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EPIC CODE: LAB681 Amitriptyline and Nortriptyline, Serum

Additional Codes

Sunquest:  AMTNOM
Mayo:         AMTRP
Previously: ARUP 0090158

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

Method Name

Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)

Reporting Name

Amitriptyline and Nortriptyline, S

Specimen Type

Serum Red

Specimen Required

Collection Container/Tube: Red top (Serum gel/SST are not acceptable)

Submission Container/Tube: Plastic vial

Specimen Volume: 1 mL

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 Minimum Volume

0.25 mL

Specimen Stability Information

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

Reject Due To

Gross hemolysis Reject
Gross lipemia Reject
Gross icterus Reject

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; 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 Values


Total therapeutic concentration: 80-200 ng/mL



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.


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).


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.

Clinical Reference

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 SHL: Antidepressant poisoning. Clin Med (Lond). 2003 Mar-Apr;3(2):114-118

3. Hiemke C, Baumann P, Bergemann N, et al: AGNP Consensus Guidelines for Therapeutic Drug Monitoring in Psychiatry: Update 2011. Pharmacopsychiatry. 2011 Sep;44(6):195-235

4. Burtis CA, Ashwood ER, Bruns DE, eds. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. 5th ed. Elsevier; 2012

Method Description

The tricyclic antidepressants are extracted from serum using a solvent crash to precipitate proteins. The supernatant is remove and analysis is by liquid chromatography-tandem mass spectrometry.(Unpublished Mayo method)

Day(s) Performed

Tuesday, Thursday, Sunday

Report Available

2 to 5 days

Specimen Retention Time

14 days

Performing Laboratory

Mayo Clinic Laboratories in Rochester

Test Classification

This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information


G0480 (if appropriate)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
AMTRP Amitriptyline and Nortriptyline, S 43106-4


Result ID Test Result Name Result LOINC Value
63506 Amitriptyline 3333-2
36755 Nortriptyline 3872-9
36756 Amitriptyline and Nortriptyline 3335-7

NY State Approved



If not ordering electronically, complete, print, and send a Therapeutics Test Request (T831) with the specimen.