Intravenous Ketamine Infusions in Treatment-Resistant Bipolar Depression: An Open-Label Naturalistic Observational Study

Abstract

Purpose Bipolar disorder is a chronic and recurrent condition often associated with treatment resistance and suicidality. There is an unmet need for effective treatment in this group of patients. Ketamine has been demonstrated to have antidepressant and antisuicidal properties in unipolar depression. Most of the available studies concern unipolar depression. Here, we present the efficacy and safety of IV ketamine as an add-on treatment in patients with bipolar I and bipolar II depression. Patients and Methods Thirteen patients with treatment-resistant bipolar depression (TRBD) received eight IV infusions of 0.5 mg/kg ketamine twice a week over four weeks. This is an open-label naturalistic observational study. Ketamine is an add-on treatment. Depressive symptoms were measured with the Montgomery–Asberg Depression Rating Scale (MADRS), and manic symptoms were measured with the Young Mania Rating Scale (YMRS). Psychomimetic symptoms were assessed with the Clinician-Administered Dissociative States Scale (CADSS) and the Brief Psychiatric Rating Scale (BPRS). Results The rates of response and remission after the seventh infusion of ketamine were 61.5% and 46.2%, respectively. A significant antisuicidal effect was observed in responders at the 7th infusion. Suicidality was measured with item 10 on the MADRS scale. The average time to respond was between 21.1 and 23.2 days to remission. There was an increase in the CADSS scores during the treatment compared to baseline and follow-up, but no differences between responders and non-responders were observed. No affective switch was observed according to the YMRS scale scores. Ketamine treatment was associated with a transient increase in arterial blood pressure. No serious adverse events, however, were observed. Conclusion This report presents the preliminary results of IV ketamine effectiveness and safety in treatment-resistant bipolar depression. The findings suggest that it is a feasible, safe and well-tolerated treatment option in this group of patients. There is a definite need for more studies in this field.

Treating bipolar depression with esketamine: Safety and effectiveness data from a naturalistic multicentric study on esketamine in bipolar versus unipolar treatment‐resistant depression

“…16 The glutamatergic hypothesis for depressive disorders has been supported by the antidepressant efficacy of ketamine, an antagonist of the ionotropic N-methyl-D-aspartate (NMDA) receptor. 16 Ketamine has shown good efficacy in both bipolar 17,18 and unipolar 19 TRD, with response rates ranging from 50-70%. 20 Furthermore, in the various studies conducted, 18,[21][22][23] no cases of manic switch after ketamine use in B-TRD have been shown, with preliminary data supporting effectiveness and safety among those patients.…”

Treatment-Resistant Bipolar Depression: Therapeutic Trends, Challenges and Future Directions

“…The studies seem to suggest higher response rates than single infusion, but further exploration is needed. 68 , 69 , 71 …”

“…The studies seem to suggest higher response rates than single infusion, but further exploration is needed. 68,69,71 Tables 2-4 summarize the available published evidence based on RCTs of the pharmacotherapies for TRBD.…”

Ketamine treatment for depression: a review

“…While these effects traditionally occur during infusion and are usually transient, the psychotomimetic symptoms may be distressing for some individuals who experience significant dissociative symptoms. Studies of ketamine in bipolar depression found similar self-limited psychotomimetic and dissociative symptoms that warrant close safety and tolerability monitoring [ 77 ]. It should be noted that ketamine’s dissociative effects have been investigated as potentially contributing to its antidepressant effects, particularly in the psychotherapy models discussed in Sect.…”