Ketamine in chronic pain: A Delphi survey

Abstract

Background: There is no recommendation in Europe for the use of ketamine in patients with chronic pain. The heterogeneity of practice highlights the need to seek the advice of experts in order to establish a national consensus. This Delphi survey aimed to reach a national consensus on the use of ketamine in chronic pain in Pain clinics.Methods: A collaborative four-round internet-based questionnaire was used. It was created after literature search on ketamine administration in chronic pain and included about 96 items. It discussed utility and advantages, adverse events and deleterious aspects, methods of administration, concomitant treatments and assessment of results.Results: Twenty-eight experts completed all rounds of the survey with a total of 81.3% items reaching a consensual answer. Neuropathic pain represents the first indication to use ketamine, followed, with a good to moderate utility, by other situations (fibromyalgia, complex regional pain syndrome, central neuropathic pain, peripheral neuropathic pain, nociceptive pain, sensitization, opioid withdrawal, palliative care, depression). Experts agreed on the rare occurrence of adverse events. Concerning routes of administration, intravenous infusion with doses of 0.5-0.9 mg/kg/d for 4 days of treatment is preferred. Place of care is hospital, as in-or out-patient, with a quarterly administration of ketamine. Finally, ketamine effectiveness is assessed 1 month after infusion, and experts encourage combination with non-pharmacological treatment.Conclusions: This Delphi survey established a consensus of pain specialists on the use of ketamine in refractory chronic pain, thus providing a basis for future comparative trials.Significance: This Delphi survey in chronic pain reached agreement on four main aspects: (1) Priority to treat neuropathic pain with evaluation of effectiveness at 1 month; (2) No deleterious effects in the majority of listed diseases/situations with the absence or <3% of suggested adverse events; (3) 0.5-0.9 mg/kg/d IV infusion; (4) Combination with non-pharmacological treatment.

Assessment of Initial Depressive State and Pain Relief With Ketamine in Patients With Chronic Refractory Pain

“…The link between depression alleviation (especially for depression with suicidal ideations) 6 , 28 and pain relief 5 with ketamine treatment is complex. 24 , 29 Comorbid pain and depression are frequent, with a bidirectional interaction, 26 , 30 but a recent activation likelihood estimation meta-analysis 31 stresses that the direction of comorbidity (ie, pain with depression vs depression with pain) is rarely addressed and may concern different cerebral areas and neurobiology mechanisms.…”

“…Drug management of chronic pain with antidepressants, antiepileptics, and opioids remains inconclusive, as 60% of patients show little improvement, experience adverse effects, and often require other treatment options . Ketamine, a nonselective N -methyl- d -aspartate receptor (NMDAR) antagonist with anesthetic properties, can relieve chronic pain . A recent clinical study in patients with refractory chronic pain identified distinct pain relief trajectories with variables that are associated with the response to a single dose of ketamine according to pain characteristics, level of anxiety, depression, or quality of life.…”

“… 1 , 2 Ketamine, a nonselective N -methyl- d -aspartate receptor (NMDAR) antagonist with anesthetic properties, can relieve chronic pain. 3 , 4 , 5 A recent clinical study 3 in patients with refractory chronic pain identified distinct pain relief trajectories with variables that are associated with the response to a single dose of ketamine according to pain characteristics, level of anxiety, depression, or quality of life.…”

Low-dose ketamine infusions for chronic pain management: Does this qualify as evidence-based practice?

“…15 However, in recent years, poorly regulated 'ketamine clinics' for chronic pain (and depression) have sprouted worldwide, 11,15 with frequent administration reported in the US, the Netherlands, France, South Korea, and the UK. 8,[37][38][39] As such, ketamine for chronic pain has bypassed the traditional, rigorous drug development sequence involving initial animal testing, then human experimental studies and clinical trials assessing efficacy and safety, followed by strict surveillance. 11 The first ketamine clinic that opened in the UK was in Bristol, charging £6000 for a course of low-dose infusions with psychotherapy for depression.…”

“…11,14,37 Surveys of pain clinics in France, South Korea, and the Netherlands have demonstrated this variability between practices, including the dose, duration, and monitoring facilities, but they report that serious adverse events are rare. [37][38][39] Therefore, although these widely varied protocols suggest a lack of evidencebased prescribing, they appear to be well-tolerated in general, particularly when accounting for the likely significant disease burden of eligible patients prior to SDKI administration. 4 In addition, the monitoring and documentation of side effects in both the research and clinical setting may be aided by the recently developed Ketamine Side Effect Tool (KSET).…”