In several previous biochemical, pharmacological, and genetic studies, the catechol-O-methyltransferase (COMT) has been suggested to be involved in the pathogenesis as well as the pharmacological treatment of affective disorders. In the present study, 256 patients with major depression (DSM-IV) of Caucasian descent were genotyped for the functional COMT val158met polymorphism and characterized for clinical response to antidepressive pharmacological treatment as measured by intra-individual changes of Hamilton Depression (HAM-D-21) scores over 6 weeks. The COMT 158val/val genotype conferred a significant risk of worse response after 4-6 weeks of antidepressant treatment in patients with major depression (week 4: p ¼ 0.003; week 5: po0.0001; week 6: po0.0001) after Bonferroni correction for multiple comparisons. The present results strongly point toward a negative influence of the higher activity COMT 158val/ val genotype on antidepressant treatment response during the first 6 weeks of pharmacological treatment in major depression, possibly conferred by consecutively decreased dopamine availability. This finding suggests a potentially beneficial effect of an antidepressive addon therapy with substances increasing dopamine availability individually tailored according to COMT val158met genotype.

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Background: This study aimed at the impact of medical comorbidity (MC) on response to antidepressant treatment over 6 weeks in diagnostic subtypes of patients with major depressive episode (MDE). Methods: In a clinical sample of 241 admitted patients with MDE, MC was assessed by medical specialists and weekly response to antidepressant treatment was assessed with the Hamilton Depression Scale (HAM-D 21). Results: Over 6 weeks of treatment, patients with melancholic depression and MC had poorer treatment response on the HAM-D scale and a worse functional outcome (GAF) as opposed to their counterparts without MC, which was first detected after 4 weeks of treatment (p = 0.02). More specifically, subjects with melancholic depression and cardiovascular or endocrinological MC showed significantly poorer treatment response over 6 weeks. Interestingly, these effects were not related to various antidepressant treatment regimens. Conclusions: MC has a negative impact on treatment response in patients with melancholic depression.