The effectiveness of ketamine on anxiety, irritability, and agitation: Implications for treating mixed features in adults with major depressive or bipolar disorder

Abstract

Objective: To determine the effectiveness of intravenous (IV) ketamine on anxiety, irritability, agitation, and suicidality, in adults with treatment-resistant major depressive disorder (MDD) or bipolar disorder (BD). Method: Adults (N = 201) with treatment-resistant MDD or BD received repeatdose IV ketamine treatment at a community-based clinic. Mixed features were measured using symptoms of anxiety, irritability, and agitation (AIA), as measured by the Generalized Anxiety Disorder-7 (GAD-7) scale. The Quick Inventory for Depressive Symptomatology Self-Report-16 (QIDS-SR 16) was used to measure overall treatment response, and the QIDS-SR 16 suicidal ideation (SI) item was used to measure change in SI symptoms with ketamine treatment. The anxiety, irritability, and agitation items How to cite this article: McIntyre RS, Lipsitz O, Rodrigues NB, et al. The effectiveness of ketamine on anxiety, irritability, and agitation: Implications for treating mixed features in adults with major depressive or bipolar disorder. Bipolar Disord.

<p>Ketamine in Bipolar Disorder: A Review</p>

“…Therefore, the authors suggest that this treatment should be considered in depression with mixed features, which is particularly common in bipolar disorders (2.2 in MDD vs 14.3% in BD) and related to high suicidality. 26,27 Rapid Antisuicidal Effect of Ketamine Suicidality accounts for 15-20% of deaths in BD patients. [28][29][30] Risk of suicidal act in BD patients with mixed or psychotic symptoms is one of the highest of all psychiatric disorders.…”

“…Therefore, the authors suggest that this treatment should be considered in depression with mixed features, which is particularly common in bipolar disorders (2.2 in MDD vs 14.3% in BD) and related to high suicidality. 26 , 27 …”

No evidence for the effectiveness of IV ketamine for treatment resistant mood disorders in retrospective study

“…Since the regression to the mean will be greater for the participants with the most extreme initial symptoms, one would expect to observe the postulated effect even in untreated participants. 2 McIntyre et al 1 COMMENTARY study could not provide any information as to whether the effect of IV ketamine treatment differed between the groups given the lack of a control group. Given these issues, the conclusions about the effectiveness of IV ketamine for treatment-resistant mood disorders drawn by McIntyre et al were not substantiated by their data.…”

“…McIntyre et al, 1 patients were referred to the treatment at a time when they were likely experiencing their most severe symptoms; even if the participants are not treated, their symptoms will diminish as a result of regression to the mean. 3 Furthermore, patients that, by various definitions, are considered treatment-resistant, experience non-trivial improvement in symptoms in trials without changes to their active treatment, 4,5 which may be attributed to both regression to the mean and placebo effects.…”

“…Better intervention strategies for patients with treatment‐resistant depression are greatly needed. McIntyre and colleagues 1 set out to investigate the effectiveness of intravenous (IV) ketamine through a chart review of 201 such outpatients who all received four IV ketamine infusions over one‐to‐two weeks. They concluded that IV ketamine was effective in treating anxiety, irritability, agitation (AIA) and suicidal ideation (SI) in adults with treatment‐resistant mood disorders and suggested that IV ketamine should be considered a treatment alternative for adults with affective disorders presenting with mixed features in addition to suggesting a need for a randomized trial based on their findings.…”