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Desipramine (NORPRAMIN)

Desipramine (NORPRAMIN)

Released in 1963, desipramine (Norpramin) was once commonly prescribed, but is rarely used today. It is exceptionally fatal in overdose. Desipramine is an active metabolite of imipramine.  In regard to side effects, “desipramine is more desirable than imipramine”.

Desipramine (Norpramin) visual mnemonic by Dr Jason Cafer MD tombstone

Desipramine (and nortriptyline) have been referred to as second generation TCAs, making imipramine (and amitriptyline) first generations.


Desipramine is “drive enhancing” (stimulating), as opposed to “anxiety reducing”. It can be described as a relatively selective norepinephrinereuptake inhibitor (NRI). The trade name Norpramin is fitting because it is the most potent noradrenergic TCA. Don’t confuse Norpramin with nortriptyline, which is also noradrenergic.

Desipramine (Norpramin) interactions and indications by Dr Jason Cafer MD

Desipramine has the weakest antihistamine activity of all TCAs, making it non-sedating. While other TCAs are useful for treating insomnia, desipramine can cause insomnia. Recommended dosing is once daily in the morning. Unlike most other TCAs, desipramine causes no weight gain, sexual dysfunction, or orthostatic hypotension. It is the only TCA that can cause hypertension.  


The observation that desipramine helped ADHD was the basis for development of the NRI atomoxetine (Strattera). 


The main disadvantage of desipramine is risk of mortality in single-dose overdose, which appears to be higher than any other antidepressant. Out of 680 single-drug overdoses, there were 11 deaths, and 52 had major serious outcomes (Nelson & Spyker, 2017).


Therapeutic serum ranges are defined for desipramine, imipramine and nortriptyline— “mosquitos DINe on your blood”. On drug screens, desipramine can cause a false positive for amphetamine or LSD.


Dosing: Start 25–50 mg q AM and increase by 25–50 mg intervals every 2–3 days to target of 150–200 mg QD; Max is 300 mg; Taper gradually to stop. Therapeutic serum level is 150–300 ng/mL.

See Tricyclic antidepressants (TCAs)

Copyright 2021 CaferMed Publishing

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