The Therapeutic Effects of Baclofen As Adjunctive Therapy on Positive and Negative Symptoms of Schizophrenia: A Double-Blind Randomized Placebo-Controlled Clinical Trial Publisher



Saheli S ; Behrouzian F ; Pourshams M ; Bitaraf S ; Riahi F
Source: Middle East Journal of Rehabilitation and Health Studies Published:2026

Abstract

Background: Schizophrenia is a chronic psychiatric disorder characterized by positive symptoms, such as hallucinations and delusions, and negative symptoms, including affective flattening and social withdrawal. Objectives: This study investigated the adjunctive effects of baclofen across multiple symptom domains, including positive and negative symptoms, anxiety, depression, disorganization, and agitation, and assessed motor safety. Methods: In this double-blind, randomized, placebo-controlled trial, 144 hospitalized patients receiving risperidone were assigned to receive baclofen (n = 72) or placebo (n = 72) for 8 weeks. Symptom severity was assessed at baseline and at weeks 2, 4, and 8 using the Positive and Negative Syndrome Scale (PANSS), the Calgary Depression Scale for Schizophrenia (CDSS), and the Abnormal Involuntary Movement Scale (AIMS). Repeated-measures ANOVA was used to evaluate the effects of time, group, and the time × group interaction. Analyses were conducted using a per-protocol approach. Results: Baseline demographic characteristics, including age and sex, were comparable between the groups. Compared with placebo, baclofen significantly reduced positive, negative, anxiety, depression, disorganization, and agitation symptoms (all P < 0.001). Improvement in positive symptoms emerged by week 2, whereas improvement in negative symptoms became more pronounced from week 4 onward. Effect sizes ranged from partial η2 = 0.100 to 0.365, indicating small-to-large interaction effects. Baclofen was well tolerated; 8 patients (11.1%) discontinued treatment because of mild adverse effects, including dizziness or nausea, and mild psychomotor slowing was observed in 8.3% of patients, with no rigidity, fasciculations, or clinically significant extrapyramidal symptoms. Conclusions: Baclofen demonstrated statistically significant adjunctive effects across multiple symptom domains of schizophrenia over 8 weeks, with a favorable short-term motor safety profile. These preliminary findings from a single-center study with fixed dosing require confirmation in larger, multicenter trials. Copyright © 2026, Saheli et al.