Clinical Information

Amitriptyline is a tricyclic antidepressant that is metabolized to nortriptyline, which has similar pharmacologic activity. The relative blood levels of amitriptyline and nortriptyline are highly variable among patients. Amitriptyline is the drug of choice in treatment of depression when the side effect of mild sedation is desirable. Nortriptyline is used when its stimulatory side effect is considered to be of clinical advantage.

Nortriptyline is unique among the antidepressants in that its blood level exhibits the classical therapeutic window effect, as blood concentrations above or below the therapeutic window correlate with poor clinical response. Thus, therapeutic monitoring to ensure that the blood level is within the therapeutic window is critical to accomplish successful treatment with this drug.

Amitriptyline displays major cardiac toxicity when the combined serum level of amitriptyline and nortriptyline is above 500 ng/mL, characterized by QRS widening (intraventricular conduction delay), which leads to ventricular tachycardia and asystole. In some patients, toxicity may manifest at lower concentrations.

Like amitriptyline, nortriptyline can cause major cardiac toxicity when the concentration is above 500 ng/mL, characterized by QRS widening, which leads to ventricular tachycardia and asystole. In some patients, toxicity may manifest at lower concentrations.