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Among the cardiovascular drugs, the usually long-term antihypertensives are particularly important in their effects on sleep, generally a decrease in the duration of REM sleep, but it is unclear how significant these effects are for patients. REM sleep is decreased by blockers of beta-adrenoreceptors like pindolol, stimulants of alpha adrenoreceptors like clonidine and guanfacine, serotonin stimulators like Ritanserin and ketanserin, and methyldopa (Aldomet). Only reserpine increases REM sleep. Both of the alpha-1-adrenoreceptor stimulators, Indoramin and prazosin, cause sedation, and propranolol impairs vigilance or attention.
Moving to the anticancer chemotherapy drugs, the patient faces numerous unpleasant side-effects which include daytime sleepiness and fatigue. Moreover, the other side-effects of these drugs--gastrointestinal distress, depression, muscle and joint pain--may disrupt sleep, as may the primary pain of the cancer itself.
Asthma patients commonly complain of sleep problems which may result from a variety of factors, including allergens (i.e., mites) in the bedding, horizontal posture, low blood oxygen, high blood carbon dioxide, low blood cortisol levels, drugs administered and drugs withdrawn. Most drugs used in treating asthma are known to alter sleep. They have varied effects, and are often used in combination, making their net effect particularly difficult to predict or understand.
Lastly, turning from asthma to Parkinson's Disease, we find sleep disturbances to be one of these patients' most common complaints, present in 74-96% and considered almost as debilitating as their impaired movement. Parkinsonism is associated with almost every kind of sleep disorder. In addition, long term treatment with the mainstay levodopa (usually prescribed as Sinemet) can also disturb sleep.
I hope that the summary above has not left those sleep-disordered patients with hypertension, asthma, cancer or parkinsonism in a state of helpless confusion. Sometimes it seems as if anything you can take to help one problem will cause a myriad of other problems.
Drugs which affect sleep may, as side effects, aggravate or simulate any of the common sleep disorders. Drugs which suppress an aspect of sleep, such as many do with REM, commonly result in REM rebound nightmares on withdrawal. While such drugs are being taken, the relative lack of REM sleep may lead to underestimation of the severity of sleep apnea.
Drugs which suppress slow-wave sleep (SWS) commonly leave the patient unrested; this might be counteracted by a sleeping medication that incrases SWS, such as zopiclone.
Insomnia is a major class of sleep disturbance. It may be caused by drugs with central stimulant effects, such as ephedrine, methoxyphenamine, and appetite-suppressing drugs [and, I would add, by sympathomimetic vasodilators like pseudoephedrine and phenylpropanolamine, commonly included as one of several ingredients in over-the-counter cold medications]. Another mechanism of drug-induced insomnia is suppression of SWS, as seen with corticosteroids, and of REM sleep, as seen with opioid analgesics.
Parasomnias are unusual behaviors during sleep such as sleepwalking, sleeptalking, teeth grinding, bedwetting, sleep starts, sleep terrors, REM behavior disorders (see Glossary), and confusional awakenings. Sleepwalking, which may occur in over 15% of healthy children and 3% of adults, typically take place during SWS. Several medications which increase this stage of sleep may induce sleep-walking: lithium, thioridazine (Mellaril), and amitriptyline (Elavil).
Drugs that suppress REM sleep increase the likelihood of some parasomnias: tricyclic antidepressants, for example, and triazolam (Halcion). Nightmares, reported at least occasionally by 40-50% of adults, occcur mainly in the second half of the night, associated with REM sleep. Drugs which predispose to nightmare include beta-blockers, especially those that more easily penetrate into the brain, like propranolol (Inderal). Clomipramine (Anafranil), a tricyclic antidepressant, may be used to suppress REM related nightmares.
Excessive daytime sleepiness can be caused both by the direct effects of sedative medications used to induce sleep and by stimulants which can disrupt sleep and thereby cause sleep deprivation. Some of the commonly prescribed sleeping medications, such as flurazepam (Dalmane), have active breakdown products that persist many hours beyond the normal period of sleep, leading to prolonged sedation. Also incriminated are antihistamines such as diphenhydramine (Benadryl), many of which are included as routine ingredients in over-the-counter sleeping medications and cold medications. Other drugs with similar effects include dopamine-blocking drugs for nausea, like prochlorperazine (Compazine) and beta-blockers. Stimulant drugs which can cause excessive daytime sleepiness by disrupting nighttime sleep include the ubiquitous drug caffeine, the antiasthmatic drug theophylline, and sympathomimetic bronchodilators such as ephedrine.
Drugs which may worsen sleep apnea include alcohol, opioid analgesics, and anesthetics. On the other hand, some drugs--thyroxine, antidepressants, progesterone, nicotine, and theophylline--are said to improve breathing patterns at night.
There is a complicated relationship between depression and sleep. Sleep disturbance, including difficulty falling asleep, periodic awakenings, and early-morning awakening, may be symptomatic of depression. Certain drugs in turn may cause depression, such as the antihypertensive drug reserpine, now rarely used. There are some typical abnormalities in sleep architecture associated with depression, such as early onset of the first REM period (but not so early as in narcolepsy), increased duration of REM sleep, and reversal of the distribution of SWS between the first and second perios of the night. Virtually all antidepressants cause REM suppression and often drowsiness during the day as well.
Beta-blockers like propranolol in particular increase wakefulness by causing insomnia and nightmares, and by suppressing REM sleep. However, the frequency of these effects may be low, especially with types of beta-blockers that do not readily penetrate to the brain, like atenolol.
There is so far a lack of research directly addressing the sleep effects of the commonly used calcium antagonist antihypertensives and the ACE inhibitors.
Sleep studies objectively confirm the disturbed sleep of asthmatics. They are often woken with coughing, wheezing, and breathlessness. Similar problems apply to patients with chronic obstructive pulmonary disease (COPD or emphysema). The result is excessive daytime sleepiness in about half of these patients. Besides direct drug effects on their sleep, asthmatics suffer many other factors affecting sleep, such as gastroesophageal reflux, which can be aggravated by the antiasthmatic drug theophylline.
Theophylline also has a central nervous system stimulatory effect that can disturb sleep, particularly in patients new to this drug. On the other hand, at least one antiasthmatic drug, salmeterol, a beta-adrenergic stimulator, has been shown to improve quality of sleep.
Other antiparkinson medications include direct stimulators of dopamine receptors such as bromocriptine or pergolide (Permax), dopamine releasing agents like amantidine (Symmetrel), drugs that block receptors for acetylcholine like trihexyphenidyl (Artane) and benztropine (Cogentin), and drugs that inhibit the breakdown of dopamine like seligiline (Eldepryl). Where the effects on sleep of even the best-studied antiparkinson drug, levodopa, remain controversial, those of the other drugs are even more obscure, though there is suggestive evidence to exempt amantidine from the generally invidious effect of the antiparkinson drugs on sleep.
This review has some of the character of the PDR in its listing of potential side effects without creating a clinical context of their frequency, severity, and offsetting benefits of their therapeutic effects. Generally I discourage patients from dwelling on the PDR descriptions of potential adverse effects of drugs. They are written less to inform the doctor and patient than to protect the drug company against suits based on the allegation that they failed to warn. Therefore, their safest path is to list everything that is ever reported by anyone taking their drug, however rare or tenuous the connection to the drug itself.
One way to think about it is that almost any drug can cause almost any side-effect you could name in some unfortunate individual, but that most patients never have the vast majority of such reported side-effects. On the other hand, if you do have a symptom you suspect to be a side-effect, it is useful supportive evidence (though still not proof) of a connection if the particular side-effect is listed with the drug. It is still more relelvant if it is described as "common." But the most relevant piece of data comes from you the patient: did the symptom start shortly after the drug, or when the drug was increased in dosage, and has it seemed to lessen with dosage decrease? This is, to my mind, the most important evidence that a drug is causing a given side-effect for a given person.
Meanwhile, don't let yourself be paralyzed by anxiety that anything you take will make matters worse. Most often, the opposite is true, that for instance the drug that relieves asthmatic symptoms helps the patient sleep better and therefore feel more alert.
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