Medically reviewed by Mary Lucas, RN
Written by Our Editorial Team
Last updated 10/27/2020
First approved by the FDA as a treatment for depression in 1969, doxepin is a widely prescribed medication. As of 2017, there were millions of prescriptions for doxepin in the United States alone.
Doxepin comes in a variety of forms. When it’s used to treat depression and anxiety, it’s usually prescribed as an oral tablet or capsule.
For insomnia, it’s approved under the brand name Silenor and is also prescribed as a tablet or capsule, albeit at a lower dosage compared to the forms used to treat depression or anxiety.
For skin conditions, such as hives and atopic dermatitis, doxepin is typically used as a topical cream.
Below, we’ve explained more about how doxepin works as a medication.
We’ve also looked at the key differences between how doxepin is used to treat conditions such as major depressive disorder and anxiety, and how it’s used at a lower dosage to treat insomnia.
As we mentioned above, doxepin is used to treat several different conditions. Because each of the conditions doxepin treats is unique, we’ve looked at each individually below.
Doxepin is a tricyclic antidepressant. Like other tricyclic antidepressants, it works by inhibiting the reuptake, or reabsorption, of the neurotransmitters serotonin and norepinephrine.
Serotonin and norepinephrine both play significant roles in numerous important brain and body functions.
You may have heard of serotonin as the brain’s “feel-good” chemical. Although serotonin’s role in the brain and body is more complicated than this, it does play a major role in regulating your mood, your appetite, your memory and your ability to learn new information.
Serotonin also helps to reduce feelings of depression and regulate feelings of anxiety. Outside the brain, it has a diverse range of other functions, from helping to manage your digestive tract to assisting in processes such as bone health and blood clotting.
Norepinephrine, on the other hand, is responsible for keeping you alert, focused, energetic and vigilant. Like serotonin, norepinephrine plays a major role in regulating your mood and ability to focus on specific tasks throughout the day.
People with depression are thought to have low serotonin and norepinephrine levels. Doxepin works by inhibiting your brain’s reuptake of these neurotransmitters, increasing the amount of serotonin and norepinephrine that can circulate throughout your brain and body.
As an older depression medication, doxepin is sometimes prescribed as an alternative to newer SSRIs. To treat depression, doxepin is typically prescribed at a dosage of 25mg to 150mg. In some cases, doxepin may be prescribed at a maximum dosage of up to 300mg per day.
To treat anxiety, doxepin is typically prescribed at a similar dosage range.
Like other antidepressants, doxepin can cause side effects. Some of these are minor, although in some cases, doxepin can cause severe side effects. This medication has a boxed warning from the FDA, indicating that it may cause serious or life-threatening side effects.
We’ve listed and explained these side effects in more detail in our full guide to the side effects of doxepin.
In addition to affecting the serotonin and norepinephrine reuptake process, doxepin has certain effects on the body’s histamine system.
More specifically, doxepin is known to block the body’s H1 histamine receptors. Histamine is an important chemical for regulating your body’s sleep-wake cycle, sending signals to your brain to keep you alert, awake and energetic.
By blocking your body’s H1 receptors, doxepin can reduce the effects of histamine in your brain and body, causing you to feel drowsy and making it easier for you to fall asleep.
Interestingly, it only takes a tiny amount of doxepin to trigger this effect. To treat depression, it’s common for doxepin to be prescribed at a dosage of 75+mg per day. For insomnia, doxepin is usually prescribed at a dosage of just 3mg to 6mg per day.
Although doxepin can still cause side effects when it’s used at a low dose to treat insomnia, the lower dosage means that severe side effects are less common than when doxepin is taken at a higher dosage for depression or insomnia.
Because of this, low-dose doxepin medications designed to treat insomnia do not have a boxed warning from the FDA.
The FDA approved doxepin as a treatment for insomnia in 2010, and it’s available under the brand name Silenor.
Numerous studies of doxepin have found that it works well as a sleep aid, helping to increase sleep duration and sleep quality.
We’ve dug into these studies and more of the science behind doxepin as an insomnia treatment in our guide to doxepin and sleep.
Doxepin is a well-studied, widely-used medication that’s been prescribed for decades. However, as with other prescription medications, it can cause a range of potential side effects.
As we mentioned above, certain serious side effects from doxepin are more common when this medication is used to treat depression or anxiety than insomnia.
Common side effects of doxepin at the dosages given for depression and anxiety include:
Changes in taste perception
Nausea and/or vomiting
Due to doxepin’s effects on alertness, you should not drive, operate machinery or engage in any other activities that require optimal alertness after using this medication.
Doxepin at the doses given for treatment of depression and anxiety can also cause potentially several severe side effects.
These include suicidal thoughts, worsened feelings of anxiety, panic attacks and impulsive behavior. Doxepin is also associated with some urinary retention side effects, such as an inability to urinate and/or bloating.
If you experience any of these serious side effects while using doxepin, contact your healthcare provider as soon as possible for assistance.
Seek immediate medical attention or call 911 if you or a loved one experience life-threatening side effects while using doxepin.
Our complete guide to doxepin side effects goes into more detail on these side effects, with data on how frequently each potential side effect can occur.
Doxepin can also interact with other medications, including medications used to treat heartburn and other stomach issues, antifungal medications, heart rhythm drugs and medications used to treat diabetes and kidney disease, to name a few.
Doxepin may also interact with other antidepressants. In particular, doxepin can cause serious, life-threatening side effects when used with monoamine oxidase inhibitors (MAOIs), which are used to treat depression and certain anxiety disorders.
If you use any other medications, make sure to inform your healthcare provider before using doxepin or any other tricyclic antidepressant.
Drinking alcohol while under the effects of doxepin may lead to increased drowsiness and lack of alertness. As such, you should not drink alcohol while using doxepin.
If you’re considering doxepin as a treatment for major depressive disorder or anxiety, it’s best to talk to your doctor.
Depending on your symptoms and needs, they’ll be able to advise you about whether doxepin is the best treatment option for you.
Our complete guide to doxepin and sleep goes into more detail about how you can use doxepin to treat insomnia and other sleep difficulties, as well as how it compares to other common sleep aids on the market.