desipramine NORPRAMIN
Class: TCA/DihydrodibenzazepineFDA Indications: MDD
Off-Label Use: Anxiety, Insomnia, Neuropathic Pain, Overactive Bladder
Prescribing
Forms: 10, 25, 50, 75, 100, 150mg tablet mg/dayStarting: 75 mg qd or in divided doses; gradually ↑ dose to achieve desired therapeutic effect; maximum dose 300 mg qd
Stopping: ↓ 50% x3 days, then ↓ another 50% x3 days, then D/C entirely.
Monitoring: Suggested plasma level 100-300 ng/mL
Precautions
Contraindications: Concomitant use of MAOIs; patient s/p MI; coadministration of other QT-prolonging agents; h/o QT ↑ or arrhythmia; caution in patients with hypo-K+ or hypo-Mg2+Serious Side Effects: 5HT syndrome; ↓ seizure threshold; QT↑, arrhythmias, tachycardia, orthostatic hypotension
Possible Risk of TdP
Side Effects: anticholinergic side effects, weight gain, sedation/somnolence, increased appetite, diarrhea, dysgeusia, dizziness, weakness/asthenia, headache, sexual dysfunction, hyperhidrosis, anxiety, restlessness
Pharmacokinetics
t½: 24 (12-54)° TMAX: 2-6°Substrate of: 2D6
Inhibits: ∅ ; Induces: ∅
Active Metabolites: ∅
DDIs
- - DO NOT CO-PRESCRIBE WITH MAOIs (need a 14-day washout period)
- - caution combining with other CNS depressants & anticholingerics
Misc
- - the most noradrenergic TCA – exhibits a greater potency and selectivity for the NET than do the other secondary TCAs
- - 30X more potent at inhibiting NET than SERT
- - desipramine is one of the few TCAs where monitoring of plasma drug levels has been well studied
- - fewer anticholinergic side effects than some other TCAs
- - desipramine is imipramine's active metabolite
Special Populations
Category C—Although the data are limited, desipramine does not appear to be a major human teratogen. When used near term, neonatal abstinence syndrome is possible.
Desipramine is excreted into breast milk. No reports of adverse effects have been located. In one patient, milk:plasma ratios of 0.4-0.9 were measured with milk levels ranging between 17 and 35 mcg/ mL. A 1996 review of antidepressant treatment during breastfeeding found no information that desipramine exposure during nursing resulted in quantifiable amounts in an infant or that the exposure caused adverse effects. In 2001, the American Academy of Pediatrics classified desipramine as a drug whose effect on the nursing infant is unknown but may be of concern.
Desipramine has a less toxic side effect profile, especially with respect to anticholinergic effects, but its efficacy has not been well studied.
Baseline ECG is recommended for patients over age 50.
2019 BEE℞S Recommendation: Avoid. Highly anticholinergic, sedating, and cause orthostatic hypotension.
No dosage adjustment necessary.
All TCAs are hepatically metabolzed, highly protein bound and will accumulate, and associated with ↑ LFTs.