Single ketamine infusion in bipolar depression resistant to antidepressants: are neurotrophins involved?

Abstract

We investigated serum brain-derived neurotrophin factor (BDNF), nerve growth factor (NGF), neurotrophin-3 (NTF3), neurotrophin-4 (NTF4) and the glial-derived neurotrophic factor (GDNF), in relation to ketamine efficacy, in bipolar depressed patients resistant to treatment with antidepressants. Twenty-five patients (4 male, 21 female), aged 27-67 years, with bipolar depression, receiving mood-stabilizing medications, were studied. Antidepressants were discontinued for at least 7 days before single intravenous ketamine infusion (0.5 mg/kg body weight). Response to ketamine was defined as ≥ 50% reduction on 17-item Hamilton Depression Rating Scale (HDRS) after 1 week, and remission as HDRS score ≤ 7. Serum BDNF, NGF, NTF3, NTF4 and GDNF levels were estimated by enzyme-linked immunosorbent assay. There were 13 ketamine responders and 12 non-responders. The remission was obtained in eight and 12 patients after seven and 14 days, respectively. At baseline, there were no differences between responders and non-responders in any of the neurotrophins. Serum BDNF was significantly reduced after 7 days in non-responders. Serum NGF, NT3, NT4 and GDNF did not significantly change. The results confirm an antidepressant effect of ketamine infusion as an add-on to mood-stabilizing drugs in bipolar depression resistant to antidepressant treatment. They may also suggest a possible involvement of BDNF in this effect.