OPEN Foundation

C. Albott

A randomized, double-blind, active placebo-controlled study of efficacy, safety, and durability of repeated vs single subanesthetic ketamine for treatment-resistant depression

Abstract

The strategy of repeated ketamine in open-label and saline-control studies of treatment-resistant depression suggested greater antidepressant response beyond a single ketamine. However, consensus guideline stated the lack of evidence to support frequent ketamine administration. We compared the efficacy and safety of single vs. six repeated ketamine using midazolam as active placebo. Subjects received either six ketamine or five midazolam followed by a single ketamine during 12 days followed by up to 6-month post-treatment period. The primary end point was the change from baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) score at 24 h after the last infusion. Fifty-four subjects completed all six infusions. For the primary outcome measure, there was no significant difference in change of MADRS scores between six ketamine group and single ketamine group at 24 h post-last infusion. Repeated ketamine showed greater antidepressant efficacy compared to midazolam after five infusions before receiving single ketamine infusion. Remission and response favored the six ketamine after infusion 4 and 5, respectively, compared to midazolam before receiving single ketamine infusion. For those who responded, the median time-to-relapse was nominally but not statistically different (2 and 6 weeks for the single and six ketamine group, respectively). Repeated infusions were relatively well-tolerated. Repeated ketamine showed greater antidepressant efficacy to midazolam after five infusions but fell short of significance when compared to add-on single ketamine to midazolam at the end of 2 weeks. Increasing knowledge on the mechanism of ketamine should drive future studies on the optimal balance of dosing ketamine for maximum antidepressant efficacy with minimum exposure.
Shiroma, P. R., Thuras, P., Wels, J., Albott, C. S., Erbes, C., Tye, S., & Lim, K. O. (2020). A randomized, double-blind, active placebo-controlled study of efficacy, safety, and durability of repeated vs single subanesthetic ketamine for treatment-resistant depression. Translational psychiatry10(1), 1-9., https://doi.org/10.1038/s41398-020-00897-0
Link to full text

Intravenous Ketamine for Adolescents with Treatment-Resistant Depression: An Open-Label Study

Abstract

BACKGROUND:

Novel interventions for treatment-resistant depression (TRD) in adolescents are urgently needed. Ketamine has been studied in adults with TRD, but little information is available for adolescents. This study investigated efficacy and tolerability of intravenous ketamine in adolescents with TRD, and explored clinical response predictors.

METHODS:

Adolescents, 12-18 years of age, with TRD (failure to respond to two previous antidepressant trials) were administered six ketamine (0.5 mg/kg) infusions over 2 weeks. Clinical response was defined as a 50% decrease in Children’s Depression Rating Scale-Revised (CDRS-R); remission was CDRS-R score ≤28. Tolerability assessment included monitoring vital signs and dissociative symptoms using the Clinician-Administered Dissociative States Scale (CADSS).

RESULTS:

Thirteen participants (mean age 16.9 years, range 14.5-18.8 years, eight biologically male) completed the protocol. Average decrease in CDRS-R was 42.5% (p = 0.0004). Five (38%) adolescents met criteria for clinical response. Three responders showed sustained remission at 6-week follow-up; relapse occurred within 2 weeks for the other two responders. Ketamine infusions were generally well tolerated; dissociative symptoms and hemodynamic symptoms were transient. Higher dose was a significant predictor of treatment response.

CONCLUSIONS:

These results demonstrate the potential role for ketamine in treating adolescents with TRD. Limitations include the open-label design and small sample; future research addressing these issues are needed to confirm these results. Additionally, evidence suggested a dose-response relationship; future studies are needed to optimize dose. Finally, questions remain regarding the long-term safety of ketamine as a depression treatment; more information is needed before broader clinical use.

Cullen, K. R., Amatya, P., Roback, M. G., Albott, C. S., Westlund Schreiner, M., Ren, Y., … & Reigstad, K. (2018). Intravenous Ketamine for Adolescents with Treatment-Resistant Depression: An Open-Label Study. Journal of child and adolescent psychopharmacology28(7), 437-444., 10.1089/cap.2018.0030

Link to full text

1001. Neurocognitive Effects of Repeated Ketamine Infusions in Co-Occurring Posttraumatic Stress Disorder and Treatment-Resistant Depression

Albott, C., Lim, K., Forbes, M., Erbes, C., Thuras, P., Tye, S., … & Shiroma, P. (2017). 1001-Neurocognitive Effects of Repeated Ketamine Infusions in Co-Occurring Posttraumatic Stress Disorder and Treatment-Resistant Depression. Biological Psychiatry81(10), S405. 10.1016/j.biopsych.2017.02.728
Link to full text

The Effect of Repeated Ketamine Infusion Over Facial Emotion Recognition in Treatment-Resistant Depression: A Preliminary Report

Abstract

In contrast to improvement in emotion recognition bias by traditional antidepressants, the authors report preliminary findings that changes in facial emotion recognition are not associated with response of depressive symptoms after repeated ketamine infusions or relapse during follow-up in treatment-resistant depression.

Shiroma, P. R., Albott, C. S., Johns, B., Thuras, P., Wels, J., & Lim, K. O. (2015). The Effect of Repeated Ketamine Infusion Over Facial Emotion Recognition in Treatment-Resistant Depression: A Preliminary Report. The Journal of Neuropsychiatry and Clinical Neurosciences. http://dx.doi.org/10.1176/appi.neuropsych.14100243
Link to full text

Crafting Music for Altered States and Psychedelic Spaces - Online Event - Jan 22nd