Desipramine (Norpramin)

Class

Tricyclic antidepressant (TCA)

Mechanism

Selective inhibition of norepinephrine reuptake with minimal serotonergic, anticholinergic, and sedative effects compared to other TCAs.

FDA-Approved Use

Major depressive disorder (MDD).

Off-Label Use

Attention-deficit/hyperactivity disorder (ADHD), neuropathic pain, enuresis, augmentation in treatment-resistant depression, depression in Parkinson’s disease (PD)

Formulation

Oral tablets.

Titration

25–50 mg p.o. daily, titrated based on clinical response and tolerability.

Dose Range

75–200 mg/day, with lower doses often sufficient for pain management.

Kinetics

Metabolized primarily by CYP2D6; half-life approximately 15–30 hours.

Common AEs

Dry mouth, constipation, insomnia, weight loss, tremor, orthostatic hypotension.

Serious/Rare AEs

Cardiac conduction abnormalities including QT prolongation; overdose risk with toxicity similar to other TCAs.

Monitoring

Baseline ECG recommended for patients over 40 or with cardiac risk factors; monitor blood pressure, heart rate, and signs of orthostatic hypotension.

Black Box Warning

Increased risk of suicidal ideation in children, adolescents, and young adults.

Considerations

Desipramine may be effective in the treatment of ADHD, especially in children and adolescents with co-occurring tic disorders. May be better tolerated in elderly or those with mild cognitive impairment (MCI) due to lower anticholinergic and sedative burden; however, still carries risk of falls and cardiac conduction changes. Use with caution and monitor closely in these populations.