Therapeutic drug monitoring of recent antidepressants in patients under polypharmacy

The introduction into clinical practice of the so-called second generation antidepressants has improved the treatment of depression, since these drugs, compared to the first generation antidepressants (such as imipramine and clomipramine), show a more favourable safety profile with respect to cardiovascular effects, whilst maintaining efficacy. Nevertheless, patients treated with these newer antidepressants can present undesired effects, including serotonin syndrome, sedation, body weight changes, sexual dysfunction and suicidal ideation. Therefore, with the aim of reducing the risk for toxic/side effects, therapeutic drug monitoring (TDM) of second generation antidepressants is advisable, particularly in case of patients under polypharmacy. During the last years, a number of methods have been developed in our Laboratory for the accurate determination of antidepressant drugs and their metabolites in plasma samples obtained from patients, including drugs belonging to different classes of second-generation antidepressants (SSRI, NaSSA, SNRI). Sertraline, together with its main metabolite N-desmethylsertraline, can be analysed in plasma samples using a method based on capillary electrophoresis with laser-induced fluorescence (LIF) detection. The method employs a 488 nm wavelength laser and a sample pre-treatment procedure consisting in solid-phase extraction followed by derivatisation with fluorescein isothiocyanate. The high selectivity obtained allows the determination of sertraline in plasma samples from patients under polypharmacy. Capillary electrophoresis with diode-array detection has been employed for the enantioselective determination of mirtazapine and its active metabolite N-desmethylmirtazapine in human plasma. The method is quite fast: after a solid-phase extraction procedure, the electrophoretic run lasts 2.5 min. HPLC with fluorescence detection has been used for the determination of venlafaxine together with its main metabolite O-desmethylvenlafaxine, while HPLC coupled to UV detection was employed for the analysis of duloxetine in plasma of depressed patients.