Back To Search Results


Editor: Carlos E. Meza Updated: 2/14/2024 10:42:11 PM


Doxepin belongs to the class of tricyclic antidepressant (TCA) medications approved by the US Food and Drug Administration (FDA) in 1969 for the treatment of major depressive disorder. Although doxepin was initially approved to treat depression, it demonstrates efficacy in targeting multiple receptors, rendering it beneficial for addressing various other conditions. Doxepin also displays antagonistic effects in the central nervous system by blocking histamine (H1), α1 adrenergic, and muscarinic receptors. 

FDA-Approved Indications

  • The oral tablet formulation of doxepin has received FDA approval for treating insomnia.[1]
  • Oral capsule and solution formulations have also been FDA-approved for the management of insomnia and anxiety, while topical formulations are indicated for the treatment of epidermal pruritus.[2][3][4] 
  • Topical doxepin (5%) is FDA-approved for treating pruritus in adult patients diagnosed with atopic dermatitis or lichen simplex chronicus.[5]

Off-Label Uses

  • In literature and research studies, doxepin has demonstrated efficacy as an analgesic in treating neuropathic pain.[6][7]
  • Doxepin also has been used as a prophylactic agent against migraines.[8][9]
  • Topical creams containing doxepin function as local anesthetics, aiding in pain management and the treatment of urethral irritation and dysuria.[10][11]

Mechanism of Action

Register For Free And Read The Full Article
Get the answers you need instantly with the StatPearls Clinical Decision Support tool. StatPearls spent the last decade developing the largest and most updated Point-of Care resource ever developed. Earn CME/CE by searching and reading articles.
  • Dropdown arrow Search engine and full access to all medical articles
  • Dropdown arrow 10 free questions in your specialty
  • Dropdown arrow Free CME/CE Activities
  • Dropdown arrow Free daily question in your email
  • Dropdown arrow Save favorite articles to your dashboard
  • Dropdown arrow Emails offering discounts

Learn more about a Subscription to StatPearls Point-of-Care

Mechanism of Action

Depression appears to result from a chemical imbalance and a lack of neurotransmitters in the brain. The different classes of antidepressant medications have been formulated to perform unique mechanisms by targeting different receptors and increasing the availability of neurotransmitters. 

Doxepin belongs to the TCA class of medications, which function by increasing the concentration of the neurotransmitter serotonin (5-hydroxytryptamine or 5-HT) and norepinephrine (NE) in the brain. This mechanism extends the availability of the neurotransmitters (5-HT and NE) within the synaptic cleft and enhances their neurotransmission by preventing their reuptake into the presynaptic terminal. 

Doxepin also displays antagonistic effects in the central nervous system by blocking receptors such as histamine (H1), α1 adrenergic, and muscarinic. Furthermore, doxepin inhibits sodium and potassium channels in cardiomyocytes, thereby broadening the drug's indications profile.[12][13] Doxepin has H1 and H2 histamine receptor-blocking actions, which explains the antipruritic effect of doxepin.[14]

Pharmacokinetics (Oral Formulation)

Absorption: The time for peak plasma concentration is 3.5 hours. The AUC of doxepin is increased by 41% and Cmax by 15% after a high-fat meal.

Distribution: Highly distributed in other body tissue compartments, the apparent volume of distribution is about 11,930 L. Plasma protein bindings are approximately 80%.

Metabolism: Doxepin is primarily metabolized by CYP2D6, with CYP1A2, CYP2C9, and CYP3A4 also involved to a lesser level.[15] The active metabolite is nordoxepin.

Elimination: Doxepin is excreted as less than 3% urine as an unchanged drug or nordoxepin. The apparent terminal half-life of doxepin is approximately 15 hours, and the half-life of nordoxepin is approximately 31 hours.[16]

Pharmacokinetics (Topical Formulation)

Absorption: Topical doxepin is available as a 5% cream. Due to its excessive absorption into the circulation, doxepin should not be used under an occlusive bandage.

Distribution: Topical doxepin is absorbed and is widely distributed in the lungs, heart, brain, and liver. The package insert reports that plasma levels of topical doxepin from percutaneous absorption range from undetectable to 47 mg/mL.

Metabolism: Hepatic; primary metabolite is nordoxepin (active).

Elimination: The elimination half-life of nordoxepin is 8 to 52 hours. The primary route of elimination is the kidney.[17]


Available Dosage Forms and Strengths

Doxepin antidepressant formulations are commercially available in oral tablets, capsules, and solutions. Oral administration is the most commonly utilized method among patients with depression.

  • Doxepin tablets are available in 2 strengths: 3 mg and 6 mg.
  • Doxepin oral capsules are available in strengths of 10 mg, 25 mg, 50 mg, 75 mg, 100 mg, and 150 mg.
  • Doxepin oral solutions are available in 10 mg/mL dosage.
  • Additional forms of doxepin available include topical creams (5%) and transdermal patches.

Transbuccal delivery of doxepin has been a research topic, but insufficient data have been reported to support its effectiveness.[18] Methods such as intranasal, sublingual, and rectal administration have yet to be studied.[19]

Adult Dosage

Insomnia: For the treatment of insomnia, doxepin tablets, typically ranging from 3 to 6 mg, are taken daily within 30 minutes of bedtime for a short duration, usually less than 4 to 8 weeks.

Major depressive disorder: For major depressive disorder (unipolar) and treatment-resistant depression, the initial dose typically ranges from 25 to 75 mg at bedtime. This dosage is gradually increased every third day by 25 to 50 mg until reaching a daily dosage of 100 to 300 mg. The drug may be given in 2 or 3 divided doses. When discontinuing, it is advisable to taper the dose.

Anxiety: The starting dose typically ranges from 25 to 75 mg at bedtime. This dosage is gradually increased every third day by 25 to 50 mg until reaching a daily dosage of 100 to 300 mg. The medication may be administered in 2 or 3 divided doses. When discontinuing, it is advisable to taper the dose.

Withdrawal: Doxepin should be tapered gradually like other antidepressants, although abrupt discontinuation usually does not precipitate symptoms as it has a long half-life.

Chronic urticaria: According to the American Academy of Allergy, Asthma & Immunology (AAAAI) and the American College of Allergy, Asthma & Immunology (ACAAI) consensus guidelines, oral doxepin can be considered as the treatment of chronic urticaria refractory to second-generation antihistamines and H2 blockers.[20] The dose of doxepin for chronic urticaria is 10 to 25 mg/day, administered at bedtime.[21]

Atopic dermatitis/lichen simplex chronicus: Doxepin cream (5%) should be applied 4 times daily. Use is generally not advised beyond a week. Chronic use beyond 8 days can lead to significant absorption, systemic adverse effects, and contact sensitization. The application of doxepin cream should be restricted to less than 10% of the body surface area (BSA). If doxepin is applied to more than 10% BSA, patients should be monitored for adverse effects, particularly sedation. Clinicians should advise the patients to decrease the frequency or discontinue doxepin if significant sedation is seen.

Specific Patient Populations

Hepatic impairment: The manufacturer label does not provide dose adjustment guidance for patients with hepatic impairment. However, doxepin is converted into the active metabolite nordoxepin in the liver, so the drug should be used cautiously in these patients. 

Renal impairment: The manufacturer's label has no dose adjustment guidance for patients with renal impairment. 

Pregnancy considerations: Doxepin is considered a former FDA pregnancy category C medicine. In animal studies, increased mortality and low body weight have been reported. However, a dose of doxepin was greater than the maximum recommended human dose (MRHD).[22]

Breastfeeding considerations: Doxepin is not recommended in nursing mothers as the active metabolite is present in breast milk.[23]

Pediatric patients: The safety and efficacy of doxepin have not been established in pediatric patients. Per the boxed warnings, it is not recommended for patients younger than 12.

Older patients: The safety and efficacy of doxepin are not systematically studied for adults versus older patients. Doxepin is listed as a potentially inappropriate medicine, which should be avoided in patients aged 65 and older by the American Geriatric Society and Beers criteria. However, the usual starting dose in older patients should be the low end of the dosing range as they have a greater probability of decreased hepatic, renal, or cardiac functions. Moreover, doxepin may cause confusion and oversedation in older patients, so close monitoring is recommended.[24]

Adverse Effects

Doxepin is a unique antidepressant because it produces different adverse effects based on the receptor it antagonizes. Doxepin antagonizes 3 different receptors: histamine, adrenergic, and muscarinic. Doxepin blocks histamine H1 receptor and causes sedation and somnolence; therefore, FDA has approved low-dose doxepin, 3 mg, and 6 mg dosages as a first-line agent in depressed patients with sleep disturbances and depression associated with anxiety. Proper education is necessary to prevent patients from self-medicating and overdosing with these doses.[25][26]

Doxepin also has the potential to cause a significant increase in weight and was assessed in a study of 329 patients treated with doxepin and amitriptyline.[27] Doxepin blocks α-adrenergic receptors and should be carefully monitored in those with cardiovascular disorders because it can cause orthostatic hypotension.[28] Lastly, doxepin blocks muscarinic receptors and produces anticholinergic adverse effects such as dry mouth, constipation, dizziness, lightheadedness, tachycardia, and prolonged QT interval.[29][30][31] The most frequent adverse effects of topical doxepin are burning and tingling sensations. Systemic absorption can lead to dizziness, dry mouth, blurred vision, and headache.[17]

Box Warning

  • Patients prescribed an antidepressant, such as doxepin, require careful observation due to the box warning that states a possible increase in suicidality.
  • Patients should be monitored closely for the clinical worsening of depression, suicidal ideation, and changes in behavior.[32]

Drug-Drug Interactions

  • Significant drug interactions with doxepin, which require dose adjustment, frequency modification, or avoidance for a certain time with MAO inhibitors. Allow 14 days between treatment with doxepin and MAO Inhibitors (eg, selegiline and phenelzine).[33][34][35]
  • CYP2D6 significantly metabolizes doxepin. Inhibitors of CYP2D6, such as quinidine and SSRI, when administered concomitantly, may increase the plasma concentration of doxepin.[36]
  • Linezolid inhibits monoamine oxidase enzyme. Concurrent administration of TCAs like doxepin with linezolid could result in potentially fatal serotonin syndrome. Avoid combination.[37]
  • Concurrent administration of doxepin with drugs that can prolong QT interval, like methadone, can increase the risk for torsades de pointes.[38][39]
  • Severe hypoglycemia has been reported due to the concomitant administration of tolazamide (sulfonylurea) and doxepin (TCA).[40]


Clinicians must obtain a thorough medical history and medication history from patients before prescribing antidepressants. Antidepressants may cause serious adverse effects when combined with other medications, such as different classes of antidepressants, opioids, alcohol, herbal medication, and psychedelics. An interaction between two different classes of antidepressants may lead to excess serotonin in the central nervous system. This effect leads to a condition known as serotonin syndrome, sometimes called serotonin toxicity. Serotonin toxicity induces symptoms such as mental status changes, autonomic stimulation, and neuromuscular excitation. Patients experience symptoms such as agitation, confusion, changes in vital signs such as tachycardia, hyperthermia, flushing, tremor, and neuromuscular changes such as rigidity, increased reflexes, and clonus.[41][42] 

Another contraindication to prescribing doxepin is in patients with cardiovascular disorders such as preexisting bundle branch blocks. Literature has reported cases where patients developed atrioventricular heart block, orthostatic hypotension, and abnormalities in conduction after taking doxepin.[43][44] Doxepin has a poor safety profile in postpartum lactating mothers and is contraindicated in breastfeeding due to its sedative and respiratory depressive effects.[45][46] 

Overdose can result in fatality, so avoid using in patients at risk of intentional overdose or a known history of suicidal attempts. Patients with hypersensitivity to doxepin or excipients should also avoid doxepin. Doxepin cream is contraindicated in patients with untreated glaucoma and a history of urinary retention.[17]


Therapeutic drug monitoring is a valuable guide used to measure the concentration of doxepin and its breakdown products in the blood. The goal is to maintain a constant concentration in the blood and optimize the drug's therapeutic outcomes, effectiveness, and safety while minimizing its potential for serious adverse effects.[47] 

Drug monitoring is useful in medications with a narrow therapeutic index; this is a ratio between the toxic and therapeutic dose of the drug. Using such a method has proven effective in many medications, including antidepressants, because it has provided a more reliable index of target drug concentration than dosage. Research cites doxepin as having a therapeutic range of 150 to 250 ng/mL. However, one study found that only 9% of samples displayed plasma levels between 150 to 250 ng/mL, while 88% remained subtherapeutic.[48] 

Adverse effects occurred more often when the serum levels were above the therapeutic range.[49] Although no definite recommendation exists, therapeutic drug monitoring of doxepin requires more research to maximize its effectiveness and benefits. Pharmacogenomic consideration for therapeutic drug monitoring: patients with CYP2D6 poor metabolizers have decreased metabolism of TCAs, including doxepin, resulting in higher plasma concentrations and increased probability of adverse effects. If a TCA like doxepin is required, reduce the dose by 50% and perform therapeutic drug monitoring. In CYP2D6 ultrarapid metabolizer, increased metabolism of TCAs, including doxepin, is evident, and pharmacotherapy failure is probable. If TCA, like doxepin, is required, therapeutic drug monitoring can guide dose adjustments. However, pharmacogenomics may not be a feasible option in primary care.[36]


TCAs are one of the most frequently ingested substances used for self-poison in an attempt to commit suicide. A case fatality index is a tool used to measure ratios and compare toxic levels of drugs to one another.[50] Tricyclics have a greater incidence of toxicity than other antidepressants, and doxepin is 2 to 3 times more toxic when compared to amitriptyline.[51][52] 

Symptoms of intoxication and overdose can be grouped based on the organ system it affects. Doxepin overdose can affect the central nervous system and cardiovascular system. Doxepin is known to block sodium and potassium channels on cardiomyocytes and can reduce cardiac action potential and depolarization and lead to cardiac arrhythmias.[53] Doxepin can increase heart rate and widen the PR, QRS, and QT interval, as assessed in a study of an individual who overdosed on 5000 mg of doxepin, developed cardiac arrest, and was persistently hypotensive.[54] 

Doxepin can also cause neurological effects such as coma, grand mal seizures, and respiratory depression.[13][55][56] Treatment options that are beneficial in patients with doxepin intoxication include sodium bicarbonate, hemodialysis/hemoperfusion, and supportive therapy.[57][58] Clinicians must recognize that doxepin has anticholinergic properties; the absorption may be impaired due to delayed gastrointestinal motility; hence, patients may require prolonged monitoring.[59]

Enhancing Healthcare Team Outcomes

Major depressive disorder affects over 17.3 million Americans in the United States, with approximately 75% of individuals suffering from mental disorders remaining untreated, and tragically, about 1 million people commit suicide. Hence, an interprofessional team approach is essential to deliver the highest quality care, ensuring accurate diagnosis, treatment, and management of patients with psychiatric disorders. Research indicates that individuals' beliefs about their mental illness can significantly impact their treatment plans and medication adherence.[60] 

Psychiatrists typically prescribe doxepin for depression and insomnia, while dermatologists and immunologists may prescribe it for refractory urticaria. Nursing staff are critical in coordinating between psychiatrists, pharmacists, and primary care clinicians. Pharmacists can monitor for drug interactions, verify dosing, and collaborate with prescribers if treatment is unsuccessful, suggesting alternative medication options, particularly if they possess board-certified psychiatric certification. Mental health specialty nurses maintain significant contact with patients, monitor medication adverse effects, and promptly inform the doctor of any concerns. In cases of overdose, emergency medicine clinicians are responsible for stabilizing the patient, while consultation with critical care physicians is necessary in cases of serotonin syndrome. 

Doxepin has been used to treat major depressive disorder since 1969. However, patients should receive comprehensive education regarding medication compliance, potential adverse effects, toxicity risks, and possible interactions with other medications. Encouraging patients to adhere to follow-up appointments and maintain open communication with their primary care clinician, psychiatrist, psychologist, and pharmacist is vital. An interprofessional team approach involving physicians, specialists, advanced practice practitioners, nurses, psychologists, and pharmacists is essential for optimizing patient outcomes associated with doxepin therapy in depression.



Owen RT. Selective histamine H(1) antagonism: a novel approach to insomnia using low-dose doxepin. Drugs of today (Barcelona, Spain : 1998). 2009 Apr:45(4):261-7. doi: 10.1358/dot.2009.45.4.1358835. Epub     [PubMed PMID: 19499091]


Wu J, Chang F, Zu H. Efficacy and safety evaluation of citalopram and doxepin on sleep quality in comorbid insomnia and anxiety disorders. Experimental and therapeutic medicine. 2015 Oct:10(4):1303-1308     [PubMed PMID: 26622482]

Level 2 (mid-level) evidence


Kouwenhoven TA, van de Kerkhof PCM, Kamsteeg M. Use of oral antidepressants in patients with chronic pruritus: A systematic review. Journal of the American Academy of Dermatology. 2017 Dec:77(6):1068-1073.e7. doi: 10.1016/j.jaad.2017.08.025. Epub 2017 Oct 21     [PubMed PMID: 29033248]

Level 1 (high-level) evidence


Eschler DC, Klein PA. An evidence-based review of the efficacy of topical antihistamines in the relief of pruritus. Journal of drugs in dermatology : JDD. 2010 Aug:9(8):992-7     [PubMed PMID: 20684150]


Ju T, Vander Does A, Mohsin N, Yosipovitch G. Lichen Simplex Chronicus Itch: An Update. Acta dermato-venereologica. 2022 Oct 19:102():adv00796. doi: 10.2340/actadv.v102.4367. Epub 2022 Oct 19     [PubMed PMID: 36250769]


Wörz R, Berlin J. [Treatment of chronic pain syndromes with antidepressants.]. Schmerz (Berlin, Germany). 1989 Mar:3(1):1-7     [PubMed PMID: 18415335]


Casale R, Symeonidou Z, Bartolo M. Topical Treatments for Localized Neuropathic Pain. Current pain and headache reports. 2017 Mar:21(3):15. doi: 10.1007/s11916-017-0615-y. Epub     [PubMed PMID: 28271334]


Hershey LA, Bednarczyk EM. Treatment of headache in the elderly. Current treatment options in neurology. 2013 Feb:15(1):56-62. doi: 10.1007/s11940-012-0205-6. Epub     [PubMed PMID: 23054583]


Punay NC, Couch JR. Antidepressants in the treatment of migraine headache. Current pain and headache reports. 2003 Feb:7(1):51-4     [PubMed PMID: 12525271]


Sandig AG, Campmany AC, Campos FF, Villena MJ, Naveros BC. Transdermal delivery of imipramine and doxepin from newly oil-in-water nanoemulsions for an analgesic and anti-allodynic activity: development, characterization and in vivo evaluation. Colloids and surfaces. B, Biointerfaces. 2013 Mar 1:103():558-65. doi: 10.1016/j.colsurfb.2012.10.061. Epub 2012 Nov 16     [PubMed PMID: 23261580]

Level 3 (low-level) evidence


McCleane G. Topical application of the tricyclic antidepressant doxepin can reduce dysuria and frequency. Scandinavian journal of urology and nephrology. 2004:38(1):88-9     [PubMed PMID: 15204434]

Level 3 (low-level) evidence


Feighner JP. Mechanism of action of antidepressant medications. The Journal of clinical psychiatry. 1999:60 Suppl 4():4-11; discussion 12-3     [PubMed PMID: 10086478]


Kołodziej M, Majewska M, Krajewska A, Szponar J. [Prolonged toxic coma and anisocoria secondary to doxepin, lorazepam and phenobarbital poisoning--case study]. Przeglad lekarski. 2012:69(8):624-6     [PubMed PMID: 23243948]

Level 3 (low-level) evidence


Pozderac I, Lugović-Mihić L, Artuković M, Stipić-Marković A, Kuna M, Ferček I. Chronic inducible urticaria: classification and prominent features of physical and non-physical types. Acta dermatovenerologica Alpina, Pannonica, et Adriatica. 2020 Sep:29(3):141-148     [PubMed PMID: 32975301]


Kirchheiner J, Meineke I, Müller G, Roots I, Brockmöller J. Contributions of CYP2D6, CYP2C9 and CYP2C19 to the biotransformation of E- and Z-doxepin in healthy volunteers. Pharmacogenetics. 2002 Oct:12(7):571-80     [PubMed PMID: 12360109]


Yan JH, Hubbard JW, McKay G, Korchinski ED, Midha KK. Absolute bioavailability and stereoselective pharmacokinetics of doxepin. Xenobiotica; the fate of foreign compounds in biological systems. 2002 Jul:32(7):615-23     [PubMed PMID: 12162857]

Level 1 (high-level) evidence


Leppert W, Malec-Milewska M, Zajaczkowska R, Wordliczek J. Transdermal and Topical Drug Administration in the Treatment of Pain. Molecules (Basel, Switzerland). 2018 Mar 17:23(3):. doi: 10.3390/molecules23030681. Epub 2018 Mar 17     [PubMed PMID: 29562618]


Gimeno A, Calpena AC, Sanz R, Mallandrich M, Peraire C, Clares B. Transbuccal delivery of doxepin: studies on permeation and histological investigation. International journal of pharmaceutics. 2014 Dec 30:477(1-2):650-4. doi: 10.1016/j.ijpharm.2014.10.060. Epub 2014 Nov 1     [PubMed PMID: 25445535]

Level 3 (low-level) evidence


Sheffler ZM, Patel P, Abdijadid S. Antidepressants. StatPearls. 2024 Jan:():     [PubMed PMID: 30844209]


Bernstein JA, Lang DM, Khan DA, Craig T, Dreyfus D, Hsieh F, Sheikh J, Weldon D, Zuraw B, Bernstein DI, Blessing-Moore J, Cox L, Nicklas RA, Oppenheimer J, Portnoy JM, Randolph CR, Schuller DE, Spector SL, Tilles SA, Wallace D. The diagnosis and management of acute and chronic urticaria: 2014 update. The Journal of allergy and clinical immunology. 2014 May:133(5):1270-7. doi: 10.1016/j.jaci.2014.02.036. Epub     [PubMed PMID: 24766875]


Özkaya E, Babuna Kobaner G, Yılmaz Z, Kutlay A. Doxepin in difficult-to-treat chronic urticaria: A retrospective, cross-sectional study from Turkey. Dermatologic therapy. 2019 Jul:32(4):e12993. doi: 10.1111/dth.12993. Epub 2019 Jul 14     [PubMed PMID: 31175673]

Level 2 (mid-level) evidence


Creeley CE, Denton LK. Use of Prescribed Psychotropics during Pregnancy: A Systematic Review of Pregnancy, Neonatal, and Childhood Outcomes. Brain sciences. 2019 Sep 14:9(9):. doi: 10.3390/brainsci9090235. Epub 2019 Sep 14     [PubMed PMID: 31540060]

Level 1 (high-level) evidence


. Doxepin. Drugs and Lactation Database (LactMed®). 2006:():     [PubMed PMID: 30000240]


By the 2019 American Geriatrics Society Beers Criteria® Update Expert Panel. American Geriatrics Society 2019 Updated AGS Beers Criteria® for Potentially Inappropriate Medication Use in Older Adults. Journal of the American Geriatrics Society. 2019 Apr:67(4):674-694. doi: 10.1111/jgs.15767. Epub 2019 Jan 29     [PubMed PMID: 30693946]


Vande Griend JP, Anderson SL. Histamine-1 receptor antagonism for treatment of insomnia. Journal of the American Pharmacists Association : JAPhA. 2012:52(6):e210-9. doi: 10.1331/JAPhA.2012.12051. Epub     [PubMed PMID: 23229983]


Yeung WF, Chung KF, Yung KP, Ng TH. Doxepin for insomnia: a systematic review of randomized placebo-controlled trials. Sleep medicine reviews. 2015 Feb:19():75-83. doi: 10.1016/j.smrv.2014.06.001. Epub 2014 Jun 19     [PubMed PMID: 25047681]

Level 1 (high-level) evidence


Sep-Kowalikowa B, Prokopowicz A, Pankiewicz P. [Weight gain during antidepressant therapy]. Psychiatria polska. 1992 Jan-Apr:26(1-2):37-43     [PubMed PMID: 1298003]


Roose SP, Dalack GW, Glassman AH, Woodring S, Walsh BT, Giardina EG. Is doxepin a safer tricyclic for the heart? The Journal of clinical psychiatry. 1991 Aug:52(8):338-41     [PubMed PMID: 1869496]


Feighner J, Hendrickson G, Miller L, Stern W. Double-blind comparison of doxepin versus bupropion in outpatients with a major depressive disorder. Journal of clinical psychopharmacology. 1986 Feb:6(1):27-32     [PubMed PMID: 3081600]

Level 1 (high-level) evidence


Feighner JP, Cohn JB. Double-blind comparative trials of fluoxetine and doxepin in geriatric patients with major depressive disorder. The Journal of clinical psychiatry. 1985 Mar:46(3 Pt 2):20-5     [PubMed PMID: 3882676]

Level 1 (high-level) evidence


Baker B, Dorian P, Sandor P, Shapiro C, Schell C, Mitchell J, Irvine MJ. Electrocardiographic effects of fluoxetine and doxepin in patients with major depressive disorder. Journal of clinical psychopharmacology. 1997 Feb:17(1):15-21     [PubMed PMID: 9004052]

Level 1 (high-level) evidence


Isacsson G, Rich CL. Antidepressant drugs and the risk of suicide in children and adolescents. Paediatric drugs. 2014 Apr:16(2):115-22. doi: 10.1007/s40272-013-0061-1. Epub     [PubMed PMID: 24452997]


Armbrust S, Nikischin W, Rochholz G, Franzelius C, Bielstein A, Kramer HH. Hypothermia in a combined intoxication with doxepin and moclobemide in an adolescent. Forensic science international. 2010 Feb 25:195(1-3):e1-3. doi: 10.1016/j.forsciint.2009.10.017. Epub 2010 Jan 13     [PubMed PMID: 20074878]

Level 3 (low-level) evidence


Hinds NP, Hillier CE, Wiles CM. Possible serotonin syndrome arising from an interaction between nortriptyline and selegiline in a lady with parkinsonism. Journal of neurology. 2000 Oct:247(10):811     [PubMed PMID: 11127542]

Level 3 (low-level) evidence


Thomas SJ, Shin M, McInnis MG, Bostwick JR. Combination therapy with monoamine oxidase inhibitors and other antidepressants or stimulants: strategies for the management of treatment-resistant depression. Pharmacotherapy. 2015 Apr:35(4):433-49. doi: 10.1002/phar.1576. Epub     [PubMed PMID: 25884531]


Hicks JK, Sangkuhl K, Swen JJ, Ellingrod VL, Müller DJ, Shimoda K, Bishop JR, Kharasch ED, Skaar TC, Gaedigk A, Dunnenberger HM, Klein TE, Caudle KE, Stingl JC. Clinical pharmacogenetics implementation consortium guideline (CPIC) for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants: 2016 update. Clinical pharmacology and therapeutics. 2017 Jul:102(1):37-44. doi: 10.1002/cpt.597. Epub 2017 Feb 13     [PubMed PMID: 27997040]


Masbough F, Roshanzamiri S, Rahimi M, Sahraei Z, Evini PET. Serotonin syndrome due to concomitant use of linezolid and methadone. Clinical case reports. 2022 Nov:10(11):e6341. doi: 10.1002/ccr3.6341. Epub 2022 Nov 5     [PubMed PMID: 36381053]

Level 3 (low-level) evidence


Campleman SL, Brent J, Pizon AF, Shulman J, Wax P, Manini AF, Toxicology Investigators’ Consortium (ToxIC). Drug-specific risk of severe QT prolongation following acute drug overdose. Clinical toxicology (Philadelphia, Pa.). 2020 Dec:58(12):1326-1334. doi: 10.1080/15563650.2020.1746330. Epub 2020 Apr 7     [PubMed PMID: 32252558]


Rademacher S, Dietz R, Haverkamp W. QT prolongation and syncope with methadone, doxepin, and a beta-blocker. The Annals of pharmacotherapy. 2005 Oct:39(10):1762-3     [PubMed PMID: 16144878]

Level 3 (low-level) evidence


Hassinger AB, Bletnisky N, Dudekula R, El-Solh AA. Selecting a pharmacotherapy regimen for patients with chronic insomnia. Expert opinion on pharmacotherapy. 2020 Jun:21(9):1035-1043. doi: 10.1080/14656566.2020.1743265. Epub 2020 Mar 23     [PubMed PMID: 32202451]

Level 3 (low-level) evidence


. Drug interactions with selective serotonin reuptake inhibitors, especially with other psychotropics. Prescrire international. 2001 Feb:10(51):25-31     [PubMed PMID: 11503857]


Isbister GK, Buckley NA, Whyte IM. Serotonin toxicity: a practical approach to diagnosis and treatment. The Medical journal of Australia. 2007 Sep 17:187(6):361-5     [PubMed PMID: 17874986]


Glassman AH, Bigger JT Jr. Cardiovascular effects of therapeutic doses of tricyclic antidepressants. A review. Archives of general psychiatry. 1981 Jul:38(7):815-20     [PubMed PMID: 7247643]


Rodriguez de la Torre B, Dreher J, Malevany I, Bagli M, Kolbinger M, Omran H, Lüderitz B, Rao ML. Serum levels and cardiovascular effects of tricyclic antidepressants and selective serotonin reuptake inhibitors in depressed patients. Therapeutic drug monitoring. 2001 Aug:23(4):435-40     [PubMed PMID: 11477329]


Lanza di Scalea T, Wisner KL. Antidepressant medication use during breastfeeding. Clinical obstetrics and gynecology. 2009 Sep:52(3):483-97. doi: 10.1097/GRF.0b013e3181b52bd6. Epub     [PubMed PMID: 19661763]


Uguz F. A New Safety Scoring System for the Use of Psychotropic Drugs During Lactation. American journal of therapeutics. 2021 Jan-Feb 01:28(1):e118-e126. doi: 10.1097/MJT.0000000000000909. Epub     [PubMed PMID: 30601177]


Fiaturi N, Greenblatt DJ. Therapeutic Drug Monitoring of Antidepressants. Handbook of experimental pharmacology. 2019:250():115-133. doi: 10.1007/164_2018_161. Epub     [PubMed PMID: 30194543]


Leucht S, Steimer W, Kreuz S, Abraham D, Orsulak PJ, Kissling W. Doxepin plasma concentrations: is there really a therapeutic range? Journal of clinical psychopharmacology. 2001 Aug:21(4):432-9     [PubMed PMID: 11476128]

Level 2 (mid-level) evidence


Müller MJ, Dragicevic A, Fric M, Gaertner I, Grasmäder K, Härtter S, Hermann E, Kuss HJ, Laux G, Oehl W, Rao ML, Rollmann N, Weigmann H, Weber-Labonte M, Hiemke C. Therapeutic drug monitoring of tricyclic antidepressants: how does it work under clinical conditions? Pharmacopsychiatry. 2003 May:36(3):98-104     [PubMed PMID: 12806567]

Level 1 (high-level) evidence


White N, Litovitz T, Clancy C. Suicidal antidepressant overdoses: a comparative analysis by antidepressant type. Journal of medical toxicology : official journal of the American College of Medical Toxicology. 2008 Dec:4(4):238-50     [PubMed PMID: 19031375]

Level 2 (mid-level) evidence


Henry JA. A fatal toxicity index for antidepressant poisoning. Acta psychiatrica Scandinavica. Supplementum. 1989:354():37-45     [PubMed PMID: 2589102]

Level 2 (mid-level) evidence


Hawton K, Bergen H, Simkin S, Cooper J, Waters K, Gunnell D, Kapur N. Toxicity of antidepressants: rates of suicide relative to prescribing and non-fatal overdose. The British journal of psychiatry : the journal of mental science. 2010 May:196(5):354-8. doi: 10.1192/bjp.bp.109.070219. Epub     [PubMed PMID: 20435959]


Brennan FJ. Electrophysiologic effects of imipramine and doxepin on normal and depressed cardiac Purkinje fibers. The American journal of cardiology. 1980 Oct:46(4):599-606     [PubMed PMID: 7416020]

Level 3 (low-level) evidence


Giardina EG, Cooper TB, Suckow R, Saroff AL. Cardiovascular effects of doxepin in cardiac patients with ventricular arrhythmias. Clinical pharmacology and therapeutics. 1987 Jul:42(1):20-7     [PubMed PMID: 3595065]


Sakka SG, Kuethe F, Demme U, Hüttemann E. [Intoxication with a tricyclic antidepressant]. Der Anaesthesist. 2007 Jun:56(6):581-6     [PubMed PMID: 17464486]

Level 3 (low-level) evidence


Degner D, Grohmann R, Kropp S, Rüther E, Bender S, Engel RR, Schmidt LG. Severe adverse drug reactions of antidepressants: results of the German multicenter drug surveillance program AMSP. Pharmacopsychiatry. 2004 Mar:37 Suppl 1():S39-45     [PubMed PMID: 15052513]


Diltoer MW, Poelmans LW, Hubloue I, Spapen HD, Maes V, Huyghens LP. Combined intoxication with a tricyclic antidepressive agent and a neuroleptic. European journal of emergency medicine : official journal of the European Society for Emergency Medicine. 1996 Mar:3(1):52-5     [PubMed PMID: 8886672]

Level 3 (low-level) evidence


Frank RD, Kierdorf HP. Is there a role for hemoperfusion/hemodialysis as a treatment option in severe tricyclic antidepressant intoxication? The International journal of artificial organs. 2000 Sep:23(9):618-23     [PubMed PMID: 11059884]

Level 3 (low-level) evidence


Mirrakhimov AE, Ayach T, Barbaryan A, Talari G, Chadha R, Gray A. The Role of Sodium Bicarbonate in the Management of Some Toxic Ingestions. International journal of nephrology. 2017:2017():7831358. doi: 10.1155/2017/7831358. Epub 2017 Aug 8     [PubMed PMID: 28932601]


Brown C, Battista DR, Bruehlman R, Sereika SS, Thase ME, Dunbar-Jacob J. Beliefs about antidepressant medications in primary care patients: relationship to self-reported adherence. Medical care. 2005 Dec:43(12):1203-7     [PubMed PMID: 16299431]