Drugs that exacerbate restless legs syndrome frequently prescribed

By Marilynn Larkin

NEW YORK (Reuters Health) - Patients with restless legs syndrome (RLS) are often prescribed drugs that exacerbate the condition, while prescriptions of drugs approved to treat it have fallen, researchers say.

"Future RLS treatment guidelines need to put more emphasis on the importance of avoiding RLS-exacerbating drugs, and provide more information on alternative pharmacological and non-pharmacological treatments to (these) drugs," Dr. Ju-Hyeun Kim of the University of Florida in Gainesville said by email.

She told Reuters Health that some patients might be able to reduce or eliminate RLS symptoms simply by stopping the RLS-exacerbating drugs, "without using the major RLS drugs."

Dr. Kim and colleagues studied drugs prescribed during U.S. physician office visits for RLS from 2007-2015, including RLS treatment drugs such as dopamine agonists (ropinirole, pramipexole and rotigotine - but not levodopa) and alpha-2-delta ligands (pregabalin, gabapentin, gabapentin enacarbil), and RLS-exacerbating drugs (first-generation antihistamines, dopamine antagonistic anti-emetics, antidepressants and antipsychotics).

As reported online November 26 in Sleep Medicine, 456 RLS-related office visits were included in the analysis, representing approximately 9.9 million office visits. During the study period, weighted percentages of visits with dopamine agonists fell from 50% to 22% (risk ratio, 0.44).

"This could be due to a concern over augmentation associated with dopamine agonists," Dr. Kim said.

Visits to neurologists were associated with a 76% increase in prescribing of the major RLS treatment drugs compared with visits to family/general or internal medicine physicians (RR, 1.76).

"The most likely reason could be a difference in RLS severity by physician specialties," Dr. Kim suggested. "However, other possibilities should not be ignored, such as family/general or internal medicine physicians being unfamiliar with RLS and RLS treatment guidelines."

RLS-exacerbating drugs - mostly antidepressants (83%) - were prescribed in 28% of RLS-related visits. Also, 35% of the RLS-related office visits in which patients were prescribed major RLS treatment drugs were associated with prescribing of RLS-exacerbating drugs.

"More investigation is necessary concerning whether clinicians assess the appropriateness of RLS-exacerbating drugs for RLS patients before newly prescribing or continuing these drugs," Dr. Kim stressed.

Further, younger patient ages (18-44 and 45-64) were predictors of RLS-exacerbating drug prescribing compared with the 65 and over group (RR 2.46 and RR 2.00, respectively).

"We hope the results of this study encourage prescribers to evaluate patient medication lists more carefully before prescribing pharmacological or non-pharmacological therapy for RLS patients," Dr. Kim said.

More research on RLS and depression is also needed, she added. "For RLS patients with moderate to severe depression, use of antidepressants may be unavoidable," she acknowledged. Future research on the effectiveness of each depressant and the extent of its RLS-exacerbating effects would "help prescribers and RLS patients to make informed decisions."

Dr. Michael Thorpy, Director, Sleep-Wake Disorders Center at Montefiore Health System in New York City, told Reuters Health, "Physicians need to be educated that the use of dopamine drugs, which are primarily recommended for RLS, can cause exacerbation or augmentation of some symptoms of RLS with long-term use. Specialists who deal with RLS should help to educate primary care physicians (and others) about the effects of these medications."

"In general," he added, "it's important for physicians to be up to date with their clinical recommendations for all medications and the associated side effects in the treatment of RLS. For example, there are some antidepressants that will have less negative impact on RLS compared with others."

Dr. Lawrence Chan, Assistant Professor of Sleep Medicine at the Ohio State University Wexner Medical Center in Columbus, noted that while it's important to increase awareness of potential worsening of RLS with serotonergic antidepressants, not using those drugs "significantly limits the treatment options for depression."

"Bupropion is an antidepressant that is not known to worsen RLS and treating both disorders simultaneously is another option," he said "In regards to other medications that can increase RLS symptoms, antihistamines and antipsychotics are often used off label for insomnia, so it is important to rule out RLS as an underlying cause of the sleep disturbance."

SOURCE: https://bit.ly/2rrUn1T

Sleep Med 2018.