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

A review of 88 articles examined how ketamine is given (oral, intravenous, intranasal, subcutaneous) for treatment-resistant depression and chronic pain. The methodological quality of studies on ketamine's antidepressant effects was low for all routes. Doses used for depression were lower than those for pain. Studies on pain suggest that oral ketamine may be acceptable for depression in terms of tolerability and side-effects, but few studies have systematically examined longer-term negative consequences. The authors conclude that rigorous randomized controlled trials are needed to study short- and longer-term depression outcomes and side-effects.

Study at a glance

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.