Placebo effects in psychiatry: mediators and moderators

Abstract

A strong placebo response in psychiatric disorders has been noted for the past 50 years and various attempts have been made to identify predictors of it, by use of meta-analyses of randomised controlled trials and laboratory studies. We reviewed 31 meta-analyses and systematic reviews of more than 500 randomised placebo-controlled trials across psychiatry (depression, schizophrenia, mania, attention-deficit hyperactivity disorder, autism, psychosis, binge-eating disorder, and addiction) for factors identified to be associated with increased placebo response. Of 20 factors discussed, only three were often linked to high placebo responses: low baseline severity of symptoms, more recent trials, and unbalanced randomisation (more patients randomly assigned to drug than placebo). Randomised controlled trials in non-drug therapy have not added further predictors, and laboratory studies with psychological, brain, and genetic approaches have not been successful in identifying predictors of placebo responses. This comprehensive Review suggests that predictors of the placebo response are still to be discovered, the response probably has more than one mediator, and that different and distinct moderators are probably what cause the placebo response within psychiatry and beyond.

Neuro-Bio-Behavioral Mechanisms of Placebo and Nocebo Responses: Implications for Clinical Trials and Clinical Practice

“…A more detailed meta-analysis of patient-related factors driving the placebo effect in psychiatric disorders recently revealed consistent positive associations between placebo effects with lower disease severity at baseline and shorter disease duration in the treatmentnaive patients (Weimer et al, 2015b). Similarly, low symptom severity at study entry was also found to correlate positively with a placebo response in other diseases such as fibromyalgia (Hauser et al, 2011), diabetic neuropathic pain (Hauser et al, 2011), binge-eating (Blom et al, 2014), or asthma (Wang et al, 2012), but not in attention deficit hyperactivity disorder (Buitelaar et al, 2012) or Parkinson's disease .…”

“…Numerous clinical studies and meta-analyses provide compelling evidence for pronounced placebo effects in psychiatric conditions such as depression, schizophrenia, or anxiety disorders (Cavanna et al, 2007;Murray and Stoessl, 2013;Weimer et al, 2015b). Compared with pain or Parkinson's disease, however, the neurobiological mechanisms underlying placebo responses in these disorders are much less well understood, which is partly because of the lack of experimental models suitable to investigate such mechanisms in healthy volunteers and patients.…”

The psychology of neurofeedback: Clinical intervention even if applied placebo.

“…Whereas the biomedical lore often discounts placebo effects (Raz & Harris, 2016), most accepted treatments that target brain function and behavior -from psychiatry (Weimer, Colloca, & Enck, 2015) to gastroenterology and the brain-gut axis (Elsenbruch & Enck, 2015) -derive substantial benefits from such psychosocial variables (e.g., see antidepressants in Kirsch, 2009;Kirsch et al, 2008).…”

When can neurofeedback join the clinical armamentarium?

“…6 Future research should explore the healing mechanisms common to true and sham neurofeedback, including the role of motivation, expectation, interaction with health professionals, and demand characteristics. …”