Also found in: Dictionary/thesaurus, Acronyms, Wikipedia.


a tricyclic antidepressant, administered orally as the hydrochloride salt; it is also used to treat panic disorder and chronic severe pain.


/nor·trip·ty·line/ (nor-trip´tĭ-lēn) a tricyclic antidepressant, used as the hydrochloride salt to treat depression and panic disorder and to relieve chronic severe pain.


Neuropharmacology A tricyclic antidepressant. See Tricyclic antidepressants.

Antidepressant Drugs (Cyclic): Amitriptyline, Nortriptyline, Protriptyline, Doxepin, Imipramine

Synonym/acronym: Cyclic antidepressants: amitriptyline (Elavil, Endep, Etrafon, Limbitrol, Triavil); nortriptyline (Allegron, Aventyl HCL, Nortrilen, Norval, Pamelor); protriptyline (Aventyl, Sinequan, Surmontil, Tofranil, Vivactil); doxepin (Adapin, Co-Dax, Novoxapin, Sinequan, Triadapin); imipramine (Berkomine, Dimipressin, Iprogen, Janimine, Pentofrane, Presamine, SK-Pramine, Tofranil PM).

Common use

To monitor subtherapeutic, therapeutic, or toxic drug levels in evaluation of effective treatment modalities.


Serum (1 mL) collected in a red-top tube.
DrugRoute of AdministrationRecommended Collection Time
AmitriptylineOralTrough: immediately before next dose (at steady state)
NortriptylineOralTrough: immediately before next dose (at steady state)
ProtriptylineOralTrough: immediately before next dose (at steady state)
DoxepinOralTrough: immediately before next dose (at steady state)
ImipramineOralTrough: immediately before next dose (at steady state)

Normal findings

(Method: Chromatography for amitriptyline, nortriptyline, protriptyline, and doxepin; immunoassay for imipramine)
DrugTherapeutic Range Conventional UnitsConversion to SI unitsTherapeutic Range SI UnitsHalf-Life (h)Volume of Distribution (L/kg)Protein Binding (%)Excretion
Amitriptyline125–250 ng/mLSI units = Conventional Units × 3.6450–900 nmol/L20–4010–3685–95Hepatic
Nortriptyline50–150 ng/mLSI units = Conventional Units × 3.8190–570 nmol/L20–6015–2390–95Hepatic
Protriptyline70–250 ng/mLSI units = Conventional Units × 3.8266–950 nmol/L60–9015–3191–93Hepatic
Doxepin110–250 ng/mLSI units = Conventional Units × 3.58394–895 nmol/L10–2510–3075–85Hepatic
Imipramine180–240 ng/mLSI units = Conventional Units × 3.57643–857 nmol/L6–189–2360–95Hepatic


Cyclic antidepressants are used in the treatment of major depression. They have also been used effectively to treat bipolar disorder, panic disorder, attention deficit-hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), enuresis, eating disorders (bulimia nervosa in particular), nicotine dependence (tobacco), and cocaine dependence. Numerous drug interactions occur with the cyclic antidepressants.

Many factors must be considered in effective dosing and monitoring of therapeutic drugs, including patient age, patient ethnicity, patient weight, interacting medications, electrolyte balance, protein levels, water balance, conditions that affect absorption and excretion, and the ingestion of substances (e.g., foods, herbals, vitamins, and minerals) that can either potentiate or inhibit the intended target concentration. Trough collection times should be documented carefully in relation to the time of medication administration.

The metabolism of many commonly prescribed medications is driven by the cytochrome P450 (CYP450) family of enzymes. Genetic variants can alter enzymatic activity that results in a spectrum of effects ranging from the total absence of drug metabolism to ultrafast metabolism. Impaired drug metabolism can prevent the intended therapeutic effect or even lead to serious adverse drug reactions. Poor metabolizers (PM) are at increased risk for drug-induced side effects due to accumulation of drug in the blood, while ultra-rapid metabolizers (UM) require a higher than normal dosage because the drug is metabolized over a shorter duration than intended. Other genetic phenotypes used to report CYP450 results are intermediate metabolizer (IM) and extensive metabolizer (EM). Genetic testing can be performed on blood samples submitted to a laboratory. The test method commonly used is polymerase chain reaction. Counseling and informed written consent are generally required for genetic testing. CYP2D6 is a gene in the CYP450 family that metabolizes drugs such as tricyclic antidepressants like nortriptyline, antipsychotics like haloperidol, and beta blockers. Testing for the most common genetic variants of CYP2D6 is used to predict altered enzyme activity and anticipate the most effective therapeutic plan. Incidence of the PM phenotype is estimated to be 10% of Caucasians and Hispanics, 2% of African Americans, and 1% of Asians.

Important note: These medications are metabolized and excreted by the liver and are therefore contraindicated in patients with hepatic disease. Information regarding medications must be clearly and accurately communicated to avoid misunderstanding of the dose time in relation to the collection time. Miscommunication between the individual administering the medication and the individual collecting the specimen is the most frequent cause of subtherapeutic levels, toxic levels, and misleading information used in calculation of future doses. If administration of the drug is delayed, notify the appropriate department(s) to reschedule the blood draw and notify the requesting health-care provider (HCP) if the delay has caused any real or perceived therapeutic harm.

This procedure is contraindicated for



  • Assist in the diagnosis and prevention of toxicity
  • Evaluate overdose, especially in combination with ethanol (Note: Doxepin abuse is unusual.)
  • Monitor compliance with therapeutic regimen

Potential diagnosis

Normal levelsTherapeutic effect
Subtherapeutic levelsAdjust dose as indicated
Toxic levelsAdjust dose as indicated
 AmitriptylineHepatic impairment
 NortriptylineHepatic impairment
 ProtriptylineHepatic impairment
 DoxepinHepatic impairment
 ImipramineHepatic impairment

Critical findings

  • It is important to note the adverse effects of toxic and subtherapeutic levels of antidepressants. Care must be taken to investigate signs and symptoms of too little and too much medication. Note and immediately report to the HCP any critically increased or subtherapeutic values and related symptoms.

  • It is essential that a critical finding be communicated immediately to the requesting HCP. A listing of these findings varies among facilities.

  • Timely notification of a critical finding for lab or diagnostic studies is a role expectation of the professional nurse. The notification processes will vary among facilities. Upon receipt of the critical finding the information should be read back to the caller to verify accuracy. Most policies require immediate notification of the primary HCP, hospitalist, or on-call HCP. Reported information includes the patient’s name, unique identifiers, critical finding, name of the person giving the report, and name of the person receiving the report. Documentation of notification should be made in the medical record with the name of the HCP notified, time and date of notification, and any orders received. Any delay in a timely report of a critical finding may require completion of a notification form with review by Risk Management.

  • Cyclic Antidepressants

  • Amitriptyline: Greater Than 500 ng/mL (SI: Greater Than 1800 nmol/L)
  • Nortriptyline: Greater Than 500 ng/mL (SI: Greater Than 1900 nmol/L)
  • Protriptyline: Greater Than 500 ng/mL (SI: Greater Than 1900 nmol/L)
  • Doxepin: Greater Than 500 ng/mL (SI: Greater Than 1790 nmol/L)
  • Imipramine: Greater Than 500 ng/mL (SI: Greater Than 1785 nmol/L)
  • Signs and symptoms of cyclic antidepressant toxicity include agitation, drowsiness, hallucinations, confusion, seizures, arrhythmias, hyperthermia, flushing, dilation of the pupils, and possible coma. Possible interventions include administration of activated charcoal; emesis; gastric lavage with saline; administration of physostigmine to counteract seizures, hypertension, or respiratory depression; administration of bicarbonate, propranolol, lidocaine, or phenytoin to counteract arrhythmias; and electrocardiographic monitoring.

Interfering factors

  • Blood drawn in serum separator tubes (gel tubes).
  • Cyclic antidepressants may potentiate the effects of oral anticoagulants.

Nursing Implications and Procedure


  • Positively identify the patient using at least two unique identifiers before providing care, treatment, or services.
  • Patient Teaching: Inform the patient this test can assist in monitoring subtherapeutic, therapeutic, or toxic drug levels.
  • Obtain a history of the patient’s complaints, including a list of known allergens, especially allergies or sensitivities to latex.
  • These medications are metabolized and excreted by the kidneys and liver. Obtain a history of the patient’s genitourinary and hepatobiliary systems, symptoms, and results of previously performed laboratory tests and diagnostic and surgical procedures.
  • Obtain a list of the patient’s current medications, including herbs, nutritional supplements, and nutraceuticals (see Effects of Natural Products on Laboratory Values online at DavisPlus). Note the last time and dose of medication taken.
  • Review the procedure with the patient. Inform the patient that specimen collection takes approximately 5 to 10 min. Address concerns about pain and explain that there may be some discomfort during the venipuncture.
  • Sensitivity to social and cultural issues, as well as concern for modesty, is important in providing psychological support before, during, and after the procedure.
  • Note that there are no food, fluid, or medication restrictions unless by medical direction.


  • Potential complications:
  • Lack of consideration for the proper collection time relative to the dosing schedule can provide misleading information that may result in erroneous interpretation of levels, creating the potential for a medication-error-related injury to the patient.

  • Avoid the use of equipment containing latex if the patient has a history of allergic reaction to latex.
  • Instruct the patient to cooperate fully and to follow directions. Direct the patient to breathe normally and to avoid unnecessary movement.
  • Observe standard precautions, and follow the general guidelines in Patient Preparation and Specimen Collection. Consider recommended collection time in relation to the dosing schedule. Positively identify the patient, and label the appropriate specimen container with the corresponding patient demographics, initials of the person collecting the specimen, date, and time of collection, noting the last dose of medication taken. Perform a venipuncture.
  • Remove the needle and apply direct pressure with dry gauze to stop bleeding. Observe/assess venipuncture site for bleeding or hematoma formation and secure gauze with adhesive bandage.
  • Promptly transport the specimen to the laboratory for processing and analysis.


  • Inform the patient that a report of the results will be made available to the requesting HCP, who will discuss the results with the patient.
  • Nutritional Considerations: Include avoidance of alcohol consumption.
  • Recognize anxiety related to test results and reinforce information given by the patient’s HCP regarding further testing, treatment, or referral to another HCP. Explain to the patient the importance of following the medication regimen and instructions regarding drug interactions. Instruct the patient to immediately report any unusual sensations (e.g., severe headache, vomiting, sweating, visual disturbances) to his or her HCP. Blood pressure should be monitored regularly. Answer any questions or address any concerns voiced by the patient or family.
  • Instruct the patient to be prepared to provide the pharmacist with a list of other medications he or she is already taking in the event that the requesting HCP prescribes a medication.
  • Depending on the results of this procedure, additional testing may be performed to evaluate or monitor progression of the disease process and determine the need for a change in therapy. Evaluate test results in relation to the patient’s symptoms and other tests performed.

Related Monographs

  • Related tests include ALT, albumin, AST, bilirubin, BUN, creatinine, CBC, electrolytes, GGT, and protein blood total and fractions.
  • See the Genitourinary and Hepatobiliary systems tables at the end of the book for related tests by body system.
References in periodicals archive ?
His analgesic regimen consisted of paracetamol, high doses of oxycodone, a ketamine infusion, nortriptyline and sodium valproate continued at his usual dose.
Sixty-eight type 2 diabetic patients with poor glycemic control, 28 of whom had active major depression (DSM-IIIR), completed a randomized, double-blind trial of eight weeks of treatment with nortriptyline in doses to achieve blood levels of 50-150 ng/ml.