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When prescribing hypnotic medications to a patient with insomnia, doctors must take several factors into consideration. These include the patient’s age, medical history, current state of health, and other medications he or she may be taking. They must also take the patient’s insomnia symptoms into account, and if the insomnia affects sleep onset (the ability to fall asleep) or sleep maintenance (the ability to stay asleep).
Until recently, the Food and Drug Administration (FDA) had not approved any prescription insomnia medication for extended use. Prior to the introduction of eszopiclone (Lunesta), all prescribed hypnotics were labeled for use for one month at the most. Due to the large number of insomnia patients whose symptoms persist beyond one month, these labels have been updated. Certain hypnotics have been shown to be mostly non-habit-forming, even after extended use — but these medications may still be psychologically addictive, and the potential for abuse is still a key consideration. Most doctors today advise insomnia patients to gradually taper off their prescribed medications when their symptoms have abated, or taking a break after an extended period of consuming the drug (also known as a drug holiday).
The following table features a breakdown of the prescription medications we will be discussing at greater length below:
|Generic Name||U.S. Brand Name||Dosage||Company||Effects||Abuse Potential||Patent|
|Zaleplon||Sonata||5,10 mg capsules||King||Induces sleep||Yes||No|
|Zolpidem||Ambien||5,10 mg tablets||Sanofi Aventis||Induces sleep||Yes||No|
|Ambien CR||6.25, 12.5 mg tablets||Sanofi Aventis||Induces sleep and improves sleep maintenance||Yes||No|
|Eszopiclone||Lunesta||1,2,3 mg tablets||Sepracor||Induces sleep and improves sleep maintenance||Yes||No|
|Triazolam||Halcion||0.125 and .25 mg tablets||Pharmacia and Upjohn||Induces sleep and improves sleep maintenance||Yes||No|
|Temazepam||Restoril||7.5, 15, 22.5 and 30 mg tablets||Novel Laboratories, Inc.||Induces sleep and improves sleep maintenance||Yes||No|
|Estazolam||ProSom||1 and 2 mg tablets||Upjohn||Induces sleep and improves sleep maintenance||Yes||No|
|Ramelteon||Rozerem||8 mg tablets||Takeda||Induces sleep||No||Yes|
|Suvorexant||Belsomra||10 mg tablets||Merck||Induces sleep and improves sleep maintenance||Unknown||Yes|
Please note: this guide to sleep medications does not include drugs that are primarily used to address other conditions, even though they may also be used to alleviate insomnia symptoms. Examples include alprazolam (Xanax), clonazepam (Klonopin), diazepam (Valium), and lorazepam (Ativan). We have also excluded flunitrazepam (Rohypnol), flurazepam (Dalmane), loprazolam (Dormonoct), lormetazepam, and other medications that are widely discouraged or unavailable/illegal in the United States.
The term ‘z-drugs’ refers to the three non-benzodiazepine drugs primarily used to treat insomnia: zaleplon, zolpidem, eszopiclone/zopiclone. Z-drugs are structured differently from benzodiazepine drugs (such as Ativan and Valium), but they are designed to act on the same benzodiazepine receptors in the brain to induce sleepiness.
Zaleplon is a hypnotic indicated for use in patients that have difficulty falling asleep, and is not intended to treat those who have difficulty staying asleep or who wake too early. Zaleplon is produced by King Pharmaceuticals and marketed in the U.S. (and many other countries) as Sonata; it is also manufactured by Gedeon Richter Plc. as Andante. Zaleplon was also sold under the brand name Starnoc in Canada for a brief period before being discontinued and removed from the market. In some countries, Zaleplon is available as Hegon, Zalep, Zaplon, or Zerene.
Sonata is available in 5 mg and 10 mg tablets; however, physicians may prescribe a 20 mg treatment consisting of two 10 mg capsules. For elderly and debilitated patients, a dosage of 5 mg or lower is recommended. Zaleplon is indicated for short term treatment of insomnia, that is, insomnia that is corrected by seven to ten days of treatment. The FDA has approved use of zaleplon for up to 30 days. Zaleplon causes sedation and sleep within one hour of administration therefore it should only be taken before bed and never before any activity that requires alertness.
Zaleplon is known to cause central nervous system (CNS) depression, a rapid condition characterized by shallow breathing, a lower heart rate, and loss of consciousness; this may result in coma and death. Like benzodiazepines, alcohol use can potentiate the effects of CNS depression; alcohol should not be consumed while taking zaleplon. Zaleplon is potentially habit-forming and dependency may occur. Because of its sedative and euphoric effects, zaleplon may be also be abused as a recreational drug. Once a patient stops taking zaleplon, he or she may experience rebound insomnia.
Zolpidem is sedative-hypnotic medication used to treat short-term insomnia. Zolpidem is marketed in the United States as Ambien but is known commercially by many other names worldwide. The patent for Ambien was previously held by Sanofi Aventis; since the patent expired in 2007, more than a dozen companies have introduced generic versions of zolpidem, and dozens of trade names are currently used worldwide.
Like zaleplon, zolpidem has been linked to CNS depression. There is also a potential for dependence and abuse with zolpidem. In addition to side effects like headache and dizziness, some patients report a ‘zombie’ effect, characterized by fogginess and poor concentration during the daytime, as well as lucid dreams at night.
Sanofi Aventis has extended the commercial viability of this drug by patenting and selling a controlled-release (CR) formulation. The CR medication is delivered in a pill layered with rapid-acting and slow-release components; this allows people with insomnia to achieve sleep easily and stay asleep throughout the night. Importantly, the fast-acting and slow-release layers share the same chemical structure, but the latter contains a blend of inactive ingredients that delay absorption and prolong the hypnotic effect. Ambien CR is available in 6.25 and 12.5 mg strengths.
Eszopiclone is a hypnotic prescribed to help insomnia patients fall asleep more easily and remain asleep throughout the night. Eszopiclone is manufactured by Sepracor Inc. and marketed as Lunesta in the U.S.. Lunesta was previously under patent with exclusivity, but as of 2014, the patent has expired and generic versions are currently available.
Eszopiclone is available in film-coated tablets. Unlike zaleplon and zolpidem, which have been proven to act on benzodiazepine receptors, the precise action mechanism of eszopiclone is unknown; however, its hypnotic effect suggests interaction with GABA-receptors located near the benzodiazepine receptors, if not the benzodiazepine receptors themselves. Due to the strength of this hypnotic effect, eszopiclone is a controlled substance and there is potential for abuse of the drug.
Unlike other z-drugs and other insomnia medications like triazolam, which are prescribed for up to four weeks, Lunesta has been approved by the FDA for long-term use of six months or more. Long-term trials indicate that Lunesta does not increase tolerance, meaning that patients do not need larger doses to obtain the same effect after long-term use. Lunesta is touted as superior to competing medications, since it not only initiates sleep but also prevents nighttime waking.
In addition to the common side effects listed above, more serious (and rarer) side effects of eszopiclone include sleepwalking/driving, abnormal thoughts, memory loss, anxiety, and allergic reactions.
Benzodiazepine medications are a class of drugs primarily used to treat anxiety disorders, though their soporific effects often make them suitable as sleep aids. Hence the name, they act on benzodiazepine receptors in the brain, much like z-drugs do. Benzodiazepines carry a much higher risk for dependency and potential abuse than z-drugs. Benzodiazepines are not recommended for people with obstructive sleep apnea (OSA) because they cause pronounced muscle relaxation, which can exacerbate symptoms of OSA. Benzodiazepine medications act quickly — typically within 10 days — but most physicians urge patients to gradually wean themselves off the drug; those who abruptly stop taking the drug have reported depression and anxiety, as well as physical withdrawal symptoms like nausea and vomiting.
Triazolam is primarily used as a sedative to treat patients with severe insomnia. Triazolam was originally manufactured by Pharmacia and Upjohn and branded as Halcion; however, the patent and exclusivity rights have expired, and several generic versions are available. These include Apo-Triazo, Hypam, and Trilam, as well as other named used in non-English-speaking countries.
Triazolam is available in 0.125 and 0.25 mg tablets and a single dose of either strength is sufficient for most insomnia patients. The maximum dose per day should not exceed 0.5 mg; elderly and debilitated patients should take lower doses. Doctors urge people not to take triazolam unless they plan on sleeping for the next seven to eight hours. Triazolam is indicated for short-term treatment of insomnia, and should not be used for longer than three consecutive weeks. In clinical studies, triazolam successfully decreased sleep latency (the time it takes to fall asleep at night), increased overall sleep duration, and reduced nighttime waking in insomnia patients.
Many patients report feeling the effects of triazolam the following day, despite a full night’s rest. As a result, this medication may not be suitable for people with jobs that require them to work early in the morning, particularly if their duties involve use of vehicles or heavy machinery.
Temazepam is used to treat sleep-onset and sleep-maintenance insomnia. The drug was first patented in 1965, and became available in the U.S. in 1981. It is most commonly marketed under the name Restoril; other trade names include Euhypnos, Normison, Remestan, and Temaze.
The maximum daily dosage for Restoril is 30 mg, but as little as 7.5 mg will be enough for some insomnia patients; this is also the recommended daily dosage for elderly and debilitated patients. Restoril is a short-term insomnia medication, and is classified as a Schedule IV controlled substance under the Convention of Psychotropic Substances. As a result, it carries high risks of dependency and abuse.
Most people who take Restoril will notice an improvement in their insomnia symptoms after as little as one week. The pills are designed to induce sleepiness for at least seven or eight hours, and those who wake up too soon may experience difficulty remembering or concentrating on things until the effects wear off.
Estazolam is a short-term insomnia medication used to help patients fall asleep and remain asleep throughout the night. It is also often used to induce sleep prior to medical operations. Estazolam was first created by Upjohn in the 1970s, and is currently marketed under the names ProSom in the U.S. and Eurodin overseas.
The standard maximum dose for adults is 2 mg per day, but a dosage of 1 mg or 0.5 mg will be sufficient for most geriatric or debilitated patients. The ‘hangover’ effect is particularly strong with ProSom, and those who take this medication may struggle with work or operating vehicles the following day. Pregnant women and people with liver failure or disease should not use estazolam. It also interacts with other medications, including HIV protease inhibitors, sodium oxybate (used to treat excessive daytime sleepiness), and clozapine (used to treat schizophrenia).
In addition to the side effects listed above, some people who take ProSom report severe side effects related to their mood and psychological well-being. These include increases agitation and aggression, and changes in regular behaviors.
Finally, we’ve included two medications commonly prescribed for insomnia that fall outside the z-drug and benzodiazepine classes.
Ramelteon is classified as a melatonin agonist, which means that it acts on melatonin receptors in the brain; melatonin is a hormone produced in the pineal gland that helps regulate natural 24-hour sleep cycle, also known as circadian rhythm. It does not act on benzodiazepine receptors or other GABA receptors, resulting in less of a hypnotic effect. Introduced as Rozerem by Takeda Pharmaceuticals, Ramelteon is relatively new to the market; it received FDA approval in 2005. The current patent is set to expire in Spring 2017, and a generic version of Rozerem has already been approved by the FDA.
Due to its mechanism of action and minimal hypnotic effects, ramelteon has not been shown to cause dependency, and no potential for abuse has been reported. Ramelteon is not a controlled substance, but is currently available by prescription only. Physicians will typically direct patients to take one tablet (8 mg) half an hour before they plan to sleep.
The most common side effects are dizziness and sleep, and few adverse health effects have been reported. In most cases, insomnia symptoms will improve after seven to 10 days of regular use. Studies are still being conducted to determine if ramelteon is more effective than standard melatonin supplements, which are available over-the-counter and produce a similar, sleep-inducing effect.
Suvorexant is classified as a sedative-hypnotic, as well as an orexin agonist because it acts on orexin receptors. Orexin (also known as hypocretin) is a neuropeptide that regulates feelings of wakefulness, arousal, and hunger. Suvorexant essentially blocks orexin neuropeptides from bonding, suppressing wakefulness and inducing sleepiness in the process. Suvorexant is manufactured by Merck & Co., and marketed under the name Belsomra. The newest medication on our list, Belsomra received FDA approval in 2014 and became available in the U.S. one year later.
Belsomra is available in 10 mg tablets, with a maximum recommended dosage of 20 mg per day. Like Rozerem, Belsomra should be taken 30 minutes before bedtime, and patients should not take the drug unless they plan to sleep for at least seven hours. Belsomra has been shown to produce limited dependency, and the potential for abuse has been noted. As a result, suvorexant is classified as a controlled substance. People with liver failure or impairment should not take Belsomra, and studies have linked the drug to fetal health problems during pregnancy.
An important consideration for Belsomra is that many people who take the drug experience little to no improvement for their insomnia symptoms. In some cases, patients have reported the opposite — symptoms like night terrors, frequent nightmares, and/or lucid dreams.
Mixing drugs without the knowledge and approval of a licensed physician is unwise, and may result in serious health risks including death. Mixing drugs refers to taking more than one prescription drug at once, as well as taking prescription drugs with over-the-counter medications. If a physician is unavailable, consult with a licensed pharmacist.
Sedatives and hypnotics prescribed for sleep problems are especially noteworthy because they reduce metabolic activity, or the chemical reactions that allow human bodies to function properly. Metabolic levels falling too quickly may result in coma or death. Fortunately, the medications available today are considered much safer than barbiturates and other drugs prescribed to treat insomnia in the past. Still, it is critical to carefully follow all instructions on the label — and to consult your physician immediately if there are any lingering questions. Never increase daily dosage without doctor approval, even for over-the-counter medications.
Alcohol is another important consideration because it is a depressant that often lowers respiration. Taking alcohol with any form of medication — including insomnia drugs — is quite risky, and can lead to fatal consequences. For more information on the dangers of mixing alcohol and medicine, please visit the report on harmful interactions published by the National Institute on Alcohol Abuse and Alcoholism, a division of the National Institutes of Health (NIH).
If you experience adverse reactions to any sort of medication, you can call the FDA’s Medwatch hotline at 1-800-FDA-1088. You can also call the National Poison Control Center’s hotline at 1-800-222-1222 if you or someone you know experiences an adverse reaction or drug overdose.
For more information on prescription sleep medication, please visit these Tuck.com links below: