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MDD: Effects of an add-on single intravenous vortioxetine dose

Key clinical point: The early antidepressant effects of an add-on single intravenous (IV) dose of vortioxetine were no different from that of placebo; however, a numerically larger improvement in anxiety symptoms was observed with vortioxetine vs placebo.

Major finding: Both vortioxetine and the placebo groups showed improvements in antidepressant effect (Montgomery–Åsberg Depression Rating scores on day 1: −3.6 and −2.8, respectively; nonsignificant difference, −0.8; P = .263). Numerically larger improvements were noted with vortioxetine in Hospital Anxiety and Depression scores (day 1: mean difference, −1.3; P = .064 and day 3: mean difference, −1.4; P = .063). IV vortioxetine was well tolerated with a favorable toxicity profile.

Study details: Patients with recurrent MDD were randomly assigned to vortioxetine group (IV 25 mg + oral 10 mg; n = 39) or to placebo group (n = 41) for 7 days.

Disclosures: The study was funded by H. Lundbeck A/S. J Zambori, M Dalsgaard, C Baayen, J Areberg, A Ettrup, and I Florea are employees of H. Lundbeck A/S. E Rancans reported ties with various pharmaceutical companies, including H. Lundbeck A/S.


“Eighty patients, hospitalized for severe depression, refractory to a six week trial of an SSRI (selective serotonin reuptake inhibitor) or SNRI (serotonin norepinephrine reuptake inhibitor), were randomized to a one-week course of vortioxetine vs placebo given intravenously x 1 day followed by oral dosing daily.

The authors studied vortioxetine, a serotonin modulator, because in addition to serotonin reuptake inhibition, its binding to 5HT1a and 5HT3 serotonin receptors might accelerate the mood response. They hypothesized that 1. 5HT1a agonism might facilitate rapid 5HT1a desensitization, and thus symptom improvement and 2. 5HT3 antagonism may indirectly increase serotonin-mediated activation of glutamatergic neurons in the frontal cortex.

Serotonin reuptake inhibition generally takes several weeks to improve depression and anxiety. Increased serotonin by SSRIs increases 5HT1a autoreceptor activity, which in turn is believed to inhibit further release of serotonin until the 5HT1a autoreceptor desensitizes over several weeks. The time until 5HT1a autoreceptor desensitization is believed to underlie the lag time between starting serotonin reuptake inhibitors and improved anxiety and depression.

Vortioxetine has been demonstrated to be an effective antidepressant after 6-12 weeks. However, after one week, vortioxetine was not significantly better than placebo in improving anxiety or depression. If a rapid antidepressant response is required, clinicians can consider ketamine, brexanolone or electroconvulsive therapy.”

Gita Ramamurthy, MD

Director, Psychiatric Consultation Service

Upstate Medical University


Rancans E et al. Int Clin Psychopharmacol. 2020 Aug 7. doi: 10.1097/YIC.0000000000000326.