Medically reviewed by Mary Lucas, RN
Written by Our Editorial Team
Last updated 10/23/2020
Dealing with insomnia can be a stressful, frustrating experience. Thankfully, a range of safe and effective medications are available to help you fall asleep easier, stay asleep for longer and feel better after waking.
One of these medications is doxepin. Originally developed as a treatment for major depressive disorder, doxepin (at much lower doses) is also highly effective at treating sleep disorders such as insomnia.
If you find it difficult to stay asleep, frequently wake up in the middle of the night or just don’t feel refreshed after waking up in the morning, doxepin may be able to help you maintain better sleep habits and enjoy a higher quality of life.
Below, we’ve explained what doxepin is and how it works as a medication for sleep. We’ve also looked at the science behind doxepin, as well as how it compares to other common medications prescribed to treat insomnia and other sleep issues.
Doxepin is a tricyclic antidepressant medication. It was first approved in the 1960s by the FDA as a treatment for depression.
After extensive scientific studies showed that it was also effective at treating sleep disorders, the FDA approved doxepin in 2010 as a treatment for insomnia.
As well as depression and insomnia, doxepin is also used to treat certain anxiety disorders and skin conditions. It’s most commonly used in tablet form, with topical doxepin cream used to treat skin rashes and disorders such as hives, atopic dermatitis and lichen simplex chronicus.
Doxepin is available as a generic medication. It’s sold under a wide range of brand names in the United States and abroad. You may have seen doxepin for sale under brand names like Silenor®, Sinequan®, Quitaxon® and Aponal®.
In the United States, Silenor is the low-dose version of doxepin that’s typically used for insomnia.
As a tricyclic antidepressant, doxepin works by affecting the way your brain absorbs and deals with certain chemicals, such as norepinephrine and serotonin.
Doxepin induces drowsiness by affecting the body’s histamine receptors, which play a major role in managing the sleep-wake cycle.
More specifically, doxepin is an antagonist of the H1 receptor, which is responsible for mediating your feelings of wakefulness and arousal. By binding to the H1 receptor, doxepin limits the effects of histamine in the body, causing users to feel drowsy and promoting sleep.
Studies of doxepin show that it can improve sleep quality in people with insomnia when taken at a low dose, with relatively few side effects compared to other sleep medications.
Several studies of doxepin show that it can increase total sleep time and reduce the risk of waking up during the night in people with insomnia.
For example, a 2013 scientific review of doxepin, which involved analysis of several large-scale studies, found that low doses of doxepin were effective at managing both chronic and transient (short-term, non-recurring) insomnia.
This review also noted that doxepin was a “safe and non-habit forming option” for treating sleep difficulties.
Another scientific review from 2014 found that 3mg and 6mg doses of doxepin helped to reduce waking after sleep onset and increase the total amount of time spent asleep in older adults with difficulty sleeping.
Another systematic review, this time from 2015, looked at nine placebo-controlled doxepin trials and concluded that that low-dose doxepin produced a small to medium effect for sleep duration and sleep maintenance when compared to a non-therapeutic placebo.
Numerous smaller studies have also found that doxepin is effective at treating insomnia. In one study from 2007, researchers found that even very small doses of doxepin (1mg, taken prior to sleep) helped to improve sleep in people with chronic insomnia.
In short, doxepin’s effectiveness as a sleep medication is backed up by a sizable body of evidence, both from large and small-scale studies.
Many sleeping pills, including prescription medications used to prevent insomnia, are associated with early-morning drowsiness and headaches — symptoms that are occasionally referred to as a sleeping pill “hangover.”
These side effects are common with older sleeping pills and can range from a minor annoyance to quite a serious issue.
For example, the FDA has urged health care professionals to caution people who are prescribed zolpidem (Ambien®) about the risk of next-morning impairment, which could affect activities such as driving or operating machinery.
Many benzodiazepines used to treat insomnia, such as alprazolam (Xanax®), are also linked to next-morning impairment and hangover-like side effects.
Doxepin’s effects as a sleep medication last for about seven hours, meaning you’ll feel tired and drowsy during this time after taking the medication. Because of this, you shouldn’t use doxepin if you need to wake up after less than eight hours of sleep.
However, most studies of doxepin show that after the medication’s effective period is finished, it typically does not cause the next-morning drowsiness or other common sleeping pill “hangover” symptoms that are associated with other insomnia medications.
In the 2013 review we mentioned above, the researchers noted that doxepin “does not cause daytime sedation (no next-day sedation).” Likewise, the 2015 review concluded that there was “no significant next-day residual effect” associated with low-dose doxepin use.
The 2007 study linked above also concluded that doxepin had “no significant hangover/next-day residual effects.”
Put simply, doxepin doesn’t appear to cause significant next-day drowsiness or hangover effects that are common with older sleep medications, provided it’s used at the recommended dose and enough time is allowed to pass before waking up.
As a popular sleeping medication, doxepin is often compared to zolpidem, the active ingredient in Ambien.
Although doxepin and zolpidem are both used to treat insomnia, there are a few key differences between these two medications, from how they work within the body to the effects they have on sleep and alertness. There’s also a significant difference in side effects.
Some of the most noticeable differences between doxepin and zolpidem are the ways in which each drug affects sleep latency, total sleep time and next-morning alertness.
Zolpidem works by reducing the amount of time required to fall asleep. In short, it induces sleep, allowing you to fall asleep faster. This makes it an effective treatment if you have difficulty falling asleep and often spend a long time awake in bed before dozing off.
For example, an eight-month study of people with insomnia found that zolpidem reduced sleep latency (the amount of time it takes to fall asleep). An older study from 1991 also reached the same conclusion, noting that zolpidem decreased time awake before persistent sleep.
Because of this effect, zolpidem is a popular option for treating insomnia in people who find it difficult to fall asleep in a normal amount of time.
Doxepin, in contrast, is more effective at helping you stay asleep and sleep for longer than it is at helping you fall asleep quickly.
Most studies, including several of the reviews mentioned above, note that doxepin doesn’t have a significant effect on sleep latency. In this 2014 review, the researchers noted that doxepin did not cause any improvement in latency to persistent sleep compared to a placebo.
However, some studies have found that doxepin does improve sleep latency in people affected by insomnia. For example, this study from 2010 found that doxepin improved both sleep quality and latency to sleep onset (time to fall asleep) in older adults with chronic primary insomnia.
In short, while there’s some evidence that doxepin may reduce sleep latency, it doesn’t appear to be as effective for reducing the amount of time required to fall asleep as zolpidem.
Zolpidem and doxepin both increase total sleep time, meaning you may sleep for longer after using either medication.
In the eight-month study listed above of zolpidem involving 91 people with insomnia, researchers found that nightly use of zolpidem resulted in an increase in overall sleep time.
Studies of doxepin have produced similar results. This 2014 review concluded that doxepin can improve sleep duration in the last third of the night, while this 2013 review concluded that even mild doses of doxepin are effective at improving total sleep time.
Put simply, zolpidem and doxepin are both effective at increasing total sleep time in people with insomnia.
As we mentioned above, studies of doxepin show that it usually doesn’t cause any noticeable next-day drowsiness. Doxepin’s effects on alertness and energy tend to last for seven to eight hours, after which the medication wears off with few or no lingering effects the next day.
Zolpidem, on the other hand, is often associated with drowsiness, tiredness and a general lack of alertness that can last into the next morning after it’s used.
The FDA label for Ambien, the most widely-used drug containing zolpidem, warns of the risk of feeling drowsy in the morning after using this medication. It also warns against driving or doing other dangerous activities after using zolpidem unless fully awake.
If you suffer from insomnia and need to be highly alert early in the morning, such as to drive to your workplace or operate machinery, doxepin (or, for mild insomnia, a non-prescription sleep aid such as melatonin) may be a more suitable treatment for you.
Several hypnotic sleep medications, including zolpidem, are associated with unusual nighttime behavior. The FDA label for Ambien also mentions that “Complex sleep behaviors including sleep-walking, sleep-driving and engaging in other activities while not fully awake may occur following use of AMBIEN”, often with the user having no memory of the activity occurring.
The label specifically mentions driving a car (“sleep-driving”), making and eating food, talking on the phone, having sex and sleep-walking as late-night activities reported by Ambien users.
If you use zolpidem for insomnia and notice any unusual nighttime behavior, you should stop the medication immediately and discuss this with your healthcare provider as soon as possible.
As a sedative, doxepin has the potential to affect your level of alertness, meaning you may not be fully aware of your behavior during the nighttime.
However, because doxepin doesn’t doesn’t affect the GABA-A receptor, it has shown no association with abuse or addiction, withdrawal, or the complex sleep behaviors as seen in medications like zolpidem.
Used for sleep conditions such as insomnia at the prescribed dose, doxepin is a safe, effective medication that’s less likely to cause side effects than many other sleeping pills.
Like other medications, doxepin has the potential to cause certain side effects. It’s also possible for doxepin to interact with other medications.
Before discussing specific side effects of doxepin, it’s important to note that doxepin is available in a range of dosages to treat different conditions.
For example, doxepin is prescribed for major depressive disorder at dosages ranging from 25mg to 300mg per day. Used for insomnia and other sleep issues, it’s prescribed at a much lower dose, typically in the 3mg to 6mg range.
This means that data on side effects for high doses of doxepin prescribed for major depressive disorder, anxiety and other conditions may not be fully comparable if you use doxepin to treat insomnia.
Used for insomnia at a dose of 3 to 6mg, the most common side effects of doxepin are drowsiness and sedation, upper respiratory tract infection and nausea. In trials of doxepin, a small percentage of users reported nausea, hypertension and gastroenteritis.
Taken at a higher dosage, doxepin may cause other side effects, including several serious ones. We’ve listed these and provided more information in our complete guide to doxepin side effects.
Although abnormal nighttime behavior is not common with doxepin, hypnotic medications have the potential to lead to behaviors such as sleep-walking and “sleep-driving.” You have a higher risk of doing these activities if you drink alcohol or combine doxepin with other medications.
If you engage in any abnormal nighttime behavior while using doxepin, you should stop taking the medication immediately and contact your doctor as soon as possible.
Like other tricyclic antidepressants, it’s possible to overdose on doxepin. If you or someone you know may have taken more than the recommended dosage of doxepin, call 911 or the national toll-free Poison Help hotline (1-800-222-1222) as soon as possible.
Doxepin is a safe, easy-to-use and effective medication for treating insomnia. Studies show that it can improve general sleep quality and increase the total amount of time people with insomnia spend asleep each night.
However, doxepin doesn’t appear to have such a strong effect on sleep latency, meaning it may not help you fall asleep faster if you’re prone to spending a long time awake late at night.
Unlike many other sleeping pills, doxepin doesn’t appear to cause early-morning drowsiness or any hangover-like side effects. This may make it a better option than other sleep medications if you need to be fully alert early in the morning after waking up.
Considering doxepin? Our complete guide to prescription sleeping pills compared doxepin to a range of other medications prescribed to treat insomnia. You can also learn more about treating insomnia in our detailed guide to why insomnia happens and how to treat it.