Opioids appear to be a good short and long-term treatment for RLS as shown in open-label, double-blind and long-term follow-up studies. However, the number of studies is more limited than for other therapeutic modalities in RLS such as
dopaminergic agents. Furthermore, the one long-term study on the
therapeutic effect of
opioids on RLS published in full paper form is retrospective; prospective long-term studies are needed.
RESULTS: Little addiction and tolerance were noted in any of the studies.
Sleep apnea was not induced or exacerbated in short-term studies, but this was not the case in the long-term study. We have recommended that RLS patients treated with chronic
opioid therapy be monitored clinically for the development of
sleep apnea. Studies consistently show that the
opiate receptor blocker
naloxone reverses the improvement in RLS induced by the
opioids, implicating the endogenous
opiate system with its
endorphins and
enkephalins in the pathogenesis of RLS. Studies are mostly consistent in showing that
naloxone does not worsen RLS symptoms in patients not treated with
opioids. This result may be related to the differential ability of
naloxone to antagonize exogenous
opioids as opposed to endogenous
opioids at the site of the
opiate receptor.
Naloxone does not block the
therapeutic effect of
dopaminergic agents on RLS symptoms, but
dopamine receptor blockers do block the
therapeutic effects of
opioids on RLS symptoms. This suggests that the endogenous
opioids act upon
dopamine systems to improve the symptoms of RLS. Some of these receptor blocking studies are blinded and, in some cases, the results are dramatic. However, with one exception, there were limited numbers of patients studied with receptor blocking agents.
CONCLUSION: The results of such studies therefore need further verification. In addition, future studies should focus on other methodologies, such as
opiate receptor PET scanning, that might further implicate the endogenous
opiate system in the pathogenesis of RLS.