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Sleep Med. 2018 May;45:39-43. doi: 10.1016/j.sleep.2017.09.028. Epub 2017 Nov 22.

Willis-Ekbom disease/restless legs syndrome in patients with opioid withdrawal.

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Department of Psychiatry, Himalayan Institute of Medical Sciences, Dehradun, Uttarakhand, India. Electronic address:
Department of Psychiatry, Himalayan Institute of Medical Sciences, Dehradun, Uttarakhand, India.



Many patients with opioid use disorder report symptoms similar to restless legs syndrome (RLS) during withdrawal. However, whether these symptoms are true RLS, their predictors and effect of treatment with pregabalin are still unknown.


A total of 19 consecutive patients with opioid use disorder who were admitted for detoxification were included in this study after obtaining informed consent. Information regarding addiction was noted, and they were screened for RLS every morning and evening. Patients were also asked to provide information regarding their sleep quality during the previous night. To control opioid withdrawal, they were prescribed buprenorphine. Pregabalin was prescribed to patients who developed RLS. For analysis, patients were divided in two groups: those with RLS and those without RLS.


The average age of the subjects included in this study was 30.2 (±10.4) years. Mean duration of substance abuse was 56.8 (±38.4) months. Ten patients developed symptoms of RLS. Groups with RLS and without RLS were comparable with reference to demographics, laboratory parameters, and dose of buprenorphine that was required to control withdrawal symptoms. On average, RLS appeared after 1.7 days of abstinence. Patients described their symptoms such as crawling, creeping sensation in the muscles or "just pain". Eight out of 10 subjects reported symptoms limited to legs; however, two described similar problems in their upper limbs as well. A change in sleep pattern was observed with delayed sleep onset at night, delayed wake time in the morning, and spending a major proportion of day asleep. Pregabalin brought significant relief to the symptoms of RLS and sleep quality.


RLS during opioid withdrawal was an independent illness seen in half of the patients. It appeared to be mediated through mu-receptors, with contributions from other factors. Pregabalin improved symptoms of RLS and quality of sleep in these patients.


Mu-receptors; Opioid withdrawal; Pregabalin; Sleep quality

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