• Mehdi Farokhnia, Maryam Sabzabadi, Hossein Pourmahmoud, Mohammad-Reza Khodaie-Ardakani, Seyed-Mohammad-Reza Hosseini, Habibeh Yekehtaz, Mina Tabrizi, Farzin Rezaei, Bahman Salehi, and Shahin Akhondzadeh.
• Psychiatric Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, South Kargar Street, Tehran, 13337, Iran.
• Psychopharmacology (Berl.). 2014 Feb 1; 231 (3): 533-42.

RationaleSeveral recent studies have focused on glutamate modulating agents for symptoms relief in schizophrenia, especially negative symptoms which are resistant to conventional therapies.ObjectivesWe aimed to assess the efficacy and tolerability of riluzole, an anti-glutamate agent with neuroprotective properties, as an adjunct to risperidone in improving negative symptoms of schizophrenia.MethodsIn this randomized double-blind placebo-controlled parallel-group study, 50 patients with chronic schizophrenia and a score of ≥20 on the negative subscale of positive and negative syndrome scale (PANSS) were enrolled in the active phase of their illness. Participants were equally randomized to receive riluzole (100 mg/day) or placebo in addition to risperidone (up to 6 mg/day) for 8 weeks. Participants were rated by PANSS every 2 weeks. The primary outcome of this study was the difference in the decrease of PANSS negative subscale score from baseline to the study endpoint between the two groups.ResultsBy the study endpoint, riluzole-treated patients showed significantly greater improvement in the negative symptoms (P < 0.001) as well as the PANSS total and general psychopathology subscale scores (P = 0.001 and P < 0.001; respectively) compared to the placebo group. Treatment group was the only significant predictor of changes in negative symptom in this trial (β = -0.56, P < 0.001). No significant difference was observed between two groups in the frequency of side effects.ConclusionThese preliminary findings suggest that riluzole may be a safe and effective medication for the treatment of negative symptoms in patients with chronic schizophrenia. Further research and replication of study findings is warranted. Clinical trial registry name and registration number: Iranian registry of clinical trials www.irct.ir , IRCT201107281556N26

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