Which is safer for patients with Restless Leg Syndrome (RLS), Belsomra (suvorexant) or trazodone?

Suvorexant (Belsomra) is Safer Than Trazodone for Patients with Restless Leg Syndrome

For patients with Restless Leg Syndrome (RLS), suvorexant (Belsomra) is safer than trazodone, as trazodone can actually worsen RLS symptoms while suvorexant has shown therapeutic efficacy in improving both sleep and RLS symptoms. 1, 2

Evidence Supporting Suvorexant for RLS

• A recent 2024 randomized, double-blind, crossover study demonstrated that suvorexant significantly improved RLS symptoms according to multiple validated measures (IRLS total score, CGI, and m-SIT) compared to placebo 2
• Suvorexant also improved periodic limb movements during sleep and periodic limb movements with arousal in RLS patients 2
• The study showed significant improvements in multiple sleep parameters including total sleep time, wake after sleep onset, sleep onset latency, and sleep efficiency 2
• Suvorexant was well tolerated with few and mild adverse events in RLS patients 2

Evidence Against Trazodone for RLS

• Case reports have demonstrated that trazodone can actually induce or worsen RLS symptoms 1
• Trazodone, like other antidepressants, particularly those affecting the serotonergic system, has been associated with triggering RLS 1
• Symptoms of RLS induced by trazodone can begin as early as the first night of treatment and include burning, tingling, and restlessness in the legs with an urge to move 1

Current Treatment Guidelines for RLS

• The American Academy of Sleep Medicine (AASM) strongly recommends alpha-2-delta ligands (gabapentin, gabapentin enacarbil, or pregabalin) as first-line therapy for RLS 3
• The AASM suggests against the use of many medications for RLS, including clonazepam, bupropion, carbamazepine, and valproic acid 4, 3
• While the AASM guidelines don't specifically mention suvorexant or trazodone, they do caution against medications that can exacerbate RLS symptoms 3
• The AASM recommends addressing potential exacerbating factors, including serotonergic medications (like trazodone) 3

Safety Considerations

• Trazodone's serotonergic effects can worsen RLS symptoms, with case reports showing immediate onset of RLS symptoms that resolved upon discontinuation 1
• Suvorexant works through a different mechanism as a dual orexin receptor antagonist, which may actually help improve both sleep and sensory/motor symptoms in RLS 2
• In RLS patients with sleep disturbance, suvorexant has shown class II evidence supporting its therapeutic efficacy 2

Treatment Algorithm for RLS with Sleep Disturbance

1. First assess and address iron status (supplement if ferritin ≤75 ng/mL or transferrin saturation <20%) 3
2. Consider first-line agents recommended by AASM (gabapentin, gabapentin enacarbil, or pregabalin) 3
3. For patients with prominent sleep disturbance who cannot tolerate or do not respond to first-line agents, suvorexant may be considered based on recent evidence 2
4. Avoid trazodone and other serotonergic medications that can potentially worsen RLS symptoms 3, 1

Conclusion

When choosing between suvorexant and trazodone for patients with RLS, suvorexant is clearly the safer option. Trazodone has documented cases of inducing or worsening RLS symptoms, while suvorexant has demonstrated therapeutic efficacy in improving both sleep and RLS symptoms in a controlled clinical trial.