Periodic limb movement disorder

Several drugs have been reported to lessen the frequency of periodic limb movements of sleep (PLMS), and have been advocated as effective treatments. However, no significant evidence exists for pharmacological treatment of primary PLMD. For many patients and their bed partners, securing a diagnosis and providing reassurance is sufficient, and no pharmacological treatment is required.

There have been no large randomised, placebo-controlled trials of therapy in primary PLMD. As such, there is no clear evidence indicating the order in which pharmacological agents should be used in clinical practice, and which pharmacological treatments are more beneficial with more severe symptoms.

Therapy does not modify the underlying pathophysiology of PLMS, which remains unclear, but may relieve symptoms.

Lifestyle measures: all patients

Results from population-based prevalence studies suggest that caffeine and alcohol intake, drugs including lithium, tricyclic antidepressants, and selective serotonin-reuptake inhibitors (SSRIs), as well as some hypnotic agents may exacerbate the symptoms of PLMD. Accordingly, physicians should advise their patients to avoid these agents, together with improving sleep hygiene (following a relatively strict sleep schedule and avoiding sleep deprivation, smoking, and late-night exercise). These measures may alleviate symptoms; however, there is no evidence to support this course of action. Additional sleep hygiene resources are available online. American Academy of Sleep Medicine: healthy sleep habits Opens in new window

Primary (idiopathic) PLMD: pharmacotherapy

Melatonin

• There has been one study of 9 patients with primary PLMD without restless legs syndrome (RLS), in which treatment with melatonin significantly reduced movement parameters, such as PLMS, PLMS index, PLMS with arousals, and PLMS-Arousal index.[32]Kunz D, Bes F. Exogenous melatonin in periodic limb movement disorder: an open clinical trial and a hypothesis. Sleep. 2001;24:183-187. http://www.ncbi.nlm.nih.gov/pubmed/11247054?tool=bestpractice.com

Bupropion

• In a case series of 5 patients, 10 weeks of treatment with bupropion in 5 depressed patients who also met criteria for having pretreatment PLMD demonstrated a reduction in measures of PLMD and an improvement in depression.[33]Nofzinger E, Fasiczka A, Berman S, et al. Bupropion SR reduces periodic limb movements associated with arousals from sleep in depressed patients with periodic limb movement disorder. J Clin Psychiatry. 2000;61:858-862. http://www.ncbi.nlm.nih.gov/pubmed/11105739?tool=bestpractice.com ​ The effect of bupropion has not; however, been studied in large double-blind placebo-controlled studies. Its efficacy and optimal dosage is therefore unclear. A trial of a low dose, with cessation of therapy if adverse effects are intolerable or if there is no clinical benefit after 1 week, seems pragmatic.

The American Academy of Sleep Medicine suggests against the use of triazolam and valproic acid for PLMD in adults because of a very low certainty of evidence.[5]Winkelman JW, Berkowski JA, DelRosso LM, et al. Treatment of restless legs syndrome and periodic limb movement disorder: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2025 Jan 1;21(1):137-52. https://jcsm.aasm.org/doi/10.5664/jcsm.11390 http://www.ncbi.nlm.nih.gov/pubmed/39324694?tool=bestpractice.com ​

PLMD associated with other conditions

PLMD may occur in association with RLS, obstructive sleep apnoea syndrome, rapid eye movement sleep behaviour disorder, narcolepsy, congestive heart failure, essential hypertension, end-stage renal disease, spinal cord injury, syringomyelia, alcohol dependence, Parkinson's disease, and Tourette's syndrome.

PLMD may cease or improve with treatment of the underlying cause (e.g., reversal of iron deficiency state or of uraemia) and cessation of certain drugs (e.g., benzodiazepines, lithium, SSRIs, tricyclic antidepressants, and barbiturates).

See Restless legs syndrome, Obstructive sleep apnoea in adults, Parasomnias in adults, Narcolepsy, Heart failure with reduced ejection fraction, Essential hypertension, Chronic kidney disease, Chronic spinal cord injury, Alcohol-use disorder, Parkinson’s disease, Tourette’s syndrome.