• CHRONIC PAIN
• Analgesics, Opioid
• Opioid-Related Disorders
• Pain Management

We read the article by Elyn et al, published in the March issue of Regional Anesthesia & Pain Medicine with keen interest. The authors report the findings of a historical cohort study gauging effectiveness of low-dose ketamine infusions for facilitating opioid tapering in chronic pain (CP) patients with opioid use disorder.1 The study included 59 patients, 42 of which completed 12-month follow-up. CP etiologies included chronic back pain (CBP) (52.5%), fibromyalgia (FM) (17%), postoperative pain (35.6%), peripheral neuropathic pain (50.8%), and widespread pain (49.2%). Ketamine was delivered via continuous slow bolus infusion over 5 days, with doses ranging from 0.15 to 0.45 mg/kg. Adverse events were mild and uncommon. Prior to infusions, the mean opioid dose was 207 mg MME (±128), this was reduced to 92 mg MME (±72) following infusions. This effect was sustained at 12-month follow-up, with a mean dose of 103 mg MME (± 106). 10 patients (23%) eliminated their opioid intake. This study makes important contributions to understanding applications for ketamine infusions, especially considering significant benefits seen from very low doses. We congratulate the authors for their conduct of a practical study with high ecological validity.

Though we were impressed by the findings of this study, we noticed that pain scores were not explicitly reported in the article and request that the authors clarify this omission. While some literature on this topic also lacks discussions of pain control, two recent case reports described ketamine-assisted opioid tapers that also generated good pain relief.2 3 Additionally, an older study with a smaller sample (n=18) cast doubt on the effectiveness of ketamine infusions for opioid tapering, finding no significant effects related to reduced pain scores or opioid requirements.4 Considering Elyn et al’s new evidence supporting the effectiveness of ketamine infusions for opioid tapering, it is of interest whether the study population concurrently saw improved pain control following infusions. Identifying and changes in functionality via disability scores to further qualify the effectiveness of ketamine therapy could also prove helpful. If the authors have data regarding changes in pain or disability scores, we request that it is disclosed in a response to this letter. Though the generalizability of this data would be limited by the study’s heterogeneous patient population and retrospective design, its release would nonetheless help clarify the article’s clinical implications.

We also found interesting the result that patients with generalized pain conditions (eg, widespread pain, FM) tended to sustain opioid tapering better than patients with other CP etiologies such as CBP.1 Current evidence suggests that ketamine’s antagonist effect at N-methyl-D-aspartate receptors can combat central sensitization pathways underlying CP in FM5 and chronic regional pain syndrome2; this benefit intuitively might not be seen in largely nociceptive CP etiologies like CBP. In light of Elyn et al’s finding better tapering effects among widespread pain patients, we are curious as to whether these patients also saw a greater analgesic benefit than patients with other CP etiologies. This data could help illuminate mechanisms behind both ketamine-induced analgesia and opioid tapering for disparate pain conditions.

Questions aside, the article describes an impressive exploration of ketamine’s opioid-sparing potential, and does so using (to our knowledge) the largest sample to date for studies on this topic. As investigations of the analgesic and opioid-sparing effects of ketamine are harmed by methodological heterogeneity and lack of controls,6 larger and better-controlled studies are needed for a complete understanding of its clinical utility. We thank the authors and encourage any further comments.