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Doxepin: 7 things you should know

Medically reviewed by Carmen Pope, BPharm. Last updated on Nov 14, 2023.

1. How it works

  • Doxepin may be used to treat depression.
  • Experts aren't exactly sure how Doxepin works but it is thought to increase levels of norepinephrine (a neurotransmitter) in the brain by preventing the reuptake of norepinephrine into the nerve terminals.
  • Doxepin belongs to a group of medicines known as tricyclic antidepressants.

2. Upsides

  • Effective for the treatment of depression and/or anxiety.
  • May be used to treat depression or anxiety including that associated with alcohol use, neurosis, or manic-depressive disorders. Should not be taken at the same time as alcohol.
  • Symptoms that respond well to doxepin include anxiety, depression, and associated somatic symptoms such as pain or fatigue, fear, guilt, sleep disturbances, tension, and worry.
  • May be used off-label to treat other conditions.
  • May be given once a day or the total dose divided and spaced out throughout the day. A higher dosage may be given at night to minimize next-day sedation.
  • Virtually devoid of euphoria as a side effect.
  • Not shown to produce physical tolerance or psychological dependence associated with addictive compounds.
  • Safe and well-tolerated by seniors.
  • Generic doxepin is available.

3. Downsides

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

  • Dry mouth, blurred vision, drowsiness, constipation, nausea, and upper respiratory tract infections. Occasionally low or high blood pressure, a fast heartbeat, gastrointestinal effects, and skin rashes or photosensitization have occurred.
  • May increase the risk of suicidal thoughts or behavior in young adults (similar to other antidepressants).
  • May cause drowsiness and affect a person's ability to drive or operate machinery; some people may develop tolerance to this effect.
  • May also cause several other side effects including high blood pressure, flushing, fast heart rate, a lowering of blood pressure on standing, weight gain, skin rash, seizures, and edema.
  • Interaction or overdosage may cause serotonin syndrome (symptoms include agitation, hallucinations, fast heart rate, dizziness, muscle tremors, nausea, vomiting, and diarrhea).
  • May cause withdrawal symptoms with abrupt discontinuation (symptoms include nausea, headache, sleep disturbance, and generalized tiredness). These are not indicative of addiction. Taper dosage off slowly under medical supervision.
  • People who are poor metabolizers of CYP 2D6 may experience higher than expected concentrations of doxepin.
  • Not recommended for children under 12 years.
  • May not be suitable for some people including those with glaucoma or prone to urinary retention, with bipolar disorder, or who are pregnant or breastfeeding.
  • May interact with several other drugs including those metabolized by CYP 2D6 hepatic enzymes (such as other antidepressants, antipsychotics, and some antiarrhythmics), cimetidine, and tolazamide.
  • Alcohol may enhance the side effects of doxepin and increase the risk of overdosage.

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

4. Bottom Line

  • Doxepin may be used to treat symptoms associated with anxiety or depression such as fear, guilt, sleep disturbances, tension, and worry. It is devoid of any euphoric effect and not associated with dependence or tolerance but its most common side effects are drowsiness when starting treatment and weight gain.

5. Tips

  • May be given with or without food.
  • The total daily dosage may be split and a higher dosage taken late afternoon or at night to minimize next-day sedation. Talk to your doctor about splitting your doxepin like this.
  • Take doxepin exactly as directed by your doctor. Do not stop suddenly as withdrawal symptoms may occur. Your doctor will advise you how to discontinue doxepin slowly when the time comes to discontinue it.
  • If you have been prescribed doxepin oral solution, use the accompanying dropper, and immediately before taking, dilute the dose with approximately 120ml of water, milk, or juice. The oral solution is not compatible with carbonated beverages.
  • Let your doctor know if you experience depression, or a worsening of depression or suicidal thoughts, particularly during the first few months of therapy. Also, monitor yourself for any symptoms of serotonin syndrome (symptoms include agitation, hallucinations, fast heart rate, dizziness, muscle tremors, nausea, vomiting, diarrhea).
  • Report any unusual or excessive side effects to your doctor (such as excessive sedation, fast heartbeat, or feeling dizzy when standing).
  • Talk to your doctor or pharmacist before taking any other medications with doxepin, including those bought over the counter, because some may not be compatible with doxepin.
  • May increase the risk of sunburn. Apply sunblock and wear sun-protective clothing when outdoors.
  • Tell your doctor if you are pregnant or intending to become pregnant before you start taking doxepin as it may not be suitable for you. There have been reports of shortness of breath and drowsiness in a breastfeeding infant whose mother was taking doxepin.

6. Response and effectiveness

  • Peak concentrations of doxepin are reached in approximately two hours. The antidepressant effect of doxepin may take several weeks to develop. The anti-anxiety effect of doxepin is usually apparent before an antidepressant effect occurs.

7. Interactions

Medicines that interact with doxepin may either decrease its effect, affect how long it works, increase side effects, or have less of an effect when taken with doxepin. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Common medications that may interact with doxepin include:

  • 5-hydroxytryptophan
  • albuterol
  • anticonvulsants, such as carbamazepine, divalproex, or phenytoin
  • antidepressants, such as amitriptyline, clomipramine, desipramine, duloxetine, escitalopram, imipramine, or nortriptyline
  • antifungals, such as voriconazole
  • antipsychotics, such as clozapine, haloperidol, thioridazine, or ziprasidone
  • barbiturates, such as phenobarbital
  • bupropion
  • buspirone
  • clonidine
  • cocaine
  • diabetes medications, such as glimepiride, glyburide, or glipizide
  • diuretics, such as furosemide
  • droperidol
  • famotidine
  • heart medications, such as amiodarone, felodipine, sotalol, quinidine, or procainamide
  • HIV medications, such as efavirenz or saquinavir
  • lithium
  • medications used to treat ADHD such as dextroamphetamine or lisdexamfetamine
  • metoclopramide
  • mifepristone
  • migraine medications, such as dihydroergotamine
  • monoamine oxidase inhibitors, such as isocarboxazid, selegiline, or tranylcypromine
  • moxifloxacin
  • nilotinib
  • norepinephrine
  • ondansetron
  • opioids, such as fentanyl, oxycodone, methadone, morphine, or codeine
  • Parkinson's disease medications, such as selegiline
  • pimozide
  • potassium chloride or potassium citrate
  • sedatives, or any medication that causes sedation, such as sleeping pills, muscle relaxants, or other antidepressants
  • St John's wort
  • tamoxifen
  • topiramate
  • tolazamide
  • tramadol
  • other medications, such as those used to treat allergies, such as azelastine or dexchlorpheniramine.

Alcohol may enhance the sedative effects of doxepin.

Note that this list is not all-inclusive and includes only common medications that may interact with doxepin. You should refer to the prescribing information for doxepin for a complete list of interactions.


Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use doxepin only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Copyright 1996-2023 Revision date: November 20, 2023.