PHOENIX – Sometimes, treating restless legs syndrome with dopaminergic agents can make the problem worse.
After months of use, patients might report that they still have symptoms in their calves, and now also in their thighs and arms, and not just at bedtime.
"It’s pretty dreadful when you see it. It happens as soon as they sit down in the evening. It might be much more intense than before," said Dr. Barbara A. Phillips a professor of medicine at the University of Kentucky, Lexington, and medical director of the school’s sleep disorders center.
The phenomena, known as augmentation, probably occurs in "something like 80%" of RLS patients treated with carbidopa-levodopa (Sinemet) nightly, and maybe up to 20% treated with pramipexole (Mirapex) and ropinirole (Requip), she said.
"The bad news is that it’s pretty common. The good news is there’s never been a case report that it didn’t go away when the drug was stopped," said Dr. Phillips, who is also the current president of the Sleep Institute of the American College of Chest Physicians.
Studies on how to manage augmentation are lacking, "but if [patients] are on Sinemet, stop it, and don’t ever use it again. If they’re on pramipexole, you could try switching them to ropinirole. If augmentation happens earlier in the day, you could split the dose and give them an earlier dose. Your strategy really has to be tailored to how the augmentation presents," she said at a meeting on sleep medicine sponsored by the American College of Chest Physicians.
Following its recent Food and Drug Administration approval for RLS, patients could also be switched to extended-release gabapentin (Horizant), an anticonvulsant, not a dopamine agonist, "but I can’t point to any science" supporting the move; "What I’m telling you here is opinion," Dr. Phillips said.
Compulsive behaviors – overeating, hair eating, gambling, and spree shopping, for instance – can also be a problem with dopaminergic agents at RLS doses. "If you’re going to use these agents, patients need to be asked ... and warned about such behaviors," she said.
Ropinirole and pramipexole must be titrated to effect; nausea is usually the limiting factor. Dr. Phillips and her colleagues typically start ropinirole patients on 0.5 mg and then titrate up every 3-6 days. In clinical trials, the average dosage was about 2 mg/day. "Sometimes, patients don’t think it’s helping, but often that’s because they’re still on 0.5 mg, which is probably not enough, or they are taking it right at bedtime," instead of 1-2 hours before bed, as required with dopaminergic RLS treatment.
Pramipexole is more potent, "so start at 0.125 mg and titrate up every 3-5 days," Dr. Phillips said. The average dosage in therapeutic trials was 0.25 mg/day, she added.
Ropinirole is hepatically metabolized and might be a good choice for people with renal failure. Pramipexole is renally excreted and might be the way to go for liver failure patients or those on other drugs metabolized by the liver.
Unlike ropinirole and pramipexole, levodopa does not carry an FDA indication for RLS, but is, nonetheless, effective. It can also cause nausea, but doesn’t have to be titrated and can be used as needed, making it a good option for people with infrequent attacks.
"Some people can predict they are going to have RLS if they are going to go out to dinner, have a glass of wine, sit in a small chair in the front row of the opera, and stay up late. But that’s only going to happen four times a year. They may not want to take a drug that has to be titrated and taken every night in order to deal with" an intermittent problem, she said.
Extended-release gabapentin is not associated with compulsive behaviors, but it’s expensive and likely associated with drowsiness at the 600-mg daily RLS dose. "And remember, all anticonvulsants carry various suicide warnings," Dr. Phillips said.
Dr. Phillips disclosed that she has been a speaker or consultant for groups funded by Cephalon, ResMed, and Respironics.