a broad clinical application can be made.