Table 1.

Characteristic of the BDNF studies included in the present review.

Study	Year of Study	Grading System by Siwek et al. [54]	Type of Study	Patient Group (n)	Duration of Study (Weeks)	Markers	Medication	Influence of Drugs on Markers	Results
Polyakova et al. [36]	2014	A	Meta-Analysis	n = 2298	2–8	serum BDNF	Paroxetine, Escitalopram, Citalopram, Sertraline, Fluoxetine, Venlafaxine, Duloxetine Mirtazapine, Tranylcypromine, Amitriptyline, Clomipramine	YES	Serum BDNF was significantly decreased in patients in a depressive state compared with controls. The BDNF levels increased upon treatment in remitters and responders, whereas in the non-responders they remained stable. Serum BDNF changes in remitters and responders were significantly larger than in the non-responders.
Zhou et al. [37]	2017	A	Meta-Analysis	n = 633		serum and plasma BDNF	venlafaxine, paroxetine, sertraline, esciltalopram	+/−	Significant decreased HDRS score. Sertraline—statistically significant effect on the serum BDNF levels pre- and post-antidepressant treatment. Plasma BDNF—no effect.
Arumugam et al. [38]	2017	A	Meta-Analysis	n = 154	5–12	serum BDNF	Venlafaxine, Fluoxetine, Paroxetine, Citalopram, Sertraline, Milnacipran	+/−	Antidepressant therapy is associated with a change in BDNF level, but did not produce any significant impact on it. HDRS score signified a positive antidepressant treatment outcome.
Chiou et al. [39]	2017	A	Longitudinal study	n = 142 (drug-naïve first-episode MDD = 71 healthy controls = (71)	4	serum BDNF	escitalopram fluoxetine mirtazapine paroxetine venlafaxine	NO	The serum BDNF levels post-treatment were not significantly elevated.
Brunoni et al. [19]	2014	A	Randomized Controlled Trial	n = 103 (73 had their baseline and endpoint BDNF plasma levels analyzed)	6	plasma BDNF	sertraline,	NO	Sertraline did not change BDNF plasma levels over time and according to clinical improvement. There were no significant correlations between MADRS or HDRS scores changes with BDNF plasma changes.
Gupta et al. [40]	2017	B	Clinical Trial	n = 60 (agomelatine = 30 fluoxetine = 30)	12	serum BDNF	Fluoxetine, Agomelatine	YES	Agomelatine responders—serum BDNF level significantly increased at 12 weeks after treatment. Fluoxetine responders group—serum BDNF level significantly increased after 12 weeks of treatment.
Troyan & Levada. [45]	2020	B	Clinical Trial	n = 73 (treatment group = 30 healthy controls HC = 32 MDD = 41)	8	serum BDNF (sBDNF)	Vortioxetin	YES	BDNF levels were significantly higher post-treatment; moreover, they were prominently higher than in healthy controls (HC). Prominent inverse relationships was estabilished between BDNF concentrations and MDD status.
Sagud et al. [42]	2016	B	Longitudinal study	n = 88 (healthy controls = 44, MDD = 44)	4	plasma BDNF	Vortioxetine	YES	Vortioxetine treatment significantly increased plasma BDNF concentration in depressed patients compared to their baseline values.
Zheng et al. [43]	2021	C	Clinical Trial	n = 94	26 days	plasma BDNF	Ketamine	YES	Correlation and regression analyses showed significant associations between pBDNF concentrations at baseline and MADRS scores at 13 d and 26 d in depressed patients.