Ketamine plus psychotherapy for neuropathic pain: feasible, and that is all this trial claims

Design

single-centre, three-arm randomised, outcome-assessor-blinded feasibility pilot trial

Population

30 adults with moderate-to-severe chronic neuropathic pain at a Canadian tertiary pain clinic; 26 completed 20-week follow-up

Primary outcome

feasibility against prespecified progression criteria

Effect

87% completion; consent, retention and data completeness criteria met, adherence partially met; 64 adverse events, mostly mild and in ketamine arms; no study-related serious adverse events

Intravenous ketamine gives short-lived analgesia in chronic neuropathic pain, and the benefit fades. The hypothesis here is that pairing the infusions with psychotherapy might extend it - a direct borrowing from the psychedelic-assisted therapy literature. Thirty adults at a Canadian tertiary pain clinic were randomised 1:1:1 to three ketamine infusions over 16 weeks, to 16 weekly sessions of cognitive behavioural therapy with mindfulness meditation, or to both, with outcome assessors blinded.

The primary outcome was feasibility, and most prespecified criteria were met: 26 of 30 (87%) completed 20-week follow-up, consent, retention and data completeness thresholds were satisfied, and adherence targets were only partially met. Sixty-four adverse events were recorded, mostly mild and concentrated in the ketamine arms, with no study-related serious adverse events. Exploratory pain outcomes improved numerically in all three groups, with clinically meaningful reductions in pain interference and intensity.

The last sentence is the one to handle carefully, because it will be quoted as though it were a result. Improvement in all three arms of a 30-patient feasibility trial with no placebo tells you nothing about whether any of the three works - regression to the mean, attention and expectation all produce exactly that. This trial was designed to answer whether a larger trial can be run, and it answers yes. For now, ketamine infusion for chronic neuropathic pain remains a treatment with short-lived benefit, and combining it with psychotherapy remains a hypothesis.

• Do not offer combined ketamine and psychotherapy as a treatment on the basis of this trial - it tested feasibility, not efficacy
• Where ketamine infusions are used for neuropathic pain, continue to counsel that benefit is typically short-lived
• Note the adverse event pattern: mild, frequent, and concentrated in ketamine arms
• Treat improvement in all three arms as uninformative about efficacy - there was no placebo comparison
• Watch for the adequately powered trial this was designed to justify

Why it matters

It is the step that determines whether the real question gets asked, and it says the trial is runnable.

Don't overread it

Thirty patients, feasibility as the primary outcome, no placebo arm - the pain improvements are exploratory and uninterpretable as efficacy.

The statistics, in plain English

In a pilot trial powered for feasibility, the pain outcomes are labelled exploratory for a reason: with ten patients per arm there is no ability to distinguish a treatment effect from chance, and the absence of a placebo arm means even within-group improvement cannot be attributed to the intervention. 'Clinically meaningful reductions' across all three groups is the pattern expected when patients entering a trial improve regardless of what they receive.

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