Many Medications Associated with Restless Legs Syndrome in Dialysis Patients
By Will Boggs MD
NEW YORK - Four classes of medications commonly prescribed for dialysis patients - antidepressants, neuroleptics, antihistamines, and antiemetics with dopamine blockade - are associated with an increased risk of restless legs syndrome (RLS), according to findings from the United States Renal Data System (USRDS).
"We have known anecdotally that these meds make RLS worse, but there are not a lot of population-based data to support that (neither positively nor negatively - just not a lot of data)," Dr. Donald L. Bliwise from Emory University School of Medicine in Atlanta, Georgia told Reuters Health by email. "So in that sense it was a bit surprising to see the finding come through so loud and clear."
Dr. Bliwise and colleagues consulted data on 16,165 patients with end-stage renal disease (ESRD) registered in the USRDS. They included 3234 patients with RLS and four matched controls for all but three of the patients (two with three matched controls and one with one matched control).
All four classes of medications showed highly significant and relatively strong associations with the presence of RLS. The odds ratios ranged from 1.47 for neuroleptics to 2.28 for antidepressants, with antiemetics (1.65) and antihistamines (1.94) falling in between.
Among the RLS patients, 58.7% had ever been prescribed antidepressants, compared to 38.7% of controls. Neuroleptics had been prescribed for 11.5% of RLS patients and 8.1% of controls; antihistamines for 43.9% and 28.9%, respectively; and antiemetics for 32.7% and 22.9%, respectively.
The association became nonsignificant for neuroleptics after adjusting for length of time receiving dialysis and for medication supply days, according to the June 13 Sleep Medicine online report.
Longer dialysis exposure was associated with an increased risk of RLS, as was taking medications belonging to an increasing number of offending classes (OR, 2.66 for two classes; OR, 3.99 for three classes; and OR, 3.97 for all four classes).
"It must be acknowledged that understanding of the etiology of RLS remains incomplete, and RLS may be an especially complex phenotype in uremic patients," the researchers say. "At the same time, the evidence we present in this study raises the possibility that some medications that see widespread usage in dialysis patients may actually increase the risk for a condition that commonly distresses large proportions of such patients."
Should physicians withhold these kinds of drugs from their dialysis patients? Dr. Bliwise said, "If patients are nauseated and need an antiemetic, then to withhold that would seem to make no sense, even if there is risk of increasing RLS. On the other hand, if an antidepressant is being used to help patients 'adapt' to the psychosocial impact of being on hemodialysis (or their general restlessness is being interpreted as a sign of depression - it could be an indicator of RLS) and that medication is contributing (and even accentuating) their misery for the three hours a day in which they must lie relatively motionless while tethered to a dialysis machine, this hardly makes sense either, does it?"
"As we state in the paper, this comes down to risk/benefit ratio," Dr. Bliwise said. "But if at all possible we should not ignore patients' symptoms while they undergo hemodialysis. They may be telling us something."
Dr. Bliwise added, "Make sure to ask your patients about whether they have restless legs syndrome (now also called Willis-Ekbom disease) and find out their level of distress with those symptoms. These may occur while they dialyze, but they may also occur in the late afternoon and early evening, since that is when RLS symptoms tend to be worse."
Dr. Hans Rittmannsberger from O.O. Landes-Nervenklinik Wagner-Jauregg in Linz, Austria has studied the association of neuroleptics with RLS. He told Reuters Health via email, "To discontinue a drug which might have caused RLS is the first option, yet it depends on the severity of the psychiatric condition it had been administered for. Not all drugs of a class carry the same risk for RLS and often it will be possible to improve RLS by changing the drug. Dopamine agonists can be helpful if no change of drug is possible."
Like Dr. Bliwise, Dr. Rittmannsberger emphasized that physicians can't help a diagnosis they don't make. "Physicians should actively question patients for symptoms of RLS, especially patients with ESRD," he concluded.
SOURCE: https://bit.ly/1s2uqOR
Sleep Med 2014.
(c) Copyright Thomson Reuters 2014. Click For Restrictions - https://about.reuters.com/fulllegal.asp
