Imipramine Level

Updated: Feb 11, 2020
  • Author: Suzanne Bentley, MD, MPH, FACEP, CHSE; Chief Editor: Eric B Staros, MD  more...
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Reference Range

Imipramine (Tofranil) is a tricyclic antidepressant that has been used for the treatment of not only depression, but also panic attacks, enuresis, and chronic pain syndromes.

The therapeutic levels of the imipramine and desimpramine concentration are 150-350 ng/mL.

Other important laboratory values associated with imipramine include the following:

  • Minimum toxic level: 300 ng/mL

  • Toxic concentration/critical laboratory value: 1000 ng/mL

  • Lethal dose: 2 g

  • Terminal elimination half-life of imipramine (parent drug): 10-16 hours

  • Terminal elimination half-life of desimpramine (active metabolite): 12-30 hours

  • Volume of distribution: 10-30 L/kg



Imipramine testing is used to measure the concentration of the drug in a patient’s blood. The imipramine level can be correlated with a patient’s clinical presentation to ascertain the therapeutic imipramine level.


Collection and Panels

Specimen: Serum

Container: Red-top tube (plain, no gel)

Collection method: Routine venipuncture

Draw volume: 3 mL (1 mL [minimum])

When the imipramine level is tested in a patient on a regular medication regimen, the specimen should be drawn immediately prior to the next imipramine dose (trough).

Serum must be separated from red blood cells (RBCs) within 2 hours of blood draw; otherwise, drug release from RBCs can cause falsely elevated drug levels.




Imipramine (Tofranil) is a tricyclic antidepressant that has been used for the treatment of not only depression, but also panic attacks, enuresis, and chronic pain syndromes. [1, 2] The drug inhibits serotonergic, alpha-adrenergic, dopaminergic, muscarinic, GABA-ergic, and histaminergic receptors. It also inhibits sodium channels and reuptake of norepinephrine and serotonin. The action of imipramine as an anticholinergic agent makes it effective for urinary incontinence. [3, 4]

A retrospective study by Tai et al indicated that although desmopressin has been preferred over imipramine for the treatment of nocturnal enuresis, owing to what is considered to be desmopressin’s superior side-effects profile, the side-effects rate of imipramine is actually minimal. In the study, side effects were reported by four out of 71 children (5.6%) treated with imipramine, while no side effects were reported by the 125 children treated with desmopressin. In addition, the response rates among the patients, all of whom had primary nocturnal enuresis, were similar for imipramine and desmopressin (81.7% and 77.6%, respectively), with relapse rates also showing no statistically significant difference. [5]

Dosage forms of imipramine include 10-, 25-, and 50-mg tablets and 75-, 100-, 125-, and 150-mg caplets.

The prescribed dosage of imipramine varies. For outpatients, the maintenance dose is 50-150 mg PO hs, without exceeding 300 mg in 24 hours. For inpatients, the typical initial dosing is 100 mg/24 hours in divided doses, eventually transitioning (over several weeks) to a maximum dose of 300 mg in 24 hours. In the pediatric population, the dosage for the treatment of depression is 1.5-5 mg/kg/24 hours divided as qid-qd; for the treatment of enuresis, the dosage for patients older than 6 years is 10-25 mg PO qhs, which can be increased by 10-25 mg every 1-2 weeks for a maximum dose of 50 mg in patients aged 6-12 years and 75 mg in patients older than 12 years. In total, the therapeutic effect of the drug takes 1-3 weeks to occur. [3, 6]

Imipramine toxicity may develop at therapeutic concentrations during the initial phase of drug therapy. The common side effects related to the drug’s anticholinergic properties include the following:

  • Xerostomia

  • Tachycardia

  • Urinary retention

  • Constipation

  • Tremor

  • Postural hypotension

  • Blurred vision

  • Sedation

  • Cardiac conduction delays (specifically increased PR, QRS, and QT intervals)

  • Weight gain

Imipramine can cause slate-gray pigmentation in a sun-exposed distribution on the body secondary to the deposition of drug metabolite-melanin complexes, which is mediated by oxygen free radicals. [7] The drug can also alter hepatic function and morphology by causing cholestasis and hepatitis. Cardiac toxicity is associated with a serum drug concentration of greater than 1000 ng/mL. [8]

A study by Fekete et al indicated that the dose-related concentration of imipramine in the blood is higher in children and adolescents than in adults, with the same found to be true for the antidepressants citalopram, clomipramine, and fluvoxamine. [9]

In patients in whom imipramine toxicity is suspected, treatment includes hypertonic sodium bicarbonate or hypertonic saline. Lidocaine is also given for ventricular tachydysrhythmias. Class IA, IC, and III antiarrhythmics should be avoided in cases of imipramine toxicity. [8]

Imipramine should not be used in patients who are concomitantly taking MAO inhibitors or patients with recent myocardial infarction, narrow angle glaucoma, congestive heart failure, angina, or a history of cardiac arrhythmias.


Cigarette smoking decreases the serum concentration of imipramine.

The peak effects of imipramine occur within 1-2 hours. The drug is highly protein bound (70%-90%).

Imipramine is predominantly metabolized by the cytochrome P-450 system enzyme 1A2. Thioridazine, chlorpheniramine, clomipramine, norfluoxetine, propranolol, citalopram, and escitalopram can cause false elevations in imipramine levels, while sertraline has opposite effects. [6]