Synonym

• Therapeutic drug monitoring - Tricyclic antidepressants
• Tricyclic antidepressant level
• TCA level

Tubes

• Red or tiger top tube
• 5 mL whole blood

Recommended sample collection time

• Trough: Just prior to when next dose is due (for therapeutic drug monitoring)
• Specimens for toxic overdose are obtained initially, then serially as clinically indicated

Additional information

• Handle sample gently to prevent hemolysis
• Send sample to lab immediately
• Prerequisites for therapeutic drug monitoring
• Dosage must be stable for at least ten days
• Dosage should not be changed or missed
• Samples are collected within 10-15 hrs after the last dose

Info

• Toxicology testing for tricyclic antidepressants (TCAs) is performed to estimate the concentration of tricyclic antidepressants and their metabolites in the blood
• TCAs are primarily used to treat depression and either treat or as prophylaxis for migraine, panic disorder, obsessive compulsive disorder, recurrent headaches, neuropathic pain, and sleep disorders
• TCAs are being increasingly used as drugs of abuse in US [Substance Abuse and Mental Health Services Administration/SAMHSA, National Institute on Drug Abuse (NIDA)], thus mandatory drug testing is done in various situations
• The toxic effects of TCAs are primarily due to:
• Anticholinergic effects
• Direct alpha-adrenergic blockade
• Inhibition of norepinephrine and serotonin reuptake
• Blockade of fast sodium channels in myocardial cells, resulting in quinidine like membrane-stabilizing effects

Clinical

• The clinical utility of toxicology testing for tricyclic antidepressants include:
• To investigate suspected drug overdose (narrow therapeutic index)
• To monitor clinical response, side effects, or signs of toxicity and poisoning
• To monitor drug levels and evaluate the therapeutic efficacy and compliance in special situations such as
• Patients with hepatic dysfunction
• Very young and old persons
• Patients on multiple medications
• To confirm the diagnosis of TCA overdose
• Mandatory drug abuse testing
• Tricyclic antidepressants include
• First generation (tertiary amines)
• Amitriptyline (Elavil)
• Clomipramine (Anafranil)
• Imipramine (Tofranil)
• Trimipramine (Surmontil)
• Doxepin (Sinequan)
• Second generation (secondary amines)
• Desipramine (Norpramin)
• Nortriptyline (Aventyl, Pamelor)
• Protriptyline (Vivactil)
• Toxicity/overdose of TCAs may clinically present as:
• Anticholinergic syndrome
• Blurred vision
• Dry mouth
• Hypoactive bowel sounds
• Myoclonic twitching
• Mydriasis (Dilated pupils)
• Pyrexia (Increased temperature)
• Urinary retention
• Cardiovascular effects
• Sinus tachycardia
• Prolonged PR, QRS, and QT intervals
• Heart block
• Peripheral vasodilatation
• Hypotension
• Cardiogenic shock
• Ventricular arrhythmias
• CNS effects
• Coma
• Confusion
• Delirium
• Drowsiness
• Extrapyramidal signs
• Hallucinations
• Ophthalmoplegia (weakness/paralysis of extraocular muscles)
• Respiratory depression
• Rigidity
• Seizures
• In overdose, determination of the specific TCA ingested should be determined, as toxic profiles may vary with different TCAs:
• Amoxapine is associated with a higher incidence of seizures
• Maprotiline is more cardiotoxic than other TCAs
• Dothiepin and amitriptyline have greater toxicity than the other TCAs
• TCAs should be avoided during pregnancy as it may lead to preterm birth
• Drug interactions:
• TCAs impair the antihypertensive effectiveness of clonidine and guanethidine
• Co-ingestion with alcohol can produce additive sedative effects
• Co-ingestion with antiparkinsonism agents can cause potent anticholinergic side effects
• Co-administration with MAO inhibitors can lead to potential hypertensive and CNS crises

Additional information

• Many factors must be considered in effective dosing and monitoring of therapeutic drugs, including patient age, weight, drug, route of administration, interacting medications, electrolyte balance, protein levels, water balance, conditions that affect absorption and excretion, and ingestion of other substances (foods, herbals, vitamins, and minerals) that can either potentiate or inhibit the intended target concentration
• Blood samples must be obtained at the appropriate time and after a sufficient number of doses for valid interpretation of results
• Factors interfering with test results include:
• Sample collection in serum separator tubes/gel tubes (gel slowly absorbs the drug)
• Hemolyzed, lipemic or icteric samples
• Miscommunication between the individual administering the medication and the individual collecting the specimen
• Associated liver disease or renal impairment
• Co-ingestion of other drugs
• Related laboratory tests include:
• Arterial blood gases
• Complete blood count (CBC)
• Creatinine
• Electrocardiogram
• Electrolytes
• Glucose
• Liver transaminases (AST/ALT)
• Screen for other potential co-ingestants (ethanol, acetaminophen, acetylsalicylic acid)
• Serum osmolality
• Urea
• Urinalysis
• Urinary chorionic gonadotropin (UCG)
• Urine toxicology testing

Nl Result

Consult your laboratory for their normal ranges as these may vary somewhat from the ones listed below.

Note that "Possibly toxic" levels listed here can result in mild toxicity; but major toxicity is not expected in most cases until levels are 2 or more times the levels listed.

High Result

Conditions associated with high levels of TCA include:

• Incorrect dosing (error in administration or prescription)
• TCA Overdose, Poisoning, Toxicity
• Drugs
• Chlorpromazine
• Diphenhydramine (at toxic concentrations)
• Flexeril (cyclobenzaprine)
• Hydrocortisone
• Methylphenidate
• Oxcarbazepine
• Phenothiazines
• Quetiapine fumarate
• Thioridazine

Low Result

Low TCA levels may occur:

• In patients prescribed TCA's, an error in dosing either due to non-compliance with prescription or with inadequate prescribed dose
• In patients undergoing evaluation of ingestion or toxicity, is consistent with no ingestion of TCAs

Co-administration of the following drugs in patients taking TCA's may lead to lower than expected levels of TCAs:

• Carbamazepine
• Felbamate
• Oxcarbazepine
• Phenobarbital
• Phenytoin
• Primidone
• Topiramate

References

• ARUP Laboratories®. Tricyclic Antidepressant Identification Quantitative, Serum. [Homepage on the internet]©2007. Last accessed on August 22, 2007. Available at URL: http://www.aruplab.com/guides/ug/tests/0090154.htm
• eMedicine from WebMD®. Toxicity, Tricyclic Antidepressant. [Homepage on the Internet] ©1996-2007. Last updated on November 3, 2006. Last accessed on August 22, 2007. Available at URL: http://www.emedicine.com/ped/topic2714.htm
• Laboratory Corporation of America®. Amitriptyline, Serum. [Homepage on the internet]©2007. Last accessed on August 22, 2007. Available at URL: http://www.labcorp.com/datasets/labcorp/html/chapter/mono/td001200.htm
• Laboratory Corporation of America®. Imipramine, Serum. [Homepage on the internet]©2007. Last accessed on August 22, 2007. Available at URL: http://www.labcorp.com/datasets/labcorp/html/chapter/mono/td011600.htm
• Laboratory Corporation of America®. Nortriptyline (Aventyl®), Serum. [Homepage on the internet]©2007. Last accessed on August 22, 2007. Available at URL: http://www.labcorp.com/datasets/labcorp/html/chapter/mono/td016500.htm
• Melanson SE et al. Interpreting tricyclic antidepressant measurements in urine in an emergency department setting: comparison of two qualitative point-of-care urine tricyclic antidepressant drug immunoassays with quantitative serum chromatographic analysis. J Anal Toxicol. 2007 Jun;31(5):270-5.
• Sakka SG et al. [Intoxication with a tricyclic antidepressant.] [German]. Anaesthesist. 2007 Jun;56(6):581-6.
• Titier K et al. Quantification of tricyclic antidepressants and monoamine oxidase inhibitors by high-performance liquid chromatography-tandem mass spectrometry in whole blood. J Anal Toxicol. 2007 May;31(4):200-7.