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

Alina Wilkowska, Adam Włodarczyk, Maria Gałuszko-Węgielnik, Mariusz S Wiglusz, Wiesław J Cubała, Alina Wilkowska, Adam Włodarczyk, Maria Gałuszko-Węgielnik, Mariusz S Wiglusz, Wiesław J Cubała

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.

Keywords: bipolar depression; intravenous ketamine; safety; tolerability; treatment-resistant bipolar disorder.

Conflict of interest statement

Dr Alina Wilkowska reports grants from Medical University of Gdańsk, during the conduct of the study and has received research support from Angelini, Biogen, Eli Lilly and Company, Janssen-Cilag, Lundbeck, Polpharma, Sanofi and Valeant. Dr Adam Włodarczyk has received research support from Actavis, Eli Lilly, Minerva Neurosciences, Sunovion Pharmaceuticals, KCR, Janssen, Otsuka, Apodemus, Cortexyme, and Acadia. Dr Maria Gałuszko-Węgielnik has received research support from Janssen, Servier, Alkermes, KCR, Lilly, Biogen, and Celon. Dr Mariusz S Wiglusz has received research support from Acadia, Apodemus, Alkermes, Auspex Pharmaceuticals, Cephalon, Ferrier, Forest Laboratories, Gedeon Richter, GWPharma-ceuticals, Janssen, Lundbeck, Orion, Otsuka, Servier, Speakers Bureau: Lundbeck, Servier. Prof. Wiesław J Cubała has received research support from Acadia, Actavis, Alkermes, Allergan, Angelini, Auspex, Biogen, Bristol-Myers Squibb, Cephalon, Cortexyme, Eli Lilly, Ferrier, Forest Laboratories, Gedeon Richter, GW Pharmaceuticals, Janssen, KCR, Lundbeck, Minerva, NeuroCo, NIH, Orion, Otsuka, Sanofi, and Ser-vier; he has served on speakers bureaus for Adamed, Angelini, AstraZeneca, Bristol-Myers Squibb, Celon, GlaxoSmithKline, Janssen, Krka, Lekam, Lundbeck, Novartis, Orion, Pfizer, Polfa Tarchomin, Sanofi, Servier, and Zentiva; and he has served as a consultant for GW Pharmaceuticals, Janssen, KCR, Quintiles, and Roche. The authors report no other conflicts of interest in this work.

© 2021 Wilkowska et al.

Figures

Figure 1
Figure 1
MADRS change after seven ketamine infusions in responders and non-responders. # indicates significant difference at a given time point when compared to baseline * indicates significant difference at a given time point between the responder and non-responder groups (p

Figure 2

Kaplan–Meier curves for time to…

Figure 2

Kaplan–Meier curves for time to response and remission among bipolar patients. Black line…

Figure 2
Kaplan–Meier curves for time to response and remission among bipolar patients. Black line indicates response, red line indicates remission.
Figure 2
Figure 2
Kaplan–Meier curves for time to response and remission among bipolar patients. Black line indicates response, red line indicates remission.

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