DESIPRAMINE HYDROCHLORIDE

Clinical safety rating: caution

Animal studies have proved adverse effects but may be safe for humans

How it works

Inhibits reuptake of norepinephrine and serotonin at presynaptic neuronal membrane, increasing their concentrations in the synaptic cleft.

What the body does with it

Metabolism	Hepatic, primarily via CYP2D6 isoenzyme; active metabolite 2-hydroxydesipramine.
Excretion	Renal excretion of metabolites accounts for approximately 70%; fecal elimination ~30%. Unchanged drug <5% in urine.
Half-life	Terminal half-life 12–30 hours (mean ~22 hours); extensive interindividual variability due to CYP2D6 polymorphism.
Protein binding	92% bound primarily to alpha-1-acid glycoprotein (AAG) and albumin.
Volume of Distribution	20–60 L/kg (mean ~42 L/kg); extensive tissue distribution including brain.
Bioavailability	Oral ~60% (range 30–70%) due to first-pass metabolism.
Onset of Action	Oral: antidepressant effect 1–3 weeks; therapeutic plasma levels achieved in 3–5 days.
Duration of Action	Antidepressant effect persists for several days after discontinuation; single dose effects last ~24 hours.

Classification & Brands

Dosing & administration

Oral: Initial 25-75 mg/day in divided doses; increase gradually to 100-200 mg/day, maximum 300 mg/day. Usual maintenance: 100-200 mg/day single or divided doses.

Dosage form	TABLET
Renal impairment	No specific guidelines; use with caution in severe renal impairment. GFR 10-50 mL/min: reduce dose by 25-50%. GFR <10 mL/min: reduce dose by 50-75%.
Liver impairment	Child-Pugh Class A: reduce dose by 25-50%. Child-Pugh Class B: reduce dose by 50-75%. Child-Pugh Class C: avoid use or use with extreme caution, maximum 100 mg/day.
Pediatric use	Adolescents: 25-50 mg/day initially, increase to 100-200 mg/day. Children (6-12 years): 1-3 mg/kg/day in divided doses, maximum 5 mg/kg/day or 150 mg/day. Not recommended for children <6 years.
Geriatric use	Initial 10-25 mg/day, increase by 10-25 mg/week; maximum 150 mg/day. Monitor for anticholinergic effects and orthostatic hypotension.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

MAOIs can cause serotonin syndrome and hyperpyrexia Strong anticholinergic effects may occur with other drugs Increased risk of suicide in children and young adults.

Breastfeeding	Desipramine is excreted in breast milk; M/P ratio not well defined (estimated ~0.5-1.5). Infant serum concentrations are low to undetectable, but adverse effects (e.g., irritability, sleep disturbance) reported rarely. Monitor infant for sedation, poor feeding. Benefits usually outweigh risks if maternal depression requires treatment.
Teratogenic Risk	First trimester: Limited data, but associated with cardiovascular malformations (e.g., VSD) in some studies; risk appears low. Second and third trimesters: Risk of neonatal withdrawal syndrome (irritability, respiratory distress) and anticholinergic effects (e.g., urinary retention, constipation). No clear teratogenicity.

Warnings & precautions

■ FDA Black Box Warning

Suicidality and antidepressant drugs: Increased risk of suicidal thinking and behavior in children, adolescents, and young adults with major depressive disorder and other psychiatric disorders.

Side Effect Profile

Common Effects	Dry mouth
Serious Effects

Absolute Contraindications

["Hypersensitivity to desipramine or other tricyclic antidepressants","Recent myocardial infarction","Concomitant use of MAOIs (within 14 days)","Concurrent use of linezolid or intravenous methylene blue"]

Clinical Precautions

Precautions

["Activation of mania/hypomania","Seizures","Cardiovascular effects (QT prolongation, arrhythmias, orthostatic hypotension)","Serotonin syndrome (especially with MAOIs)","Anticholinergic effects (urinary retention, narrow-angle glaucoma)","Bone marrow suppression"]

Clinical Tips & Counseling

Drug interactions

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