Can Trazodone Cause Leg Restlessness?
Yes, trazodone can cause restless legs syndrome (RLS), though this appears to be an uncommon adverse effect based on current evidence.
Evidence for Trazodone-Induced RLS
A case report documented a 39-year-old woman who developed RLS symptoms (burning, tingling, and restlessness in her legs with an urge to move) starting the first night after initiating trazodone 100mg/day for insomnia, with complete resolution of symptoms within one day of discontinuation 1
The American Academy of Sleep Medicine specifically identifies serotonergic medications as potential exacerbating factors for RLS that should be addressed in all patients with clinically significant symptoms 2
A systematic review of antidepressants and RLS found that sedating antidepressants such as trazodone do not appear to aggravate periodic limb movements in most cases, suggesting the risk may be lower compared to other antidepressants like SSRIs or mirtazapine 3
Clinical Context and Mechanism
Trazodone has complex agonistic/antagonistic effects on the serotonergic system and moderate histamine receptor blockage, which may explain its variable effects on RLS 1
While trazodone-induced RLS appears uncommon based on prospective studies, individual susceptibility varies, and onset or exacerbation of RLS following antidepressant initiation can occur 3
Management Approach
If a patient develops RLS symptoms after starting trazodone:
Discontinue trazodone immediately, as symptoms typically resolve rapidly (within 1-2 days) after cessation 1
Consider alternative treatments for insomnia that do not exacerbate RLS, avoiding other serotonergic agents 2
Check iron studies (ferritin and transferrin saturation) if RLS symptoms persist, as iron deficiency may be an underlying contributor requiring supplementation if ferritin ≤75 ng/mL or transferrin saturation <20% 2
Important Caveats
The relationship between trazodone and RLS is based primarily on case reports rather than large prospective trials, so the true incidence remains uncertain 1, 3
Patients with pre-existing RLS may experience worsening of symptoms when trazodone is added, even if they were previously asymptomatic or well-controlled 2
Monitor for RLS symptoms (urge to move legs with uncomfortable sensations, worsening at rest, relief with movement, evening/nighttime predominance) when initiating trazodone, particularly in the first few days of treatment 1