Restless Legs Syndrome

Opioids

Though the specific physiologic action of opioids remains unclear, stimulation of opiate receptors serves to decrease the release of neurotransmitters, producing analgesic effects in the CNS. Opioid agents vary greatly in potency, ranging from mild (e.g., codeine), to moderate (e.g., oxycodone), to extremely strong (e.g., methadone) (Table 10).

Table 10

Opioids
Drug	Typical starting dose, mg/day	Usual therapeutic range, mg/day	Potency	Half-life, h	Schedule class	Receptor
Codeine	15-30	15-120	Low	3-4	C-II	µ, Κ
Propoxyphene	65-130	130-520	Low	6-12	C-IV	µ
Oxycodone	4.5-5.0	5-20	Moderate	3-6	C-II	µ, Κ
Methadone	5-10	5-30	High	13-47	C-II	µ, Κ

In clinical studies, with a relatively small number of patients, the use of opioids has been shown to alleviate paresthesias or dysesthesias, motor restlessness, and sleep disturbances associated with RLS.144,182,217-222 A review of long-term monotherapy for RLS with opioids in 20 patients found that one patient developed problems related to addiction or tolerance; two of the seven patients who were followed with polysomnography subsequently developed sleep apnea, and one had a worsening of apnea. Although opioid therapy produces minimal side effects and appears to carry little risk of tolerance or dependency, some patients with RLS have become addicted to opioids. The major adverse effects of opioid therapy include nausea and constipation. In some patients, mental changes such as confusion may also occur. RLS symptoms may reemerge or intensify after opioid therapy has been discontinued. Tramadol, µ-receptor agonist, may be considered as an alternative treatment of RLS.