protriptyline

Adjunctive therapy

Brands: Vivactil

Last reviewed 2025-10-05

Reviewed by PsychMed Editorial Team.

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Quick answers

What is protriptyline?
Protriptyline (Vivactil) is an activating secondary amine tricyclic antidepressant reserved for legacy treatment-resistant depression regimens and, rarely, narcolepsy-related hypersomnolence or cataplexy due to its pronounced anticholinergic and cardiotoxic risks.
What is Vivactil?
Vivactil is a brand name for protriptyline.
What is Vivactil (protriptyline) used for?
Label indications include: Depression; off-label adjunct for narcolepsy-related cataplexy.
What drug class is Vivactil (protriptyline)?
Secondary amine tricyclic antidepressant; enhances norepinephrine with minimal sedative effect.
What strengths does Vivactil (protriptyline) come in?
Oral tablets: 5 mg, 10 mg (brand Vivactil; limited generic supply that often requires special ordering).

Snapshot

Class: Adjunctive therapy
Common US brands: Vivactil
Therapeutic drug monitoring recommended; reference range 70–250 ng/mL.
Last reviewed: 2025-10-05

Label indications

Depression; off-label adjunct for narcolepsy-related cataplexy.

View labelExact

Clinical Highlights

Protriptyline (Vivactil) is an activating secondary amine tricyclic antidepressant reserved for legacy treatment-resistant depression regimens and, rarely, narcolepsy-related hypersomnolence or cataplexy due to its pronounced anticholinergic and cardiotoxic risks. Continuation therapy should involve clinicians comfortable with therapeutic drug monitoring, ECG surveillance, and constipation management because safer antidepressants are usually preferred first-line.

Because the drug has a long half-life, narrow therapeutic window, and lethal overdose potential, assess alternatives when initiating therapy and coordinate care with cardiology or sleep specialists for ongoing use.
The compare view can help contrast activation, anticholinergic load, and cardiotoxicity, and the Protriptyline evidence feed can support decisions about maintaining legacy regimens.
Major depressive disorder (FDA 1967)
Generic: Generics exist but shortages are common—confirm sourcing before refills.

Dosing & Formulations

Oral tablets: 5 mg, 10 mg (brand Vivactil; limited generic supply that often requires special ordering). Initiate 5 mg three to four times daily (15–20 mg/day) and increase by 5 mg every 3–5 days as tolerated to a usual target of 20–40 mg/day (maximum 60 mg/day).

Once steady state is achieved, consolidate dosing to morning and early afternoon administrations (e.g., 20 mg at 0800, 10 mg at 1300) to limit insomnia.
In older adults, frail patients, or those with cardiac disease, start 5 mg twice daily, titrate cautiously with baseline/follow-up ECGs, and rely on plasma levels to keep concentrations below 150 ng/mL.

Monitoring & Risks

Boxed warning: Antidepressants increase suicidality risk in children, adolescents, and young adults; monitor closely during initiation and dose changes. Anticholinergic effects: Dry mouth, constipation, urinary retention, blurred vision—prophylactic bowel regimens and hydration counseling recommended.

Orthostatic hypotension: Advise slow positional changes and monitor blood pressure regularly.
Tachycardia: Baseline and follow-up vitals needed, especially if combined with stimulants.
Weight change: Despite its activating profile, modest weight gain can occur; monitor BMI.
Insomnia, agitation, or tremor—minimize with earlier dosing.

Drug Interactions

Strong CYP2D6 or CYP2C19 inhibitors (e.g., fluoxetine, paroxetine, bupropion, quinidine, ritonavir) markedly increase concentrations—halve the dose and recheck plasma levels. MAOIs, linezolid, and methylene blue are contraindicated; enforce a 14-day washout to prevent hypertensive crisis or serotonin toxicity.

Sympathomimetics and stimulants used for narcolepsy can amplify hypertension and tachycardia—monitor closely.
Additive QT prolongation with class Ia/III antiarrhythmics, certain antipsychotics, macrolides, or methadone warrants ECG monitoring.
Cumulative anticholinergic burden with first-generation antihistamines, clozapine, or bladder antispasmodics increases delirium and constipation risk.

Practice Notes

Obtain baseline ECG, electrolytes, and weight before titration; repeat ECG after reaching target dose or if plasma levels exceed 150 ng/mL. Order therapeutic drug monitoring after 2–3 weeks on a stable dose and after dose or interacting medication changes to maintain 70–250 ng/mL.

Educate patients on securing medication, recognizing cardiac or serotonin toxicity, and maintaining hydration/fiber to mitigate gastrointestinal hypomotility.
Screen for bipolar spectrum symptoms—protriptyline can precipitate mania/hypomania; coordinate care with the bipolar disorder hub when activation appears.

References

Protriptyline hydrochloride tablets prescribing information — DailyMed (2023)
Therapeutic drug monitoring of protriptyline — Therapeutic Drug Monitoring (2022)
Use of protriptyline in narcolepsy management — Sleep Medicine (2021)
APA Clinical Practice Guideline for the Treatment of Depression — American Psychiatric Association (2023)Guidelinedepressionclinical
CANMAT 2024 Clinical Guidelines for Major Depressive Disorder — Canadian Journal of Psychiatry (2024)