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Side Effects of Doxepin (Silenor, Sinequan, Adapin)


Description: Doxepin is a tricyclic antidepressant medication that is used to treat depression, anxiety, and insomnia. Doxepin is marketed under the brand names Adapin, Silenor, and Sinequan. This article focuses solely on the side effects of doxepin in its topical form, specifically Silenor side effects, Sinequan side effects, and Adapin side effects.

Serious Side Effects of Doxepin: Suicidal Behavior

When Adapin, Silenor, and Sinequan, or the generic doxepin, are used to treat patients with mood disorders, particularly individuals suffering from major depressive disorder or bipolar disorder, there is a temporarily increased risk of suicide and suicidal thoughts and behaviors. Patients suffering from these mental health conditions should be closely monitored while taking doxepin, especially during the first several weeks of treatment.


Adapin, Silenor, Sinequan, and the generic doxepin are metabolized by the liver. This means that the liver is the principal organ responsible for breaking down the drug for excretion from the body. As such, physicians typically reduce the dosage of doxepin for individuals who suffer from liver disease, recommending a 3 mg dosage instead of the typical 6 mg dosage, at least initially.

Common Side Effects of Doxepin

The most common doxepin side effects in people using the drug to treat insomnia include sedation, high blood pressure, upper respiratory tract infection, and nausea.

Drug Interactions: MAO inhibitors

People who take an MAO inhibitor should not also take Adapin, Silenor, and Sinequan or generic doxepin. When switching between medications, the patient should stopped taking the MAO inhibitor at least two weeks prior to starting doxepin. Taking MAO inhibitors in conjunction with Adapin, Silenor, Sinequan, or the generic doxepin may cause the accumulation of unsafe levels of serotonin (also known as “serotonin syndrome”). This adverse effect may be even worse in people with unusual liver enzyme activities (see below).

How the Liver Metabolizes Doxepin

Both branded and generic forms of doxepin are broken down by several liver enzymes called cytochrome p450s. Doxepin is a major substrate of CYP2D6 and minor substrate of CYP1A2, CYP2C19, and CYP3A4. Consequently, doxepin may interfere or interact with other substances or medications that are metabolized by these enzymes. Metabolism by these liver enzymes may also cause negative interactions between doxepin and other drugs.

Individuals with abnormally high or low CYP2D6 activity may develop abnormally low or high levels of doxepin in the blood and body. In other words, doxepin may be broken down more quickly or more slowly than in the average person. This metabolism can be the source Silenor side effects.

Understand Your Risk for Side Effects with the Rxight® Genetic Test

People don’t necessarily know if they have low, normal, high, or ultra-high liver enzyme activity. Rxight® is one of the leading providers of CLIA pharmacogenetic testing. Rxight® offers a simple, accurate way to test the activity of your liver enzymes. This information can empower you and your doctor to make better treatment decisions regarding Adapin, Silenor, and Sinequan and generic doxepin.

Contributors to this Article:
Michael Sapko, MD, PhD; Deborah Kallick, PhD, Medicinal Chemistry

Read more about Rxight® Genetic Testing for Medication