Clinical Information

Imipramine and its metabolite desipramine are tricyclic antidepressants used to treat endogenous depression requiring 1 to 3 weeks of treatment before therapeutic effectiveness becomes apparent. Desipramine is used for treatment of endogenous depression when the patient needs a drug with significant stimulatory side effects. These drugs have also been employed in the treatment of enuresis (involuntary urination) in childhood and severe obsessive-compulsive neurosis.

Imipramine

The optimal dosage of imipramine yields trough (just before the next dose) blood levels of imipramine and desipramine combined from 175 to 300 ng/mL. If desipramine is given, no imipramine should be detected and the therapeutic concentration for desipramine alone is 100 to 300 ng/mL.

Toxicity associated with imipramine is characterized by QRS widening leading to ventricular tachycardia and asystole. In some patients, toxicity may manifest at lower concentrations, or at therapeutic concentrations in the early state of therapy. Cardiac toxicity (first-degree heart block) is usually associated with blood concentrations in excess of 300 ng/mL.

Desipramine

Desipramine is the antidepressant of choice in patients where maximal stimulation is indicated.

The therapeutic concentration of desipramine is 100 to 300 ng/mL. About 1 to 3 weeks of treatment are required before therapeutic effectiveness becomes apparent.

The most frequent side effects are those attributable to anticholinergic effects; dry mouth, constipation, dizziness, tachycardia, palpitations, blurred vision, and urinary retention. These occur at blood concentrations in excess of 300 ng/mL, although they may occur at therapeutic concentrations in the early stage of therapy. Cardiac toxicity (first-degree heart block) is usually associated with blood concentrations in excess of 300 ng/mL.