Section 06 · Monograph

Desipramine

Reviewed Nov 2026FDA label

NorpraminTCA

Black Box Warning

Antidepressants increased the risk compared to placebo of suicidal thinking and behavior in children, adolescents, and young adults (ages 18-24) in short-term studies of MDD and other psychiatric disorders
Risk must be weighed against clinical need; depression itself is associated with increased suicide risk
Not approved for use in pediatric patients
Close monitoring for clinical worsening and suicidality is warranted, especially during initial months of therapy and at times of dose changes

Neuropathic pain (diabetic peripheral neuropathy, postherpetic neuralgia)Off-label
Attention-deficit/hyperactivity disorder (ADHD, second-line)Off-label
Chronic pain syndromes and migraine prophylaxisOff-label

Tricyclic antidepressant (secondary amine, active metabolite of imipramine) that predominantly and potently inhibits presynaptic neuronal reuptake of norepinephrine, with comparatively weaker effects on serotonin reuptake
Increased norepinephrine (and to a lesser degree serotonin) availability is believed to underlie antidepressant efficacy
Analgesic effect in neuropathic pain thought to be independent of antidepressant activity, involving enhancement of descending noradrenergic inhibitory pain pathways and sodium-channel blocking activity
Has relatively less anticholinergic and sedative activity than tertiary amine TCAs

Adults: initial 100-200 mg/day; may increase gradually to 300 mg/day in severe cases under close supervision
Adolescents and elderly: initial 25-100 mg/day, maximum 150 mg/day
For neuropathic pain (off-label), typical starting dose 10-25 mg at bedtime, titrated slowly to 50-150 mg/day
Onset of antidepressant effect: earliest changes in 2-5 days, full benefit typically after 2-3 weeks
Consider plasma level monitoring in patients on high doses, with poor response, or with signs of toxicity
Taper gradually rather than stopping abruptly

Concurrent use of, or use within 14 days of discontinuing, an MAOI (including linezolid and IV methylene blue)
Acute recovery phase following myocardial infarction
Known hypersensitivity to desipramine or other dibenzazepine tricyclic antidepressants

MAOIs: contraindicated — risk of hyperpyrexia, severe seizures, serotonin syndrome, death
CYP2D6 inhibitors: substantially raise desipramine plasma levels
Serotonergic agents: risk of serotonin syndrome
CNS depressants and alcohol: additive sedation and CNS/respiratory depression
Sympathomimetic amines: potentiated cardiovascular effects
Anticholinergic agents: additive anticholinergic burden
Class 1C antiarrhythmics/QT-prolonging drugs: additive cardiac conduction risk

Dry mouth, blurred vision, constipation, urinary retention (anticholinergic)
Orthostatic hypotension
Cardiac arrhythmias, conduction delays (QRS/QT prolongation), tachycardia; sudden death reported, particularly in children given TCAs
Sedation, though generally less than tertiary amine TCAs
Tremor, seizures (lowered seizure threshold)
Confusion and agitation, especially in elderly
Hyponatremia/SIADH
Weight gain, sexual dysfunction

Monitor for suicidal ideation and behavioral changes, especially early in treatment
Baseline and periodic ECG (QRS widening is a marker of cardiotoxicity/overdose risk)
Blood pressure and heart rate, including orthostatic measurements
CBC if fever, sore throat, or other signs of blood dyscrasia occur
Serum sodium in patients at risk of hyponatremia
Plasma desipramine levels in patients on high doses or with poor response/tolerability

Safety not established; use only if potential benefits justify potential risks to mother and fetus
A pregnancy exposure registry exists for antidepressant use during pregnancy
Neonates exposed late in third trimester may experience withdrawal-type symptoms
Excreted into breast milk; caution advised and infant should be monitored for sedation or anticholinergic effects