Pharmacological impact on sleep architecture and polysomnographic measures in Restless Legs Syndrome: A systematic review

Restless Legs Syndrome (RLS) is a sensorimotor disorder with diverse clinical manifestations that significantly impact sleep and quality of life, particularly among women. Polysomnography (PSG) plays a key role in evaluating motor features of RLS, such as periodic leg movements during sleep (PLMS). This review examines the effects of pharmacological treatments on PSG parameters and sleep architecture in RLS. Dopamine agonists are the most studied, consistently reducing PLMS but offering limited improvements in sleep structure and carrying risks of augmentation with long-term use. In contrast, alpha-2-delta ligands (e.g., pregabalin, gabapentin) improve sleep efficiency and reduce wakefulness, particularly benefiting patients with sensory symptoms or insomnia. Research on opioids and intravenous iron remains limited, though both show potential: opioids may reduce PLMS and improve sleep but raise respiratory safety concerns, while intravenous iron has shown efficacy, especially in pregnant women and children. We also conducted a meta-analysis assessing treatment effects of dopamine agonists on total sleep time, wakefulness after sleep onset, and sleep stage percentages (N1, N2, N3, REM). Given the heterogeneity of RLS and variable treatment responses across age and sex, future research should prioritize individualized therapeutic strategies and further investigate underexplored options to support precision medicine in RLS.