OPEN Foundation

Day: 1 August 2017

Oral Ketamine in Treatment-Resistant Depression: A Clinical Effectiveness Case Series

Abstract

PURPOSE:
The aim of the study was to assess the effectiveness, tolerability, and safety of oral ketamine as an antidepressant treatment in adults with treatment-resistant depression.
METHODS:
We reviewed retrospective data on 22 patients with treatment-resistant depression, who failed at least 3 adequate antidepressant treatment trials and 1 adequate trial of repetitive transcranial magnetic stimulation; subsequently, they received open-label treatment with oral ketamine, commenced at a dose of 50 mg every 3 days, titrated up by 25 mg every 3 days, according to response and tolerability. The primary outcome measure was the Beck Depression Inventory II, which was used to rate subjective mood improvement at baseline and then at each follow-up visit. Data about adverse effects related to ketamine and a self-harm risk assessment were also obtained.
FINDINGS:
Over the course of treatment, 18% of the patients showed greater than 50% reduction in the Beck Depression Inventory II scores, 14% reported partial improvement in mood symptoms, while 45% had no response to ketamine and 23% showed a mild worsening in their depressive symptoms. The most frequent adverse effects were acute dissociation, dizziness, blurred vision, numbness and sedation. Neither serious adverse effects, nor any cases of abuse or dependence were observed.
CONCLUSIONS:
Although this case series found oral ketamine to be safe and well tolerated, the findings also showed rather modest effectiveness of oral ketamine in treatment-resistant depression, with only approximately 30% reporting some benefit and approximately 70% reporting no change or worsening of mood. However, bearing in mind the limitations of this small, open-label case series, further exploration of the effectiveness of oral ketamine is warranted.
Al Shirawi, M. I., Kennedy, S. H., Ho, K. T., Byrne, R., & Downar, J. (2017). Oral Ketamine in Treatment-Resistant Depression: A Clinical Effectiveness Case Series. Journal of Clinical Psychopharmacology37(4), 464. 10.1097/JCP.0000000000000717
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A Systematic Review Of Research On N,N-Dimethyltryptamine

Abstract

Introduction: The effects of the endogenous hallucinogen N,N-dimethyltryptamine are poorly understood and its medical significance is widely unknown. A small number of  studies regarding its biochemical, pharmaceutical and physiological role have been conducted and the efficacy of its therapeutic potential is presently disregarded. How can scientists proceed in gaining insight into DMT and discovering possible medical uses of this substance?
Materials and Methods: Published articles from  1964 to the present year have been reviewed and the outcome of the studies summarized. The results of drug action,  therapeutic use and potential were investigated . Studies that appeared to have little medical purpose or those, which focus on the use of  Ayahuasca, a South American ritual drink containing N,N-dimethyltryptamine and a monoamine oxidase (MAO)  inhibitor of plant origin, have been excluded.
Results: The research conducted between 1964 and 1987 seems to be an approach to understanding general chemical and biochemical properties of the substance (e.g. metabolites, tolerance, distribution, toxicity, etc.). Rick Strassman, who conducted a broad study from 1990 till 1994 has initiated a recurring interest in the field of psychopharmacology towards DMT. Thus, in the following years, the research was focused on the therapeutic gain of N,N-dimethyltryptamine but resulted mostly inconclusively leading to suggestions of further research. The findings have shown contradictions of already established knowledge, especially for receptors like the sigma-1 receptor, the only direct agonist of which is found to be N,N-dimethyltryptamie.
Conclusion: The studies that now need to be conducted should analyze the correlations between psychiatric diseases (e.g. schizophrenia), purpose of the normal endogenous production and exact action, and the already suggested in various studies therapeutic importance. The low amount of knowledge about the drug action (in case of pharmaceutical use), its targets and drug effect should motivate researchers to gain more insight.
Hristova, D., & Zhelyazkova-Savova, M. (2017). A SYSTEMATIC REVIEW OF RESEARCH ON N, N-DIMETHYLTRYPTAMINE. Scripta Scientifica Vox Studentium1(1).
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Oral Ketamine in Treatment-Resistant Depression: A Clinical Effectiveness Case Series

Abstract

Purpose The aim of the study was to assess the effectiveness, tolerability, and safety of oral ketamine as an antidepressant treatment in adults with treatment-resistant depression.
Methods We reviewed retrospective data on 22 patients with treatment-resistant depression, who failed at least 3 adequate antidepressant treatment trials and 1 adequate trial of repetitive transcranial magnetic stimulation; subsequently, they received open-label treatment with oral ketamine, commenced at a dose of 50 mg every 3 days, titrated up by 25 mg every 3 days, according to response and tolerability. The primary outcome measure was the Beck Depression Inventory II, which was used to rate subjective mood improvement at baseline and then at each follow-up visit. Data about adverse effects related to ketamine and a self-harm risk assessment were also obtained.
Findings Over the course of treatment, 18% of the patients showed greater than 50% reduction in the Beck Depression Inventory II scores, 14% reported partial improvement in mood symptoms, while 45% had no response to ketamine and 23% showed a mild worsening in their depressive symptoms. The most frequent adverse effects were acute dissociation, dizziness, blurred vision, numbness and sedation. Neither serious adverse effects, nor any cases of abuse or dependence were observed.
Conclusions Although this case series found oral ketamine to be safe and well tolerated, the findings also showed rather modest effectiveness of oral ketamine in treatment-resistant depression, with only approximately 30% reporting some benefit and approximately 70% reporting no change or worsening of mood. However, bearing in mind the limitations of this small, open-label case series, further exploration of the effectiveness of oral ketamine is warranted.
Al Shirawi, M. I., Kennedy, S. H., Ho, K. T., Byrne, R., & Downar, J. (2017). Oral Ketamine in Treatment-Resistant Depression: A Clinical Effectiveness Case Series. Journal of clinical psychopharmacology37(4), 464. 10.1097/JCP.0000000000000717
Link to full text