The Effect of Age and Concomitant Treatment with Other Psychoactive Drugs on Serum Concentrations of Citalopram Measured with a Nonenantioselective Method

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Abstract
We measured citalopram and desmethylcitalopram concentrations in serum from 169 psychiatric patients, who were treated with common therapeutic drug doses. Altogether 202 serum samples were assayed by a nonenantioselective high-performance liquid chromatography (HPLC) method. The results indicate that the kinetic variability (maximum concentration/minimum concentration) in dose- and weight-related serum citalopram (10.6-fold) and desmethylcitalopram (7.2-fold) is large even during monotherapy. Log serum citalopram (r = 0.36, p < 0.05) and desmethylcitalopram (r = 0.51, p < 0.01) concentrations of individual patients increased significantly with increasing drug doses. Dose- and weight-related (calculated as mg/kg dose basis) log serum citalopram (r = 0.29) but not desmethylcitalopram (r = 0.06) concentrations increased with aging (p < 0.001). No sex-related differences were found. Nineteen patients (19 samples) had concomitant treatment with neuroleptics, 84 patients (101 samples) with benzodiazepines, and 18 patients (28 samples) with tricyclic antidepressants. The concentrations in these patients were compared with those of 48 nonsmoking patients (54 samples) without any concomitant psychotropic drug treatment. None of the single neuroleptics alone had a significant effect on dose- and weight-related serum citalopram or desmethylcitalopram concentrations. However, citalopram concentrations increased by 121% (338 +/- 165 vs. 747 +/- 505, mean +/- SD; p < 0.01) and desmethylcitalopram by 85% (124 +/- 53 vs. 229 +/- 138; p < 0.05) when neuroleptics were pooled. Among single benzodiazepines, only alprazolam increased serum citalopram (338 +/- 165 vs. 391 +/- 267; p < 0.01) and desmethylcitalopram (124 +/- 53 vs. 186 +/- 175; p < 0.01) concentrations. When all the benzodiazepines were pooled, they still increased the serum concentration of the parent drug by 23% (338 +/- 165 vs. 414 +/- 303; p < 0.05) and those of the metabolite by 47% (124 +/- 53 vs. 182 +/- 163; p < 0.01). In patients who were simultaneously treated with clomipramine, serum citalopram (338 +/- 165 vs. 655 +/- 409; p < 0.001) and desmethylcitalopram (124 +/- 53 vs. 435 +/- 347; p < 0.001) concentrations were consistently higher than those of the controls. Even when the tricyclic antidepressants were pooled, they increased citalopram concentrations by 44% (338 +/- 165 vs. 486 +/- 312; p < 0.001) and desmethylcitalopram concentrations by 111% (124 +/- 53 vs. 261 +/- 260; p < 0.001). The results suggest that interindividual variability in serum citalopram concentrations is pronounced and that increased serum citalopram levels are related to advancing age and concomitant treatment with other psychotropic drugs. The citalopram dose should therefore ideally be individualized by therapeutic drug monitoring.