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Doxepin belongs to the class of tricyclic antidepressant medications approved by the US Food and Drug Administration (FDA) for the treatment of major depressive disorder, anxiety, and insomnia, as well as for managing skin pruritus. Doxepin functions 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. This activity provides an overview of doxepin's indications, administration, mechanism of action, adverse effects, contraindications, and toxicity to improve the competence of the interprofessional healthcare team in administering the drug safely and effectively. This activity highlights the importance of utilizing a team-based approach to treat patients with major depressive disorder. Collaborative care involving primary care, psychiatry, and other related disciplines would optimize patient outcomes. Objectives: Identify the appropriate indications for prescribing doxepin, including its approved uses in the treatment of major depressive disorder, anxiety disorders, and insomnia. Implement appropriate dosing strategies for initiating doxepin therapy, considering the recommended titration schedule and the need for dosage adjustments based on individual patient response and tolerability. Select the most appropriate formulation, dose, and dosing schedule of doxepin based on individual patient factors, preferences, and treatment goals. Collaborate with interdisciplinary healthcare team members to provide comprehensive care for patients receiving doxepin therapy, addressing both psychiatric and psychosocial needs. Access free multiple choice questions on this topic.

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]

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.