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A. Schatzberg

Attenuation of antidepressant and antisuicidal effects of ketamine by opioid receptor antagonism.

August 29, 2019 / Depressive Disorders, Ketamine, Papers, Psychology, Publications / By / , , , , , ,

Abstract

We recently reported that naltrexone blocks antidepressant effects of ketamine in humans, indicating that antidepressant effects of ketamine require opioid receptor activation. However, it is unknown if opioid receptors are also involved in ketamine’s antisuicidality effects. Here, in a secondary analysis of our recent clinical trial, we test whether naltrexone attenuates antisuicidality effects of ketamine. Participants were pretreated with naltrexone or placebo prior to intravenous ketamine in a double-blinded crossover design. Suicidality was measured with the Hamilton Depression Rating Scale item 3, Montgomery-Åsberg Depression Rating Scale item 10, and Columbia Suicide Severity Rating Scale. In the 12 participants who completed naltrexone and placebo conditions, naltrexone attenuated the antisuicidality effects of ketamine on all three suicidality scales/subscales (linear mixed model, fixed pretreatment effect, p < 0.01). Results indicate that opioid receptor activation plays a significant role in the antisuicidality effects of ketamine.
Williams, N. R., Heifets, B. D., Bentzley, B. S., Blasey, C., Sudheimer, K. D., Hawkins, J., … & Schatzberg, A. F. (2019). Attenuation of antidepressant and antisuicidal effects of ketamine by opioid receptor antagonism. Molecular psychiatry, 1-8., https://doi.org/10.1038/s41380-019-0503-4
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A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders

April 1, 2017 / Depressive Disorders, Ketamine, Papers, Psychology / By / , , , , , ,

Abstract

IMPORTANCE:
Several studies now provide evidence of ketamine hydrochloride’s ability to produce rapid and robust antidepressant effects in patients with mood and anxiety disorders that were previously resistant to treatment. Despite the relatively small sample sizes, lack of longer-term data on efficacy, and limited data on safety provided by these studies, they have led to increased use of ketamine as an off-label treatment for mood and other psychiatric disorders.
OBSERVATIONS:
This review and consensus statement provides a general overview of the data on the use of ketamine for the treatment of mood disorders and highlights the limitations of the existing knowledge. While ketamine may be beneficial to some patients with mood disorders, it is important to consider the limitations of the available data and the potential risk associated with the drug when considering the treatment option.
CONCLUSIONS AND RELEVANCE:
The suggestions provided are intended to facilitate clinical decision making and encourage an evidence-based approach to using ketamine in the treatment of psychiatric disorders considering the limited information that is currently available. This article provides information on potentially important issues related to the off-label treatment approach that should be considered to help ensure patient safety.

Sanacora, G., Frye, M. A., McDonald, W., Mathew, S. J., Turner, M. S., Schatzberg, A. F., … & Nemeroff, C. B. (2017). A consensus statement on the use of ketamine in the treatment of mood disorders. Jama psychiatry, 74(4), 399-405. 10.1001/jamapsychiatry.2017.0080
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Ketamine: Promising Path or False Prophecy in the Development of Novel Therapeutics for Mood Disorders?

October 22, 2014 / Depressive Disorders, Ketamine, Neuroscience, Papers, Psychology, Publications / By / ,

Abstract

Large ‘real world’ studies demonstrating the limited effectiveness and slow onset of clinical response associated with our existing antidepressant medications has highlighted the need for the development of new therapeutic strategies for major depression and other mood disorders. Yet, despite intense research efforts, the field has had little success in developing antidepressant treatments with fundamentally novel mechanisms of action over the past six decades, leaving the field wary and skeptical about any new developments. However, a series of relatively small proof-of-concept studies conducted over the last 15 years has gradually gained great interest by providing strong evidence that a unique, rapid onset of sustained, but still temporally limited, antidepressant effects can be achieved with a single administration of ketamine. We are now left with several questions regarding the true clinical meaningfulness of the findings and the mechanisms underlying the antidepressant action. In this Circumspectives piece, Dr Sanacora and Dr Schatzberg share their opinions on these issues and discuss paths to move the field forward.

Sanacora, G., & Schatzberg, A. F. (2015). Ketamine: Promising Path or False Prophecy in the Development of Novel Therapeutics for Mood Disorders&quest. Neuropsychopharmacology, 40(2), 259-267. https://dx.doi.org/10.1038/npp.2014.261

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