Imipramine and Desipramine, Serum
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Imipramine and its metabolite desipramine are tricyclic antidepressants used to treat endogenous depression requiring 1 to 3 weeks of treatment before therapeutic effectiveness becomes apparent. Desipramine is used for treatment of endogenous depression when the patient needs a drug with significant stimulatory side effects. These drugs have also been employed in the treatment of enuresis (involuntary urination) in childhood and severe obsessive-compulsive neurosis.
The optimal dosage of imipramine yields trough (just before the next dose) blood levels of imipramine and desipramine combined from 175 to 300 ng/mL. If desipramine is given, no imipramine should be detected and the therapeutic concentration for desipramine alone is 100 to 300 ng/mL.
Toxicity associated with imipramine is characterized by QRS widening leading to ventricular tachycardia and asystole. In some patients, toxicity may manifest at lower concentrations, or at therapeutic concentrations in the early state of therapy. Cardiac toxicity (first-degree heart block) is usually associated with blood concentrations in excess of 300 ng/mL.
Desipramine is the antidepressant of choice in patients where maximal stimulation is indicated.
The therapeutic concentration of desipramine is 100 to 300 ng/mL. About 1 to 3 weeks of treatment are required before therapeutic effectiveness becomes apparent.
The most frequent side effects are those attributable to anticholinergic effects; dry mouth, constipation, dizziness, tachycardia, palpitations, blurred vision, and urinary retention. These occur at blood concentrations in excess of 300 ng/mL, although they may occur at therapeutic concentrations in the early stage of therapy. Cardiac toxicity (first-degree heart block) is usually associated with blood concentrations in excess of 300 ng/mL.
Monitoring serum concentration during therapy
Evaluating potential toxicity
The test may also be useful to evaluate patient compliance
Most individuals display optimal response to imipramine when combined serum levels of imipramine and desipramine are between 175 and 300 ng/mL. Risk of toxicity is increased with levels > or =300 ng/mL.
Most individuals display optimal response to desipramine with serum levels of 100 to 300 ng/mL. Risk of toxicity is increased with desipramine levels > or =300 ng/mL.
Some individuals may respond well outside of these ranges, or may display toxicity within the therapeutic range, thus interpretation should include clinical evaluation.
Therapeutic ranges are based on specimen drawn at trough (ie, immediately before the next dose).
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Imipramine analytical interference: sertraline may cause falsely low results, and clomipramine, thioridazine, chlorpheniramine, propranolol, norfluoxetine, citalopram, or escitalopram may cause false elevations.
Desipramine analytical interferences: sertraline may cause falsely low results.
This test cannot be performed on whole blood. Serum must be separated from cells within 2 hours of draw; if serum is not removed within this time, tricyclic antidepressants levels may be falsely elevated due to drug release from RBCs. Specimens that are obtained from gel tubes are not acceptable.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
IMIPRAMINE AND DESIPRAMINE
Total therapeutic concentration: 175-300 ng/mL
Total toxic concentration: > or =300 ng/mL
Therapeutic concentration: 100-300 ng/mL
Toxic concentration: > or =300 ng/mL
Note: Therapeutic ranges are for specimens drawn at trough (ie, immediately before next scheduled dose). Levels may be elevated in non-trough specimens.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Wille SM, Cooreman SG, Neels HM, Lambert WE: Relevant issues in the monitoring and the toxicology of antidepressants. Crit Rev Clin Lab Sci 2008;45(1):25-89
2. Thanacoody HK, Thomas SH: Antidepressant poisoning. Clin Med 2003;3(2):114-118
3. Baumann P, Hiemke C, Ulrich S, et al: The AGNP-TDM expert group consensus guidelines: therapeutic drug monitoring in psychiatry. Pharmacopsychiatry 2004;37(6):243-265