Maintenance Ketamine Infusions for Treatment-Resistant Bipolar Depression

This open-label trial (n=60) aims to assess the efficacy and safety of repeated subanesthetic maintenance doses of intravenous (IV) ketamine in patients with treatment-resistant bipolar depression (TRBD) over a period of twelve weeks.

The trial, sponsored by the University Health Network, Toronto, will provide open-label ketamine infusions on a flexible schedule (every 2-4 weeks) with doses ranging from 35-70mg/70kg over 40 minutes.

The primary goal is to determine acute antidepressant efficacy, safety, and tolerability. Secondary aims include evaluating effects on suicidal ideations, quality of life, function, and duration of effects.

Participants aged 21 to 65 must meet DSM-5 criteria for Bipolar I or II Disorder and have experienced an antidepressant response or remission following an acute course of ketamine infusions in a parent trial. Exclusion criteria include active suicidality, substance use disorder within the past 3 months, or contraindications to ketamine.

The primary outcome measure is the change in depression severity assessed by the Montgomery-Åsberg Depression Rating Scale (MADRS) over 12 weeks. Secondary measures include recruitment and retention rates, treatment-emergent adverse events, and quality of life.

Recruitment is expected to continue until 60 participants are enrolled, with an estimated study completion date of August 31, 2024.

Trial Details

Growing evidence has supported rapid and robust antidepressant effects with subanesthetic doses of intravenous (IV) ketamine for treatment resistant depression (TRD). However, no completed or ongoing RCTs have evaluated the effects of repeated doses of IV ketamine for a homogenous sample of patients with treatment-resistant bipolar disorder depression (TRBD). The primary research goal is to determine the acute antidepressant efficacy, safety and tolerability of repeated sub-anesthetic maintenance doses of IV ketamine in, over a period of twelve weeks. Open-label ketamine infusions will be provided on a flexible schedule (every 2-4 weeks) with flexible dosing (0.5-1.0mg/kg over 40 minutes) titrated to optimize benefits, while minimizing the dosage and frequency over a 12-week extension period. All patients participating in this open-label study will have completed an acute course of infusions in a parent two-site, phase II, double-blinded midazolam-controlled RCT trial. In addition to this acute course of four infusions, a maximum of six infusions will be provided over the 12-week period. Secondary aims include evaluating effects of IV ketamine on suicidal ideations, quality of life, function and duration of effects. Herein, a two-site (University Health Network and Canadian Rapid Treatment Centre of Excellence), single-arm, open label, 12-week extension trial evaluating the effects of flexibly-dosed adjunctive ketamine infusions for TRBD to maintain antidepressant effects in participants who achieved an antidepressant response (MADRS decrease by >50%) or remission (MADRS < 12) following an acute course of four ketamine infusions is proposed. The primary outcome will be Montgomery-Åsberg Depression Rating Scale (MADRS) scores, determining by a linear mixed model from baseline to week 12. Secondary outcomes include evaluating response and remission rates, safety, tolerability (including treatment-emergent mania), and effects on suicidality, anxiety, quality of life, function and the duration of effects.

NCT Number NCT05339074

Data attribution

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