Last reviewed 2026-04-20 · How we verify

Endep (AMITRIPTYLINE)

Endep (amitriptyline) is a tricyclic antidepressant developed by AstraZeneca, targeting the histamine H1 receptor. It is a small molecule modality, FDA-approved in 1961 for treating depressive disorder and mixed anxiety and depressive disorder. As an off-patent medication, Endep is available from 33 generic manufacturers. Key safety considerations include its potential for cardiac side effects and interactions with other medications. Commercially, Endep is widely available in generic form.

At a glance

Approved indications

• Depressive disorder
• Mixed anxiety and depressive disorder

Boxed warnings

• Suicidality and Antidepressant Drugs: Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of amitriptyline hydrochloride tablets or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Amitriptyline hydrochloride is not approved for use in pediatric patients. (See WARNINGS: Clinical Worsening and Suicide Risk , PRECAUTIONS: Information for Patients , and PRECAUTIONS: Pediatric Use )

Common side effects

• Myocardial infarction
• Stroke
• Hypertension
• Tachycardia
• Palpitation
• Hypotension
• Syncope
• Heart block
• Arrhythmias
• Nonspecific ECG changes and changes in AV conduction
• Seizures
• Coma

Drug interactions

• carbamazepine
• cimetidine
• cisapride
• clonidine
• duloxetine
• erythromycin
• fluconazole
• fluoxetine
• fluvoxamine
• isocarboxazid
• itraconazole
• ketoconazole

Key clinical trials

• Responding With Evidence and Access for Childhood Headaches (NA)
• Evaluating Use of Topical Imipramine and Amitriptyline in Reducing Ultraviolet B Light-Induced Redness in Patients With Rosacea (PHASE2)
• Efficacy of Two Doses of Duloxetine and Amitriptyline in Subjects With Refractory Chronic Cough (PHASE2)
• Efficacy of Two Doses of Duloxetine & Amitriptyline in Interstitial Lung Disease-related Cough (PHASE2)
• Different Transcutaneous Electrical Nerve Stimulation Modes in Pudendal Neuralgia Post-prostatectomy (NA)
• Efficacy of Amitriptyline for Painful Bladder Syndrome (PBS) (PHASE3)
• Multiprofen-CC to Reduce Pain in Hand Arthritis (PHASE3)
• Effectiveness of AI-Guided Exercise and Pain Neuroscience Education for Fibromyalgia (FIBROIA) (NA)

Primary sources

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