Vascular endothelial growth factor (VEGF) has been implicated in mediating the effect of antidepressants (AD) and electroconvulsive therapy on depression since it plays a significant role in the neurogenesis. However, the serum VEGF level has not been investigated so far in association with rTMS treatment in patients with major depressive disorder (MDD).

The aim of our study was to compare the effect of the antidepressants and of the repetitive transcranial magnetic stimulation on the serum vascular endothelial growth factor and its association with the responsiveness to the treatments.

A dataset of 50 patients with TRD who were treated with AD (n=33) and bilateral rTMS for 2x5 days (n=17) was analysed (sample ’rTMS&AD’). Montgomery-Asberg Depression Scale (MADRS) was used for monitoring the symptom changes. The serum VEGF levels and symptoms were assessed on the first (V1), on the 14th (V2) and on the 28th day (V3). The VEGF levels were measured by ELISA assay.

The baseline VEGF levels were significantly higher in non-responders both in the rTMS&AD (p=0.04) and AD samples (p=0.02) compared to responders. The MADRS reduction and the changes in VEGF levels between V1 and V3 were significantly associated in responders only in the AD&rTMS sample (p=0.03). The baseline VEGF level has been proven as a significant predictive factor of treatment response in the total sample (p=0.018).

The baseline VEGF level can be a predictive factor to be a non-responder to different treatments. Change of the VEGF level is associated with the improvement of depressive symptoms only due to rTMS.

This study was supported by the FK 131315 grant of the National Research, Development and Innovation Office, Hungary. Authors declare no conflict of interest.

For patients with major depressive disorder (MDD) experiencing side-effects or non-response to their first antidepressant, little is known regarding the effect of switching between a tricyclic antidepressant (TCA) and a selective serotonin reuptake inhibitor (SSRI).

To compare the switch between the TCA nortriptyline and the SSRI escitalopram.

Among 811 adults with MDD treated with nortriptyline or escitalopram for up to 12 weeks, 108 individuals switched from nortriptyline to escitalopram or vice versa because of side-effects or non-response (trial registration: EudraCT No.2004-001723-38 (https://eudract.ema.europa.eu/) and ISRCTN No.03693000 (http://www.controlled-trials.com)). Patients were followed for up to 26 weeks after switching and response was measured with the Montgomery–Åsberg Depression Rating scale (MADRS). We performed adjusted mixed-effects linear regression models with full information maximum likelihood estimation reporting β-coefficients with 95% CIs.

Switching antidepressants resulted in a significant decrease in MADRS scores. This was present for switchers from escitalopram to nortriptyline (n = 36, β = −0.38, 95% CI −0.51 to −0.25, P<0.001) and from nortriptyline to escitalopram (n = 72, β = −0.34, 95% CI −0.41 to −0.26, P<0.001). Both switching options resulted in significant improvement among individuals who switched because of non-response or side-effects. The results were supported by analyses on other rating scales and symptom dimensions.

These results suggest that switching from a TCA to an SSRI or vice versa after non-response or side-effects to the first antidepressant may be a viable approach to achieve response among patients with MDD.

K.J.A. holds an Alberta Centennial Addiction and Mental Health Research Chair, funded by the Government of Alberta. K.J.A. has been a member of various advisory boards, received consultancy fees and honoraria, and has received research grants from various companies including Johnson and Johnson Pharmaceuticals Research and Development and Bristol-Myers Squibb Pharmaceuticals Limited. D.S. has served on advisory boards for, and received unrestricted grants from, Lundbeck and AstraZeneca. A.F. and P.M. have received honoraria for participating in expert panels for Lundbeck and GlaxoSmithKline.