Despite significant advances in our understanding and treatment of mental health disorders, the incidence of suicide continues to rise. Major Depressive Disorder (MDD) is associated with a 20-fold increase in risk of suicide, and the period after discharge from psychiatric hospitalization has been identified as a time of heightened risk for suicidal ideation (SI) and suicide attempt (SA). Although many treatments are available for the treatment of depression and SI, they require weeks or months to become fully effective; given this limitation, these interventions are inadequate during this window of increased risk for suicide.
Within the past decade, numerous trials have shown that ketamine, a noncompetitive antagonist of NMDA glutamate receptors, has rapid (typically within hours of administration) antisuicidal and antidepressant effects in depressed patients. A typical protocol for the acute treatment of depression consists of six intravenous (IV) infusions of ketamine over 2 to 3 weeks and is associated with a reduction in SI and depressive symptoms. Unfortunately, ketamine’s effects are short-lived, with most patients reporting recurrent depressive symptoms within 2 to 4 weeks after stopping treatment.
Long-term clinical trials of ketamine treatment have not been conducted, and the feasibility and efficacy of integrating IV ketamine treatment for suicidality into inpatient clinical settings has not been carefully studied. Finally, it is not clear which patients are most likely to benefit from IV ketamine treatment.
In a study funded by the American Foundation for Suicide Prevention, Cristina Cusin, MD and Paola Pedrelli, PhD from the Depression Clinical and Research Program at Mass General will systematically evaluate the feasibility and efficacy of IV ketamine for the treatment of suicidal ideation among 100 individuals with MDD who have been recently admitted to a psychiatric inpatient unit as a result of suicide ideation or attempt. After acute treatment with IV ketamine and discharge, participants will receive maintenance treatment with intranasal esketamine after discharge. Measures of depressive symptoms and suicidality will be used to assess efficacy. Healthcare utilization and rates of rehospitalization will be assessed in ketamine-treated patients and will be compared to a historical control group. This study will also examine predictors of treatment response and will employ advanced statistical methods including latent growth analyses, machine learning, and time series analyses to examine clinical outcomes and to optimize treatment protocols.
Ketamine holds great promise for those with treatment-refractory and/or severe depressive symptoms; increasing our knowledge of the long-term efficacy, safety, and tolerability of ketamine treatment will increase its utility across a greater diversity of clinical settings. Patients with mood disorders are particularly vulnerable after discharge from inpatient treatment, and this study will evaluate the use of IV ketamine as a strategy for reducing risk of rehospitalization and suicidal behaviors in this population.
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Sakurai H, Jain F, Foster S, Pedrelli P, Mischoulon D, Fava M, Cusin C. Long-term outcome in outpatients with depression treated with acute and maintenance intravenous ketamine: A retrospective chart review. J Affect Disord. 2020 Nov 1; 276:660-666.
Cristina Cusin, MD is the Founder and Director of the MGH Ketamine Clinic, a psychiatrist in the Depression Clinical and Research Program, and an Associate Professor in Psychiatry at Harvard Medical School. Her research and clinical work has focused on the treatment of treatment-refractory mood disorders, using innovative strategies including ketamine and deep brain stimulation.
Paola Pedrelli, PhD is the Director Of Dual Diagnoses Studies at the Depression Clinical and Research Program. She is an Assistant in Psychology at Massachusetts General Hospital and an Assistant Professor in Psychiatry at Harvard Medical School. Her research focuses on investigating the etiology, assessment, and treatment of comorbid Affective Disorders and Alcohol Use Disorders (AUDs).
