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Memantine Add-On to Risperidone for Treatment of Negative Symptoms in Patients With Stable Schizophrenia: Randomized, Double-Blind, Placebo-Controlled Study

Rezaei, Farzin MD*; Mohammad-karimi, Maryam MD; Seddighi, Sahar MD; Modabbernia, Amirhossein MD; Ashrafi, Mandana MD; Salehi, Bahman MD; Hammidi, Siran MA*; Motasami, Hamid MD*; Hajiaghaee, Reza PhD§; Tabrizi, Mina MD, PhD; Akhondzadeh, Shahin PhD

Journal of Clinical Psychopharmacology: June 2013 - Volume 33 - Issue 3 - p 336–342
doi: 10.1097/JCP.0b013e31828b50a7
Original Contributions

We aimed to evaluate the efficacy of memantine add-on in the treatment of primary negative symptoms of patients with stable schizophrenia. In a double-blind placebo-controlled clinical trial, 40 patients with schizophrenia (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) who were stabilized on risperidone for a minimum of 8 weeks were randomized to either memantine (20 mg) or placebo in addition to risperidone, 6 mg/d, for eight weeks. Assessment was done using the Positive and Negative Syndrome Scale at baseline, week 4, and week 8. The Hamilton Depression Rating Scale and the Extrapyramidal Symptom Rating Scale at baseline and week 8 were used to assess depression and extrapyramidal symptoms, respectively. All 40 patients had at least one postbaseline measurement, and 38 patients completed the trial. Patients in the memantine group showed a significantly greater improvement on negative subscale than the placebo group at end point (P < 0.001). The same effect was observed for the total score (P < 0.001) and the general psychopathology subscale score (P = 0.002). There was no significant difference in reduction of positive symptoms score between the 2 groups (P = 0.757). Changes in the Hamilton Depression Rating Scale and the Extrapyramidal Symptom Rating Scale scores and frequency of adverse effects did not differ between the 2 groups. Our study showed that memantine is a tolerable and efficacious add-on treatment for primary negative symptoms of schizophrenia.

From the *Department of Psychiatry, Kurdistan University of Medical Sciences, Sanandaj; †Psychiatric Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran; ‡Department of Psychiatry, Arak University of Medical Sciences, Arak; §Department of Pharmaceutics, Institute of Medicinal Plants, ACECR, Karaj; and ∥Department of Medical Genetics, Tehran University of Medical Sciences, Tehran, Iran.

Received February 28, 2012; accepted after revision September 2, 2012.

Reprints: Shahin Akhondzadeh, PhD, Psychiatric Research Center, Roozbeh Psychiatric Hospital, Tehran University of Medical Sciences, South Kargar Street, Tehran 13337, Iran (e-mail:

This study was Dr Maryam Mohamad-Karimi’s postgraduate thesis toward qualification for the Iranian Board of Psychiatry under the supervision of Professor Shahin Akhondzadeh. This study was supported by a grant from Tehran University of Medical Sciences to Professor Shahin Akhondzadeh (Grant No. 9498). The trial was registered in the Iranian registry of clinical trials (Registration number: IRCT138902241556N13,

© 2013 Lippincott Williams & Wilkins, Inc.