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Antidepressants and their effects on biological markers in depression

It has been assumed that depression is associated with a dysfunction of the central serotonergic (5-hydroxytryptamine, 5-HT) neurotransmission, and increased activity of the hypothalamic-pituitary-adrenal (HPA) axis. Most antidepressants act by affecting 5-HT neurotransmission. The remission in depression is associated with a decreased HPA axis activity and lowered plasma cortisol levels. Platelet 5-HT concentration (a limited peripheral model for the central 5-HT synaptosomes) was determined by the spectrofluorimetric method, and plasma cortisol by a RIA method. Clinical improvement to 5 weeks treatment with a selective serotonin reuptake inhibitor (SSRI), paroxetine (20 mg/day) or 24 weeks of treatment with sertraline (50 mg/day) in nonsuicidal, nonpsychotic female patients with major depression (DSM-IV criteria) was defined as a reduction of ≥ 50% in Hamilton Rating Scale for Depression (HAMD) total scores when compared to baseline scores. The aim of the study was to evaluate whether pre-treatment platelet 5-HT or plasma cortisol concentration might predict the therapeutic response to SSRI paroxetine or sertraline. Data (expressed as means ± SD) were evaluated using one-way ANOVA followed by Tukey's test. In paroxetine treated group, at baseline, pre-treatment platelet 5-HT concentration (nmol/mg protein) was significantly (F=41.86 ; df=4, 172 ; p<0.001) lower in 34 responders (1.09 ± 0.21) than in 16 non-responders (1.48 ± 0.55). Baseline platelet 5-HT concentration was increased in non-responders when compared to corresponding 77 female drug-free healthy controls (1.18 ± 0.21). Before treatment platelet 5-HT values in responders were similar to values in healthy subjects. Post-treatment platelet 5-HT concentration was similarly decreased in both responders (0.40 ± 0.32) and non-responders (0.60 ± 0.31). In sertraline treated group platelet 5-HT concentration was significantly (F=16.06 ; df=5, 54 ; p<0.001) different, with marginal increase in baseline platelet 5-HT concentration in non-responders when compared to responders, and significant reduction in responders and non-responders after treatment. Plasma cortisol levels (nmol/l) were increased significantly (F=5.60 ; df=1, 45 ; p<0.001) in 21 depressed patients (512 ± 195) as compared to 26 healthy subjects (410 ± 91). Fifteen patients finished the study, and 14 patients were responders to 24 weeks of sertraline treatment. After treatment plasma cortisol levels did not differ significantly between responders (481 ± 172 vs. 465 ± 264) and one non-responder (935 vs. 312). Since treatment with SSRIs is long, costly and one third of the patients does not improve and does not respond to treatment, there is a search for the possible biological predictor of the therapeutic outcome. In our group of depressed patients clinical improvement was not related to decreased plasma cortisol levels. Our preliminary data indicate that pre-treatment values of platelet 5-HT, but not of plasma cortisol, in drug-free female depressed patients might have a prognostic value as a biological marker for the treatment response to paroxetine or sertraline.

antidepressants; depression; platelet serotonin; cortisol; prolactin; tyroid hormones; biomarkers; therapeutic response

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