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Sildenafil adjunctive therapy to risperidone in the treatment of the negative symptoms of schizophrenia: a double-blind randomized placebo-controlled trial



It has been suggested that phosphodiesterase 5 inhibitors such as sildenafil may be effective in the treatment of negative symptoms of schizophrenia.


This study was designed to investigate the effect of sildenafil added to risperidone as augmentation therapy in patients with chronic schizophrenia and prominent negative symptoms in a double-blind and randomized clinical trial.


Eligible participants in the study were 40 patients with chronic schizophrenia with ages ranging from 18 to 45 years. 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: 20 to risperidone (6 mg/day) plus sildenafil (75 mg/day) and 20 to risperidone (6 mg/day) plus placebo. The principal measure of 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 sildenafil showed a significant superiority over risperidone alone in decreasing negative symptoms and PANSS total scores over the 8-week trial (between-subjects factor; F = 4.77, df = 1; P = 0.03; F = 5.91, df = 1, P = 0.02 respectively).


Therapy with 75 mg/day of sildenafil was well tolerated, and no clinically important side effects were observed. The present study indicates sildenafil as a potential adjunctive treatment strategy for treatment of negative symptoms of schizophrenia. This trial is registered with the Iranian Clinical Trials Registry (IRCT1138901151556N11).

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This study was Dr. Raofeh Ghayyoumi’s postgraduate thesis toward the Iranian Board of Psychiatry.

Conflict of interest statement

We declare no conflict of interest.

Role of funding source

This study was supported by a grant from Tehran University of Medical Sciences to Prof. Shahin Akhondzadeh (grant no. 6551).

Competing interest


Ethics approval

The protocol was approved by the Institutional Review Board (IRB) of Tehran University of Medical Sciences (grant no. 6651).

The trial group

Shahin Akhondzadeh was the principal investigator and provided statistical support. He was also the clinical neuropsychopharmacologist from December 2008 to May 2010. Raofeh Ghayyoumi was the resident psychiatrist and trialist from December 2008 to May 2010. Farzin Rezaei, Bahman Salehi, Azad Maroufi, and Mehrangiz Naderi were the clinical coordinators and psychiatrists from December 2008 to May 2010. Gholam-Reza Esfandiari and Fariba Ghebleh were the psychologists from December 2008 to May 2010. Amir-Hossein Modabbernia and Mina Tabrizi were the methodologists from December 2008 to May 2010.

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Corresponding author

Correspondence to Shahin Akhondzadeh.

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Akhondzadeh, S., Ghayyoumi, R., Rezaei, F. et al. Sildenafil adjunctive therapy to risperidone in the treatment of the negative symptoms of schizophrenia: a double-blind randomized placebo-controlled trial. Psychopharmacology 213, 809–815 (2011).

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  • Adjunctive therapy
  • Sildenafil
  • Negative symptoms
  • Schizophrenia