Comparative pharmacotherapeutic efficacy and dose-related safety profiles of intrathecal baclofen: a systematic review and meta-analysis in neurological spasticity.

BACKGROUND: Intrathecal baclofen (ITB) acts as a selective GABAB receptor agonist to modulate spinal inhibitory pathways. While effective for severe spasticity, the pharmacotherapeutic efficacy and safety profile across distinct neurological etiologies-cerebral palsy (CP), spinal cord injury (SCI), and brain injury (BI)-remain poorly characterized from a comparative pharmacological perspective. METHODS AND FINDINGS: We systematically searched five global databases (up to August 2025) for trials evaluating ITB therapy. Random-effects models were employed to synthesize efficacy data, focusing on dose-response relationships and clinical outcomes. 15 studies (6 RCTs, 9 observational) were analyzed. Our results demonstrate that ITB significantly reduced Ashworth Scale scores across all subgroups, but with marked etiology-specific variations in effective dosage requirements. Specifically, SCI patients exhibited the most significant reduction in spasm frequency. Safety pharmacology analysis revealed that pharmacological adverse events (AEs), such as somnolence and respiratory depression, were dose-dependent and more prevalent in BI populations. In contrast, hardware-related complications (e.g., catheter malfunction) were idiosyncratic but clinically severe. CONCLUSION: ITB therapy provides robust anti-spasticity effects mediated through its targeted action on spinal inhibitory circuits. However, the heterogeneity in dosage efficacy suggests etiology-driven differences in GABAB receptor sensitivity or drug distribution. These findings underscore the necessity for precision titration strategies based on patient-specific pathophysiology and highlight the importance of differentiating between pharmacodynamic side effects and mechanical complications to optimize the therapeutic index of ITB. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251112388, identifier CRD420251112388.