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Additional Safety Considerations Before Prescribing Opioids to Manage Restless Legs Syndrome

      To the Editor:
      Silber et al
      • Silber M.H.
      • Becker P.M.
      • Buchfuhrer M.J.
      • et al.
      for the Scientific and Medical Advisory Board, Restless Legs Syndrome Foundation
      The appropriate use of opioids in the treatment of refractory restless legs syndrome.
      are commended for espousing the merit of low and stable dose opioid treatment of refractory restless legs syndrome (RLS) given the risks of suicide and severely compromised quality of life if untreated. Opioid agreements reduce risks of RLS treatment with opioids as agreements mandate drug testing as well as frequent query of prescription drug monitoring programs.
      Clinicians will maximize the quality of care for patients with RLS keeping in mind several additional considerations before prescribing opioids.
      Adherence monitoring should include random pill counting as it is invaluable for early identification of dangerous misuse characterized by autonomous dose escalation to self-treat medical symptoms as well as finding evidence suggesting nonmedical abuse euphoria pursuit and/or diversion.
      Trials with a drug class rotation of nonopioids with the associated holiday of consumption of previously efficacious agents
      • Kurlan R.
      • Richard I.H.
      • Deeley C.
      Medication tolerance and augmentation in restless legs syndrome: the need for drug class rotation.
      may be helpful in delaying the onset of the initiation of opioids, potentially averting a proportion of patients otherwise destined for iatrogenic addiction.
      Similarly, rotation of opioids in the treatment of RLS
      • Schulte E.C.
      • Gross N.
      • Slawik H.
      • Winkelmann J.
      When restless legs syndrome turns malignant.
      may successfully minimize opioid toxicities.
      Before prescribing opioids, nonpharmacological therapies should be encouraged, such as relaxing music, reading, petting the dog/cat, aromatherapy, aerobic exercise, stretching, vibration, yoga meditation, and pneumatic compression, as they are often symptomatically advantageous. Similarly, education should include avoidance of caffeine and stress before sleep.
      Essential documentation of informed consent must include education that patients accept repeated findings that opioids consumed before sleep not uncommonly induce central sleep apnea, even after years of continuous consumption, as clinical expression of absence of ventilatory tolerance to opioids is “most probably grossly underreported…. eventually fatal apnea may occur.”
      • Boom M.
      • Niesters M.
      • Sarton E.
      • Aarts L.
      • Smith T.W.
      • Dahan A.
      Non-analgesic effects of opioids: opioid-induced respiratory depression.
      Walker et al
      • Walker J.M.
      • Farney R.J.
      • Rhondeau S.M.
      • et al.
      Chronic opioid use is a risk factor for the development of central sleep apnea and ataxic breathing.
      reported that the prevalence of chronic opioid–induced nocturnal ventilatory suppression is pervasive, affecting up to 92% of patients, without sparing those who consume methadone and with accentuated risks at higher dosing.
      Apneas with clinically significant desaturation still present even with appropriately low opioid dosing, which customarily characterizes most clinical scenarios for the safest opioid treatment.
      As such, if patients with RLS can fall asleep with only a short duration of action opioid, this minimizes the duration of opioid-induced ventilatory drive as well as rapid eye movement and stage III and IV restorative sleep suppression to which the brain is exposed, though often such patients also require a safe, long half-life, deep sleep facilitator that does not suppress ventilatory drive to maintain unconsciousness.
      Although the authors stated that it is “preferable” to avoid co-consumption, the Centers for Disease Control and Prevention, Food and Drug Administration, and Federation of State Medical Boards all far more strongly advocate extreme caution about the dangers of prescribing opioids to benzodiazepine or barbiturate narcotic consumers, even designating co-ingestion of these ventilatory suppressants contrary to “best practice policy.” These agents should usually be completely tapered off before initiating opioids.
      Opioids are an invaluable tool in the safe management of RLS and many medical conditions, but the authors are correct that prescribers need to exercise extreme caution in prescribing, educating, and diligent monitoring before and after the initiation of opioids and in the totality of risk vs potential benefit stratification considerations to achieve appropriate patient selection for judicious opioid dosing.

      References

        • Silber M.H.
        • Becker P.M.
        • Buchfuhrer M.J.
        • et al.
        • for the Scientific and Medical Advisory Board, Restless Legs Syndrome Foundation
        The appropriate use of opioids in the treatment of refractory restless legs syndrome.
        Mayo Clin Proc. 2018; 93: 59-67
        • Kurlan R.
        • Richard I.H.
        • Deeley C.
        Medication tolerance and augmentation in restless legs syndrome: the need for drug class rotation.
        J Gen Intern Med. 2006; 21: C1-C4
        • Schulte E.C.
        • Gross N.
        • Slawik H.
        • Winkelmann J.
        When restless legs syndrome turns malignant.
        Sleep Med. 2013; 14: 575-577
        • Boom M.
        • Niesters M.
        • Sarton E.
        • Aarts L.
        • Smith T.W.
        • Dahan A.
        Non-analgesic effects of opioids: opioid-induced respiratory depression.
        Curr Pharm Des. 2012; 18: 5994-6004
        • Walker J.M.
        • Farney R.J.
        • Rhondeau S.M.
        • et al.
        Chronic opioid use is a risk factor for the development of central sleep apnea and ataxic breathing.
        J Clin Sleep Med. 2007; 3 ([published correction appears in J Clin Sleep Med. 2007;3(6):table of contents]): 455-461

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