By Naomi Carr

Last updated: 21 March 2024 & medically reviewed by Morgan Blair

Doxepin is a tricyclic antidepressant that is prescribed to treat anxiety, depression, insomnia, and skin conditions. It is available as generic and brand-name medications, in various strengths and forms. Doxepin can cause side effects, particularly in higher doses, and should be used exactly as prescribed to prevent adverse effects. 

Doxepin (Silenor)

What is doxepin?

Doxepin is a tricyclic antidepressant (TCA) that was first approved by the FDA in 1969 for the treatment of major depressive disorder (MDD). It has since been approved for various other uses and is available in varying strengths. Doxepin can be prescribed as an oral capsule, tablet, or liquid, and as a topical cream.[1]

Doxepin impacts the levels of neurotransmitters serotonin and norepinephrine and blocks various receptors that impact the central nervous system, all of which contribute to its antidepressant effects and effects on a range of other symptoms.[1][2]

What is doxepin used for?

In low doses, doxepin is approved for use in the treatment of insomnia.[3]

In higher doses, doxepin is approved for use in the treatment of anxiety, major depressive disorder, and symptoms of anxiety or depression that occur in the context of alcoholism, organic disease, or bipolar disorder.[4]

As a cream, doxepin is used to treat itching caused by skin conditions such as eczema.[5]

What are the brand names for doxepin?

Brand names for doxepin include:[5][6][7]

  • Silenor: Oral tablets used to treat insomnia

  • Sinequan: Oral capsules and liquid, used to treat depression and anxiety (discontinued)

  • Prudoxin: Cream, used to treat itching caused by eczema

  • Zonalon: Cream, used to treat itching caused by eczema

What doses does doxepin come in?

Silenor is available as 3mg and 6mg tablets. This is typically prescribed as a dose of 3mg or 6mg to be taken once per day, 30 minutes before bed.[3]

Sinequan or generic alternatives are available as 10mg, 25mg, 50mg, 75mg, 100mg, and 150mg oral capsules. A typical dose is 75mg-150mg per day, usually split into 1-3 doses. Individuals with milder symptoms may require a smaller dose of 25-50mg per day, while those with more severe symptoms may require up to 300mg per day.[4][7]

Concentrated liquid solutions are available at 10mg/mL. Doses should be diluted in water or other non-carbonated soft drinks. Liquid medication should be measured carefully using a syringe or spoon specifically designed for this purpose.[7]

It is important to always take doxepin exactly as prescribed. Taking too much, missing doses, or taking it at the wrong times can cause adverse effects. 

Doxepin side effects

When starting a new medication, it is common to experience side effects. Typically, these will only last a short period and will reduce without intervention. If side effects persist or become severe, it is advised to consult a medical professional.

Low doses of doxepin, such as those prescribed for insomnia, are likely to cause fewer side effects than higher doses, such as those prescribed for depression and anxiety.[3][4]

Common side effects of Silenor include:[3][6]

  • Nausea

  • Drowsiness

  • Dizziness

Severe side effects of Silenor include:[3]

  • Engaging in behaviors and actions while not fully awake, such as driving, walking, or daily activities. This can cause a risk of accidents and potential harm.

  • New or worsening depression and suicidal thoughts. The risk of this is very low with Silenor but may still occur.

  • Oversedation

Higher doses of doxepin are more likely to cause side effects. Common side effects of Sinequan and generic doxepin prescribed for depression and anxiety can include:[4][7]

  • Nausea

  • Vomiting

  • Constipation

  • Diarrhea

  • Headache

  • Drowsiness

  • Fatigue

  • Changes in appetite and weight

  • Dry mouth

  • Excessive thirst and urination

  • Difficulty urinating

  • Sexual dysfunction

  • Sweating

  • Chills

  • Hair loss

  • Galactorrhea (breast discharge)

Severe side effects of Sinequan and generic doxepin in higher doses include:[4][7]

  • Irregular, rapid, or slowed heartbeat

  • Unexplained bleeding or bruising

  • Yellowing of the eyes or skin

  • Rash, hives, itchiness, or swelling

  • Changes in vision or eye pain, redness, or swelling

  • Hallucinations

  • Seizures

  • Mood changes, including anxiety, agitation, aggression, hostility, irritability, panic attacks, mania, hypomania, depression

  • New or worsening suicidal ideation (the risk of this is higher in individuals under 24 years old)

Is doxepin addictive?

Doxepin is not considered to be an addictive substance and low doses are unlikely to cause a physical dependence. All forms of doxepin are considered a low abuse risk, although abuse and overdose can still occur.[1][8]

Higher doses may cause mild withdrawal symptoms or discontinuation syndrome when the medication is stopped. As such, it is recommended to gradually reduce the dosage rather than stopping abruptly. If it is safe and appropriate to stop taking doxepin, the prescribing doctor will advise on safe medication cessation.[4]

Doxepin interactions

Several medications and substances can cause interactions if combined with doxepin. This can increase the risk of side effects or reduce the therapeutic impact of the medication.

Interactions include:[1][3][4][7]

  • MAOIs: Monoamine oxidase inhibitors (MAOIs) are a type of antidepressant medication, including medications such as selegiline, phenelzine, and isocarboxazid. Using MAOIs at the same time as doxepin can cause severe or even fatal effects. It is recommended to wait at least two weeks between doses of MAOIs and doxepin. The prescribing doctor will advise exactly how long to wait between MAOI discontinuation and starting doxepin treatment.

  • Cimetidine: Cimetidine is a medication used to treat gastric conditions such as reflux, ulcers, and heartburn. Combining cimetidine and doxepin can cause severe side effects, such as urinary retention and blurred vision, and may decrease the therapeutic effect of doxepin.

  • CNS depressants: Central nervous system depressants are all medications and substances that cause sedating effects, such as opioids, benzodiazepines, and other tranquilizers or hypnotics. Typically, these medications are used to treat anxiety and sleep disorders. Combining CNS depressants with doxepin can cause oversedation, confusion, cardiac issues, and breathing difficulties, so they should be avoided or used with caution.

  • Sedating antihistamines: Similarly, antihistamines with a sedating effect can cause oversedation and breathing difficulties when combined with doxepin.

  • Alcohol: Alcohol consumption should be avoided while taking doxepin as it can increase the risk of overdosage, oversedation, and risk of accidents.

  • Tolazamide: Tolazamide is a medication used to treat Type 2 diabetes. Combining tolazamide and doxepin can increase the risk of hypoglycemia.

  • Antidepressants: Combining other antidepressants, such as SSRIs, SNRIs, MAOIs, and tricyclic antidepressants, with doxepin, can increase the risk of serotonin syndrome, which is caused by a dangerously high level of serotonin. It is advised to gradually taper doses when changing antidepressant medications.

It is important to discuss all medications, prescribed or over-the-counter, with the prescribing doctor before starting a new medication. It is also advised to discuss any alcohol or substance use before commencing doxepin treatment, as adverse effects can occur.