Early augmentation therapy with dextromethorphan in mild to moderate major depressive disorder: A group sequential, response adaptive randomized controlled trial.
Shampa Maji, Archana Mishra, Debadatta Mohapatra, Biswa Ranjan Mishra, Monalisa Jena, Anand Srinivasan, Rituparna Maiti
Psychiatry Research December 1, 2024 DOI: 10.1016/j.psychres.2024.116257 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Placebo-controlled Double-blind Peer reviewed |
|---|---|
| Sample size | 60 |
| Population | Patients with major depressive disorder |
| Interventions | Dextromethorphan SSRI |
| Dose | 30 mg/day |
| Duration | 8-week intervention |
| Topics | Depression |
| Keywords | Adjunct therapy Dextromethorphan Remission rate Response rate Depression treatment Antidepressant therapy Clinical trials Psychiatric medicine Drug repurposing |
| Citations | 5 |
| Registration | NCT05181527 |
| Key findings | Adjunct dextromethorphan (30 mg/day) to SSRIs significantly improved depression symptoms, response rate, and remission rate compared to placebo in patients with mild to moderate MDD. |
Abstract
Therapeutic latency, lack of response, and adverse drug reactions are major challenges in current treatment approaches for major depressive disorder (MDD). Following the success of ketamine, more clinical research on NMDA antagonists is needed for a safe and long-term therapy in MDD. Hence, this study was conducted to evaluate the efficacy and safety of adjunct dextromethorphan to SSRIs in MDD. In this randomized, double-blind, add-on, placebo-controlled, group sequential design clinical trial, 60 patients with MDD were randomized to receive either adjunct dextromethorphan (30 mg) or adjunct placebo to SSRI for eight weeks. The primary outcome was the change in the MADRS score over eight weeks, and the secondary outcome parameters were response rate, remission rate, change in CGI-S, CGI-I, change in serum BDNF and serum dextromethorphan. The results showed a significantly greater reduction in MADRS score from baseline (MD: -3.94; 95 %CI: -5.81 to -2.06; p < 0.001; Cohen's d: 1.05), reduction in CGI-S score (p = 0.002), higher response (p = 0.008) and remission (p = 0.007) rate in the test group compared to the control group. The test group also showed significantly better CGI-I score (p = 0.001) compared to the control group. However, no significant difference was found in the change in serum BDNF (p = 0.751) between the groups. In the test group, serum dextromethorphan levels in all patients were within the therapeutic range. The occurrence of adverse events was comparable in both study groups. Early augmentation of SSRIs with dextromethorphan (30 mg/day) for the treatment of mild to moderate MDD may improve clinical outcomes significantly in terms of improvement in symptoms, response rate and remission rate. Trial registration ClinicalTrials.gov identifier: NCT05181527.
Comparable studies
Other randomized controlled trials on depression, most cited first.
Citations in the library
Cites 21
- Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Archives of General Psychiatry March 1, 1994
- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
- Mechanisms of Ketamine Action as an Antidepressant Molecular Psychiatry March 13, 2018
- Glutamatergic Neurotransmission: Pathway to Developing Novel Rapid-Acting Antidepressant Treatments The International Journal of Neuropsychopharmacology November 14, 2018
- Long-term safety of ketamine and esketamine in treatment of depression Expert Opinion on Drug Safety April 13, 2022
and 16 more in the library