Drug-induced parasomnias, sleep apnea, and restless legs syndrome …

Linda A Hershey MD PhD FAAN FANA

Sleep Disorders

Updated 06.15.2025
Released 07.19.2021
Expires For CME 06.15.2028

Drug-induced parasomnias, sleep apnea, REM sleep disorder, and restless legs syndrome

Author: Linda A Hershey MD PhD FAAN FANA

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Editor: Antonio Culebras MD FAAN FAHA FAASM

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Drug-induced parasomnias, sleep apnea, REM sleep disorder, and restless legs syndrome

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Introduction

Overview

Several drugs may induce sleep disorders. Drug-induced insomnia and daytime sleepiness as well as drowsiness are described in a companion MedLink Neurology article. This article starts with a classification of various drug-induced parasomnias and lists drugs associated with each one. Some sleep disorders, such as sleepwalking, have been associated with the use of hypnotics for insomnia. This knowledge may help in the modification of drug therapy.

Key points

	• Several sleep disorders have been reported as secondary to the adverse effects of drugs or to the discontinuation of certain drugs.
	• Various drug-induced parasomnias as well as disorders of breathing and movement may occur during sleep.
	• Recognition of drug-induced sleep disorders and their distinction from primary sleep disorders and sleep disturbances that occur in neurologic diseases is important for the management of patients.

Historical note and terminology

Sleep disorders, particularly insomnia, and the use of sleep-inducing drugs have been well known throughout medical history. Similarly, sleep disturbances induced by ill-timed use of beverages such as alcohol and coffee, as well as by the desired or undesired effects of recreational drugs, are common knowledge.

Drugs are also associated with parasomnias, a category of sleep behavioral disorders in which abnormal events occur during sleep. Although the broad term “sleep-induced sleep disorders” is used frequently; this is usually based on observed association, and the causality is not always proven.

In contrast to the therapy of sleep disorders, little attention was paid to the adverse effects of therapeutic drugs on sleep until the introduction of barbiturates as hypnotics. The long-term use of hypnotics as a cause of drug-induced insomnia was recognized in 1970s. Reports of sleep disturbances associated with other therapeutic drugs also started to appear in the 1970s and 1980s. Nightmares (sleep terrors) were observed with the initiation or withdrawal of tricyclic antidepressants and with the use of neuroleptic drugs (38). Although levodopa was introduced in the 1960s, reports of levodopa-induced sleep disruptions did not appear until several years later (36).

This article describes sleep disorders associated with the use of therapeutic drugs. The information is based on a review of the literature and on reports of adverse reactions received by pharmaceutical manufacturers. The causal relationship is not always proven by the usual scientific criteria, but the list of drugs should be considered during investigation of patients with sleep disorders. The International Classification of Sleep Disorders ICSD-3 mentions "sleep disorders resulting from a drug or substance" under the following categories: (1) central sleep apnea; (2) sleep-related hypoventilation; (3) hypersomnia; (4) parasomnia; and (5) sleep-related movement disorders (01). “Drug or substance” can be a prescription medication, recreational drug, caffeine, alcohol, food item, or exposure to an environmental toxin. A practical classification of drug-induced sleep disorders, which reflects how they are reported in the literature, is shown in Table 1.

Table 1. Classification of Drug-Induced Breathing Disorders, Abnormal Movements, and Parasomnias

Drug-induced sleep-related breathing disorders
	• snoring • sleep apnea
Drug-induced sleep-related movement disorders
	• restless legs syndrome (RLS) • periodic limb movements (PLMs) • bruxism
Drug-induced parasomnias: sleep behavioral disorders
	• disorders of arousal (arising from NREM sleep) • sleepwalking • sleep terror • confusional arousal • sleep-related eating disorder • REM sleep parasomnias • REM sleep behavior disorder (RBD) • nightmare • sleep paralysis
Other
	• enuresis

Clinical manifestations

Presentation and course

	• Clinical features of drug-induced parasomnias are similar to those due to other causes.
	• An important feature is temporal association with the use of drugs.

The main potential drug-induced sleep disorders are listed in Table 1. Complex clinical pictures may arise when two or more drug-induced sleep disorders co-occur or a drug-induced sleep disorder occurs in a subject with other preexisting sleep disorders.

Restless legs syndrome. Primary (idiopathic) restless legs syndrome is one of the most common of all movement disorders (prevalence is 5% to 15% in the general population) (34). Patients with restless legs syndrome experience the urge to move their legs, as well as an uncomfortable feeling in the legs when they sit still or are asleep. Primary restless legs syndrome often occurs in families. Secondary restless legs syndrome can be associated with antipsychotic medications, antidepressant drugs, alcohol overuse, or iron deficiency (08; 34). Secondary restless legs syndrome is not only associated with opioid drugs, but with worsening during the supervised withdrawal of opioid medications (26).

Bruxism. Idiopathic bruxism is another common movement disorder (prevalence in adults is 5% to 20%) (10). The bruxism that is brought on by antidepressants can produce the same symptoms (jaw pain, teeth grinding, and/or trismus). The symptoms usually begin within 3 to 4 weeks of starting an antidepressant; fluoxetine, sertraline, and venlafaxine were the most common offending agents (10). According to an earlier study, the most common offending agents were paroxetine, venlafaxine, and duloxetine (41).

REM sleep behavior disorder. Patients with idiopathic REM sleep behavior disorder experience dream enactment behavior at night. They may kick their legs if they are dreaming of playing a soccer game. They may scream loudly if they are dreaming of a speeding train coming at them. Those with secondary REM sleep behavior disorder have these symptoms in addition to those of one of the synucleinopathies, such as Parkinson disease or dementia with Lewy bodies (12).

Obstructive sleep apnea. Patients with idiopathic obstructive sleep apnea have repeated episodes of apnea and hypopnea during sleep. Drugs can worsen the symptoms of obstructive sleep apnea by different mechanisms (17).

Prognosis and complications

Restless legs syndrome. In one study, the frequency of restless legs syndrome symptoms was observed to be about 28% among opioid-abusing patients on entry into a pain rehabilitation clinic (26). The symptom frequency increased to 41% two weeks after discharge from the clinic, finally returning to baseline 3 months after discontinuation of the opioids.

Drug-induced bruxism. One review concluded that the symptoms of drug-induced bruxism usually resolved within 3 to 4 weeks after tapering off of the antidepressant that had caused the original symptoms (10).

Drug-induced REM sleep behavior disorder. Guidelines from the American Academy of Sleep Medicine recommend drug discontinuation for patients who have drug-induced REM sleep behavior disorder (12). Several months are usually required before the symptoms resolve.

Biological basis

Etiology and pathogenesis

Drug-induced sleep disorders are due to interaction of a drug with one or more of the neurotransmitters or receptors that are involved in sleep and wakefulness.

Multiple interactions may occur between the disease being treated, preexisting sleep disorders, genetic factors, and effects of drugs.

Biological basis of drug-induced sleep disorders is interaction of a drug with one or more of the neurotransmitters or receptors that are involved in sleep and wakefulness. Multiple interactions between the disease being treated, preexisting sleep disorders, genetic factors, and direct or indirect effects of drugs are possible (42).

Restless legs syndrome. There are genetic factors leading to the increased risk of restless legs syndrome or increased restless legs syndrome severity (08). Some haplotypes of the MAO-A gene are associated with severe restless legs syndrome in schizophrenic patients (34).

Drug-induced REM sleep behavior disorder. Most cases of drug-induced REM sleep behavior disorder are brought on by one of the serotonergic antidepressant drugs, such as sertraline or citalopram (12).

Sleep apnea. Partial or complete obstruction of the upper airway is the main cause of idiopathic obstructive sleep apnea (24; 02). Drugs that worsen symptoms of obstructive sleep apnea include a large variety of agents that work by different mechanisms (17). For example, opioid analgesics can worsen collapse of the upper airway. Some benzodiazepines can aggravate obstructive sleep apnea by depressing central respiratory drive. Baclofen can worsen symptoms of obstructive sleep apnea by relaxing skeletal muscle tissue. Drugs that cause weight gain (tricyclic antidepressants, antipsychotic agents, and valproic acid) can exacerbate symptoms of obstructive sleep apnea by aggravating obstruction of the upper airway.

Vivid dreams and nightmares. Drugs affecting the neurotransmitters norepinephrine, serotonin, and dopamine are associated with patient reports of nightmares, and agents affecting immunological response to infectious disease are likely to induce nightmares in some patients. Opioids are well known to be associated with vivid dreams and nightmares (31). Ketamine, a non-opiate analgesic/anesthetic agent, is used for management of chronic pain, and it occasionally causes vivid dreams or nightmares, which can be prevented by gradual dose titration. Drugs that have been reported to be associated with these phenomena are listed in Table 2.

Table 2. Drugs Associated with Vivid Dreams and Nightmares

Analgesics
	• nonsteroidal anti-inflammatory drugs:
		- naproxen
	• non-opiate analgesics:
		- ketamine infusions
	• opioids
Antianxiety agent: bupropion Antibiotics
	• erythromycin • fluoroquinolone
		- fleroxacin - ciprofloxacin
	• Antivirals
		- efavirenz for treatment of HIV (18) - ganciclovir
Antidepressants:
	• Selective serotonin reuptake inhibitors
		- fluoxetine - paroxetine (20) - venlafaxine
	• Tricyclic antidepressants • Monoamine-oxidase inhibitors
Antiepileptics: valproic acid Antiparkinsonian drugs
	• amantadine • cabergoline • levodopa • selegiline
Antipsychotics
	• chlorpromazine • thiothixene
Cardiovascular drugs
	• ACE-inhibitor: captopril • Beta-blockers: bisoprolol • Calcium channel blocker: verapamil • Candesartan: angiotensin II receptor blocker for hypertension • Digoxin • Ivabradine for treatment of coronary heart disease (21) • Statins: atorvastatin for lowering cholesterol
Corticosteroids, high dose CNS stimulants
	• amphetamine • methylphenidate • phenmetrazine
Drugs for Alzheimer disease
	• Donepezil, cholinesterase inhibitors • Galantamine (05) • Memantine
Hypnotics and sedatives
	• Barbiturates, short-acting • Benzodiazepines: nitrazepam • Ketamine
Miscellaneous drugs
	• Alpha-agonists • Flutamide • Mefloquine (30) • Oxybutynin • Procarbazine • Rauwolfia alkaloids • tizanidine • Varenicline for smoking cessation
Withdrawal of drugs
	• Alcohol/opioid withdrawal • Benzodiazepine withdrawal • Hypnotic withdrawal
From: (14)

Sleepwalking. Sleepwalking (somnambulism) occurs out of deep NREM sleep and represents a disorder of arousal. It is one form of parasomnia. Subjects with epilepsy and those with a past or family history of sleepwalking are more liable to manifest this as an adverse reaction to drugs. A systematic review of the literature identified 29 drugs, primarily in four classes as possible triggers for sleepwalking: (1) benzodiazepine receptor agonists and other gamma aminobutyric acid (GABA) modulators; (2) antidepressants and other serotonergic agents; (3) antipsychotics; and (4) beta-blockers (37). The strongest evidence for medication-induced sleepwalking was for zolpidem and sodium oxybate. A case report of a patient who suffered a fractured leg during sleepwalking and literature review suggest that propranolol, a beta blocker, can trigger somnambulism, especially if it already occurred in the patient’s past medical history (39). The authors recommend listing somnambulism as a potential side effect of propranolol and treating sleepwalking as an absolute contraindication of propranolol.

The FDA, based on its review of the Adverse Event Reporting System database, found 62 cases of serious injuries from complex sleep behaviors such as sleepwalking, sleep-driving, and sleep-using-a-stove after taking eszopiclone, zaleplon, or zolpidem. A review of the medical literature revealed four more cases reported from 1992 to 2018. Deaths occurred in 20 of these 66 cases. The FDA issued the following statement: "As a result, we are requiring a Boxed Warning, our most prominent warning, to be added to the prescribing information and the patient Medication Guides for these medicines. We are also requiring a Contraindication, our strongest warning, to avoid use in patients who have previously experienced an episode of complex sleep behavior with eszopiclone, zaleplon, and zolpidem."

Sleepwalking has been reported in association with the use of the drugs listed in Table 3.

Table 3. Drugs Associated with Sleepwalking

Antipsychotic and psychotropic agents
	• Lithium and neuroleptics • Olanzapine, an atypical antipsychotic agent
Sedatives and hypnotics
	• Chloral hydrate derivatives • Benzodiazepines • Zolpidem, an imidazopyridine hypnotic agent (32)
Antidepressants
	• Paroxetine, a selective serotonin reuptake inhibitor for the treatment of depression and anxiety • Reboxetine
Miscellaneous drugs
	• Bupropion, a noradrenergic and dopaminergic drug, used for smoking cessation • Sodium oxybate • Beta blockers, eg, propranolol • Topiramate (25)

Sleep disordered breathing during sleep. Snoring is known to increase after intake of alcohol or sedative hypnotics in the evening before going to bed. Snoring alone, in the absence of sleep apnea, has not been proven to disrupt sleep or have a serious adverse effect on health. Obstructive sleep apnea, which is a risk factor for cardiovascular diseases and cognitive decline, is a cause for concern. Drugs that have been reported to be associated with central or obstructive sleep apnea are listed in Table 4.

Table 4. Drugs Reported to be Associated with Sleep Apnea with Central or Obstructive Sleep Apnea

• Alcohol
• Anesthetics
• Antihypertensives
• Baclofen
• Growth hormone
• Narcotics, eg, opioids
• Nitrous oxide inhalation
• Sedative-hypnotics
• Testosterone
• Benzodiazepines
• Neuroleptics
• Sodium oxybate
• Drugs that cause weight gain

Opioids have been shown as cause of central sleep apnea, which resolves after discontinuation of the drug (16). The overall prevalence of central sleep apnea in patients taking chronic opioids is 24% (06). Sleep apnea has been reported in patients receiving methadone as opiate replacement therapy, and prescription of benzodiazepine is not recommended in such situations. Polysomnography may unmask adverse pharmacological effects, eg, central sleep apnea due to central depressant effect of high dose baclofen that resolves with reduction of dose (23).

Sedative-hypnotics, anesthetics, and analgesics alter sleep architecture, which likely contributes to abnormal postoperative sleep architecture with exacerbation of obstructive sleep apnea and postoperative complications (28). The main drugs involved in case reports of drug-induced sleep apnea in the French pharmacovigilance database are benzodiazepines, neuroleptics, and opioids (22).

Data concerning the occurrence of obstructive sleep apnea in subjects using prescription opioids are mixed, with some reports indicating high occurrence, whereas others reporting low, nonsignificant occurrence. Inter-individual variability, age range, sex of the subjects investigated, and different phenotypes of obstructive sleep apnea may account for the discrepancies between opioid use and obstructive sleep apnea occurrence in the literature (09).

Sleep paralysis. Sleep paralysis is the transient inability to move or speak during the onset of sleep, or on wakening. It may occur as a manifestation of narcolepsy and is often associated with mental disorder, namely depression. Isolated sleep paralysis during awakening from sleep may occur in the absence of other clinical features of narcolepsy. It is more common in users of anxiolytic medications and hypnotics, such as dual orexin receptor antagonists (DORA).

Enuresis. Enuresis (bedwetting) has been associated with several drugs, as shown in Table 5. The enuretic event is a predominantly non-rapid eye movement sleep phenomenon. Enuresis is an underreported adverse drug reaction of antiepileptic drugs for treatment of childhood epilepsy as it is a condition that could cause embarrassment (35).

Table 5. Drugs Reported to be Associated with Enuresis

Alprazolam Antiepileptic drugs Antipsychotics
	• clozapine • risperidone
Chemotherapy Selective serotonin reuptake inhibitors Pimozide Urapidil Valproic acid

Sleep bruxism. Drugs reported to be associated with sleep bruxism are listed in Table 6.

Table 6. Drugs Reported to be Associated with Sleep Bruxism

Antidepressants
	• citalopram • duloxetine • fluoxetine • venlafaxine • paroxetine • sertraline
Antihistaminic agents Antiparkinsonian drugs
	• entacapone • levodopa • selegiline
Antipsychotics
	• quetiapine • risperidone
CNS stimulants
	• amphetamine • dextroamphetamine • methylphenidate
Drug abuse
From: (14)

Sleep-related eating disorders. There are several case reports of sleep-related eating disorders in association with use of zolpidem, with recovery following discontinuation of the drug. Most of the published cases involve females, but a male on zolpidem was reported to exhibit an unexpected and bizarre eating behavior during somnambulistic state (07). Zolpidem-induced sleep-related eating disorder has been reported in a patient with restless legs syndrome (43). Drug-induced sleep-related eating disorders should be considered when evaluating patients with nocturnal sleep-related eating disorders.

Rapid eye movement sleep behavior disorder. REM sleep behavior disorder may precede by years or occur within the context of neurodegenerative diseases (namely synucleinopathies), particularly Parkinson disease and dementia with Lewy bodies. Furthermore, it can be drug-induced or occur on drug withdrawal. Antidepressants are among the drugs associated with this disorder.

A retrospective study of idiopathic REM sleep behavior disorder implied direct or indirect correlations with medication use, although causal relationship could not be demonstrated (40). However, REM sleep behavior disorder has been reported to occur in patients with Parkinson disease after start of mirtazapine therapy, and to resolve after discontinuation of the drug. It has been suggested that development of REM sleep behavior disorder with antidepressants can be an early signal of an underlying synucleinopathies (33).

Finally, antidepressants were reported to increase REM sleep muscle tone in patients with and without REM sleep behavior disorder (27).

Sleep-related leg cramps. These have been reported as adverse reactions to treatment with diuretics, vincristine, beta2 agonists, sodium oxybate, donepezil, oxcarbazepine, statins, and cholinesterase inhibitors.

Analgesics. Ketamine, an N-methyl-D-aspartate antagonist, is an effective nonopioid analgesic for headaches and peripheral neuropathic pain. Adverse effects of repeated administration, even at low doses, include increased liver enzymes, nightmares, and hallucinations, as the patients do not develop tolerance against these effects (29).

Antidepressants. Sleep disturbances are generally more prevalent among patients with depression. These disturbances may improve with antidepressant treatment, but there may also be adverse effects due to antidepressant drugs. Some antidepressants adversely affect the physiological structure of sleep, whereas others restore it. Most antidepressants cause REM sleep reduction, generally with increased serotonin function. Intense and prolonged dreams often accompany abrupt withdrawal from antidepressant drugs as a manifestation of REM sleep rebound after drug-induced REM sleep suppression. Investigations suggest patterns of NREM disturbances associated with depression and antidepressants, which may result in a disturbance of the stability of NREM sleep that may predispose to one or more parasomnias (19).

Tricyclic antidepressants promote sleep in patients with insomnia due to depression and are likely to cause drowsiness. Tricyclic antidepressants also disturb REM sleep and are likely to cause nightmares.

Antiparkinsonian drugs. Patients with Parkinson disease treated with dopaminergic agents have frequent abnormal sleep patterns and hallucinations.

Cardiovascular drugs. Lorcainide, an antiarrhythmic agent, is associated with sleep disturbances (difficulty in falling asleep, nightmares, and vivid dreams).

Hypnotic drugs. The FDA has requested all manufacturers of sedative-hypnotic drug products to strengthen their product labeling by including stronger language concerning potential risks. These risks include complex sleep-related behaviors like sleep-driving, defined as driving when not fully awake after ingestion of a sedative-hypnotic product, with no memory of the event. Revised labeling includes the following medications:

• Estazolam
• Eszopiclone
• Ethchlorvynol
• Flurazepam hydrochloride
• Pentobarbital and carbromal combination
• Quazepam
• Ramelteon
• Secobarbital
• Butabarbital sodium
• Temazepam
• Triazolam
• Zaleplon
• Zolpidem

Pathomechanism of drug-induced sleep apnea. Several drugs may adversely affect respiration during sleep through direct (depression of central respiratory centers, induction of upper airway muscles hypotonia) and indirect effects (induction of sleep structure alterations or weight gain) and are reported to cause/worsen obstructive as well central sleep apnea. Depression of the hypercapnic and hypoxic ventilatory responses are crucial in the pathogenesis of opioid-induced central sleep apnea and ataxic breathing during sleep. A comprehensive review of pathophysiologic mechanisms underpinning central sleep apnea has been published (15).

Sleep in normal people predisposes to hypoventilation, but reflex muscular dilatation of the pharynx occurs to prevent narrowing and increase respiratory effort. This reflex is depressed by some drugs, resulting in pharyngeal narrowing, which may induce/worsen obstructive sleep apnea. Benzodiazepines have a depressant effect on upper airway muscles and, given as pre-anesthetics to patients with sleep apnea, can lead to severe airway obstruction even when awake.

Management

• Management usually involves discontinuation or reduction of the dose of offending medication.

Antipsychotic-induced sleep disorders. Drug-induced restless legs syndrome generally resolves when the dose of antipsychotic drug is reduced or the drug is withdrawn. For management of periodic limb movement disorder in sleep in psychotic patients, switching the antipsychotic and additional use of a second line medication, such as an antiepileptic or a benzodiazepine, is recommended (04). Increase in doses above 80 mg/d of lurasidone, an antipsychotic for schizophrenia, does not seem to increase efficacy and may be associated with a dose-related increase in sleepiness (03). To manage this side effect, the dose should be reduced to the usually recommended range between 40 and 80 mg/d. The addition of gabapentin at a dose of 200 or 300 mg qhs is sometimes helpful for managing symptoms of drug-induced restless legs syndrome (34). Patients with restless legs syndrome should also be encouraged to take part in regular moderate exercise and to abstain from cigarettes, caffeine, and alcohol.

Drug-associated bruxism. The dose of the suspected offending medication may be lowered or the drug may be discontinued, switching to another in the same therapeutic class. The use of a drug such as buspirone may be added if the antidepressant cannot be tapered or discontinued (10; 11).

Drug-induced REM sleep behavior disorder. The first recommendation of the American Academy of Sleep Medicine is to discontinue the offending antidepressant drug (12). If the symptoms persist after several months, it could be that the person has an underlying case of idiopathic REM sleep behavior disorder. In that case, a course of clonazepam or melatonin may then be required.

Drug-induced worsening of obstructive sleep apnea. There are several alternative agents to drugs that exacerbate obstructive sleep apnea symptoms. For example, if valproic acid is causing weight gain and worsening of obstructive sleep apnea symptoms, then alternative antiepileptic drugs, such as topiramate or lamotrigine, should be considered (17). If a tricyclic agent is causing weight gain and worsening of obstructive sleep apnea symptoms, then an alternative antidepressant drug, such as trazodone, might be helpful (02).

References

01: American Academy of Sleep Medicine. International Classification of Sleep Disorders. 3rd ed. Darien, Illinois, 2014.
02: Carter SG, Eckert DJ. Effects of hypnotics on obstructive sleep apnea endotypes and severity: novel insights into pathophysiology and treatment. Sleep Med Rev 2021;58:101492. PMID 33965721
03: Citrome L. Lurasidone for schizophrenia: a brief review of a new second-generation antipsychotic. Clin Schizophr Relat Psychoses 2011;4(4):251-7. PMID 21177242
04: Cohrs S, Rodenbeck A, Hornyak M, Kunz D. Restless legs syndrome, periodic limb movements, and psychopharmacology. Nervenarzt 2008;79(11):1263-72. PMID 18958441
05: Corbo JM, Brown JN, Moss JM. Galantamine-associated nightmares and anxiety. Consult Pharm 2013;28(4):243-6. PMID 23552705
06: Correa D, Farney RJ, Chung F, Prasad A, Lam D, Wong J. Chronic opioid use and central sleep apnea: a review of the prevalence, mechanisms, and perioperative considerations. Anesth Analg 2015;120(6):1273-85. PMID 25988636
07: Dang A, Garg G, Rataboli PV. Zolpidem induced Nocturnal Sleep-Related Eating Disorder (NSRED) in a male patient. Int J Eat Disord 2009;42(4):385-6. PMID 19107832
08: Elrassas HH, Elsayed YAR, Abdeen MS, Shady MM, Shalash A, Morsy M. Restless legs syndrome among patients receiving antipsychotic and antidepressant drugs. Human Psychopharmacol 2022;37(2):e2817. PMID 345233852
09: Freire C, Sennes LU, Polotsky VS .Opioids and obstructive sleep apnea. J Clin Sleep Med 2022;18(2):647-52. PMID 34672945
10: Garrett AR, Hawley JS. SSRI-associated bruxism: a systematic review of published cased reports. Neurol Clin Pract 2018;8(2):135-41.** PMID 29708207
11: Goodchild JH, Donaldson M. The intersection between stress and drug-induced bruxism. Gen Dent 2021;69(2):12-5. PMID 33661106
12: Howell M, Avidan AY, Foldvary-Schafer N, et al. Management of REM sleep behavior disorder: an American Academy of Sleep Medicine clinical practice guideline. J Clin Med 2023;19(4):759-68.** PMID 36515157
13: Imam SH, Landry K, Kaul V, Gambhir H, John D, Kloss B. Free phenytoin toxicity. Am J Emerg Med 2014;32(10):1301. PMID 24768668
14: Jain KK. Drug-induced neurological disorders. 4th ed. Cham (Switzerland): Springer, 2021.**
15: Javaheri S, Badr MS. Central sleep apnea: pathophysiologic classification. Sleep 2023;46(3):zsac113. PMID 35551411
16: Javaheri S, Patel S. Opioids cause central and complex sleep apnea in humans and reversal with discontinuation: a plea for detoxification. J Clin Sleep Med 2017;13(6):829-33. PMID 28454596
17: Jullian-Desayes I, Revol B, Chareyre E, et al. Impact of concomitant medications on obstructive sleep apnea. Br J Clin Pharmacol 2017;83(4):688-708.** PMID 27735059
18: Kenedi CA, Goforth HW. A systematic review of the psychiatric side-effects of efavirenz. AIDS Behav 2011;15(8):1803-18. PMID 21484283
19: Kierlin L, Littner MR. Parasomnias and antidepressant therapy: a review of the literature. Front Psychiatry 2011;2:71. PMID 22180745
20: Kobayashi T, Yamauchi M. A case of serial nightmares and oneiroid state under paroxetine for senile depression. Psychogeriatrics 2012;12(1):54-7. PMID 22416829
21: Lappegard KT, Nordmo E. Ivabradine and nightmares: a previously unreported adverse reaction. Eur J Clin Pharmacol 2011;67(12):1313-4. PMID 21701883
22: Linselle M, Montastruc F, Jantzen H, et al. Drugs and sleep apneas? A review of the French Pharmacovigilance database. Therapie 2015;70(4):347-50. PMID 25679185
23: Locatelli F, Formica F, Galbiati S, et al. Polysomnographic analysis of a pediatric case of baclofen-induced central sleep apnea. J Clin Sleep Med 2019;15(2):351-4.** PMID 30736882
24: Mason M, Cates CJ, Smith I. Effects of opioid, hypnotic and sedating medications on sleep-disordered breathing in adults with obstructive sleep apnea. Cochrane Database Syst Rev 2015;14(7):CD011090. PMID 26171909
25: Mathew T, Sarma GR, Nadig R, Varghese R. Topiramate-induced somnambulism in a migraineur: a probable idiosyncratic adverse effect. J Clin Sleep Med 2012;8(2):197-8. PMID 22505867
26: McCarter SJ, Labott JR, Mazumder MK, et al. Emergence of restless legs syndrome during opioid discontinuation. J Clin Sleep Med 2023;19(4):741-8. PMID 36692170
27: McCarter SJ, St Louis EK, Sandness DJ, et al. Antidepressants increase REM sleep muscle tone in patients with and without REM sleep behavior disorder. Sleep 2015;38(6):907-17. PMID 25325487
28: McEntire DM, Kirkpatrick DR, Kerfeld MJ, et al. Effect of sedative-hypnotics, anesthetics and analgesics on sleep architecture in obstructive sleep apnea. Expert Rev Clin Pharmacol 2014;7(6):787-806.** PMID 25318836
29: Mendelson AM, Kohan L, Okai J, et al. Adverse drug effects related to multiday ketamine infusions: multicenter study. Reg Anesth Pain Med 2020;rapm-2019-101173.** PMID 32054666
30: Nevin RL, Leoutsakos JM. Identification of a syndrome class of neuropsychiatric adverse reactions to mefloquine from latent class modeling of FDA adverse event reporting system data. Drugs R D 2017;17(1):199-210. PMID 28063022
31: Okamoto Y, Tsuneto S, Tanimukai H, et al. Can gradual dose titration of ketamine for management of neuropathic pain prevent psychotomimetic effects in patients with advanced cancer. Am J Hosp Palliat Care 2013;30(5):450-4. PMID 22833552
32: Perez-Diaz H, Iranzo A, Santamaría J. Zolpidem-induced sleep-related behavioural disorders [Spanish]. Neurologia 2010;25(8):491-7. PMID 20965000
33: Postuma RB, Gagnon JF, Tuineaig M, et al. Antidepressants and REM sleep behavior disorder: isolated side effect or neurodegenerative signal? Sleep 2013;36(11):1579-85. PMID 24179289
34: Saber WK, Almuallim AR, Algahtani R. Restless legs syndrome and the use of antipsychotic medication: an updated literature review. Cureus 2022;14(8):e27.** PMID 36134065
35: Sathyan A, Scaria R, Arunachalam P, et al. Antiepileptic drugs–induced enuresis in children: an overview. J Pharm Tech 2021;37(2):114-9. PMID 34752569
36: Sharf B, Moskovitz C, Lupton MD, Klawans HL. Dream phenomena induced by chronic levodopa therapy. J Neural Transm 1978;43(2):143-51. PMID 104005
37: Stallman HM, Kohler M, White J. Medication induced sleepwalking: A systematic review. Sleep Med Rev 2018;37:105-13. PMID 28363449
38: Strayhorn JM, Nash JL. Frightening dreams and dosage schedule of tricyclic and neuroleptic drugs. J Nerv Ment Dis 1978;166:878-80. PMID 31416
39: Szabo J, Vida Z. Fracture of the leg while sleeping: drug-induced somnambulism in adulthood. Sleep Vigilance 2020;4:43-5.**
40: Teman PT, Tippmann-Peikert M, Silber MH, Slocumb NL, Robert Auger R. Idiopathic rapid-eye-movement sleep disorder: associations with antidepressants, psychiatric diagnoses, and other factors, in relation to age of onset. Sleep Med 2009;10(1):60-5. PMID 18226952
41: Uca AU, Uğuz F, Kozak HH, et al. Antidepressant-induced sleep bruxism: prevalence, incidence, and related factors. Clin Neuropharmacol 2015;38(6):227-30.** PMID 26536018
42: Van Gastel A. Drug-induced insomnia and excessive sleepiness. Sleep Med Clin 2018;13(2):147-59. PMID 29759266
43: Yun CH, Ji KH. Zolpidem-induced sleep-related eating disorder. J Neurol Sci 2010;288(1-2):200-1. PMID 19822330

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All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.

Author

Linda A Hershey MD PhD FAAN FANA

Dr. Hershey of the University of Oklahoma Health Sciences Center has no relevant financial relationships to disclose.
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Editor

Antonio Culebras MD FAAN FAHA FAASM

Dr. Culebras of SUNY Upstate Medical University at Syracuse has no relevant financial relationships to disclose.
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Former Authors

K K Jain MD†
Raffaele Manni MD

Patient Profile

Age range of presentation: 0 month to 65+ years
Sex preponderance: male=female
Heredity: heredity may be a factor
Population groups selectively affected: none selectively affected
Occupation groups selectively affected: none selectively affected

ICD & OMIM codes

ICD-10: Sleep disorder, unspecified: G47.9
ICD-11: Parasomnia disorders, unspecified: 7B0Z

Central sleep apnoeas: 7A40

Obstructive sleep apnoea: 7A41

REM sleep behaviour disorder: 7B01.0

Restless legs syndrome: 7A80

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Drug-induced parasomnias, sleep apnea, REM sleep disorder, and restless legs syndrome

Associated Disorders

Sleep apnea
Sleep paralysis
Sleepwalking

Differential Diagnosis

advanced Parkinson disease
delirium
disorders known to occur as a manifestation of diseases being treated with drugs

Also Relevant

Central sleep apnea
Drug-induced insomnia and excessive daytime sleepiness
Drug-induced neurologic disorders
Insomnia
Narcolepsy
- Nightmares
- Obstructive sleep apnea
- Sleep disorders
- Sleep and alcohol use and abuse
- Sleep paralysis
- Sleepwalking
- Stimulant-dependent sleep disorder

Clinical Categories

Sleep Disorders

	• Complete drug history.
	• Urine multidrug test
	• Measurement of blood levels of suspected drug.
	• Overnight polysomnographic study.

	• Good sleep hygiene reduces the probability of drug-induced sleep disorders.
	• Drugs known to be associated with parasomnias or other sleep disorders should be avoided if possible.
	• Alcohol and cigarettes also need to be avoided.

Drug-induced parasomnias, sleep apnea, REM sleep disorder, and restless legs syndrome

Cite this article

Introduction

Overview

Key points

Historical note and terminology

Table 1. Classification of Drug-Induced Breathing Disorders, Abnormal Movements, and Parasomnias

Clinical manifestations

Presentation and course

Prognosis and complications

Biological basis

Etiology and pathogenesis

Table 2. Drugs Associated with Vivid Dreams and Nightmares

Table 3. Drugs Associated with Sleepwalking

Table 4. Drugs Reported to be Associated with Sleep Apnea with Central or Obstructive Sleep Apnea

Table 5. Drugs Reported to be Associated with Enuresis

Table 6. Drugs Reported to be Associated with Sleep Bruxism

Epidemiology

Prevention

Differential diagnosis

Confusing conditions

Diagnostic workup

Management

Special considerations

Anesthesia

References

Contributors

Author

Editor

Former Authors

Patient Profile

ICD & OMIM codes

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Also in This Category

Non-24-hour sleep-wake disorder

Sleep and parkinsonism

Sleep and alcohol use and abuse

Idiopathic hypersomnia

Jet lag disorder

Sleep and multiple sclerosis

Sleep and aging

Sleep and chronic pulmonary disorders

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