BLACK BOX WARNING
- suicidality in children, adolescents, and young adults
desipramine
Brand: Norpramin
⚠ BBW Beers Criteria TDM Required Prototype: amitriptyline
Drug Class: tricyclic antidepressant (TCA)
Drug Family: antidepressant
Subclass: secondary amine TCA
Organ Systems: cns
Mechanism of Action
Active demethylated metabolite of imipramine; has the highest selectivity for NET over SERT among TCAs, producing primarily noradrenergic effects. The reduced receptor promiscuity compared to tertiary amine TCAs results in fewer anticholinergic and sedating side effects.
NET (norepinephrine transporter)SERT (serotonin transporter)
Indications
- major depressive disorder
- off-label: ADHD
- off-label: neuropathic pain
- off-label: chronic pain
Contraindications
- concurrent MAOI use
- acute post-MI recovery
- QT prolongation
Adverse Effects
Common
- dry mouth (less than amitriptyline)
- insomnia (activating)
- tremor
- tachycardia
- orthostatic hypotension
Serious
- QT prolongation
- sudden cardiac death risk (pediatric cardiac monitoring required)
- seizures in overdose
Pharmacokinetics (ADME)
| Absorption | well absorbed orally; bioavailability ~51-73% |
| Distribution | protein binding ~90%; large Vd ~22-59 L/kg |
| Metabolism | primarily via CYP2D6; subject to significant CYP2D6 polymorphism effects |
| Excretion | primarily renal as metabolites |
| Half-life | 12-24 hours |
| Onset | 2-4 weeks for antidepressant effect |
| Peak | 3-4 hours |
| Duration | 24 hours |
| Protein Binding | 90% |
| Vd | 22-59 L/kg |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| MAOIs | serotonin syndrome and hypertensive crisis | contraindicated |
| CYP2D6 inhibitors | increase desipramine levels significantly | major |
| sympathomimetics | potentiation of cardiovascular effects | moderate |
Nursing Considerations
- Desipramine is more activating than amitriptyline; insomnia rather than sedation is common — schedule dosing in the morning to minimize sleep disruption.
- Pediatric cardiac monitoring is required if used for ADHD in children; sudden cardiac death has been reported in pediatric patients receiving desipramine.
- Therapeutic plasma levels are 125-300 ng/mL; TDM guides dosing and reduces toxicity risk.
- Baseline ECG and periodic monitoring are mandatory; QRS widening is an early marker of cardiotoxicity in overdose.
Clinical Pearls
- Desipramine has the highest norepinephrine-to-serotonin selectivity among TCAs, making it useful for understanding mechanistic differences within the TCA class in pharmacology education.
- Its activation profile (insomnia rather than sedation) makes it more suitable for patients with hypersomnia-predominant depression but problematic for those with severe insomnia.
Safety Profile
Pregnancy use-with-caution
Lactation use-with-caution
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.