Restless legs syndrome (RLS) and periodic limb movement disorder (PLMD) are common, frequently missed in psychiatric practice, and clinically significant — they produce substantial sleep disruption and they overlap with multiple psychiatric medications and conditions in ways that change clinical decisions. Recognition is the first step; the iron workup is the second; the dopaminergic question and the psychiatric medication audit follow. The longevity-psychiatry frame engages RLS as part of comprehensive sleep care, not as a niche neurology problem.
The clinical recognition. RLS is defined by four criteria: urge to move legs, often with uncomfortable sensations; worse at rest, particularly evening and night; partially or completely relieved by movement; circadian pattern with evening worsening. The patient describes the legs as feeling "crawly," "achy," "electric," "the need to move." Symptoms typically emerge in the evening, interfere with sleep onset, and produce the daytime fatigue that often presents as the chief complaint. PLMD is the sleep-study finding of repetitive limb movements; it overlaps with RLS but can occur without subjective leg discomfort. Both fragment sleep architecture and produce the non-restorative sleep pattern.
The iron workup is the first specific test. Ferritin below 50 ng/mL is the threshold for iron repletion in RLS (not the standard 15–20 anemia threshold; brain iron status is the relevant measure). Order ferritin alongside CBC, iron, TIBC, and transferrin saturation. Repletion is oral ferrous sulfate 325mg daily or IV iron in selected cases (lower GI tolerance, malabsorption, severe presentations). Iron repletion alone resolves a substantial fraction of RLS cases without further intervention; the workup that misses iron deficiency misses the treatable contributor.
The psychiatric medication audit is the second key step. SSRIs, SNRIs, mirtazapine, TCAs, and antipsychotics can each precipitate or worsen RLS. The mechanism varies (serotonergic effects on dopamine pathways; antihistaminergic and antidopaminergic effects; direct effects on movement control). Patients who develop RLS-like symptoms after starting a psychiatric medication frequently benefit from medication review and adjustment. Mirtazapine is the most common psychiatric medication-driven RLS; bupropion is comparatively RLS-neutral and may be a substitute in patients with depression and RLS comorbidity.
The dopaminergic agents address what iron does not. Pramipexole, ropinirole, and rotigotine are FDA-approved for RLS, with rotigotine (patch) often preferred in older adults due to smoother pharmacokinetics. Gabapentin and pregabalin are first-line non-dopaminergic options with comparable or better evidence for moderate-to-severe RLS and less augmentation risk than dopamine agonists. The augmentation problem — symptoms worsening over time on dopamine agonists, requiring earlier-day dosing and producing a worse clinical picture — is the central clinical concern with chronic dopamine-agonist use. Many sleep medicine specialists now prefer gabapentin/pregabalin as first-line for RLS to avoid augmentation.
The psychiatric implications are substantial. RLS is associated with elevated depression and anxiety risk, the sleep disruption drives ongoing biological cost, and the medication overlap requires careful navigation. The patient with depression, insomnia, and undiagnosed RLS who is started on mirtazapine for sleep often gets worse rather than better. The workup that includes RLS evaluation — clinical screening, ferritin, sleep study if PLMD suspected — and the medication selection that respects the RLS context produces better outcomes. The discipline is to recognize RLS as part of sleep workup, treat iron status when ferritin is below 50, and choose psychiatric medications and dopaminergic/non-dopaminergic agents with the longevity perspective on augmentation and chronic use.