Carbamazepine augmentation in depressive patients non-responding to citalopram: a pharmacokinetic and clinical pilot study.
Citalopram is a chiral antidepressant drug. Its eutomer, S-citalopram (escitalopram), has recently been introduced as an antidepressant. In an open pilot study, four outpatients and two inpatients with a major depressive episode (ICD-10), and who were nonresponders to a 4-week pretreatment with 40-60 mg/day citalopram, were comedicated for another 4-week period with carbamazepine (200-400 mg/day). Some of the patients suffered also from comorbidities: Phobic anxiety disorder with panic attacks (n=2), generalised anxiety disorder, alcohol abuse, dependent personality disorder, hypertension (n=1). After a 4-week augmentation therapy with carbamazepine, a significant (P<0.03) decrease of the plasma concentrations of S-citalopram and R-citalopram, by 27 and 31%, respectively, was observed. Apparently, the probable induction of CYP3A4 by carbamazepine results in a nonstereoselective increase in N-demethylation of citalopram. Moreover, there was a significant (P<0.03) decrease of the ratio S/R-citalopram propionic acid derivative, the formation of it being partly regulated by MAO-A and MAO-B. Already, within 1 week after addition of carbamazepine, there was a slight but significant (P<0.03) decrease of the MADRS depression scores, from 27.0+/-7.7 (mean+/-S.D.) to 23.3+/-6.6, and the final score on day 56 was 18.8+/-10.9. The treatment was generally well tolerated. There was no evidence of occurrence of a serotonin syndrome. After augmentation with carbamazepine, treatment related adverse events were: Nausea in one case, diarrhea in one case, and rash in two cases. In conclusion, the results of this pilot study suggest that carbamazepine augmentation of a citalopram treatment in previous nonresponders to citalopram may be clinically useful, but that in addition carbamazepine can lead to a decrease of the plasma concentrations of the active enantiomer escitalopram.
Steinacher
Lina
L
Praxis am Zweierplatz, Badenerstrasse 67, CH-8004 Zurich, Switzerland.
Vandel
Pierre
P
Zullino
Daniele F
DF
Eap
Chin B
CB
Brawand-Amey
Marlyse
M
Baumann
Pierre
P
D000328:Adult; D000704:Analysis of Variance; D018687:Antidepressive Agents, Second-Generation / Q000097:blood / Q000627:therapeutic use*; D018692:Antimanic Agents / Q000627:therapeutic use*; D002220:Carbamazepine / Q000627:therapeutic use*; D015283:Citalopram / Q000097:blood / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000523:psychology; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D018709:Statistics, Nonparametric; D013237:Stereoisomerism
D018687:Antidepressive Agents, Second-Generation; D018692:Antimanic Agents; D015283:Citalopram; D002220:Carbamazepine