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Drug-Induced Sleep Disorders / Sleep Disturbances

September 15, 2007 By Diseases & Conditions

There is a multitude of drugs the side effects of which can affect sleep by stimulating or aggravating sleep disorders. Drugs may suppress rapid eye movement (REM) sleep, affect slow-wave sleep (SWS), or cause insomnia, parasomnias, nightmares, excessive sleep, difficulty falling asleep, early-morning awakening, and periodic awakenings. These common sleep disorders and disturbances may be symptoms of, or result in secondary conditions that can prove severely consequential to one’s health.

Many drugs suppress REM sleep. Withdrawal of these drugs often result in REM rebound nightmares, which will be discussed further. While the drugs are being taken, the severity of sleep apnea, a temporary suspension of breathing occurring repeatedly during sleep, may be underestimated. Alcohol, anesthetics, and opioid analgesics tend to worsen sleep apnea while thyroxine, progesterone, nicotine, theophylline, and antidepressants have been known to improve nighttime breathing patterns.

Suppression of REM sleep is frequently seen with opioid analgesics, long-term antihypertensives, beta-blockers like pindolol and propranolol, stimulants of alpha adrenoreceptors like guanfacine  and clonidine, serotonin stimulators like ketanserin and ritanserin, and methyldopa (Aldomet). In fact, most antidepressants suppress REM sleep, and may also cause insomnia and increase the likelihood of experiencing some parasomnias.

But while most antidepressant drugs cause sleep disturbances, some drugs such as the now rarely used antihypertensive drug reserpine can actually cause depression. There is a complex relationship between sleep and depression. Symptoms of depression often include sleep disturbances such as periodic awakenings, difficulty falling asleep, and early-morning awakening.

Common sleep abnormalities observed in those with depression include the early onset of the first REM period (although not as early as that in narcolepsy, which is characterized by brief attacks of deep sleep, sometimes with cataplexy and hypnagogic hallucinations), increased duration of REM sleep, and a reversal of the occurrence of slow wave sleep (SWS) between the first and second periods of sleep.

SWS suppression, such as seen with use of corticosteroids, leaves a patient “unrested” after sleeping, and may induce insomnia. SWS suppression may be counteracted with medications such as zopiclone. Sleepwalking, a parasomniac behavior to be discussed further, usually occurs during SWS, and may be induced by drugs that increase this state of sleep.

Insomnia may be induced by both REM sleep and SWS suppression. It may be caused by drugs with central stimulant effects like methoxyphenamine and ephedrine, appetite-suppressing drugs, and possibly sympathomimetic vasodilators like phenylpropanolamine and pseudoephedrine, which is commonly included in over-the-counter cold medications.

Parasomnias are sleep behaviors that include sleepwalking, sleep talking, sleep starts, sleep terrors, REM behavior disorders, teeth grinding, bedwetting, and “confusional awakenings”. Tricyclic antidepressants and triazolam (Halcion) increase the likelihood of some parasomnias by suppressing REM sleep.

Sleepwalking occurs in about three percent of adults and possibly in over 15 percent of healthy children. Drugs that may induce sleepwalking by increasing the SWS state include lithium, amitriptyline (Elavil), and thioridazine (Mellaril).

Nightmares are reported to occur at least occasionally by 40 to 50 percent of adults. Nightmares are associated with REM sleep and occur primarily in the second half of the sleep period. Some beta-blockers, such as propranodol (Inderal), can predispose a patient to experiencing nightmares. Clomipramine (Anafranil), on the other hand, may suppress REM related nightmares.

Excessive daytime sleepiness can be caused by sedatives as well as by stimulants that disrupt sleep and cause sleep deprivation. Stimulants that can disrupt nighttime sleep include the anti-asthmatic drug theophylline, sympathomimetic bronchodilators such as ephedrine, and even caffeine. The effects of commonly prescribed sleeping medications, such as flurazepam (Dalmane) and antihistamines such as diphenhydramine (Benadryl) can persist beyond the normal period of sleep. Other drugs with similar effects include beta-blockers and prochlorperazine (Compazine), a dopamine-blocking drug used for nausea.

Anticancer chemotherapy, antiasthmatic, and  antiparkinson medications can also cause sleep disturbances. In the case of chemotherapy drugs, daytime sleepiness and fatigue are only a couple of the numerous side effects a patient faces. The other side effects, such as depression, gastrointestinal distress, and muscle and joint pain contribute to sleep disruptions, not to mention the primary pain of the cancer itself.

Most antiasthmatic drugs are known to alter sleep, but in varied ways. And since they are often used in combination with other drugs, the net effect is difficult to predict or understand. Asthmatics also suffer from symptoms and secondary conditions that affect sleep. One of these symptoms, gastroesophageal reflux, can also be aggravated by the antiasthmatic drug theophylline. Conversely, at least one antiasthmatic drug, salmeterol, a beta-adrenergic stimulator, has been shown to improve the quality of sleep.

Patients with Parkinson’s Disease complain frequently with regard to sleep disturbances. 74–96 percent of those who suffer from Parkinson’s report some kind of sleep disturbance, and sleep disorders associated with the disease vary greatly. And although antiparkinson’s medications are known to cause sleep disturbances, the mechanism behind this is not understood. Antiparkinson medications include levodopa (Sinemet), direct stimulators of dopamine receptors such as pergolide (Permax) and bromocriptine, drugs that inhibit the breakdown of dopamine like seligiline (Eldepryl), dopamine releasing agents like amantidine (Symmetrel), and drugs that block receptors for acetylcholine like benztropine (Cogentin) and trihexyphenidyl (Artane).

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Filed Under: Sleep Disorders / Sleep Disturbances

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