Desipramine

Desipramine (Norpramin, Pertofane) is a tricyclic antidepressant (TCA). It inhibits the reuptake of norepinephrine and to a lesser extent serotonin. It is used to treat depression, but not considered a first line treatment since the introduction of SSRI antidepressants. Desipramine is an active metabolite of imipramine.

Along with other tricyclics, desipramine has found use in treating neuropathic pain. The mechanism of action seems to involve the activation, through norepinephrine reuptake inhibition, of descending pathways in the spinal cord that block pain signals from ascending to the brain. Desipramine is one of the most potent and selective medications in this respect. It may also be used to treat symptoms of Attention Deficit Hyperactivity Disorder, as the underproduction of norepinephrine has been increasingly linked to symptoms associated with Attention Deficit Disorder. It may also be used to treat symptoms of cocaine withdrawal.

Cardiac arrhythmia
On December 2, 2009, the US Food and Drug Administration (FDA) and Sanofi-Aventis are warning healthcare professionals to use caution when prescribing the antidepressant desipramine hydrochloride (Norpramin) in patients with a family history of dysrhythmias or sudden cardiac death.

"The new safety information states that extreme caution should be used when this drug is given to patients who have a family history of sudden death, cardiac dysrhythmias, and cardiac conduction disturbances," according to an alert sent today from MedWatch, the FDA's safety information and adverse event reporting program.

The FDA and the manufacturer also warn that some patients may have seizures before cardiac dysrhythmias and death. Desipramine overdose is more likely to result in death than overdose with other tricyclic antidepressants, notes a company letter sent to healthcare professionals.

The "warnings" and "overdosage" sections of the drug's labeling are being changed to reflect these potential adverse events.

Genotoxicity
Desipramine has been shown to be genotoxic in fruit flies and associated with an increased risk of breast cancer in women.