Baclofen for Spasticity in Multiple Sclerosis: A Comprehensive Narrative Review

Baclofen, a GABA-B receptor agonist developed as an anticonvulsant in the 1960s and repurposed for spasticity in the 1970s, is recommended as a first-line oral treatment for spasticity in multiple sclerosis (MS) by UK NICE guidance and is used similarly, though not necessarily designated identically, in many other jurisdictions. It acts at two sites within the spinal stretch reflex arc: presynaptically on Ia afferent terminals in the dorsal horn, where it reduces excitatory neurotransmitter release, and postsynaptically on ventral horn interneurons and α-motoneurons, where it hyperpolarises the cell and suppresses firing. Only a small fraction of an oral dose crosses the blood-CNS barrier, so oral dosing requires high systemic doses that cause sedation, ataxia and CNS depression. Intrathecal delivery bypasses the barrier, allowing a much lower dose and fewer brain-mediated side effects. Other drawbacks include a short, variable half-life, GABA-B receptor downregulation contributing to adverse effects and intrathecal tolerance, and withdrawal that has proved fatal. The narrow efficacy-to-side-effect margin is probably intrinsic to GABA-B receptor activation. This narrative review covers baclofen's neuroanatomy, pharmacokinetics, administration routes, efficacy, comparators, long-term outcomes, interactions, special populations, and regulatory history. Long-term follow-up shows durable control without worsening sedation, but the one study using validated quality-of-life measures found no significant improvement despite clear spasticity reduction. Weighing benefit against harm, this review concludes that baclofen offers a net benefit, but conditionally: only for carefully selected, individually titrated, and actively monitored patients. Because this is a narrative rather than systematic review, source selection was not governed by a prespecified protocol, some clinical estimates rely on secondary or aggregate data, and the underlying literature is heterogeneous in design and quality.