desipramine

Desipramine is a tricyclic antidepressant (TCA) developed by Geigy in the 1960s. It is a secondary amine TCA, closely related to imipramine, and is characterized by relatively selective inhibition of the norepinephrine transporter (NET) with weaker effects on the serotonin transporter (SERT). This NE-focused profile contributes to a stimulant-like effect and typically carries a lower burden of sedation and anticholinergic effects than many tertiary amine TCAs.

Therapeutic use of desipramine has been for the treatment of major depressive disorder. It is less commonly prescribed today due to safety concerns and the availability of newer antidepressants. Desipramine has been used off-label for conditions such as attention-deficit/hyperactivity disorder and certain chronic pain syndromes, reflecting the role of norepinephrine reuptake inhibition in multiple syndromes.

Adverse effects and safety considerations include dry mouth, constipation, urinary retention, blurred vision, and orthostatic hypotension. Sedation tends to be less pronounced than with some TCAs but cardiotoxic risks persist, including tachycardia and arrhythmias, particularly in overdose. Like other TCAs, desipramine can prolong the QT interval and has notable anticholinergic effects compared with non-TCA antidepressants. It may interact with monoamine oxidase inhibitors and other serotonergic agents; caution is advised in elderly patients and those with heart disease or seizure disorders.

Pharmacokinetics: Desipramine is taken orally and undergoes extensive hepatic metabolism, with the major active metabolite 2-hydroxydesipramine. It has a relatively long elimination half-life, often allowing once-daily dosing, and is excreted primarily in the urine.