The most studied psychiatric medication for children, and arguably the most broad-spectrum medication available, is placebo. It has proven itself repeatedly to be as good or better than a number of FDA-approved medications that are effective in adults. It has been found to be effective in up to half of pediatric patients for conditions as different as seizures and ADHD, and is well known to treat dozens of conditions. Yet, we rarely review its risks and benefits, or the unique role it plays in the treatment of children.
We know a lot about placebo effects in adults, so is it really necessary to specifically study it in children? Several meta-analyses suggest that the answer is yes. Children with epilepsy, migraines, IBS, ADHD, obsessive compulsive disorder (OCD), anxiety disorders, and major depressive disorder (MDD) all have a greater response to placebos than adults with these conditions (Rheims S et al, PLoS Med 2008;5(8):e166).
This has particular significance in MDD where arguments regarding clinical effectiveness of antidepressants rage due to the ambiguity of short clinical trials that do not show conclusive benefit of drug versus placebo. Does that mean the drug doesn’t work? Or does it mean placebo works too well?
How Well Do Children Respond to Placebo?
Children with MDD have a placebo response rate greater than that in adults and in other pediatric conditions. One pediatric MDD study estimated the average placebo response rate to be 48% (Rutherford BR et al, Am Acad Child Adolesc Psychiatry 2011;50(8):782-795). Another calculated that it was 54.3% in children under 12 and 44.9% in those age 12 to 18 (Enuck Pl et al, Pediatric Research 2013;74:1). Compare that to adults: rates of placebo response are 29.7% to 38% (Brunoni AR et al, PLoS ONE 2009;4(3): e4824; Enuck Pl et al, Pediatric Research 2013;74:1).
Placebo effects might also play a bigger role in MDD than other psychiatric conditions. The author of a review that found placebo response rates around 50% in MDD suggested that one reason for the high rate could be that interaction with the clinician unintentionally provides support and helps to increase self-esteem, which are key factors in treating depression (Cohen D et al, PLoS ONE 2008;3(7):e2632).
Interestingly, one meta-analysis (Whiteford HA, Psychological Medicine 2013;43:1569-1585) looking at waitlist trials estimated the spontaneous remission rate to be between 19% and 44% (excluding trials less than six weeks long), suggesting that the placebo response represents an actual improvement in symptoms rather than the mere passage of time.
Why Are Children More Responsive to Placebo?
Expectancy plays a large role in the placebo effect in adults, but the same might not be true for children. Studies show that the placebo effect doesn’t necessarily increase when there is a high probability of receiving an active drug (Rutherford BR et al, Am Acad Child Adolesc Psychiatry 2011;50(8):782-795). However, one study that involved exposure to pain stimulus suggested that conditioning and learning by social observation contribute significantly to placebo responses in children. In other words, seeing other children respond a certain way may make kids more likely to respond themselves (Bendetti F and Collaca L, Pain 2009;l44(1-2):28-44).
Another possibility is that interactions with healthcare workers contribute to the placebo effect. One study showed that with older youths there was a correlation between the amount of time spent with clinicians and the response rate to placebo (Rutherford BR op.cit). There may be an effect due to the therapeutic alliance which is unintentionally created during a trial.
How Can Placebos Benefit Patients?
Placebos can be used to benefit patients in clinical practice. A study of children with ADHD suggests that we can “harvest” the placebo benefits without deception. Some children on the optimum dose of a stimulant had no change in symptoms when their doses were reduced by way of an active pill that was half their previous dose, plus a pill they knew was a placebo (Bodfish JW et al, J Dev Behav Pediatr 2010;31(5):369-375).
And there’s another form of placebo that physicians should be aware of. When a patient begins a treatment, it affects the thoughts, emotions and responses of doctors, family members, and friends through a process called “placebo by proxy” (Grelotti D et al, BMJ 2011;343:d4345). Parents get relief from worry, even if the drugs are nothing more than “impure placebos.” Through understanding the grip that “placebo by proxy” has on us, we can avoid it pushing us away from evidence-based medicine.
CCPR’s VERDICT: Placebo can be a safe and surprisingly effective treatment. We should take time to make use of the placebo effect without deception in our own practices.