Amitriptyline and Nortriptyline, Serum
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
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.
Nortriptyline is unique among the antidepressants in that its blood level exhibits the classical therapeutic window effect; 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.
Like amitriptyline, nortriptyline can cause major cardiac toxicity when the concentration 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.
Monitoring serum concentration during therapy
Evaluating potential toxicity
The test may also be useful to evaluate patient compliance
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).
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Amitriptyline analytical interferences; sertraline may cause falsely low results, and clomipramine, amlodipine, chlorpheniramine, chlorpromazine, promazine, trihexyphenidyl, citalopram, or escitalopram may cause false elevations.
Nortriptyline analytical interferences; sertraline may cause falsely low results, and metformin may cause false elevations.
This test cannot be performed on whole blood. Serum must be separated from cells within 2 hours of drawing; if serum is not removed within this time, tricyclic antidepressant levels may be falsely elevated due to drug release from RBCs. Specimens that are obtained from gel tubes are not acceptable.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
AMITRIPTYLINE AND NORTRIPTYLINE
Total therapeutic concentration: 80-200 ng/mL
Total toxic concentration: > or =300 ng/mL
Therapeutic concentration: 70-170 ng/mL
Toxic concentration: > or =300 ng/mL
Note: Therapeutic ranges are for specimens drawn at trough (ie, immediately before next scheduled dose). Levels may be elevated in non-trough specimens.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Wille SM, Cooreman SG, Neels HM, Lambert WE: Relevant issues in the monitoring and the toxicology of antidepressants. Crit Rev Clin Lab Sci 2008;45(1):25-89
2. Thanacoody HK, Thomas SH: Antidepressant poisoning. Clin Med 2003;3(2):114-118
3. Baumann P, Hiemke C, Ulrich S, et al: The AGNP-TDM expert group consensus guidelines: therapeutic drug monitoring in psychiatry. Pharmacopsychiatry 2004;37(6):243-265