Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Citalopram (Celexa) and S-citalopram (escitalopram, Lexapro) are approved for treatment of depression. Celexa is a racemic mixture containing equal amounts of R- and S-enantiomer. Metabolites of citalopram (N-desmethylcitalopram) are less active than citalopram and do not accumulate in serum to clinically significant concentration.
Citalopram metabolism is carried out by cytochrome P450 (CYP) 2C19 and 3A4-5. CYP 2D6 may play a minor role in citalopram metabolism. Citalopram is known to reduce CYP 2D6 activity. Citalopram clearance is significantly affected by reduced hepatic function, but only slightly by reduced renal function.
A typical Celexa dose administered to an adult is 40 mg per day. A typical Lexapro dose is 20 mg per day. Citalopram is 80% protein bound, and the apparent volume of distribution is 12 L/Kg. Bioavailability is 80% and protein binding is 56% for either form of the drug. Time to peak serum concentration is 4 hours, and the elimination half-life is 35 hours. Half-life is increased in the elderly. Dosage reductions may be necessary for patients who are elderly or have reduced hepatic function.
Monitoring citalopram therapy
While regular blood level monitoring is not indicated in most patients, the test is useful to identify noncompliance
When used in conjunction with CYP 2C19 and CYP 3A4-5 genotyping, the test can identify states of altered drug metabolism
Steady-state serum concentrations associated with optimal response to citalopram are in the range of 100 to 250 ng/mL when the patient is administered the R,S-enantiomeric mixture (Celexa) and 50 to 130 ng/mL when S-citalopram (Lexapro) is administered.
The most common toxicities associated with excessive serum concentration are fatigue, impotence, insomnia, and anticholinergic effects. The toxic range for R,S-citalopram is >400 ng/mL and S-citalopram is >250 ng/mL.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Test interpretation requires knowledge of which enantiomers (R, S- or S-) are prescribed; this assay does not distinguish the enantiomers.
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.
R,S-Citalopram: 100-250 ng/mL
S-Citalopram: 50-130 ng/mL
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Physicians' Desk Reference (PDR). 59th edition. Montvale, NJ, Medical Economics Company, 2005
2. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 10th edition. Edited by JG Hardman, LE Limbird. New York, McGraw-Hill Book Company, 1994, p 1934