API: Doxepin

What Is Doxepin and How Does It Work?

Doxepin is a dibenzoxazepine-derivative tricyclic antidepressant (TCA). Based on the location of the alkyl amine substituent on its central tricyclic ring, doxepin is classified as a tertiary amine TCA and believed to be more potent than secondary amine TCAs. The drug’s antidepressant effects are mediated by its ability to block serotonin and norepinephrine reuptake in presynaptic terminals. Doxepin also works as a sedative by blocking the histamine H(1) and H(2) receptors. It exerts anticholinergic effects by blocking muscarinic receptors and hypotensive effects by blocking alpha-1 adrenergic receptors.1 In oral form, doxepin is used to treat depression, anxiety, and insomnia. In topical form, doxepin works as an antipruritic by blocking the H(1) and H(2) histamine receptors, so it can relieve itching caused by several different skin conditions.2


  • Depression: Because of its antidepressant effects, doxepin can be taken in oral form to treat endogenous and psychotic depression. It can also treat depression associated with alcoholism, brain damage, or a concomitant organic disease.3
  • Other Psychiatric Disorders: Doxepin can also be effective for treating anxiety disorders and psychotic disorders, such as bipolar disorder.
  • Insomnia: Because its sedative effects, doxepin has been approved to treat insomnia.4
  • Skin Conditions: In topical form, doxepin can relieve itching from atopic dermatitis, lichen simplex chronicus, idiopathic urticaria (chronic hives), eczema, and other skin conditions.
  • Irritable Bowel Syndrome: Doxepin is frequently used off-label to treat abdominal pain from irritable bowel syndrome.
  • Fibromyalgia: Doxepin is commonly used off-label to treat pain and sleep problems caused by fibromyalgia.
  • General Chronic Pain: The drug is sometimes used as an off-label treatment for chronic pain associated with a wide range of conditions, including arthritis, diabetes, herpes, migraine headaches, and cancer.5   

Side Effects and Drug Interactions

Common side effects of doxepin include6: 

  • Drowsiness
  • Dizziness
  • Blurred vision
  • Urinary Retention
  • Constipation
  • Dry mouth
  • Orthostatic hypotension
  • Rash or hives
  • Rapid or irregular heart rate
  • Weight gain
  • Breast swelling
  • Decreased sex drive

Patients should contact a doctor immediately if they experience worsening symptoms of depression, anxiety, or insomnia, or if they feel unusually impulsive, aggressive, or hyperactive. Other serious side effects that require immediate medical attention include tremors in the face or neck, severe tingling, muscle weakness, and seizures.7 Patients who abruptly discontinue use of doxepin may experience withdrawal symptoms, including dizziness, headache, nausea, and mood changes.

Medications that interact with doxepin include anticholinergic drugs (such as benztropine and belladonna alkaloids), thyroid supplements (such as levothyroxine), centrally-acting drugs used to treat high blood pressure (such as clonidine and reserpine), and MAO inhibitors (such as isocarboxazid, linezolid, moclobemide, and phenelzine). Drugs that may affect the efficacy of doxepin by changing the rate at which it is removed by the body include cimetidine, St. John’s Wort, terbinafine, quinidine, and SSRIs (such as paroxetine, fluoxetine, and fluvoxamine).

The sedative effects of doxepin may increase when taken alongside other drugs that cause drowsiness, including alcohol, antihistamines, sleep aids, muscle relaxants, and narcotic pain relievers.8

Latest News and Research

Doxepin has been used as an oral antidepressant since the 1980’s. In the United States, the drug was originally marketed as Sinequan, but it has since gone to generic. Topical doxepin was approved for the treatment of skin conditions in April 1994 under the trade name Zonalon and has also gone to generic. In March 2010, the FDA approved the use of doxepin for the treatment of insomnia under the name Silenor.

The latest research on doxepin highlights ways for the drug to be used to treat an even wider range of conditions. For instance, doxepin can provide effective treatment for symptoms of physical and mental fatigue in patients with Parkinson’s Disease.9 It may also reduce pain in patients with bladder pain syndrome and interstitial cystitis.10 Researchers have also recently developed a doxepin-based mouth rinse for patients with head and neck cancer. When these patients receive radiation therapy, they often develop adverse side effects such as oral mucositis, which can interrupt the radiation treatment schedule and thereby decrease the likelihood of recovery. Doxepin mouthwash reduces pain from oral mucositis, allowing treatment to get back on schedule.11

Doxepin is involved in a recent price-fixing scandal in the United Kingdom. Four pharmaceutical companies have been accused of remarketing off-patent drugs under new names. When a drug’s patent expires, it is no longer subject to the UK’s cost-limiting Pharmaceutical Price Regulation Scheme. Companies chose drugs that have little or no market competition, so they were able to increase prices by up to a thousand percent. Over the last five years, the cost of 50mg doxepin tablets was raised from £5.71 to £154. A report in The Times has claimed that the artificially inflated price of doxepin and other drugs increased the National Health Service’s annual spending by £262 million, and a government investigation is underway.12

Buying Guide

Many compound pharmacists prefer Amitriptyline, another tertiary amine tricyclic antidepressant that is similar in structure to Doxepin and treats most of the same conditions, but has less pronounced sedative effects. For pain, many pharmacists prefer NSAIDs such as Diclofenac Sodium, Flurbiprofen, Ketoprofen, Meloxicam, and Piroxicam. Please find more information about our Bulk APIs here.

Show 12 footnotes

  1. “Doxepin,” 2016, https://pubchem.ncbi.nlm.nih.gov/compound/3158#section=Top
  2. “Doxepin Topical,” September 1, 2010, https://www.nlm.nih.gov/medlineplus/druginfo/meds/a605040.html
  3. “Sinequan,” July 29, 2014, http://www.rxlist.com/sinequan-drug/indications-dosage.htm
  4. “Doxepin,” May 2, 2016, https://www.drugs.com/cdi/doxepin.html
  5. “Psychiatric Medication,” 2016, http://whatmeds.stanford.edu/medications/adapin.html
  6. “Doxepin (Sinequan and Adapin are discontinued brand in the US; Silenor,)” August 7, 2015, http://www.medicinenet.com/doxepin/page2.htm
  7. “Sinequin Side Effects Center,” April 29, 2015, http://www.rxlist.com/sinequan-side-effects-drug-center.htm
  8. “Doxepin,” 2016, http://www.webmd.com/drugs/2/drug-8647-47/doxepin-oral/doxepin-liquid—oral/details#interactions
  9. “Treatment of Fatigue in Parkinson Disease,” June 7, 2016, http://www.ncbi.nlm.nih.gov/pubmed/27272586
  10. “Treatment of bladder pain syndrome and interstitial cystitis: a systematic review,” August 14, 2015, http://www.ncbi.nlm.nih.gov/pubmed/26272202
  11. “Doxepin for Radiation Therapy-Induced Mucositis Pain in the Treatment of Oral Cancers,” December 9, 2015, http://www.oncologyreviews.org/index.php/or/article/view/290
  12. “NHS drugs bill fattened by corporate profiteering, investigation claims,” June 6, 2016, http://www.pharmatimes.com/news/nhs_drugs_bill_fattened_by_corporate_profiteering,_investigation_claims_1034841