Amitriptyline and nortriptyline, serum

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.

Amitriptyline displays major cardiac toxicity when the concentration of amitriptyline and nortriptyline is in excess of 300 ng/mL, characterized by QRS widening leading to ventricular tachycardia and asystole. In some patients, toxicity may manifest at lower concentrations.

Most individuals display optimal response to amitriptyline when combined serum levels of amitriptyline and nortriptyline are between 80 and 200 ng/mL. Risk of toxicity is increased with combined levels > or =300 ng/mL.

Most individuals display optimal response to nortriptyline with serum levels between 70 and 170 ng/mL. Risk of toxicity is increased with nortriptyline levels > or =300 ng/mL.

Some individuals may respond well outside of these ranges, or may display toxicity within the therapeutic range, thus interpretation should include clinical evaluation.

Therapeutic ranges are based on specimens drawn at trough (ie, immediately before the next dose).

• Sample of blood serum
• We perform the test upon request