Desipramine

NORPRAMIN

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Pronunciation: des-IP-ra-meen

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

Desipramine NORPRAMIN mascot mnemonic cartoon — Visual mnemonic: Desipramine mascot
**“Deceased Norman”**

What it isSecondary amine tricyclic; depression and neuropathic pain.

Why it mattersThe least anticholinergic and least sedating tricyclic, and it has a defined therapeutic level range.

What it changesLethal in overdose from sodium channel blockade. CYP2D6 substrate; it is the active metabolite of imipramine.

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

FDA-approved for

depression (~1964)

Off-label

neuropathic pain

FDA label

Read the full label on DailyMed ↗

BOXED WARNING Increased suicidal thinking and behavior in children, adolescents, and young adults; not for pediatric use.

FDA dosing	Population	Start	Target	Max
Depression	Adult	100 mg/day (initiate low)	100-200 mg/day	300 mg/day
Depression	Adolescent / geriatric	25 mg/day (initiate low)	25-100 mg/day	100 mg/day (150 mg if severe)

Renal Undefined

Hepatic Undefined

Instructions

Initiate at a low dose and increase per clinical response and tolerance
Doses up to 300 mg/day generally initiated in hospital with ECG monitoring
Not recommended for use in children

Available strengths

tab 10, 25, 50, 75, 100, 150 mg

Contraindications

MAOIs (concurrently or within 14 days) due to risk of serotonin syndrome
Acute recovery period following myocardial infarction

Cautions

Suicidality - monitor for worsening depression/emergent suicidality
Serotonin syndrome with serotonergic/MAOI co-administration
Cardiovascular: arrhythmias, conduction disturbance, MI, stroke; QRS/QT prolongation signals toxicity
Seizures; lowers seizure threshold
Anticholinergic effects; caution in urinary retention, glaucoma
Sudden death reported in children

Adverse reactions

Cardiovascular: orthostatic hypotension, arrhythmias, tachycardia, conduction block
Psychiatric/neurologic: confusion (elderly), anxiety, insomnia, tremor, seizures
Anticholinergic: dry mouth, blurred vision, constipation, urinary retention
Hematologic: bone marrow depression, agranulocytosis, thrombocytopenia

Pregnancy Undefined

Lactation Undefined

Cost

Desipramine (NORPRAMIN)

What pharmacies pay · NADAC 9/30/26

Strength		#/mo	generic $/unit	CostPlus
10 mg	tab	per unit	$0.14/ea	offered
25 mg	tab	per unit	$0.13/ea	offered
50 mg	tab	per unit	$0.22/ea	offered
75 mg	tab	per unit	$0.28/ea	offered
100 mg	tab	per unit	$0.45/ea	offered
150 mg	tab	per unit	$0.83/ea	offered

Generic entry1987

⚠ 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 / Torsades3 / 4

Direct muscarinic antagonism1 / 4

Embryofetal risk2 / 4

Legacy pregnancy categoryC

Defining liabilityAnticholinergic effects and cardiac sodium-channel blockade make overdose rapidly life-threatening.

Serotonicity

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

Potent NRI with negligible SRI activity; no Gillman-type serotonin-toxicity mechanism.

Label contraindicationMAOIs (concurrently or within 14 days) due to risk of serotonin syndrome. 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.