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Oral ketamine for the treatment of pain and treatment-resistant depression

  • Robert A. Schoevers (a1), Tharcila V. Chaves (a1), Sonya M. Balukova (a1), Marije aan Het Rot (a2) and Rudie Kortekaas (a3)...



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.


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.


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.


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.


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.

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Corresponding author

Robert A. Schoevers University Medical Center Groningen, Department of Psychiatry, Hanzeplein 1, P.O. Box 30001(CC-11), 9700 RB Groningen, The Netherlands. Email:


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See editorial, pp. 101–103, this issue.

Declaration of interest




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Table DS1 ketamine for depression studies

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Supplementary materials

Schoevers et al. supplementary materials
Table DS2 ketamine for pain studies

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Oral ketamine for the treatment of pain and treatment-resistant depression

  • Robert A. Schoevers (a1), Tharcila V. Chaves (a1), Sonya M. Balukova (a1), Marije aan Het Rot (a2) and Rudie Kortekaas (a3)...


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Oral ketamine for the treatment of pain and treatment-resistant depression

  • Robert A. Schoevers (a1), Tharcila V. Chaves (a1), Sonya M. Balukova (a1), Marije aan Het Rot (a2) and Rudie Kortekaas (a3)...
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