Trokendi (Topiramate) for Restless Legs Syndrome
Trokendi (topiramate) should not be used for treating restless legs syndrome—it can actually cause or worsen RLS and is not included in any evidence-based treatment guidelines for this condition. 1
Why Topiramate is Contraindicated
Topiramate is documented to induce or exacerbate restless legs syndrome rather than treat it, making it an inappropriate choice for RLS management. 1
The American Academy of Sleep Medicine explicitly excludes topiramate from current evidence-based treatment guidelines for RLS due to its potential to worsen the condition. 1
When patients develop RLS symptoms after starting topiramate, discontinuation of the medication is the primary intervention, with full recovery documented in all cases rather than adding additional RLS treatments. 1
Evidence-Based First-Line Treatment Algorithm
Step 1: Assess and Correct Iron Status
Check morning fasting serum ferritin and transferrin saturation in all patients with clinically significant RLS, avoiding iron supplements for at least 24 hours before testing. 2
Supplement with oral ferrous sulfate if ferritin ≤75 ng/mL or transferrin saturation <20% (note this threshold is higher than general population guidelines). 2
Consider IV ferric carboxymaltose for patients with appropriate iron parameters who don't respond to oral therapy. 2
Step 2: Initiate Alpha-2-Delta Ligands as First-Line Pharmacotherapy
The American Academy of Sleep Medicine strongly recommends gabapentin, gabapentin enacarbil, or pregabalin as first-line therapy with moderate certainty of evidence. 2, 3
These agents avoid the augmentation phenomenon (paradoxical worsening of symptoms) seen with dopamine agonists and do not cause impulse control disorders. 2, 4
Start gabapentin at 300 mg three times daily and titrate up to 1800-2400 mg/day divided three times daily based on response. 2
Step 3: Address Exacerbating Factors
Discontinue or avoid medications that worsen RLS including antihistamines, serotonergic antidepressants, antidopaminergic agents, and topiramate. 2, 1
Reduce or eliminate alcohol and caffeine intake. 2
Treat untreated obstructive sleep apnea if present. 2
Medications to Avoid
The American Academy of Sleep Medicine suggests against the standard use of dopamine agonists (pramipexole, ropinirole, rotigotine) due to significant risk of augmentation with long-term use, despite short-term efficacy. 2, 3
The American Academy of Sleep Medicine strongly recommends against cabergoline and suggests against bupropion, carbamazepine, clonazepam, and valproic acid for RLS treatment. 2
Critical Pitfall to Avoid
The most important pitfall is using topiramate thinking it might help RLS when it actually causes the condition. If a patient on topiramate develops new or worsening RLS symptoms (urge to move legs with uncomfortable sensations, worse at rest, relieved by movement, worse in evening/night), immediately discontinue topiramate rather than adding RLS medications on top of it. 1