Gerard Sancora Esketamine is Effective

Intranasal Esketamine is Effective for Depression

Peter ForsterGPS, Major Depression, Treatments of Depression Leave a Comment

Intranasal esketamine is effective for treating severe depression and suicidality when added to comprehensive standard of care treatment in patients who were felt to be at imminent risk of suicide.

68 patients seen in an emergency department were randomized to receive esketamine or placebo as well as comprehensive treatment including inpatient care and antidepressant medications.

Patients receiving esketamine had a greater improvement in depression on the Montgomery–Åsberg Depression Rating Scale (MADRS) at 4 hours and at 24 hours but not at day 25.

The effect was quite dramatic. The average score in both esketamine and placebo groups at entry into the study on the MADRS scale was 39 corresponding to severe depression.

Four hours after treatment the patient is receiving esketamine had an average 13 point drop on the MADRS (a reduction from severe depression to moderate depression) and 24 hours after treatment those in the esketamine group experienced an average 19 point reduction in depression, corresponding to a drop from severe depression to mild depression.

Significantly greater improvement was also observed in the esketamine group on the MADRS suicidal thoughts item score at 4 hours (effect size=0.67), but not at 24 hours (effect size=0.35) or at day 25 (effect size=0.29). Between-group reductions in clinician global judgment of suicide risk scores were not statistically different at any time point.

The most common adverse events among participants in the esketamine group were nausea, dizziness, dissociation, unpleasant taste, and headache.

A transient increase in blood pressure was seen in the esketamine group (after infusion average systolic blood pressure in the esketamine group went up by 17 points compared with nine points in the placebo group) and one patient in the esketamine experienced a transient increase in depressive symptoms that was felt to be possibly related to the medication. Dissociative symptoms began shortly after the the dose, peaked at 40 minutes and were resolved by two hours.

Given the significant difference between placebo and esketamine treatments in terms of side effects one important question is whether patients and the clinical staff were able to distinguish between the two treatments (whether the double-blind was maintained) and it is that this is not discussed in the article.

“This is a significant and important study because it provides early evidence demonstrating that esketamine produces antidepressant effects greater than that found with intensive standard of care approaches over the first hours and days of treatment in patients believed to be at imminent risk of suicide requiring hospitalization,” study co-author Gerard Sanacora, M.D., Ph.D. (pictured at left), told Psychiatric News. “If confirmed, this type of rapid onset antidepressant effect could potentially shorten hospital stays or possibly even allow patients to avoid hospitalization altogether and more rapidly return to their normal lives.”

The study was sponsored by Janssen Research and Development LLC.

A quick glance at for the status of clinical trials of esketamine suggests that we may be nearing submission of the clinical trial data for review by the FDA, which means that this new treatment may be available sometime in the next year or two.

For More Information

Depression Therapeutics and Mechanisms

Ketamine Reduces Suicidal Thoughts



Daly EJ, Singh JB, Fedgchin M, Cooper K, Lim P, Shelton RC, Thase ME, Winokur A, Van Nueten L, Manji H, Drevets WC. Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression: A Randomized Clinical Trial. JAMA Psychiatry. 2018 Feb 1;75(2):139-148. doi: 10.1001/jamapsychiatry.2017.3739. PubMed PMID: 29282469; PubMed Central PMCID: PMC5838571.