Desipramine

NORPRAMIN

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.

FDA-approved for

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

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

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

⚠ BOXED WARNING

Cost, est. cash$10–$300/month

Generic entry1987

Therapeutic safety burden3 / 4

Overdose danger4 / 4

Weight-gain liability1 / 4

Sedation liability1 / 4

QT / Torsades2 / 4

Direct muscarinic antagonism1 / 4

Embryofetal risk2 / 4

Legacy pregnancy categoryC

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

CYP2D6 substrate