Oral esketamine for treatment-resistant depression: rationale and design of a randomized controlled trial.
Sanne Y Smith-Apeldoorn, Jolien K E Veraart, Jeanine Kamphuis, Antoinette D I van Asselt, Daan J Touw, Marije Aan Het Rot, Robert A Schoevers
BMC psychiatry November 29, 2019 DOI: 10.1186/s12888-019-2359-1 via PubMed
Summary
AI-generated from the abstractA triple-blind randomized placebo-controlled trial investigates daily oral esketamine versus placebo as an add-on to regular antidepressants in patients with treatment-resistant depression over 6 weeks, followed by a 4-week follow-up. This is the first such trial to examine the efficacy, safety, tolerability, mechanisms of action, and economic impact of repeated oral esketamine administration. If effective and tolerated, oral esketamine offers practical advantages over intravenous administration. The study aims to address the urgent need for additional treatment strategies for treatment-resistant depression.
Study at a glance
| Characteristics | Randomized controlled trial Placebo-controlled Peer reviewed |
|---|---|
| Population | Patients with treatment-resistant depression |
| Intervention | Esketamine |
| Duration | 6-week intervention, 4-week follow-up |
| Topics | Depression Esketamine |
| Keywords | Clinical trial Oral administration |
| Key finding | This is the first RCT investigating repeated oral esketamine administration in patients with treatment-resistant depression; results will determine efficacy and tolerability. |
Abstract
There is an urgent need to develop additional treatment strategies for patients with treatment-resistant depression (TRD). The rapid but short-lived antidepressant effects of intravenous (IV) ketamine as a racemic mixture have been shown repeatedly in this population, but there is still a paucity of data on the efficacy and safety of (a) different routes of administration, and (b) ketamine's enantiomers esketamine and arketamine. Given practical advantages of oral over IV administration and pharmacodynamic arguments for better antidepressant efficacy of esketamine over arketamine, we designed a study to investigate repeated administration of oral esketamine in patients with TRD. This study features a triple-blind randomized placebo-controlled trial (RCT) comparing daily oral esketamine versus placebo as add-on to regular antidepressant medications for a period of 6 weeks, succeeded by a follow-up of 4 weeks. The methods support examination of the efficacy, safety, tolerability, mechanisms of action, and economic impact of oral esketamine in patients with TRD. This is the first RCT investigating repeated oral esketamine administration in patients with TRD. If shown to be effective and tolerated, oral esketamine administration poses important advantages over IV administration. Dutch Trial Register, NTR6161. Registered 21 October 2016.