Arketamine for bipolar depression: Open-label, dose-escalation, pilot study.
Igor D. Bandeira, Gustavo C. Leal, Fernanda S. Correia-Melo, Breno Souza-Marques, Samantha S. Silva, Daniel H Lins-Silva, Rodrigo P Mello, Flávia Vieira, Ingrid Dorea-Bandeira, Daniela Faria-Guimarães, Beatriz A Carneiro, Ana Teresa Caliman-Fontes, Flávio Kapczinski, Ângela Miranda-Scippa, Acioly L T Lacerda, Lucas C Quarantini
Journal of Psychiatric Research August 1, 2023 DOI: 10.1016/j.jpsychires.2023.06.028 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Pilot study Open-label Peer reviewed |
|---|---|
| Sample size | 6 |
| Population | Adults with bipolar disorder types I and II in a current depressive episode for at least four weeks |
| Intervention | Arketamine intravenous infusion |
| Dose | 0.5 mg/kg first, then 1 mg/kg one week apart |
| Duration | Two infusions one week apart, with assessments 24 hours after each infusion |
| Topics | Ketamine Depression |
| Keywords | Antidepressant Bipolar depression Bipolar disorder Glutamate Major depression Nmda |
| Key points | Arketamine infusions produced rapid reductions in depression severity in bipolar depression with good tolerability and no manic symptoms. |
Abstract
There are significantly fewer options for the treatment of bipolar depression than major depressive disorder, with an urgent need for alternative therapies. In this pilot study, we treated six subjects with bipolar disorder types I and II (according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria) who had been in a current depressive episode for at least four weeks. Four subjects were female (66.66%), and the mean age was 45.33 (±12.32). Subjects received adjunct treatment with two arketamine intravenous infusions one week apart-0.5 mg/kg first and then 1 mg/kg. The mean baseline Montgomery-Åsberg Depression Rating Scale (MADRS) total score was 36.66, which decreased to 27.83 24h after the first infusion of 0.5 mg/kg of arketamine (p = 0.036). In respect of the 1 mg/kg dose, the mean MADRS total score before the second infusion was 32.0, which dropped to 17.66 after 24h (p < 0.001). Arketamine appears to have rapid-acting antidepressant properties, consistent with previous animal studies on major depression. All individuals tolerated both doses, exhibiting nearly absent dissociation, and no manic symptoms. To the best of our knowledge, this pilot trial is the first to test the feasibility and safety of the (R)-enantiomer of ketamine (arketamine) for bipolar depression.