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Imipramine; desipramine (imipramine metabolite)
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.
Liquid chromatography/tandem mass spectrometry (LC/MS-MS)
Therapeutic: imipramine + desipramine: 175−300 ng/mL
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
Serum or plasma
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.
Transfer separated serum or plasma to a plastic transport tube. For therapeutic monitoring, collect specimen immediately prior to next dose.
Causes for Rejection
|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|