Sleep architecture can be affected by acute or chronic Ingestion of medications or substances of abuse, as well as by abrupt withdrawal of these agents. Antidepressant drugs consist of tricyclic antidepressants (TCAs), selective serotonin reuptake Inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), and noradrenaline reuptake Inhibitors (NARIs). Acute Intake of TCAs, except trimIpramine, decreases WASO, Increases stage 2 nrem sleep, increases delta sleep, and reduces REM sleep with varying degrees of residual daytime sedation. During withdrawal, WASO Is Increased and REM sleep rebound occurs. Trimlpramine Ingestion Increases SWS, but has no effect on REM sleep. MAOIs, such as moclobemide, phenelzine, and trancylpromine, Increase sleep continuity, Increase REM sleep latency, and reduce REM sleep amount, but do not affect SWS. However, moclobemide can result in Insomnia.75,76
Acute ingestion of SSRIs may cause insomnia or hypersomnia. WASO may be normal or Increased, but SWS Is not affected. REM latency Is Increased and REM sleep Is reduced. SSRI agents, such as fluoxetine, sertraline, and paroxetine, may Induce sleep bruxism, which may improve with buspirone.75,77-79
Acute Ingestion of trazodone decreases WASO, Increases or has no effect on SWS, and decreases or has no effect on REM sleep. Buproprion reduces REM latency, Increases REM sleep, and normalizes a propensity for sleep-onset REM periods on multiple sleep latency testing.75
MIrtazapine Increases SWS, but does not affect stage 2 NREM sleep, nor does It affect REM latency or REM percentage of total sleep. NARIs Increase the duration of stage 2 NREM sleep, lengthen REM latency, and shorten REM sleep.
Mood stabilizers are used for bipolar disorders and Include lithium and anticonvulsant drugs. Lithium Ingestion acutely decreases REM sleep and Increases delta sleep. Anticonvulsant drugs utilized In bipolar disorders Include sodium valproate (VPA), carbamazeplne, topiramate, gabapentln, lamotriglne, tiagablne, and zonisamlde. Valproic acid disrupts sleep by Increasing stage 1 sleep.80
Carbamazeplne increases sleep efficiency, shortens sleep latency, decreases REM percentage of TST, and decreases REM density.75,80
Gabapentin Increases REM sleep percentage, Increases mean duration of REM periods, reduces number of awakenings, reduces stage 1 sleep percentage, and Increases SWS.80-82
Lamotrlgine Increases REM sleep, reduces the number of entries Into REM sleep, decreases the number of phase shifts, and decreases the percentage of SWS.81
Tiagablne significantly Increases sleep efficiency, decreases wakefulness, and Increases SWS and low-frequency activity during NREM sleep.83
Zonlsamide is associated with daytime somnolence and fatigue.
Like the antidepressants, antipsychotic medications have different effects on sleep. Traditional neuroleptic agents (dopamine [D2
] antagonists, such as thorazine, haloperldol) Increase sleep onset, sleep efficiency, and stage 3 NREM sleep; reduce REM sleep; Increase periodic limb movements of sleep; and may Induce restless legs syndrome-like akathisia. The newer non-D2
neuroleptics, such as clozapine, olanzapine, and risperidone, increase sedation, reduce SWS, and increase restless legs syndrome and periodic leg movements. Use of quetlapIne fumarate can result In Insomnia. Withdrawal of narcoleptics results In reduction In sleep continuity and REM sleep. As mentioned previously, some of the atypical antipsychotic drugs have Important metabolic effects, with development of obesity and subsequent obstructive sleep apnea. Atypical antipsychotics vary In their potential to cause metabolic abnormalities: olanzapine and clozapine carry the highest risks; risperidone and quetlaplne have lower risks; and zlprasidone and arlpiprazole have minimal metabolic risks.84,85
Psychotic patients who relapse have greater reductions In TST, sleep efficiency, total NREM sleep, and stage 2 NREM sleep compared to nonrelapsers.75
Antianxiety drugs and hypnotic drugs, such as barbiturates and benzodiazepines, also affect sleep. Acute Ingestion of barbiturates leads to Increased TST, decreased WASO, Increased stage 2 NREM sleep with Increased spindles, variable effects on SWS, and reduced REM sleep. Tolerance to barbiturates rapidly develops, and withdrawal leads to Insomnia and reduced TST Acute Ingestion of benzodiazepines decreases sleep latency (agents vary In onset), increases TST, Increases stage 2 NREM sleep and spindles, decreases WASO and REM sleep, and usually suppresses stages 3 and 4 NREM sleep.22
Withdrawal from benzodiazepines reduces TST Rebound insomnia lasting for one to two nights occurs following withdrawal from short-acting benzodiazepines. Benzodiazepine receptor agents, such as Zolpidem or zaleplon, reduce sleep latency and Increase TST, but do not affect either SWS or REM sleep. Withdrawal from these agents leads to Increased WASO.
Substances of abuse also Impact sleep. Acute and chronic alcohol Ingestion and withdrawal from alcohol affect sleep, as has been described above under substanceinduced sleep disorder. Acute ingestion of opioids, such as heroin or methadone, profoundly disrupts sleep continuity and staging with increased brief arousals, reduces TST, decreases stages 3 and 4 NREM sleep, and reduces REM sleep.86-88
Withdrawal from methadone can produce nocturnal Insomnia lasting for 3 to 5 weeks. After methadone withdrawal, REM sleep and delta sleep Increase.88
Amphetamines and methylphenldate are utilized to treat ADHD, but also have high abuse liability. Acute ingestion of amphetamines Increases sleep latency, reduces sleep efficiency, reduces REM latency, and suppresses REM sleep. Withdrawal from amphetamines leads to Increased TST and Increased REM sleep, which can remain elevated for three to five nights. Methamphetamlnes increase average dally sleep latency on the MSLT in a dose-dependent manner for both normal subjects and narcoleptics.75
Methlyphenidate reduces TST, Increases REM latency, and reduces REM sleep duration. Nicotine produces a dose-dependent Increase In wakefulness and reduction in REM sleep. Discontinuation of chronic nicotine use leads to Increased number of arousals, awakenings, and sleep stage changes during the week of cessation.