Effects of vortioxetine and escitalopram on plasma brain derived neurotrophic factor level and platelet monoamine oxidase B activity in subjects with depressive disorder

Antidepresivi nemaju učinak u svih bolesnika na simptome depresije, uključujući i kognitivne simptome. Za sada ne postoje pouzdani predskazatelji učinka antidepresiva, a jedan od kandidata je moždani neurotrofni čimbenik (BDNF). Njegova je koncentracija snižena u depresivnih bolesnika, dok neki antidepresivi povisuju koncentraciju BDNF-a. Ovo prospektivno, randomizirano, longitudinalno istraživanje uključilo je 121 depresivnog bolesnika, među kojima je 61 bolesnik liječen vortioksetinom, a 60 escitalopramom. Nakon 4 tjedna terapije, unatoč podjednakom poboljšanju simptoma depresije, vortioksetin je izazvao porast koncentracije BDNF-a u plazmi, dok uz terapiju escitalopramom nije zapažena promjena. Oba antidepresiva podjednako su ublažila kognitivnu disfunkciju, osim što escitalopram nije pokazao učinak na testu pažnje. Nadalje, escitalopram je izazvao veći pad koncentracije trombocitnog serotonina u usporedbi s vortioksetinom, pri čemu je veći pad koncentracije serotonina predvidio dobar odgovor na escitalopram. Oba lijeka nisu značajno utjecala na aktivnost trombocitne MAO-B. Rezultati istraživanja upućuju na razlike u biološkom učinku escitaloprama i vortioksetina, koje mogu biti povezane i s kliničkim učinkom. Istraživanje predstavlja doprinos razumijevanju mehanizma djelovanja antidepresiva i naglašava potrebu individualnog pristupa u liječenju.Antidepressants are not effective in all patients in treating depressive symptoms, as well as cognitive dysfunction. So far, there are no established predictors of treatment response, and brain derived neurotrophic factor (BDNF) is potential biomarker candidate. While its concentration has been decreased in depressed patients, some antidepressants increase BDNF levels. This prospective, randomized, longitudinal study included 121 patients with depression: 61 patients were treated with vortioxetine and 60 with escitalopram. After 4 weeks of treatment, despite similar improvement in depressive symptoms, vortioxetine increased plasma BDNF concentration, while escitalopram had no effects. Escitalopram induced larger reduction in platelet serotonin concentration than vortioxetine, whereas greater decrease in serotonin concentration predicted better response to escitalopram. Both antidepressants produced similar improvement of cognitive symptoms, although escitalopram has not affected attention. Both antidepressants have not changed platelet MAO-B activity. Our findings suggest different biological effects of escitalopram and vortioxetine, which may be associated with clinical outcome. This research contributes to better understanding of antidepressant mechanism of action and emphasizes the need for personalized treatment approach

Effects of vortioxetine and escitalopram on plasma brain derived neurotrophic factor level and platelet monoamine oxidase B activity in subjects with depressive disorder

Antidepresivi nemaju učinak u svih bolesnika na simptome depresije, uključujući i kognitivne simptome. Za sada ne postoje pouzdani predskazatelji učinka antidepresiva, a jedan od kandidata je moždani neurotrofni čimbenik (BDNF). Njegova je koncentracija snižena u depresivnih bolesnika, dok neki antidepresivi povisuju koncentraciju BDNF-a. Ovo prospektivno, randomizirano, longitudinalno istraživanje uključilo je 121 depresivnog bolesnika, među kojima je 61 bolesnik liječen vortioksetinom, a 60 escitalopramom. Nakon 4 tjedna terapije, unatoč podjednakom poboljšanju simptoma depresije, vortioksetin je izazvao porast koncentracije BDNF-a u plazmi, dok uz terapiju escitalopramom nije zapažena promjena. Oba antidepresiva podjednako su ublažila kognitivnu disfunkciju, osim što escitalopram nije pokazao učinak na testu pažnje. Nadalje, escitalopram je izazvao veći pad koncentracije trombocitnog serotonina u usporedbi s vortioksetinom, pri čemu je veći pad koncentracije serotonina predvidio dobar odgovor na escitalopram. Oba lijeka nisu značajno utjecala na aktivnost trombocitne MAO-B. Rezultati istraživanja upućuju na razlike u biološkom učinku escitaloprama i vortioksetina, koje mogu biti povezane i s kliničkim učinkom. Istraživanje predstavlja doprinos razumijevanju mehanizma djelovanja antidepresiva i naglašava potrebu individualnog pristupa u liječenju.Antidepressants are not effective in all patients in treating depressive symptoms, as well as cognitive dysfunction. So far, there are no established predictors of treatment response, and brain derived neurotrophic factor (BDNF) is potential biomarker candidate. While its concentration has been decreased in depressed patients, some antidepressants increase BDNF levels. This prospective, randomized, longitudinal study included 121 patients with depression: 61 patients were treated with vortioxetine and 60 with escitalopram. After 4 weeks of treatment, despite similar improvement in depressive symptoms, vortioxetine increased plasma BDNF concentration, while escitalopram had no effects. Escitalopram induced larger reduction in platelet serotonin concentration than vortioxetine, whereas greater decrease in serotonin concentration predicted better response to escitalopram. Both antidepressants produced similar improvement of cognitive symptoms, although escitalopram has not affected attention. Both antidepressants have not changed platelet MAO-B activity. Our findings suggest different biological effects of escitalopram and vortioxetine, which may be associated with clinical outcome. This research contributes to better understanding of antidepressant mechanism of action and emphasizes the need for personalized treatment approach

Effects of vortioxetine and escitalopram on plasma brain derived neurotrophic factor level and platelet monoamine oxidase B activity in subjects with depressive disorder

Antidepresivi nemaju učinak u svih bolesnika na simptome depresije, uključujući i kognitivne simptome. Za sada ne postoje pouzdani predskazatelji učinka antidepresiva, a jedan od kandidata je moždani neurotrofni čimbenik (BDNF). Njegova je koncentracija snižena u depresivnih bolesnika, dok neki antidepresivi povisuju koncentraciju BDNF-a. Ovo prospektivno, randomizirano, longitudinalno istraživanje uključilo je 121 depresivnog bolesnika, među kojima je 61 bolesnik liječen vortioksetinom, a 60 escitalopramom. Nakon 4 tjedna terapije, unatoč podjednakom poboljšanju simptoma depresije, vortioksetin je izazvao porast koncentracije BDNF-a u plazmi, dok uz terapiju escitalopramom nije zapažena promjena. Oba antidepresiva podjednako su ublažila kognitivnu disfunkciju, osim što escitalopram nije pokazao učinak na testu pažnje. Nadalje, escitalopram je izazvao veći pad koncentracije trombocitnog serotonina u usporedbi s vortioksetinom, pri čemu je veći pad koncentracije serotonina predvidio dobar odgovor na escitalopram. Oba lijeka nisu značajno utjecala na aktivnost trombocitne MAO-B. Rezultati istraživanja upućuju na razlike u biološkom učinku escitaloprama i vortioksetina, koje mogu biti povezane i s kliničkim učinkom. Istraživanje predstavlja doprinos razumijevanju mehanizma djelovanja antidepresiva i naglašava potrebu individualnog pristupa u liječenju.Antidepressants are not effective in all patients in treating depressive symptoms, as well as cognitive dysfunction. So far, there are no established predictors of treatment response, and brain derived neurotrophic factor (BDNF) is potential biomarker candidate. While its concentration has been decreased in depressed patients, some antidepressants increase BDNF levels. This prospective, randomized, longitudinal study included 121 patients with depression: 61 patients were treated with vortioxetine and 60 with escitalopram. After 4 weeks of treatment, despite similar improvement in depressive symptoms, vortioxetine increased plasma BDNF concentration, while escitalopram had no effects. Escitalopram induced larger reduction in platelet serotonin concentration than vortioxetine, whereas greater decrease in serotonin concentration predicted better response to escitalopram. Both antidepressants produced similar improvement of cognitive symptoms, although escitalopram has not affected attention. Both antidepressants have not changed platelet MAO-B activity. Our findings suggest different biological effects of escitalopram and vortioxetine, which may be associated with clinical outcome. This research contributes to better understanding of antidepressant mechanism of action and emphasizes the need for personalized treatment approach

Distinct association of plasma BDNF concentration and cognitive function in depressed patients treated with vortioxetine or escitalopram

Rationale: Cognitive dysfunction is frequent in major depressive disorder (MDD), and brain-derived neurotrophic factor (BDNF) is involved both in regulation of cognition and in therapeutic response in MDD. ----- Objectives: The aim of this study was to determine if baseline plasma BDNF might predict change in cognitive function in MDD patients treated with vortioxetine or escitalopram, and whether the alterations in BDNF levels correlate with changes in cognitive performance during treatment. ----- Methods: Drug-naive or drug-free patients with MDD (N=121) were sampled and evaluated at baseline and 4 weeks after treatment initiation with vortioxetine or escitalopram. Cognitive function was evaluated using the F-A-S test, Digit Span test, and Digit Symbol Coding test. Plasma BDNF was determined using ELISA. ----- Results: The results of the study indicate that both vortioxetine (V) and escitalopram (E) improved cognitive functions evaluated with F-A-S test (V: p<0.001; r=-0.427, E: p<0.001; r=-0.370), Digit Symbol Coding test (V: p<0.001; r=-0.706, E: p<0.001; r=-0.435), and Digit Span test-backward span (V: p=0.001; r=-0.311, E: p=0.042; r=-0.185), while only vortioxetine (p<0.001; r=-0.325) improved cognition evaluated with the Digit Span test-forward span. A moderate positive correlation between pretreatment plasma BDNF levels and improvement in cognitive performance was only detected in patients treated with vortioxetine (delta F-A-S test: p=0.011; r=0.325, delta Digit Span test-forward span: p=0.010, r=0.326). ----- Conclusions: These results suggest that higher baseline plasma BDNF levels might be associated with improvements in verbal fluency and working memory in vortioxetine, but not escitalopram treated patients. Vortioxetine treatment was superior in simple attention efficiency

Effect of vortioxetine vs. escitalopram on plasma BDNF and platelet serotonin in depressed patients

Escitalopram and vortioxetine are efficacious antidepressants. They directly target serotonin (5-HT) system, but vortioxetine mechanism of action is distinct from the one of selective serotonin reuptake inhibitors (SSRIs). Treatment with SSRIs decrease platelet 5-HT concentration and increase peripheral brain-derived neurotrophic factor (BDNF) levels. Since vortioxetine has a multimodal mechanism of action, it is expected to have a greater effect on circulatory BDNF concentration, compared to conventional antidepressants. This longitudinal study aimed to explore and compare the effects of 4-weeks of treatment with vortioxetine and escitalopram on plasma BDNF and platelet 5-HT concentration in patients with major depressive disorder (MDD). The results revealed that vortioxetine significantly increased plasma BDNF concentration (p = .018) and significantly decreased platelet 5-HT concentration (p < .001). Treatment with escitalopram significantly decreased platelet 5-HT concentration (p < .001), but it did not affect plasma BDNF concentration (p = .379). Response to vortioxetine was not predicted by baseline plasma BDNF or platelet 5-HT concentration, but response to escitalopram was predicted by baseline platelet 5-HT concentration. These effects might be due to vortioxetine unique mechanism of action, but the clinical implications are unclear. It remains to be determined whether this finding extends during long-term vortioxetine treatment, and which, if any, clinical effects emerge from BDNF increase