Pentoxifylline Adjunct to Risperidone for Negative Symptoms of Stable Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled Trial Publisher Pubmed



Shamabadi A¹ ; Rafieitabatabaei ES¹ ; Kazemzadeh K¹ ; Farahmand K¹ ; Fallahpour B² ; Khodaei Ardakani MR² ; Akhondzadeh S¹ Show Affiliations
Source: International Journal of Neuropsychopharmacology Published:2025

Abstract

Background: Negative symptoms of schizophrenia represent an unmet therapeutic need for many patients in whom pentoxifylline may be effective in terms of its dopaminergic, anti-inflammatory, and cerebral blood flow–increasing properties. This study aimed to evaluate pentoxifylline as a therapeutic agent for improving negative symptoms of schizophrenia. Methods: Chronic schizophrenia outpatients experiencing significant negative symptoms were randomly allocated to receive pentoxifylline 400 mg or matched placebo every 12 hours for 8 weeks. All patients were clinically stable as they had received risperidone for at least 2 months, which was continued. The participants were assessed using the Positive and Negative Syndrome Scale (PANSS), Hamilton Depression Rating Scale, Extrapyramidal Symptom Rating Scale, and side effect checklist. Results: The patients’ baseline characteristics were comparable between the groups. There was a significant time–treatment interaction effect on PANSS negative subscale scores (η2P=0.075), with the pentoxifylline group showing significantly greater reductions until weeks 4 (Cohen d = 0.512) and 8 (Cohen d = 0.622). Also, this group showed a significantly better response by week 8. Other PANSS scores, Hamilton Depression Rating Scale scores, Extrapyramidal Symptom Rating Scale scores, and side effect frequencies were comparable between the groups. Pentoxifylline showed a nonsignificant higher remission of 37.1% compared with 14.7% in the placebo group. Conclusions: Pentoxifylline was safely and tolerably beneficial for the primary negative symptoms of chronic schizophrenia. © The Author(s) 2024.