Plasma BDNF concentrations and the antidepressant effects of six ketamine infusions in unipolar and bipolar depression

Abstract

Objectives Accumulating evidence has implicated that brain derived neurotrophic factor (BDNF) is thought to be involved in the pathophysiology of depression, but its correlation with ketamine’s antidepressant efficacy focusing on Chinese individuals with depression is not known. This study was aim to determine the correlation of plasma BDNF (pBDNF) concentrations and ketamine’s antidepressant efficacy. Methods Ninety-four individuals with depression received six intravenous infusions ketamine (0.5 mg/kg). Remission and response were defined as Montgomery-Asberg Depression Rating Scale (MADRS) scores less than 10 and a reduction of 50% or more in MADRS scores, respectively. Plasma was collected at baseline and at 24 h and 2 weeks after completing six ketamine infusions (baseline, 13 d and 26 d). Results A significant improvement in MADRS scores and pBDNF concentrations was found after completing six ketamine infusions compared to baseline (all ps < 0.05). Higher baseline pBDNF concentrations were found in ketamine responders/remitters (11.0 ± 6.2/10.1 ± 5.8 ng/ml) than nonresponders/nonremitters (8.0 ± 5.5/9.2 ± 6.4 ng/ml) (all ps < 0.05). Baseline pBDNF concentrations were correlated with MADRS scores at 13 d (t = − 2.011, p = 0.047) or 26 d (t = − 2.398, p = 0.019) in depressed patients (all ps < 0.05). Subgroup analyses found similar results in individuals suffering from treatment refractory depression. Conclusion This preliminary study suggests that baseline pBDNF concentrations appeared to be correlated with ketamine’s antidepressant efficacy in Chinese patients with depression.

Effects of Antidepressant Treatment on Neurotrophic Factors (BDNF and IGF-1) in Patients with Major Depressive Disorder (MDD)

“…The only study concerning intravenous infusions of ketamine was conducted by Zheng et al [ 43 ]. The plasma BDNF levels were measured at baseline and after 13 and 26 days.…”

“…A significant improvement in MADRS scores and pBDNF concentrations was found after completing six ketamine infusions compared to baseline (all p < 0.05). Baseline pBDNF concentrations were correlated with MADRS scores at 13 d (t = −2.011, p = 0.047) or 26 d (t = −2.398, p = 0.019) in depressed patients (all p < 0.05) [ 43 ].…”

“…The aim of our review was to update the knowledge on how antidepressants affect the level of neurotrophic markers (BDNF and IGF-1) and to assess whether the conclusions drawn in previous studies can be repeated after taking into account the studies included in the review. The review included four control trials [ 19 , 40 , 43 , 45 ], three meta-analyses [ 36 , 37 , 38 ] and two longitudinal studies [ 39 , 42 ] regarding BDNF levels (a total of 4643 people) and four clinical trials [ 41 , 44 , 45 , 46 ] on IGF-1 levels (3082 people) in plasma and/or serum before and after antidepressant treatment. In our review, we found that most of the studies conducted on serum BDNF [ 36 , 37 , 38 , 39 , 40 , 41 ] indicated that antidepressant treatment could increase BDNF concentration in remitters and responders.…”

“…Category A and B studies by Siwek et al [ 54 ] concerning plasma BDNF [ 19 , 42 ] levels indicated that antidepressant treatment did not affect plasma BDNF levels. Treating treatment-resistant depression is an increasing problem; hence, this review includes the C category study of plasma BDNF levels before and after ketamine infusions [ 43 ]. Interestingly, the BDNF levels increased after an average time of 4 h after a low-dose infusion of ketamine, completely different from the evidence with other antidepressants, which require a more prolonged time [ 43 ].…”

“…There is evidence of a modulating effect of antidepressants on depression via the neurotrophins in preclinical and clinical models of depression; however, the results are conflicting; therefore, the therapeutic role of antidepressants cannot be clearly stated [ 21 , 22 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ]. The pharmacotherapy of depression most frequently used in clinical practice is based on the use of drugs that increase the level of monoamines.…”