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Interpretive Handbook

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Test 500509 :
Tricyclic Antidepressant Screen, Serum

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Amitriptyline:

Amitriptyline is a tricyclic antidepressant (TCA) 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:

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.

 

Nortriptyline is a TCA used for treatment of endogenous depression. It also is a metabolite of the antidepressant amitriptyline. Nortriptyline is used when its stimulatory side effect is considered to be of clinical advantage; amitriptyline is used when the side effect of mild sedation is desirable.

 

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.

 

Imipramine:

Imipramine and its metabolite desipramine are TCAs used to treat endogenous depression requiring 1 to 3 weeks of treatment before therapeutic effectiveness becomes apparent. Desipramine is used for treatment of endogenous depression when the patient needs a drug with significant stimulatory side effects. These drugs have also been employed in the treatment of enuresis (involuntary urination) in childhood and severe obsessive-compulsive neurosis.

 

The optimal dosage of imipramine yields trough (just before the next dose) blood levels of imipramine and desipramine combined from 175 to 300 ng/mL. If desipramine is given, no imipramine should be detected and the therapeutic concentration for desipramine alone is 100 to 300 ng/mL.

 

Toxicity associated with imipramine is characterized by QRS widening leading to ventricular tachycardia and asystole. In some patients, toxicity may manifest at lower concentrations, or at therapeutic concentrations in the early state of therapy. Cardiac toxicity (first-degree heart block) is usually associated with blood concentrations in excess of 300 ng/mL.

 

Desipramine:

Desipramine is a TCA; it also is a metabolite of imipramine. These drugs have also been employed in the treatment of enuresis (involuntary urination) in childhood and severe obsessive-compulsive neurosis. Desipramine is the antidepressant of choice in patients where maximal stimulation is indicated.

 

The therapeutic concentration of desipramine is 100 to 300 ng/mL. About 1 to 3 weeks of treatment are required before therapeutic effectiveness becomes apparent.

 

The most frequent side effects are those attributable to anticholinergic effects; dry mouth, constipation, dizziness, tachycardia, palpitations, blurred vision, and urinary retention. These occur at blood concentrations in excess of 300 ng/mL, although they may occur at therapeutic concentrations in the early stage of therapy. Cardiac toxicity (first-degree heart block) is usually associated with blood concentrations in excess of 300 ng/mL.

  

Doxepin:

Doxepin is recommended for the treatment of psychoneurotic patients with depression or anxiety, and depression or anxiety associated with alcoholism or organic disease. Nordoxepin (N-desmethyldoxepin) is the major metabolite and is usually present at concentrations equal to doxepin. Optimal efficacy occurs at combined serum concentrations between 50 and 150 ng/mL.

 

Like other TCA, the major toxicity of doxepin is expressed as cardiac dysrhythmias, which occur at concentrations in excess of 300 ng/mL. Other side effects include nausea, hypotension, and dry mouth.

Useful For Suggests clinical disorders or settings where the test may be helpful

Monitoring serum concentration during therapy

 

Evaluating potential toxicity

 

Evaluating patient compliance

Interpretation Provides information to assist in interpretation of the test results

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

 

Amitriptyline and Nortriptyline:

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 ng/mL 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.

 

Imipramine:

Most individuals display optimal response to imipramine when combined serum levels of imipramine and desipramine are between 175 and 300 ng/mL. Risk of toxicity is increased with levels > or =300 ng/mL.

 

Despramine:

Most individuals display optimal response to desipramine with serum levels of 100 to 300 ng/mL. Risk of toxicity is increased with desipramine 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.

 

Doxepin:

Most individuals display optimal response to doxepin when combined serum levels of doxepin and nordoxepin are between 50 and 150 ng/mL. Some individuals may respond well outside of this range, or may display toxicity within the therapeutic range; thus, interpretation should include clinical evaluation. Risk of toxicity is increased with combined levels > or =300 ng/mL.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

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 (TCA) levels may be falsely elevated due to drug release from RBCs. Specimens that are obtained from gel tubes are not acceptable.

 

Amitriptyline and Nortriptyline:

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.

 

Imipramine and Desipramine:

Imipramine analytical interference: sertraline may cause falsely-low results, and clomipramine, thioridazine, chlorpheniramine, propranolol, norfluoxetine, citalopram, or escitalopram may cause false elevations.

 

Desipramine analytical interferences: sertraline may cause falsely-low results.

  

Doxepin:

Doxepin analytical interferences: sertraline may cause falsely-low results, and venlafaxine, diphenhydramine, chlorpromazine, promazine, ethopropazine, or amlodipine may cause false elevations.

 

Nordoxepin analytical interference: sertraline may cause falsely-low results.

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

Therapeutic concentration: 80-200 ng/mL

Toxic concentration: > or =300 ng/mL

 

NORTRIPTYLINE

Therapeutic concentration: 70-170 ng/mL

Toxic concentration: > or =300 ng/mL

 

IMIPRAMINE AND DESIPRAMINE

Therapeutic concentration: 175-300 ng/mL

Toxic concentration: > or =300 ng/mL

 

DESIPRAMINE

Therapeutic concentration: 100-300 ng/mL

Toxic concentration: > or =300 ng/mL

 

DOXEPIN AND NORDOXEPIN

Therapeutic concentration: 50-150 ng/mL

Toxic concentration: > or =300 ng/mL

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


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