Sertraline is an antidepressant extensively metabolized by the polymorphic CYP2C19 enzyme.
Based on CYP2C19 genotype, patients can be classified as:
Normal metabolizers (Normal CYP2C19 enzyme capacity)
Intermediate metabolizers (Decreased CYP2C19 enzyme capacity)
Poor metabolizers (No CYP2C19 enzyme capacity)
Ultra rapid metabolizers (Increased CYP2C19 enzyme capacity)
Adequate sertraline exposure is needed to achieve optimal clinical response in the treatment
of depression: too low drug plasma levels can lead to the lack of pharmacological effect,
whereas too high drug plasma levels increases the incidence of adverse effects. There is
evidence that patients with variant CYP2C19 genotypes have abnormal sertraline exposure and
could benefit from sertraline dose personalization, but precise evidence-based protocol for
personalized dosing of sertraline has not been developed yet. This multicentric observational
clinical trial is designed to collect crucial information for the development of such
protocol that will be based on drug plasma level monitoring and/or CYP2C19 genotyping.
Course of the study will be as follows:
Initial Visit (V0):
Participant will be enrolled at this point if inclusion criteria are met. Sertraline therapy
will be initiated at the standard dose of 100 mg/day during next 2 weeks, or alternatively,
started with 50 mg/day during first week and then increased to 100 mg/day during second week.
General and socio-demographic information about the participant will be collected together
with the baseline measurements: clinical questionnaires, anthropometric measurements,
cardiological assessments, and the blood sample will be taken for biochemical analyses.
Mid-Visit (VK):
This visit takes place two weeks after the initial visit (V0) when sertraline blood level is
expected to reach the steady state. Blood sample will be taken from the participants at the
end of the dose interval (before the morning dose) for the purpose of therapeutic drug
monitoring. Plasma sertraline levels will then be measured before the next visit and an
independent clinician will allocate patients into one out of two cohorts based on whether or
not sertraline levels were optimal (20-40 ng/ml). If sertraline levels were outside this
interval, independent clinician will adjust the dose; sertraline level lower than 3 ng/ml
indicates noncompliance and results in dropout, level between 3 and 10 ng/ml results in dose
increase to 200 mg/day, level between 10 and 20 ng/ml results in dose increase to 150 mg/day,
level between 20 and 40 ng/ml results in treatment continuation with 100 mg/day, and level
higher than 40 ng/ml results in dose decrease to 50 mg/day.
Visit 1 (V1):
Visit 1 takes place two weeks after VK and 4 weeks after the initiation of the sertraline
therapy. Without the knowledge of the attending clinician, independent clinician will adjust
sertraline doses accordingly. Attending clinician will then assess the participants using
standardized questionnaires, participants will be anthropometrically and cardiologically
examined, and blood samples will be taken for the purposes of therapeutic drug monitoring and
biochemical analyses.
Visit 2 (V2):
Visit 2 is the final follow-up visit and it will be done 4 weeks after the Visit 1 and 8
weeks after the sertraline initiation. All participants will be assessed for psychometrical,
anthropometrical and cardiological parameters, and blood samples will be taken again for the
purposes of therapeutic drug monitoring and biochemical analysis.
If needed, additional participants who are already on the stable sertraline monotherapy can
be enrolled into study starting from VK. In this case, besides the blood sample for the
therapeutic drug monitoring, all assessment usually done at initial visit (V0) will be
performed during VK.