Eight-year-old Grace refuses school due to intense separation anxiety. After eight weeks of therapy, you start fluoxetine 5 mg. Grace’s mom tells her, “This pill will make you brave!” She attends school with little anxiety for a few days after taking her first dose. But by six weeks, she’s crying each morning again, suggesting her rapid response was a placebo effect. How do you respond?

The placebo effect is a therapeutic benefit associated with a patient’s belief in an inert treatment. While the placebo response shows us the limits of medication (eg, antidepressant studies in kids) and may be the mechanism of hard-to-prove approaches such as homeopathy, placebos have utility in psychiatry, and children typically show a stronger response than adults. This article will help you understand and use placebos more effectively with children and teens.

History
“Placebo” is Latin for “I shall please.” In traditional communities, trust in the practitioner and treatment method may have triggered improvement via the placebo effect (Kaptchuk TJ, Ann Intern Med 2002;136(11):817–825). By the 20th century, placebos were part of clinical research, used to sort actual treatment effects from patients’ expectations. Yet research and historical records suggest that placebos are underutilized as a mind/body healing tool.

Placebo and the mind
With placebos, trusting the treatment and the person giving it can trigger physiological improvements. Functional imaging demonstrates that placebo activates brain areas tied to therapeutic responses in depression, anxiety, tantrums, autism, cerebral palsy, and pain management (Curie A et al, PLoS One 2015;10(7):e0133316; Simmons K et al, Pain 2014;155(11):2229–2235).

While blind belief often fuels placebo, open-label trials reveal that placebos can work even when patients know they are receiving one (Simmons et al, 2014). These are called “open-label placebos.” For example, in one ADHD study, an open-label placebo paired with a 50% reduced dose of stimulant medication produced outcomes comparable to a full dose (Sandler AD et al, J Dev Behav Pediatr 2010;31(5):369–375). Another study demonstrated efficacy of open-label placebo treatments for IBS (Kaptchuk TJ et al, PLoS One 2010;5(12):e15591).

Research studies note that larger pills, more expensive pills, and pills with actual side effects are often more effective placebos (Meissner K and Linde K, Int Rev Neurobiol 2018;139:357–378). The neurobiological mechanism of the placebo effect may be related to dopaminergic release with the expectation of relief, and cultural practices may also align with placebo effects (Anderson S and Stebbins GT, Int Rev Neurobiol 2020;153:27–47).

Response in children
Placebo responses vary by individual, developmental, and environmental factors, including family dynamics, parental stress, and caregiver attitudes. “Placebo by proxy” occurs when a caregiver’s belief in a treatment affects a child’s response to it. The nocebo effect is the “evil twin” of the placebo effect, referring to worsening symptoms from negative expectations. “Nocebo by proxy” can occur when a caregiver’s skepticism influences the child (Weik E et al, Br J Pain 2021;16(1):60–70).

Young children are more responsive to placebos due to their underdeveloped prefrontal cortex. This limits critical judgment and makes them more suggestible, allowing caregivers to shape their expectations (Weimer K et al, Pediatr Res 2013;74(1):96–102). By contrast, adolescents (who are psychologically separating from parents) and adults with Alzheimer’s dementia have less responsiveness to placebos.

Placebo in practice
You tell Grace and her mother that the early placebo effect was a hopeful signal that a part of her wants to let go of her anxiety, and that a higher 10 mg dose of fluoxetine can help her do that.

Start low, go slow
Low doses often help, especially when paired with strong expectancy effects. They also bring fewer side effects. Track progress with objective measures, like behavioral observations or ADHD teacher ratings (Sandler et al, 2010; Parellada M et al, Eur Neuropsychopharmacol 2012;22(11):787–799).

Balance optimism and honesty
Most medical providers implicitly use placebo-related techniques. While many are leery of intentionally using placebo due to ethical concerns around deception, published recommendations favor open-label approaches (Evers AWM et al, Psychother Psychosom 2018;87(4):204–210). Emphasize the potential benefits of a treatment in a confident, reassuring manner, while still being realistic about limitations. The goal is not to trick the child or their family, but rather to create a space where the power of the person’s expectations can enhance the actual pharmacological effects of the medication.

You tell Grace, “I know kids who have felt calmer and happier when they use this medicine. It’s not the pill doing everything—it’s you being strong and wanting you to get back to feeling better!”

Build a positive clinical relationship
Take time to develop trust and rapport with children and families; this will help reduce their anxiety and enhance their therapeutic response to treatment (Tates K and Meeuwesen L, Soc Sci Med 2001;52(6):839–851). Most people, including kids, think in stories, and you can use simple, age-appropriate stories when talking to them (Bruner JS. Actual Minds, Possible Worlds. Cambridge, MA: Harvard University Press; 1986).

Hedge the bet. Tell the patient that the medication may or may not work. If it works, you have a win—and if it doesn’t work, you’ve still built trust with the patient and family. Since the effect may be short-lived, placebos may be best utilized for short-term plans.

Finally, don’t underestimate the impact your physical space has on patients. Make it a welcoming, playful place, with comfortable furniture, natural light, engaging toys, and no digital screens.

Two months later, Grace tells you: “It worked!” She is happily back at school and benefiting from therapy. She has learned coping tools in therapy, and now she understands that her brain is strong. Together with Grace and her mother, you discuss continuing the medication for about six months, then trying a very gradual taper of the fluoxetine.

CARLAT VERDICT
Placebos can be helpful to supplement care in some cases, particularly for short-term situations. Set modest but positive expectations and coach parents to avoid negative expectations. Track symptoms. If a placebo works, remember that it might not last; if it does not work, rethink the care plan.