Emergence of restless legs syndrome during opioid discontinuation

Abstract

Study objectives: The development of restless legs syndrome (RLS) has been rarely reported during and following opioid withdrawal. We aimed to determine the presence and severity of RLS symptoms during and after supervised opioid tapering.

Methods: Ninety-seven adults enrolled in the Mayo Clinic Pain Rehabilitation Center who underwent supervised prescription opioid tapering were prospectively recruited. RLS presence and severity was assessed with the Cambridge-Hopkins Questionnaire 13 and International Restless Legs Syndrome Study Group Rating Severity Scale at admission, midpoint, and dismissal from the program as well as 2 weeks, 4 weeks, and 3 months after completion. Frequency and severity of RLS symptoms were compared between admission and each time point.

Results: Average age of the cohort was 52.6 ± 13.3 years with a morphine milligram equivalent dose for the cohort of 45.6 ± 48.3 mg. Frequency of RLS symptoms increased from 28% at admission to peak frequency of 41% at 2 weeks following discharge from the Mayo Pain Rehabilitation Clinic (P = .01), returning to near baseline frequency 3 months after opioid discontinuation. International Restless Legs Syndrome Study Group Rating Severity Scale increased from baseline and then remained relatively stable at each time point following admission. Thirty-five (36.1%) participants developed de novo symptoms of RLS during their opioid taper, with those being exposed to higher morphine milligram equivalent doses having higher risk of developing RLS.

Conclusions: Moderately severe symptoms of RLS, as assessed by survey, occur commonly in individuals undergoing opioid tapering, particularly if exposed to higher doses. In many cases, symptoms appear to be self-limited, although a minority develop persistent symptoms. Our results may have implications for successful opioid tapering, but future confirmatory studies with structured clinician interview are needed to establish that these symptoms truly represent restless legs syndrome given the potential for RLS-mimicking symptoms in individuals with chronic pain syndromes.

Citation: McCarter SJ, Labott JR, Mazumder MK, et al. Emergence of restless legs syndrome during opioid discontinuation. J Clin Sleep Med. 2023;19(4):741-748.

Keywords: chronic pain; opioids; restless legs syndrome; taper; withdrawal.

Figure 1. Frequency of definitive RLS by Cambridge Hopkins Questionnaire during and after opioid withdrawal.

DC = discharge, No RLS = participants with negative response on Cambridge Hopkins compared with prior timepoint, PRC = pain rehabilitation clinic, RLS = restless legs syndrome, RLS appear = participants who had a negative response on Cambridge Hopkins at prior timepoint but screened positive at the next timepoint, RLS disappear = participants who had positive response on Cambridge Hopkins at prior timepoint but no longer screen positive at the next timepoint, RLS symptoms remain = participants with positive response on Cambridge Hopkins compared with prior timepoint.

Figure 2. Severity of RLS symptoms as measured by the International Restless Legs Study Group Severity Scale in participants meeting criteria for definite RLS by Cambridge Hopkins Questionnaire during and after opioid withdrawal.

DC = discharge, PRC = Mayo Clinic Pain Rehabilitation Center, RLS = restless legs syndrome.

Figure 3. Insomnia Severity Index score during and after opioid withdrawal.

DC = discharge, ISI = insomnia severity index, PRC = Mayo Clinic Pain Rehabilitation Center.