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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
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
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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