Medications associated with the treatment of insomnia
Below, I will briefly describe the medications and OTC remedies that are often associated with the treatment of insomnia:
Sedative-hypnotics (e.g., Ambien [zolpidem], Lunesta [eszopiclone], Sonata [zaleplon])
These medications are often prescribed by doctors for the short-term management of insomnia. These medications are not intended to be taken indefinitely. Short acting sedatives are best for sleep onset insomnia (e.g., zolpidem, zaleplon). Longer acting sedatives are best for sleep maintenance insomnia (e.g., eszopliclone, zolpidem controlled release). Side effects can include: Residual daytime sedation, cognitive impairment, motor incoordination, headache, dizziness, nausea, abdominal pain, respiratory suppression, they may be habit forming with long-term use, and they can cause rebound insomnia on discontinuance. A less common side effect of zolpidem involves inappropriate behaviors while not fully awake (e.g., sleep walking, driving, making telephone calls, eating, or having sex).
Anti-anxiety medications (aka Benzodiazepines) (e.g., Xanax [alprazolam], Ativan [lorazepam], Klonapin [clonazepam], Valium [diazepam]).
These medications may be prescribed by doctors for the short-term management of anxiety and sometimes for anxiety-related insomnia. They are not intended to be taken on a regular basis for the long-term because they are habit forming and cause withdrawal symptoms and rebound insomnia upon discontinuance. Research has found an increased risk for cognitive impairment (including dementia) with long-term benzodiazepine use, particularly by older adults. Other side effects are similar to the sedative-hypnotics (described above).
Anti-depressants (e.g., Prozac [fluoxetine], Zoloft [venlafaxine], Paxil [paroxetine], Celexa [citalopram], Lexapro [escitalopram]).
Most of the antidepressants are not recommended for the treatment of insomnia in patients without depression. Doxepin (Silenor) is an antidepressant that has been approved by the FDA. Some other antidepressants are sedating (e.g., amitriptyline, trazodone) and may be useful in the management of insomnia associated with depression, although they are not approved by the FDA for treatment of insomnia.
Melatonin agonists: Ramelteon (Rozerem). Short-term use is associated with some modest improvement in some sleep parameters. It is more effective in treating sleep onset insomnia compared with sleep maintenance insomnia. Adverse effects are generally milder than those associated with benzodiazepines and sedative-hypnotics, and it has little abuse potential.
Orexin receptor antagonists: Suvorexant (Belsomra). Short-term use is associated with improvement in some sleep parameters. It has the potential for dependence and abuse. It can cause daytime somnolence, and worsen sleep-disordered breathing in vulnerable patients. Other potential side effects include headaches, sleepwalking, REM sleep behavior disorder, suicidal ideation, and the emergence of sleep paralysis, hypnogogic hallucinations, and mild cataplexy.
Antihistamines (most commonly diphenhydramine). Over-the-counter (OTC) brand name examples include: Benadryl, Unisom, and Tylenol PM. There is little evidence that diphenhydramine improves insomnia and it may cause sedation the next day (due to its long half-life). Additional side effects include changes in sleep architecture (particularly a reduction in REM sleep), decreased alertness, diminished cognitive function (e.g., concentration, memory), delirium, dry mouth, blurred vision, urinary retention, constipation, and increased intraocular pressure. Recent research has shown an increased risk for dementia, particularly when used long-term and by older adults. Routine use of diphenhydramine to treat insomnia is not recommended.
Melatonin. Melatonin is a hormone that your brain makes. It regulates the “circadian clock” that sends signals that influence wakefulness or sleepiness. The body produces melatonin when it is dark. Melatonin production is suppressed by light, including artificial light. Melatonin is available as an over-the-counter dietary supplement. Melatonin at low doses (< 1mg) taken at the right time helps to regulate the circadian clock. Melatonin taken at higher doses can produce sleepiness in some people, but for most people, it may dysregulate the sleep clock, worsen insomnia, and cause daytime grogginess. There is little evidence that melatonin is helpful for most people with insomnia. However, it can be helpful in the management of insomnia associated with a Circadian Rhythm Sleep Disorder. If you are going to use melatonin, sleep medicine experts recommend the use of a low dose formulation (e.g., 300 micrograms) [see example], and to consistently take 300 mcg (i.e., 0.3mg) at 5 hours before bedtime, and take 600mcg at bedtime every night for at least 90 days, and do not expect immediate results.
Herbal products. There is little evidence from randomized controlled trials about the efficacy of many herbals, however, and for those that have been well studied (e.g., valerian), there is little evidence of benefit. Valerian has been associated with a greater number of adverse events per person compared with placebo, and it may also produce liver damage.
Alcohol. Alcohol is commonly self-prescribed as a sleep aid because it decreases the time required to fall asleep, at least in the short-term. However, alcohol can promote sleep disturbances later in the night and promotes upper airway instability and sleep apnea. These negative effects, coupled with the significant risk of dependence and interaction with other medications, preclude the use of alcohol to treat insomnia.
Marijuana. There insufficient research to inform a recommendation. That said, I have not been impressed by the effects I have observed in my patients with insomnia and other psychiatric disorders (e.g., depression, anxiety) who report using marijuana for these disorders.
Additional notes about medications for sleep
Older adults: Older adults have a particularly high risk of adverse effects from hypnotic drugs, including excessive sedation, cognitive impairment, delirium, night wandering, agitation, postoperative confusion, balance problems, and impaired performance of daily activities. An increased risk of falls with severe consequences, including traumatic brain injury and hip fracture, has been observed in association with both benzodiazepines and sedatives. A review of studies showed that improvements in sleep were relatively small compared with the two- to fivefold increase in adverse cognitive or psychomotor events. This suggests that additional caution is necessary when deciding whether pharmacotherapy is indicated for an older patient with insomnia.
Drug interactions: Concurrent use of any sleeping medication and alcohol (or another central nervous system depressant, including diphenhydramine, benzodiazepines, and opioid pain medication) increases the risk of central nervous system depression which results in suppressed breathing, and, therefore, is contraindicated.
Disclaimer: The content of this page is for informational purposes only. Before starting or stopping any medication or substance for sleep or any other condition, please consult a professional qualified to prescribe.
Credits: The information in this handout was largely adapted from: Bonnett, M. H., & Arand, D. L. (2016, September). Treatment of insomnia. Up To Date.