Amitriptyline

CPT: 80335
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Test Details

Synonyms

  • Elavil®
  • Endep®

Test Includes

Amitriptyline; nortriptyline (amitriptyline metabolite)

Use

Evaluate toxicity; monitor therapeutic levels

Methodology

Liquid chromatography/tandem mass spectrometry (LC/MS-MS)

Reference Interval

Therapeutic: amitriptyline + nortriptyline: 80−200 ng/mL

Additional Information

Amitriptyline is a tricyclic antidepressant that blocks the reuptake of serotonin at nerve endings and possesses high anticholinergic activity and cardiovascular toxicity. The drug is extensively metabolized to many polar compounds, the chief of which is nortriptyline. It is also an antidepressant. Both drugs are prescribed for depression and a range of other disorders.

Amitriptyline has a peak serum concentration two to six hours postoral dose, and steady-state is achieved after three to eight days of chronic oral dosing. The half-life is 17 to 40 hours and the usual therapeutic range (predose sample at steady-state) includes nortriptyline and is 80−200 ng/mL. Nortriptyline is administered orally, has a half-life of 15 to 90 hours, and peak serum values two to six hours postoral dose. Steady-state is achieved after 4 to 20 days of chronic dosing. Therapeutic levels of nortriptyline alone are 50−150 ng/mL.

All the tricyclic antidepressants have significant drug interactions. Being potent inducers of hepatic drug-metabolizing enzymes, particularly CYP3A4, CYP1A2, and CYP2C9, the antiepileptic drugs, carbamazepine, phenytoin, phenobarbital, and primidone stimulate the oxidative transformation of concurrently prescribed antidepressants.1 This results in decreased drug levels of the antidepressant. To a lesser extent, co-administration of oxcarbazepine, topiramate, and felbamate can also result in decreased antidepressant levels. Other tricyclic antidepressant drug interactions: hydrocortisone, methylphenidate, and phenothiazines increase tricyclic levels; tricyclics impair the antihypertensive effectiveness of clonidine and guanethidine; tricyclics and alcohol produce additive sedative effects, tricyclics and antiparkinsonism agents have potent anticholinergic side effects, and tricyclics and MAO inhibitors should not be co-administered because of the potential for antihypertensive and CNS crises.

Tricyclics should be avoided in pregnant and lactating women because these drugs have not been established as safe. Geriatric patients are especially prone to postural hypotension, urinary retention, and sedation.2 In general, it has been reported that, “Therapeutic drug monitoring of antidepressants allows us to take into account the influence of factors such as co-medications, diet, smoking habit, impaired organ function, and compliance. Therapeutic drug monitoring and genotyping are thus complementary, and their combined use contributes to improve pharmacotherapy with antidepressants and other drugs.”3

Specimen Requirements

Specimen

Serum or plasma

Volume

1 mL

Minimum Volume

0.3 mL

Container

Red-top tube, lavender-top (EDTA) tube, or green-top (heparin) tube. Do not use a gel-barrier tube. The use of gel-barrier tubes is not recommended due to slow absorption of the drug by the gel. Depending on the specimen volume and storage time, the decrease in drug level due to absorption may be clinically significant.

Collection

Transfer separated serum or plasma to a plastic transport tube. For therapeutic monitoring, collect specimen immediately prior to next dose unless specified otherwise.

Storage Instructions

Room temperature

Stability Requirements

Temperature

Period

Room temperature

14 days

Refrigerated

14 days

Frozen

14 days

Freeze/thaw cycles

Stable x3

Causes for Rejection

Gel-barrier tube

Clinical Information

Footnotes

1. Spina E, Perucca E. Clinical significance of pharmacokinetic interactions between antiepileptic and psychotropic drugs Epilepsia. 2002; 43(Suppl 2):37-44. 11903482
2. Montamat SC, Cusack BJ, Vestal RE. Management of drug therapy in the elderly. N Engl J Med. 1989; 321(5):303-309. 2664519
3. Eap CB, Sirot EJ, Baumann P. Therapeutic monitoring of antidepressants in the era of pharmacogenetics studies. Ther Drug Monit. 2004; 26(2):152-155. 15228156

References

AMA, Division of Drugs and Toxicology. Drug Evaluations Subscription. Chicago, Ill: American Medical Association; Spring 1992.
Rodríguez de la Torre B, Dreher J, Malevany I, et al. Serum levels and cardiovascular effects of tricyclic antidepressants and selective serotonin reuptake inhibitors in depressed patients. Ther Drug Monit. 2001; 23(4):435-440. 11477329

LOINC® Map

Order Code Order Code Name Order Loinc Result Code Result Code Name UofM Result LOINC
007476 Amitriptyline (Elavil), Serum 017475 Amitriptyline, Serum ng/mL 3333-2
007476 Amitriptyline (Elavil), Serum 017483 Nortriptyline, Serum ng/mL 3872-9
007476 Amitriptyline (Elavil), Serum 017485 Total (Ami+Nor) ng/mL 3335-7
Reflex Table for Total (Ami+Nor)
Order Code Order Name Result Code Result Name UofM Result LOINC
Reflex 1 007000 See below: 007000 See below: N/A

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