Oral ketamine for the treatment of pain and treatment-resistant depression
This systematic review (2016; s=88) examined the efficacy and safety of various ketamine administration routes for depression and chronic pain. It concludes that while intravenous studies show short-term success, oral ketamine appears well-tolerated in pain management settings, suggesting potential utility for the longer-term treatment of treatment-resistant depression.
Authors
- Robert Schoevers
Published
Abstract
Background
Recent studies with intravenous (i.v.) application of ketamine show remarkable but short-term success in patients with MDD. Studies in patients with chronic pain have used different ketamine applications for longer time periods. This experience may be relevant for psychiatric indications.
Aims
To review the literature about the dosing regimen, duration, effects and side-effects of oral, intravenous, intranasal and subcutaneous routes of administration of ketamine for treatment-resistant depression and pain.
Method
Searches in PubMed with the terms ‘oral ketamine’, ‘depression’, ‘chronic pain’, ‘neuropathic pain’, ‘intravenous ketamine’, ‘intranasal ketamine’ and ‘subcutaneous ketamine’ yielded 88 articles. We reviewed all papers for information about dosing regimen, number of individuals who received ketamine, number of ketamine days per study, results and side-effects, as well as study quality.
Results
Overall, the methodological strength of studies investigating the antidepressant effects of ketamine was considered low, regardless of the route of administration. The doses for depression were in the lower range compared with studies that investigated analgesic use. Studies on pain suggested that oral ketamine may be acceptable for treatment-resistant depression in terms of tolerability and side-effects.
Conclusions
Oral ketamine, given for longer time periods in the described doses, appears to be well tolerated, but few studies have systematically examined the longer-term negative consequences. The short- and longer-term depression outcomes as well as side-effects need to be studied with rigorous randomised controlled trials.
Research Summary of 'Oral ketamine for the treatment of pain and treatment-resistant depression'
Introduction
Schoevers and colleagues frame the review around the discovery that ketamine, an NMDA receptor antagonist, produces rapid antidepressant effects when given intravenously. Earlier clinical trials and open-label reports in treatment-resistant unipolar and bipolar depression found symptom reductions within hours to days after a 0.5 mg/kg i.v. infusion, implicating glutamatergic modulation and downstream synaptic plasticity as mechanisms distinct from traditional monoaminergic antidepressants. However, the antidepressant effect of single i.v. doses is typically short-lived, and efforts to prolong benefit (for example, by repeated infusions or adjunctive agents) have had mixed results. The pain-management literature, by contrast, includes more experience with non-intravenous routes and longer treatment durations, suggesting that insights from chronic pain practice could inform psychiatric applications. This paper sets out to review the clinical literature on ketamine across routes of administration, with particular focus on oral ketamine: dosing regimens, duration of treatment, effects and adverse events for treatment-resistant depression and for chronic pain. The authors aim to bring together evidence from both fields to evaluate whether oral (and other non-intravenous) ketamine might offer a tolerable maintenance strategy for depression and what safety, pharmacokinetic and methodological gaps remain.
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Study Details
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- APA Citation
Schoevers, R. A., Chaves, T. V., Balukova, S. M., Rot, M. A. H., & Kortekaas, R. (2016). Oral ketamine for the treatment of pain and treatment-resistant depression. British Journal of Psychiatry, 208(2), 108-113. https://doi.org/10.1192/bjp.bp.115.165498
References (7)
Papers cited by this study that are also in Blossom
Vollenweider, F. X., Kometer, M. · Nature Reviews Neuroscience (2010)
Berman, R. M., Cappiello, A., Anand, A. et al. · Biological Psychiatry (2000)
Diazgranados, N., Ibrahim, L., Brutsche, N. E. et al. · JAMA Psychiatry (2010)
Zarate, C. A., Brutsche, N. E., Ibrahim, L. et al. · Biological Psychiatry (2012)
Sos, P., Klirova, M., Novák, T. et al. · Neuropsychiatric Disease And Treatment (2013)
Murrough, J. W., Iosifescu, D. V., Chang, L. C. et al. · American Journal of Psychiatry (2013)
Bowdle, A. T., Radant, A. D., Cowley, D. S. et al. · Anesthesiology (1998)
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Smith-Apeldoorn, S. Y., Veraart, J., Kamphuis, J. et al. · Molecular Psychiatry (2024)
Meshkat, S., Haikazian, S., Di Vincenzo, J. D. et al. · Biological Psychiatry (2023)
Breeksema, J. J., Niemeijer, A. R., Kuin, B. et al. · Frontiers in Psychiatry (2022)
Shamabadi, A., Ahmadzade, A., Hasanzadeh, A. · British Journal of Clinical Pharmacology (2022)
Nikkheslat, N. · Brain Behavior and Immunity - Health (2021)
Murrough, J. W., Abdallah, C. G., Mathew, S. J. · Nature Reviews Drug Discovery (2021)
Kheirabadi, D., Kheirabadi, G. R., Mirlohi, Z. et al. · Journal of Clinical Psychopharmacology (2020)
Kraus, C., Rabl, U., Vanicek, T. et al. · International Journal of Psychiatry in Clinical Practice (2017)
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