2.3 Exposure: assessment of antidepressant concentration
in plasma
Blood samples were obtained from participants in the morning.
Participants were in a fasted state, or had had a light breakfast.
Venous blood was drawn in an EDTA tube at both baseline and follow up
study visits, and stored at -80°C until analysis.
The plasma concentrations of the following antidepressants and their
corresponding (active) metabolites were analyzed using LC-MS with
electrospray ionization (Thermo Finnigan TSQ Access, Waltham, MA, USA):
amitriptyline, nortriptyline, citalopram and metabolite
des(methyl)-citalopram, fluoxetine and metabolite norfluoxetine,
fluvoxamine, paroxetine, venlafaxine and metabolite desmethylvenlafaxine
and sertraline and metabolite norsertraline. A detailed description of
the analysis method can be found in the supporting information(Supporting information appendix S1 ). With regard to the
assessment of total drug exposure metabolite concentrations of the
parent drug and metabolite were summed as in line with clinical
practice. Some amitriptyline and nortriptyline users had plasma
concentration below the lower limit of quantification (LLQ) of the LC-MS
method. In these samples, it was possible to determine semi-quantitative
concentration values (Supporting information appendix S1) .