Doxepin

This article provides an overview of doxepin, including its beneficial mechanisms, uses and indications, side effects, and interactions.

Key Takeaways

• Doxepin is a type of tricyclic antidepressant. It increases the activity of serotonin and norepinephrine in the brain, and decreases the effects of other neurotransmitters.
• Oral doxepin is most often used for insomnia, anxiety associated with depression, and depression, in the form of tablets, capsules, or a solution. Dosing starts low and is increased gradually as needed.
• There are numerous possible side effects, drug interactions, and precautions with doxepin, some of which are severe.

Understanding Doxepin

Doxepin is a prescription medication that belongs to the class of tricyclic antidepressants (TCAs). It was initially approved by the US Food and Drug Administration (FDA) in 1969 for treating major depressive disorder (MDD). Today, doxepin is primarily used for depression, anxiety associated with depression, and trouble sleeping. ^[1]

How Does it Work?

It is thought that individuals with depression, anxiety, and other mental health conditions have certain abnormalities with regards to neurotransmitter production and/or function. Therefore, doxepin may help improve mental health by supporting certain neurotransmitters.

Doxepin primarily works by increasing levels of serotonin and norepinephrine in the brain, which are both neurotransmitters vital for brain function and mental health. For example, serotonin is tightly involved in the regulation of mood, appetite, sexual function, sleep, and anxiety, while norepinephrine plays important roles in mood, energy, arousal, and stress. ^[1]

Doxepin also blocks histamine, adrenergic, and muscarinic receptors, which partially inhibits the effects of histamine, adrenaline, and acetylcholine, respectively. ^[1]

Brand Names

There are several brand names of doxepin, including: ^[2]

• Silenor®
• Prudoxin®
• Sinequan®
• Zonalon®

What is Doxepin Used For?

Doxepin is approved to treat several conditions, including: ^{[1] [2] [3]}

• Depression
• Insomnia
• Anxiety and/or depression associated with:
• Alcoholism
• Organic disease
• Psychotic depressive disorders with anxiety, including:
• Involutional depression
• Manic-depressive disorders

In these instances, doxepin helps relieve several important symptoms, especially anxiety, tension, depression, sleep disturbances, guilt, lack of energy, fear, apprehension, worry, and somatic (physical) symptoms and complaints. ^[3]

Additionally, topical formulations of doxepin are approved to treat epidermal pruritus in adults diagnosed with atopic dermatitis or lichen simplex chronicus. Epidermal pruritus is a skin condition characterized by itchiness and irritation, causing a strong desire to scratch. Doxepin primarily works for skin itching due to its antihistamine properties. ^[1]

Off-Label Uses

Doxepin is used off-label for several conditions and symptoms, including: ^[1]

• Neuropathic pain
• Chronic pain
• Migraines
• Urethral irritation and dysuria
• Anxiety

Doxepin Side Effects

There are a significant number of possible side effects with doxepin. Possible side effects of doxepin include: ^{[1] [3] [4] [5]}

• Sleepiness/drowsiness
• Sedation
• Dry mouth
• Constipation
• Dizziness
• Headache
• Lightheadedness
• Nightmares
• Nervousness
• Irritability
• Nausea
• Vomiting
• Diarrhea
• Taste disturbances
• Changes in libido
• Tinnitus
• Weight gain
• Sweating
• Fatigue
• Weakness
• Flushing
• Hair loss
• Jaundice
• Chills
• Urinary retention
• Breast swelling or tenderness (in both males and females)
• Testicular swelling
• Erectile dysfunction

(There may be other possible side effects, as this is not an exhaustive list.)

The multitude of possible side effects is due, in part, to the fact that doxepin affects many different receptors and systems in the body. It’s important to tell your doctor or healthcare provider right away if you notice any side effects when taking doxepin.

Rare and Severe Side Effects

There are also several less common side effects of doxepin, some of which may be severe and possibly life-threatening.

Rare side effects of doxepin include: ^{[1] [3] [4] [5]}

• Hypo- or hypertension (low or high blood pressure)
• Tachycardia (rapid heart rate)
• Prolonged QT interval: This is a change in the heart’s rhythm, which can cause fainting, seizures, and a heart attack or sudden cardiac death in severe instances.
• Worsening of depression and increased risk of suicidal ideation: This is most common in children, adolescents, and young adults under the age of 25.
• The risk is greatest when someone initially starts taking doxepin and when there is a change in dosage
• Various central nervous system (CNS) effects, such as:
• Hallucinations
• Delusions
• Confusion
• Disorientation
• Numbness
• Paresthesia
• Extrapyramidal symptoms: This is a group of movement disorder-related symptoms, including:
• Tremors
• Muscle spasms
• Restlessness/inability to sit still
• Tardive dyskinesia (involuntary movements, especially of the eyes, mouth, and/or tongue)
• Stiff or rigid muscles

Addiction Potential

Doxepin is not considered addictive, and it is not a controlled substance. Doxepin does not cause euphoria after use, nor is it associated with drug cravings, which are both the key features of addiction. However, long-term use of doxepin may cause dependence, which can lead to withdrawal symptoms, especially if it is suddenly stopped. ^[3]

Doxepin Dosage

The dosage of doxepin varies based on the intended use. Specific therapeutic doses of doxepin for adults are as follows: ^[1]

• Insomnia: 3 to 6 mg daily, about 30 minutes before bedtime
• Usually short-duration treatment, less than 4 to 8 weeks
• MDD/depression: Starting dose is usually 25 to 75 mg daily at bedtime. May reach as high as 100 to 300mg daily
• Anxiety associated with depression: Starting dose typically 25 to 75mg daily at bedtime. May reach as high as 100 to 300mg per day. It may be divided into 2 or 3 doses

Methods of Administration

Doxepin is available in oral tablets, capsules, and solutions. The specific strengths of doxepin formulations are: ^[1]

• Oral tablets: 3 mg and 6 mg
• Oral capsules, 10 mg, 25 mg, 50 mg, 75 mg, 100 mg, and 150 mg
• Oral solutions: 10mg/mL solution

Doxepin is also formulated as a topical cream, which is used for skin itching. The topical cream form is not used for mental health-related disorders or symptoms.

Precautions

There are several precautions to consider with doxepin. Understanding these precautions is important to assess if doxepin is right for you. Of course, always talk with your doctor. He or she will determine if doxepin is the right medication for your needs, and if the benefits outweigh the risks.

The following populations require extra caution when using doxepin: ^{[1] [3]}

• Individuals with hepatic (liver) impairment: A lower dose may be needed
• Pregnant women: A lower dose may be needed, or avoidance altogether
• Breastfeeding women: Doxepin use is not recommended
• Children: Doxepin is not recommended for children under 12
• Older adults: Doxepin may need to be avoided in adults 65 and over. If used, the starting dose should be low

Doxepin can lead to unusual behavior changes, worsening depression, and the emergence of suicidal symptoms. It’s essential to watch out for any of these behaviors or mood changes, including aggression, irritability, panic attacks, impulsivity, insomnia, and anxiety. ^{[1] [3]}

Doxepin may also cause serotonin syndrome, especially when combined with other drugs that increase serotonin levels. Symptoms of serotonin syndrome include dilated pupils, rapid heart rate, confusion, agitation, sweating, and muscle spasms, among others. In severe cases, it can lead to seizures, coma, and death. ^{[1] [4]}

Doxepin can have dangerous effects on the body at doses higher than the therapeutic range. Doxepin has been shown to cause cardiac arrest and seizures in overdose, both of which can be lethal. It is important to take this medication exactly as prescribed, never exceeding the prescribed doses. It is also important to report any side effects you are experiencing to your prescriber to help avoid any risks associated with higher doses. ^{[3] [4]}

Some individuals who take doxepin experience odd behaviors during sleep, such as driving, walking, having sex, making and/or eating food, and using the phone. They often do not remember doing these activities the next morning. ^{[4] [6]}

Doxepin can cause drowsiness, which may make it unsafe to drive, operate machinery, or perform complex tasks. ^[3]

In addition, doxepin can also cause mild pupil dilation. In certain individuals, this can lead to angle-closure glaucoma. ^[3]

Harmful Interactions

Doxepin can affect the way other medications work, and vice versa. Due to its action on many areas of the body, numerous drug interactions with doxepin are possible.

Doxepin may interact with the following medications and substances: ^{[1] [3] [4] [5]}

• Monoamine oxidase inhibitors (MAOIs) (e.g., selegiline, phenelzine)
• Selective-serotonin reuptake inhibitors (SSRIs) (e.g., escitalopram, fluoxetine, citalopram)
• Antiarrhythmic medications (e.g., quinidine)
• CNS depressants, such as:
• Alcohol
• Opioids (e.g., hydrocodone)
• Benzodiazepines (e.g. clonazepam, alprazolam)
• Allergy medications (e.g. cetirizine, diphenhydramine, loratidine)
• Linezolid
• Cimetidine
• Phenothiazine antipsychotics (e.g. fluphenazine, chlorpromazine)
• St. John’s wort
• Tolazamide

This is not an exhaustive list. Be sure to tell your doctor everything you take or have taken in the past, including prescription medications, over-the-counter medicines, herbs, and supplements.

Safe Storage

Store doxepin tightly closed in the original container it came from, and out of the reach of children. It should be stored at room temperature and away from heat, moisture, and direct light.

Doxepin FAQs

Listed below are frequently asked questions about the use of doxepin.

Can you take doxepin after eating?

If you are taking the 3 mg or 6 mg tablets (generic Silenor for insomnia), then no. For this indication, it should be taken on an empty stomach, at least 3 hours after your last meal. Taking any closer to the meal can reduce its effectiveness and increase next-day drowsiness.

Higher-dose doxepin capsules or liquid used for depression or anxiety, however, do not have this restriction and may be taken with food.

Does doxepin cause weight gain?

Doxepin may cause weight gain in some individuals, as this is a documented side effect. It does not happen to everyone.

Who shouldn’t use doxepin?

Doxepin may not be suitable for pregnant or breastfeeding women, adults over 65, children, anyone who is allergic or hypersensitive to its effects, and individuals with certain medical conditions, such as heart arrhythmias, seizures, or bipolar disorder. It’s essential to consult with your doctor to see if doxepin is safe for you.

Author

Jack Cincotta

Jack Cincotta holds a M.S. degree in Psychology. He is also a board-certified holistic health practitioner through AADP and an AFPA-certified holistic health coach and nutritionist.

Activity History - Last updated: March 19, 2026, Published date: March 19, 2026

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Reviewer

David MilesPharmD

David is a seasoned Pharmacist, natural medicines expert, medical reviewer, and pastor.

Activity History - Medically reviewed on March 30, 2026 and last checked on March 19, 2026