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 repeat‐dose 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 on the GAD‐7 were used to assess effectiveness of IV ketamine in treating symptoms of mixed features.

Results: In this retrospective analysis, 113 participants met AIA criteria. Participants with AIA experienced a significantly greater reduction in overall depressive symptoms ( F (1, 558) = 9.49, P = .002), SI ( F (1, 558) = 3.103, P = .079), anxiety ( F (1, 198) = 5.52, P = .007), irritability ( F (1, 198) = 28.35, P < .001), and agitation as measured by “trouble relaxing” ( F (1, 198) = 6.70, P = .010) from baseline compared to the non‐AIA group, regardless of number of treatments received.

Conclusions: Our preliminary results suggest that IV ketamine is effective in rapidly treating AIA and SI in adults with treatment‐resistant mood disorders. This observation suggests that IV ketamine could be considered a treatment alternative for adults with MDD or BD presenting with mixed features.