Amitriptyline and Nortriptyline, Serum (AMTRP)

Test Code: AMNORSO

Overview
Ordering
Specimen
Performing
Clinical/Interpretive
Contacts
Coding

Synonyms/Keywords

Amitriptyline (Elavil); Elavil (Amitriptyline); Elavil, Tryptanol, Endep, Elatrol, Tryptizol, Trepiline, Laroxyl, Saroten, Triptyl, Redomex (Amitriptyline); Nortriptyline (Pamelor); Pamelor (Nortriptyline); Sensoval, Aventyl, Pamelor, Norpress, Allegron, and Nortrilen (Nortriptyline); TCA (Tricyclic Antidepressants); Tricyclic Antidepressants (TCA)

Useful For

Monitoring amitriptyline and nortriptyline serum concentrations during therapy

Evaluating potential amitriptyline and nortriptyline toxicity

The test may also be useful to evaluate patient compliance

Specimen Requirements

Specimen Type	Preferred Container/Tube	Acceptable Container/Tube	Specimen Volume	Specimen Minimum Volume (allows for 1 repeat)	Pediatric Minimum Volume (no repeat)
Serum	Red Top Tube (RTT)		1 mL	0.25 mL

Collection Processing Instructions

Collection Instructions:

1. Collect specimen immediately before next scheduled dose (minimum 12 hours after last dose).

2. Centrifuge and aliquot serum into plastic vial. Serum must be separated from cells within 2 hours of collection.

Specimen Stability Information

Specimen Type	Temperature	Time
Serum	Refrigerated (preferred)	28 days
	Frozen	28 days
	Ambient	7 days

Rejection Criteria

Gross hemolysis
Gross lipemia
Gross icterus
Serum gel tube

Interference

This test cannot be performed on whole blood. Serum must be separated from cells within 2 hours of collection; if serum is not removed within this time, tricyclic antidepressant levels may be falsely elevated due to drug release from red blood cells.

Specimens that are obtained from gel tubes are not acceptable because the drug can absorb on the gel and lead to falsely decreased concentrations.

Performing Laboratory Information

Performing Location	Day(s) Test Performed	Report Available	Methodology/Instrumentation
Mayo Clinic Laboratories	Tuesday, Thursday, Sunday	2 to 5 days	Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)

Reference Lab

Mayo Clinic Laboratories

Test 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; 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, 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.

Reference Range Information

AMITRIPTYLINE AND NORTRIPTYLINE

Total therapeutic concentration: 80-200 ng/mL

NORTRIPTYLINE ONLY

Therapeutic concentration: 70-170 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.

Interpretation

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 are above 500 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 above 500 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 collected at trough (ie, immediately before the next dose).

Outreach CPTs

CPT	Modifier (if needed)	Quantity	Description	Comments
80335