Rapid effectiveness of intravenous ketamine for ultraresistant depression in a clinical setting and evidence for baseline anhedonia and bipolarity as clinical predictors of effectiveness
This retrospective, open-label, database study (n=50) examined the efficacy of ketamine (35mg/70kg) treatment for patients with ultra-resistant depression and found that baseline anhedonia and bipolar disorder strongly predicted treatment response (44%) and the rate of symptom remission (16%) across participants.
Authors
- Thomas, R. K.
- Baker, G.
- Lind, J.
Published
Abstract
Background
Intravenous ketamine has been established as an efficacious and safe treatment, with transient effect, for treatment-resistant depression. However, the effectiveness of intravenous ketamine in non-research settings and with ultraresistant depression patients remains understudied.
Aims
This study aims to measure the response and remission rates in ultraresistant depression patients in a clinical setting by means of a retrospective, open label, database study. Secondarily, the study will attempt to support previous findings of clinical predictors of effectiveness with intravenous ketamine treatment.
Methods
Fifty patients with ultraresistant depression were treated between May 2015-December 2016, inclusive, in two community hospitals in Edmonton using six ketamine infusions of 0.5 mg/kg over 40 min over 2-3 weeks. Data were collected retrospectively from inpatient and outpatient charts. Statistical analysis to investigate clinical predictors of effectiveness included logistic regression analysis using a dependent variable of a 50% reduction in rating scale score at any point during treatment.
Results
At baseline, the average treatment resistance was severe, with a Maudsley Staging Method score of 12.1 out of 15, 90.0% were resistant to electroconvulsive therapy, and the average Beck Depression Inventory score was 34.2. The response rate was 44% and remission rate was 16%. As a single predictor, moderate or severe anhedonia at baseline predicted a 55% increased likelihood of response. As a combined predictor, this level of anhedonia at baseline with a diagnosis of bipolar depression predicted a 73% increase in likelihood of response.
Conclusion
In a clinical setting, intravenous ketamine showed effectiveness in a complex, severely treatment-resistant, depressed population on multiple medication profiles concurrently. This study gave support to anhedonia and bipolar depression as clinical predictors of effectiveness.
Research Summary of 'Rapid effectiveness of intravenous ketamine for ultraresistant depression in a clinical setting and evidence for baseline anhedonia and bipolarity as clinical predictors of effectiveness'
Introduction
Thomas and colleagues frame the study around an underserved subgroup of depressed patients who have failed extensive prior treatments — antidepressants, augmentation strategies, psychotherapy, and electroconvulsive therapy (ECT) — and describe this population as ultraresistant depression (URD). Previous research indicates that a substantial proportion of major depressive disorder (MDD) patients develop treatment-resistant depression (TRD) and that higher levels of treatment resistance predict poorer outcomes. Intravenous (IV) ketamine, an NMDA receptor antagonist acting on the glutamatergic system, has shown rapid antidepressant and anti‑suicidal effects in TRD in controlled research settings, but evidence is limited for its effectiveness in routine clinical practice and specifically in patients with URD. The authors note prior work suggesting clinical predictors of ketamine response (for example anhedonia, family history of alcohol use disorder, higher body mass index and early response) but highlight the need for replication and investigation in more severely resistant samples. This study set out to measure response and remission rates after a six‑infusion course of IV ketamine delivered in routine clinical settings to patients with URD, and to assess whether previously reported clinical predictors of ketamine effectiveness could be supported in this population. The investigators used a retrospective, open‑label database approach to examine outcomes and applied logistic regression to test clinical and demographic predictors of response, defined primarily as a 50% reduction on standard depression rating scales at any point during treatment. The study therefore aimed to provide real‑world effectiveness data and to explore feasible clinical predictors that could help stratify patients most likely to benefit from ketamine.
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
- APA Citation
Thomas, R. K., Baker, G., Lind, J., & Dursun, S. (2018). Rapid effectiveness of intravenous ketamine for ultraresistant depression in a clinical setting and evidence for baseline anhedonia and bipolarity as clinical predictors of effectiveness. Journal of Psychopharmacology, 32(10), 1110-1117. https://doi.org/10.1177/0269881118793104
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