"First do no harm": Why don't we measure adverse events routinely in psychological treatment trials for people with chronic pain?

“First do no harm” was a phrase drummed into me in my first week of clinical training nearly 30 years ago. This was based on the following rationale. First, using a psychological therapy in the absence of evidence when an evidence-based treatment was available is harmful because problems continue unabated and can deteriorate. Second, that psychological therapies can, at least in theory, be damaging to people. Indeed, in my early work, we argued that providing a psychological treatment for patients recently diagnosed with rheumatoid arthritis could have unwanted negative effects and as a result did not provide a treatment to our standard care group. The results showed that cognitive-behaviour therapy (CBT) was associated with improvements in depression and joint function after treatment, and at 6-month follow-up, further improvements were evident in disability 18 months later and health care utilization 5 years after treatment. However, we did not measure adverse events during our trial. It turns out, we were not alone. Palermo et al. in this issue of PAIN show that only 10% to 13% of clinical trials of psychological treatments for adults and children with chronic pain define adverse events in their methods, and only 25% to 39% report adverse events during the trial. The lack of monitoring of adverse events likely stems, at least in part, from the absence of a consensual definition of adverse events in the context of psychological treatments. In pharmacological trials, the side-effect profiles of medications allow specific adverse events to be predetermined and monitored. This begs the question of what an adverse event would be in a trial of psychological therapy. Palermo et al make a strong argument that adverse events in psychological trials (as in pharmaceutical trials) should include any unwanted event that occurs during therapy that causes a burden or distress to a participant, regardless of whether it can be directly attributed to the treatment. There are compelling reasons that we need to ensure that future clinical trials of psychological therapies adopt this position. First, successive Cochrane reviews have confirmed that psychological treatments have small to moderate effects on outcomes, such as disability and mood, over and above treatment as usual for chronic pain in adults and chronic and recurrent pain in children. The effect sizes are similar to shortterm effects found with opioids in the management of chronic pain. We need safe and effective interventions that are nonaddictive for chronic pain, and psychological treatments appear well placed to meet these needs. Indeed, gold standard multidisciplinary pain management programs have been shown to reduce opioid use without increasing pain (and in some instances reducing pain concurrently), and internet-based pain management approaches can also reduce opioid use. However, if we claim psychological treatments are a safe alternative to opioids, the onus is on researchers to demonstrate that they are indeed safe. It should be noted that amongst those studies that did measure adverse events, these were rare or rarely associated with the treatment. For example, in the child studies reviewed, there were no adverse events deemed attributable to the intervention; however, the low rates of adverse events do not negate the need to measure them. Second, there are chronic pain conditions for which there is currently insufficient evidence to conclude that psychological treatments are efficacious, such as neuropathic pain or migraines. Where the problem is absence of evidence rather than the absence of an effect, clinicians need to make decisions about whether to offer a psychological treatment if a client presents wanting treatment based on available evidence. In migraine, for example, a recent Cochrane review showed insufficient evidence to conclude that psychological treatments affected migraine frequency, although there was very low quality evidence that migraine was reduced by 50% in one in fewer than 3 participants. If a patient is presenting wanting psychological treatment, and evidence is equivocal, the clinical decision needs to balance the uncertain benefit against any harms. Only 2 studies (10%) in that review provided evidence on adverse events, and both did so because they included a pharmacotherapy arm. Although both studies showed numerically fewer adverse events than in the control arms, it remains important to assess adverse events because without strong evidence relating to potential harms, clinical decision-making is compromised. Third, there is evidence that psychological treatments are effective in the management of pain conditions, but there is little evidence comparing different psychological treatments, such as mindfulness-based interventions, CBT, or acceptance commitment therapy. In trials that have directly compared different approaches, the majority have found that the treatments are equally efficacious on the primary outcomes. However, if one or other treatment has higher rates of adverse events, then this could be a reason to choose one treatment over another. For example, Cherkin et al. compared mindfulness-based stress Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.