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Desipramine

Norpramin

Tricyclic AntidepressantGeneric availableTDM data

Mechanism of Action Available evidence suggests that many depressions have a biochemical basis in the form of a relative deficiency of neurotransmitters such as norepinephrine and serotonin. Norepinephrine deficiency may be associated with relatively low urinary 3-methoxy-4-hydroxyphenyl glycol (MHPG) levels, while serotonin deficiencies may be associated with low spinal fluid levels of 5-hydroxyindoleacetic acid. While the precise mechanism of action of the tricyclic antidepressants is unknown, a leading theory suggests that they restore normal levels of neurotransmitters by blocking the re-uptake of these substances from the synapse in the central nervous system. Evidence indicates that the secondary amine tricyclic antidepressants, including NORPRAMIN, may have greater activity in blocking the re-uptake of norepinephrine. Tertiary amine tricyclic antidepressants, such as amitriptyline, may have greater effect on serotonin re-uptake. NORPRAMIN is not a monoamine oxidase inhibitor (MAOI) and does not act primarily as a central nervous system stimulant. It has been found in some studies to have a more rapid onset of action than imipramine. Earliest therapeutic effects may occasionally be seen in 2 to 5 days, but full treatment benefit usually requires 2 to 3 weeks to obtain.

Compare Desipramine

FDA-Approved Indications

  • depression

Common Off-Label Uses

  • ADHD
  • Neuropathic pain
  • Panic disorder
  • Cocaine dependence (adjunct)

What Sets This Drug Apart

  • Most noradrenergic TCA (secondary amine); least sedating and least anticholinergic of the TCAs
  • Active metabolite of imipramine — sometimes used as the 'cleaner' noradrenergic option when imipramine's mixed profile causes excessive side effects
  • Sudden-death case reports in children make it the highest-cardiac-risk TCA in pediatric populations; avoid in children when alternatives exist
  • Plasma level monitoring established (optimal 125-300 ng/mL); CYP2D6 substrate with pharmacogenomic implications for poor metabolizers
  • Off-label noradrenergic agent for smoking cessation, cocaine dependence, and ADHD
  • Simplest CYP profile among TCAs (primarily CYP2D6 only) but still a moderate CYP2D6 inhibitor
Boxed Warning
Suicidality and Antidepressant Drugs Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality)