Low-dose ketamine infusion to facilitate opioid tapering in chronic non-cancer pain with opioid-use disorder: a historical cohort study.

Long-term opioid use for chronic pain can lead to tolerance, misuse, and hyperalgesia, making dose reduction difficult, especially when opioid-use disorder is present. Ketamine, an NMDA receptor antagonist with antihyperalgesic effects, may help. In a historical cohort of 59 chronic pain patients with opioid-use disorder who had failed outpatient tapering, a 5-day hospital stay with low-dose ketamine infusion reduced the average daily opioid dose from 207 mg morphine milligram equivalent to 92 mg at discharge and 103 mg at 12 months. Over half of patients achieved more than 50% tapering immediately, and seven stopped entirely. Ketamine was well tolerated with no significant withdrawal symptoms. Controlled studies are needed to confirm these results.

Study at a glance

Abstract

Long-term opioid use is associated with pharmacological tolerance, a risk of misuse and hyperalgesia in patients with chronic pain (CP). Tapering is challenging in this context, particularly with comorbid opioid-use disorder (OUD). The antihyperalgesic effect of ketamine, through N-methyl-D-aspartate (NMDA) antagonism, could be useful. We aimed to describe the changes in the dose of opioids consumed over 1 year after a 5-day hospitalisation with ketamine infusion for CP patients with OUD. We performed a historical cohort study using a medical chart from 1 January 2014 to 31 December 2019. Patients were long-term opioid users with OUD and CP, followed by the Pain Center of the University Hospital of Toulouse, for which outpatient progressive tapering failed. Ketamine was administered at a low dose to initiate tapering during a 5-day hospitalisation. 59 patients were included, with 64% of them female and a mean age of 48±10 years old. The most frequent CP aetiologies were back pain (53%) and fibromyalgia (17%). The baseline opioid daily dose was 207 mg (±128) morphine milligram equivalent (MME). It was lowered to 92±72 mg MME at discharge (p<0.001), 99±77 mg at 3 months (p<0.001) and 103±106 mg at 12 months. More than 50% tapering was achieved immediately for 40 patients (68%), with immediate cessation for seven patients (12%). 17 patients were lost to follow-up. A 5-day hospitalisation with a low-dose ketamine infusion appeared useful to facilitate opioid tapering in long-term opioid users with CP and OUD. Ketamine was well tolerated, and patients did not present significant withdrawal symptoms. Prospective and comparative studies are needed to confirm our findings.