engleski

Characterisation of response to antidepressants in a pharmacogenetic trial

The power of clinical trials and pharmacogenetic studies depends on accurate measurement of therapeutic response. We previously performed psychometric analysis of three instruments measuring depression severity in the pharmacogenetic clinical trial GENDEP. We found that the measurement scales, including the 17-item Hamilton Depression Rating Scale (HDRS-17), Montgomery-Asberg Depression Rating Scale (MADRS), and Beck Depression Inventory (BDI) were multidimensional and did not fulfill assumptions for summed scoring. We proposed that depression severity may better be described by three dimensions, including observed mood, cognitive and neurovegetative symptoms, derived by factor analysis and scored according to the Item Response Theory (Uher et al., 2007). Here we explore the therapeutic response and its moderation by the length polymorphism in the serotonin transporter gene (5HTTLPR) comparing the three dimensional measures with the original scales. GEDNEP included 800 adult outpatients with unipolar depression recruited in nine centers in eight European countries. Participants were randomly allocated to receive escitalopram up to 20 mg daily or nortriptyline up to 150 mg daily. Where contraindications for one drug were present, the other antidepressant was given non-randomly. The HDRS-17, MADRS, and BDI were administered on 13 occasions. The effects of drugs and moderating variables were tested in linear mixed models with study centre and individual as hierarchical random effects. The treatment effect size of treatment effect was larger on the observed mood dimension (d = 2.9), than on the original scales. Mixed effect regression revealed no significant difference between escitalopram and nortriptyline on the three original scales (all p > 0.1). However, the three symptom dimensions have shown a different picture.

measurement scales; unipolar depression; GENDEP

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