Therapeutic drug monitoring of trazodone: are there pharmacokinetic interactions involving citalopram and fluoxetine?
OBJECTIVE
Therapeutic drug monitoring (TDM) of the new generation antidepressants is subject of controversial discussion. Nonetheless, TDM may safeguard against drug-drug interactions, can be used to control compliance and is valuable in the investigation of overdose.


METHODS
The aim of this prospective study was to investigate serum levels of trazodone when prescribed as monotherapy or when used in combination with the selective serotonin reuptake inhibitors citalopram and fluoxetine in a simultaneous assay using high-performance liquid chromatography (HPLC). Over a 1-year period, we studied 97 patients (63 females) with depressive syndrome who were subdivided into 3 main diagnostic groups. Fifty-two patients were smokers, the mean age was 39.9 years and the mean weight was 72.4 kg; 40 patients were taking trazodone alone, 41 trazodone in combination with citalopram and 16 patients trazodone in combination with fluoxetine.


RESULTS
The use of citalopram and fluoxetine in combination with trazodone had no significant impact on trazodone serum levels, and the same was true for differences in body weight and smoking behavior. On the other hand, age and sex had a significant influence on the pharmacokinetic pattern of trazodone, causing higher concentrations in females and in older patients. Since the polypharmacy investigated did not change the serum levels of trazodone, we assume that there is no metabolic interaction between trazodone and citalopram and trazodone and fluoxetine. We observed none of the adverse effects which might have been expected, including dizziness, severe headache, daytime sedation, fatigue or the serotonin syndrome even in a mild form.


CONCLUSIONS
A "double-tracked" antidepressive treatment using trazodone and the SSRIs citalopram and fluoxetine is associated with a wide safety margin.
Prapotnik
M
M
Department of Psychiatry I, Regional Hospital of Rankweil, Austria. michael.prapotnik@vol.at
Waschgler
R
R
König
P
P
Moll
W
W
Conca
A
A
D000328:Adult; D000928:Antidepressive Agents / Q000097:blood / Q000493:pharmacokinetics*; D015283:Citalopram / Q000494:pharmacology; D004347:Drug Interactions; D016903:Drug Monitoring; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology; D006801:Humans; D008297:Male; D011446:Prospective Studies; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D014196:Trazodone / Q000097:blood / Q000493:pharmacokinetics*
D000928:Antidepressive Agents; D015283:Citalopram; D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors; D014196:Trazodone