Restless Legs Syndrome

Benzodiazepines

Benzodiazepines act upon the hypothalamic, thalamic, and limbic regions, causing varying levels of depression in the CNS. This action is thought to be mediated through GABA receptors (i.e., increasing the affinity GABA for its receptors) or through serotonergic mechanisms (Table 9).

Table 9

Benzodiazepines
Drug	Usual therapeutic range, mg/day	Half-life, h
Clonazepam	0.5-2.0	18-40
Temazepam	7.5-30.0	1.5-5.5
Diazepam	5-15	30-60
Triazolam	0.125-0.5	8-15

Benzodiazepine therapy may improve sleep and reduce arousals due to PLMS,213 yet may be less effective in eliminating movement and sensory abnormalities associated with RLS.144,214-216 However, in some patients with severe RLS, benzodiazepine therapy significantly decreases the total number of abnormal leg movements during rest. Overall, long-term nightly benzodiazepine therapy has been shown to remain effective with a low risk of adverse effects, tolerance, or abuse. Patients with mild or intermittent symptoms of RLS, particularly young individuals, may receive the most benefit from such therapy. If combined with carbidopa/levodopa or dopamine receptor agonists, benzodiazepines may assist in the management of severe RLS symptoms and are usually administered orally shortly before or at bedtime.

Potential adverse effects associated with benzodiazepine therapy for RLS include somnolence, especially with the use of long-acting medications (e.g., clonazepam); decreased libido; a risk of falls during the night, particularly in elderly patients; and exacerbation of comorbid obstructive sleep apnea. Depending upon dosage levels, therapy with such agents may result in tolerance and dependency; in addition, if therapy is discontinued abruptly rather than through gradually tapered dosages, there may be precipitation of withdrawal.