Imipramine

CPT: 80335
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Test Details

Synonyms

  • Tofranil-PM®
  • Tofranil®

Test Includes

Imipramine; desipramine (imipramine metabolite)

Use

Imipramine is the most thoroughly studied tricyclic antidepressant for the treatment of agoraphobia and panic disorder. Several small, placebo-controlled studies and open trials have confirmed the panic-blocking effects of this drug; however, many of these studies also employed behavioral therapy, thus obscuring the relative contribution of imipramine. A recent placebo-controlled, dose-response study confirmed that imipramine alone has significant antipanic and antiphobic effects. The best response was obtained at a dosage of 150−200 mg/day (mean, 185 mg/day). Most other studies also emphasize titrating the dosage to establish plasma concentrations within the range used for the treatment of depression; however, some patients may respond to doses <100 mg/day. Imipramine also has been given with high-potency benzodiazepines for panic disorder.

Methodology

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

Reference Interval

Therapeutic: imipramine + desipramine: 175−300 ng/mL

Critical Value

Potentially toxic: >500 ng/mL

Additional Information

Imipramine is a tertiary tricyclic antidepressant prescribed for the treatment of various depressive disorders. Imipramine is metabolized to desipramine which is pharmacologically active and which is marketed separately. Both drugs have anticholinergic and antihistamine effects and are cardiotoxic. Imipramine reaches a peak serum concentration in one to two hours (desipramine two to six hours), has a half-life of 9 to 24 hours (desipramine 12 to 54 hours), and reaches steady-state levels in two to five days (desipramine 3 to 11 days). Drug interactions and effects in geriatric patients1 are the same as listed under amitriptyline.

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.2 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.1 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.

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

References

American medical Association, Division of Drugs and Toxicology. Drug Evaluations Subscription. Chicago, Ill: AMA, 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 Aug; 23(4):435-440. 11477329

LOINC® Map

Order Code Order Code Name Order Loinc Result Code Result Code Name UofM Result LOINC
007468 Imipramine (Tofranil), Serum 017442 Imipramine, Serum ng/mL 3690-5
007468 Imipramine (Tofranil), Serum 017459 Desipramine, Serum ng/mL 3531-1
007468 Imipramine (Tofranil), Serum 017458 Total (Imi+Des) ng/mL 9627-1
Reflex Table for Total (Imi+Des)
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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