Protriptyline

VIVACTIL

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Pronunciation: proe-TRIP-ti-leen

Protriptyline ballicule: receptor binding, kinetics and half-life diagram — Mechanism of action: Protriptyline ballicule

Protriptyline VIVACTIL mascot mnemonic cartoon — Visual mnemonic: Protriptyline mascot
**“Vivactil the pterodactyl’s Pro tip (to lean)”**
tricycle → tricyclic antidepressant

What it isActivating tricyclic inhibiting norepinephrine and serotonin reuptake; depression.

Why this oneIt is among the most activating and least sedating tricyclics, suiting anergic depression better than bedtime use.

What limits itInsomnia and anticholinergic effects limit use; overdose can be fatal, and long persistence makes titration slow.

Protriptyline molecular structure (skeletal formula) — Molecular structure: Protriptyline

FDA-approved for

depression (~1967)

FDA label

Read the full label on DailyMed ↗

BOXED WARNING Increased risk of suicidal thinking and behavior in children, adolescents, and young adults; not approved for pediatric use — monitor for clinical worsening and suicidality.

FDA dosing	Population	Start	Target	Max
Depression	Adults	15–40 mg/day divided TID–QID		60 mg/day
Depression	Adolescent / elderly	5 mg TID, titrate gradually

Renal Undefined

Hepatic Undefined

Instructions

Initiate at a low dose and increase gradually; make increases in the morning dose
In elderly, monitor cardiovascular system closely if daily dose exceeds 20 mg
Allow a minimum of 14 days after discontinuing an MAOI before starting protriptyline

Available strengths

tab 5, 10 mg

Contraindications

MAOIs (concurrently or within 14 days) due to risk of hyperpyretic crises, severe convulsions, and death
Concomitant cisapride (QT prolongation, cardiac arrhythmias, conduction disturbances)
Acute recovery phase following myocardial infarction

Cautions

Suicidality — monitor for clinical worsening (boxed)
More likely than other TCAs to aggravate agitation and anxiety
Cardiovascular reactions — tachycardia, orthostatic hypotension, arrhythmias
Anticholinergic effects (urinary retention, blurred vision, constipation, paralytic ileus)
Lowers seizure threshold
Confusional states/hallucinations, esp. in the elderly

Adverse reactions

Orthostatic hypotension
Tachycardia/palpitations
Arrhythmias/heart block
Confusional states with hallucinations (elderly)
Agitation/anxiety/insomnia
Anticholinergic effects (dry mouth, blurred vision, urinary retention, constipation)
Tremor
Drowsiness/dizziness
Weight change
Sexual dysfunction/gynecomastia

Pregnancy Undefined

Lactation Undefined

Cost

Protriptyline (VIVACTIL)

What pharmacies pay · NADAC 9/30/26

Strength		#/mo	generic $/mo	CostPlus
5 mg	tab	90 TID	$235.64	offered
10 mg	tab	90 TID	$243.99	offered

Generic entry1995

⚠ BOXED WARNING

Suicidal thoughts and behaviors in patients under 25

Classes and tags

Clinical profile

Therapeutic safety burden3 / 4

Overdose danger4 / 4

Weight-gain liability1 / 4

Sedation liability1 / 4

QT / Torsades1 / 4

Direct muscarinic antagonism3 / 4

Embryofetal risk2 / 4

Legacy pregnancy categoryC

Defining liabilityTricyclic anticholinergic and cardiac toxicity become life-threatening in overdose.

Serotonicity

This drug is routinely called serotonergic. By Gillman’s human-effect criteria it does not raise serotonin in the synapse.

Predominantly NRI activity; no established clinically meaningful SRI mechanism.

Label contraindicationMAOIs (concurrently or within 14 days) due to risk of hyperpyretic crises, severe convulsions, and death. The label governs prescribing; Gillman’s point concerns serotonin toxicity only.

It binds the serotonin transporter, and its SERT peg is drawn to that textbook affinity. The pale halo around the peg marks binding that, by Gillman’s human-effect criteria, does not produce clinical serotonin reuptake inhibition.

Gillman’s four human testsA measurable SERT affinity that fails all four is not clinical serotonicity.