What medications can reduce or deprive REM (Rapid Eye Movement) sleep?

Medications That Reduce or Deprive REM Sleep

The most clinically significant REM-suppressing medications include tricyclic antidepressants (particularly desipramine and protriptyline), SSRIs (fluoxetine, paroxetine), benzodiazepines (clonazepam), and certain dopaminergic agents, with the degree of REM suppression varying by drug class and mechanism of action. 1

Antidepressants with Strong REM-Suppressing Effects

Tricyclic Antidepressants (TCAs)

• Desipramine specifically suppresses both phasic and tonic components of REM sleep, making it one of the most potent REM-reducing agents 2, 1
• Protriptyline reduces the proportion of REM sleep through inhibition of serotonin and noradrenaline reuptake, though it causes significant anticholinergic side effects (dry mouth, urinary symptoms) and has no role in routine OSA treatment 2
• Imipramine and amitriptyline also reduce REM sleep through similar mechanisms 2
• Most antidepressants that increase serotonin function by blocking reuptake or inhibiting metabolism have the greatest effect on REM sleep, with reductions in REM amount and increases in REM onset latency 3

Selective Serotonin Reuptake Inhibitors (SSRIs)

• Fluoxetine significantly decreases REM sleep amount and increases both sleep-onset latency and REM latency even at low doses (20 mg/day) 4
• Paroxetine reduces REM sleep time and lengthens REM latency in healthy volunteers, with positive impact on respiratory events during non-REM sleep but no effect in REM sleep 2, 5
• Paroxetine at 20-40 mg showed variable efficacy for REM sleep behavior disorder, with 14 of 19 participants noting improvement but none achieving complete symptom elimination 2
• The REM-suppressing effects of SSRIs are greatest early in treatment and gradually diminish during long-term use, except with MAO inhibitors where REM sleep may be absent for many months 3

Other Antidepressants

• Mirtazapine acts as a serotonin receptor agonist but showed no consistent benefit in reducing sleep apnea and causes problematic side effects including sleepiness and weight gain 2
• Venlafaxine, reboxetine, and bupropion have activating effects that can worsen sleep despite REM-suppressing properties 6
• Trazodone increased arousals in a small RCT and is not recommended for insomnia treatment by the American Academy of Sleep Medicine 2, 7

Benzodiazepines and Related Agents

Primary Benzodiazepines

• Clonazepam (0.25-2.0 mg at bedtime) is the first-line treatment for REM sleep behavior disorder, working through GABAergic inhibition by increasing chloride channel opening frequency 2, 1
• Clonazepam showed efficacy in 306 of 339 treated subjects across 22 studies for REM sleep behavior disorder 2
• Temazepam, triazolam, and alprazolam also decrease REM sleep through similar GABAergic mechanisms 2, 1
• Use clonazepam with caution in patients with dementia, gait disorders, or concomitant obstructive sleep apnea 1

Alternative Agents

• Zopiclone showed efficacy in 9 of 12 subjects at doses of 3.75-7.5 mg at bedtime 2
• Sodium oxybate improves daytime sleepiness and treats cataplexy while also suppressing REM sleep intrusion into wakefulness 2

Dopaminergic and Cholinergic Agents

Dopaminergic Medications

• L-DOPA may paradoxically promote REM sleep behavior disorder in some patients, with prospective data showing onset of RBD in 5 of 15 L-DOPA naïve participants within one year 2, 1
• Pramipexole showed variable efficacy with only 13 of 29 subjects responding in RBD treatment studies 2

Cholinergic Agents

• Acetylcholinesterase inhibitors (donepezil 10-15 mg, rivastigmine 4.5-6 mg twice daily) may affect REM sleep patterns in patients with neurodegenerative disorders 2, 1
• Donepezil showed efficacy in 4 of 6 treated RBD patients 2
• Physostigmine (given intravenously) reduced apneas during REM sleep but is impractical for home use 2

Other Medication Classes

Cardiovascular Agents

• ACE inhibitors (enalapril, perindopril, ramipril) may contribute to OSA and disrupt normal REM sleep patterns, particularly in patients who develop cough or upper airway symptoms 2, 1
• Withdrawal of ACE inhibitors in nine OSA patients with cough resulted in significant decrease in apnea-hypopnea index 2

Anticonvulsants

• Carbamazepine showed efficacy in 5 of 5 treated RBD subjects at doses ranging from 100 mg three times daily to 500-1500 mg daily 2

Atypical Antipsychotics

• Clozapine demonstrated efficacy in all 3 treated RBD cases, though doses were not specified 2

Melatonin (Paradoxical Effect)

• Melatonin (3-12 mg at bedtime) suppresses REM sleep motor tone and normalizes circadian features of REM sleep, showing efficacy in 31 of 38 treated subjects for RBD 2, 1
• Despite being used to treat RBD, melatonin works by suppressing abnormal REM motor activity rather than increasing REM sleep 8

Clinical Monitoring Considerations

When prescribing REM-suppressing medications, monitor for daytime sedation, cognitive impairment, and falls, particularly in elderly patients 1

• Some antidepressants may paradoxically induce or worsen REM sleep behavior disorder symptoms in certain patients despite their REM-suppressing properties 1
• The REM-suppressing effects can be therapeutic in REM sleep behavior disorder by reducing dream enactment behaviors 1
• Patients with restless legs syndrome or REM sleep behavior disorder should be identified before choosing antidepressant treatment, as some agents worsen these conditions 3
• For patients with REM sleep behavior disorder, neither clonazepam nor melatonin is likely to completely stop dream enactment behaviors, so targeting moderate dosages (melatonin 6 mg or clonazepam 0.5 mg) that reduce attack frequency while avoiding adverse effects is the most reasonable strategy 8

Physiological Factors

• Stress significantly disrupts normal REM sleep patterns by activating the hypothalamic-pituitary-adrenal axis, which has inhibitory effects on REM sleep 1
• Addressing underlying stress factors should be prioritized in patients experiencing stress-related REM sleep disruptions 1