Efficacy of Ketamine in Anesthetic Dosage for the Treatment of Refractory Complex Regional Pain Syndrome: An Open-Label Phase II Study

Advanced complex regional pain syndrome (CRPS) remains very difficult to treat. While subanesthetic low-dose ketamine has shown promise in early localized CRPS, its use in advanced CRPS has not been as effective. Since ketamine's analgesic potency and duration of effect in neuropathic pain are directly dose-dependant, we investigated the efficacy of ketamine in anesthetic dosage in refractory CRPS patients that had failed available standard therapies. Twenty ASA I-III patients suffering from refractory CRPS received ketamine in anesthetic dosage over 5 days. Outcome criteria were pain relief, effect on the movement disorder, quality of life, and ability to work at baseline and up to 6 months following treatment. Significant pain relief was observed at 1, 3, and 6 months following treatment (93.5 +/- 11.1%, 89.4 +/- 17.0%, 79.3 +/- 25.3%; P < 0.001). Complete remission from CRPS was observed at 1 month in all patients, at 3 months in 17, and at 6 months in 16 patients. If relapse occurred, significant pain relief was still attained at 3 and 6 months (59.0 +/- 14.7%, P < 0.004; 50.2 +/- 10.6%, P < 0.002). Quality of life, the associated movement disorder, and the ability to work significantly improved in the majority of patients at 3 and 6 months. This open-label trial suggests benefit in pain reduction, associated CRPS symptoms, improved quality of life and ability to work following anesthetic ketamine in previously refractory CRPS patients. However, a randomized controlled trial will be necessary to prove its efficacy.