Last reviewed 2026-04-20 · How we verify

Triptil (PROTRIPTYLINE)

Triptil (Protriptyline) is a tricyclic antidepressant small molecule that targets the adenosine receptor A3. Originally developed by, it was FDA approved in 1967 for the treatment of depressive disorder. Currently off-patent, it has four generic manufacturers. Key safety considerations include its potential for cardiac side effects and interactions with other medications.

At a glance

Approved indications

• 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 protriptyline hydrochloride 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. Protriptyline 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
• Heart block
• Arrhythmias
• Hypertension
• Tachycardia
• Palpitation
• Hypotension
• Seizures
• Confusional states
• Hallucinations
• Disorientation

Drug interactions

• rifabutin
• rifampicin
• rifapentine
• ritonavir
• selegiline
• sertraline
• tapentadol
• tranylcypromine
• valproic acid
• ziprasidone

Key clinical trials

• Bioequivalency Study of Protriptyline 10 mg Tablets Under Fasted Conditions (NA)
• Treatment-Resistant Depression, Hippocampus Atrophy and Serotonin Genetic Polymorphism (PHASE4)

Primary sources

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