Prescription Drugs and Their Effect on Sleep

Medicines can profoundly affect sleep quality. Indeed, secondary insomnia is often caused by drugs.

Cardiovascular Drugs

Heart drugs can influence sleep architecture and may contribute to the prevalence of insomnia in older people. Beta blockers, prescribed for hypertension, seem to give people insomnia and even hallucinations. Whether the drugs directly cause these symptoms is of some question, but they are associated with them. Beta blockers do seem to reduce the amount of time spent in REM and increase nighttime awakenings. Medicinal chemists often classify substances as hydrophilic (liking water) or lipophilic (liking fat). It’s the lipophilic beta blockers such as propranolol that cause the problems rather than hydrophilic ones.

Alpha adrenergic agonists like clonidine increase sleep fragmentation and diminish REM sleep. They also increase sleepiness during daytime. Another heart drug, theophylline, has been shown to increase the amount of shallow stage 1 sleep and to increase sleep latency.

Stimulants and Sleep

Stimulants can make it difficult to sleep (duh). Ritalin and Adderall or other amphetamines make it harder to fall asleep, and shift the period during sleep away from deep stage 3 sleep to shallow stage 1 sleep. REM sleep also declines. Cold medicines often include ephedrine and/or pseudoephedrine, which are chemically related to amphetamine and have stimulant effects. Caffeine also impedes sleep, and is often used to stay awake. Some find stimulants help them to sleep. More find the same stimulant helps them sleep at times and stay awake at other times.

Pain Drugs and Sleep

Opioid drugs have a profound effect on sleep (morphine was named after Morpheus, god of sleep). Opioids are often given as analgesics to reduce severe pain. In healthy people they result in a lengthening of time spent in stage 2 and a reduction in stage 3 and REM sleep. Taking opioids can actually cause apnea as they can cause excessive relaxation of the throat muscles. Milder over-the-counter analgesics called NonSteroidalAntiInflammatory Drugs (e.g. aspirin, ibuprofen) might slightly reduce sleep efficiency, but the effect is minor. Pain drugs, although they may directly degrade sleep quality, can result in better sleep for the patient if they reduce discomfort that otherwise keeps the patient awake.

Antidepressant Medications and Sleep

Depression and sleep problems are intertwined. Both insomnia and hypersomnia are considered indicating symptoms of depression, and both depression and sleep disorders are common symptoms of other disorders. Antidepressant drugs – which encompass a large number of medicines – are prescribed widely today. Selective serotonin reuptake inhibitors (SSRIs) are the most well known and others include tricyclic drugs, monoamine oxidase inhibitors (MAOIs), and serotonin antagonist reuptake inhibitors (SARIs). Although SSRIs are technically stimulants, they facilitate sleep in many people. MAO inhibitors and tricyclic antidepressants are sedatives and patients tend to develop tolerance to the sedating effects within a couple weeks, so the FDA does not label these drugs for insomnia treatment unless the insomnia is a symptom of depression. Many doctors prescribe low doses of the tricyclic antidepressant doxepin (trade name Sinequan) off-label for insomnia.

With the exception of SARIs, antidepressant drugs suppress REM sleep. Patients spend less of their sleep time in REM than when they are not on the medication. Whether this is good or bad is not clear. Sleep restriction – stopping a person from sleeping as much as they want to – is an effective short-term treatment for depression in some cases. There could be a causal relationship between reducing REM sleep and increasing the patient’s mood.

Ritanserin, eplivanserin, and similar antidepressants are being investigated for their ability to enhance slow-wave sleep.

Epilepsy Drugs and Sleep

Older drugs used to treat epilepsy affect the central nervous system and extend slow-wave sleep in patients while decreasing REM sleep. Patients tend to develop tolerance to these effects in a few weeks. Newer epilepsy drugs work in the brain’s GABA (a neurotransmitter) system, enhancing activity there. They also extend slow-wave sleep and do not produce the tolerance that older drugs produce.

Others of Note

The gastroesophageal reflux disease medicine cimetidine, some steroids and laxatives, the anticonvulsant drug phenytoin, and the respiratory drug theophylline are all known to cause insomnia in some patients.

Drugs explicitly used to influence sleep

Benzodiazepines are used for anxiety disorders and other psychiatric indications. For years they were the go-to insomnia drug, and although less often prescribed just for sleep disorders today, they certainly affect patients’ sleep. Newer benzodiazepine receptor agonists (which have some similar biochemical actions) are the most common type of prescription insomnia medication used today. All of these drugs reduce sleep latency and the amount of time the patient spend waking during their time in bed. The true benzodiazepine derivatives reduce the amount of time spent in deep (stage 3) sleep. The newer benzodiazepine receptor agonists do not, which is partly why they are better as sleep aids. All of these drugs reduce the amount of time in stage 1 sleep, and none seem to have an effect on REM sleep time.

The melatonin agonist ramelteon was approved in 2005 and has proven effective in treatment of sleep onset insomnia. It binds to two of the three melatonin receptors in the body; this seems to limit the suprachiasmatic nucleus’ wake-promoting activity.

The benzodiazepine receptor agonists do not induce rapid tolerance, the way other sedative drugs do, which is why they are good for treating insomnia. There is rebound insomnia when the drug is discontinued, but that happens with most sleep aids.

Smoking, Caffeine, and Alcohol

Many pendants like to point out that the most widely used drugs are legal, non-prescription ones. People have been influencing/modifying their sleep and waking architecture with drugs forever.  Alcohol has been used to help people relax for millennia and caffeine use is widespread and deeply entrenched in human culture.  Anyone thinking about sleep aids has to consider their consumption of alcohol and caffeine as well.

Nicotine is a stimulant and smokers tend to have higher rates of insomnia.  Studies with polysomnography show that the smokers get less slow wave sleep (the most refreshing kind) than non-smokers.  Smokers also have longer sleep latency (time to fall asleep after getting into bed) and lower overall sleep time.

Caffeine is a stimulant that appears to work by slowing the action of the neurotransmitter adenosine. Individual reactions to caffeine vary considerably. Some people find it causes insomnia. Other seem to sleep better on caffeine. Indeed, the short-term caffeine nap involves intentional consumption of caffeine before sleep.

See our page on alcohol and sleep for information on that topic.

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