Wednesday, October 7, 2009

Placebo Power in Pediatric Gastrointestinal Pain

Chronic abdominal pain is a common and challenging complaint in childhood, largely due to pain-predominant functional gastrointestinal disorders (FGIDs) that include irritable bowel syndrome (IBS), functional dyspepsia, functional abdominal pain, and abdominal migraine. According to a new study reported in the journal Gastroenterology, both placebo and the tricyclic antidepressant amitriptyline work equally well in treating these disorders in children — a result that may have important implications for how practitioners can maximize placebo effects in children.

Investigators from multiple centers in the United States conducted a prospective, randomized placebo-controlled trial in which children, ages 8 to 17, with irritable bowel syndrome, functional abdominal pain, or functional dyspepsia were administered either 4 weeks of placebo or amitriptyline [Saps et al. 2009]. Of the 83 children (78% girls) completing the study, 63% reported feeling better and 5% feeling worse taking amitriptyline compared with 57.5% feeling better and 2.5% feeling worse in the placebo group. Pain relief was excellent or good in 45% of children receiving placebo compared with 50% of those treated with amitriptyline. Essentially, there were no significant differences between amitriptyline and placebo after 4 weeks of treatment; both groups had generally good therapeutic response. There also were no differences found between groups regarding psychologic variables, such as depression and somatization; however, amitriptyline did significantly reduce anxiety (p<.0001).

Clinical Concepts: Past investigations in adults have found significant beneficial effects of antidepressants, including amitriptyline, for IBS; so, the extraordinary placebo response in this study of children was unexpected. Therefore, a companion editorial in the journal focuses on a better understanding of the benefits of placebo effects in children with IBS and other FGIDs [Benninga and Mayer 2009]. Significant progress has been made in the identification of brain networks and signaling systems underlying placebo responses. For example, several studies have shown that painful stimuli engage prefrontal cortex regions associated with the expectation of symptom relief, which results in the inhibition of limbic regions (reducing anxiety and excitatory arousal) and the increased activity of endogenous pain inhibition systems (involving opioid and dopamine channels). It is possible that a “healing context” — eg, comforting advice of a trusted practitioner and/or sugar pills — may stimulate these naturally occurring pain-relieving systems. Furthermore, research indicates that mind-based therapies for IBS, such as cognitive behavioral therapy (CBT) and hypnotherapy, activate similar brain networks, which in turn reduces pain perception and presumably clinical symptoms. Therefore, hypnotherapy or CBT might be considered as options for treatment prior to pharmacologic interventions in some cases.

Additionally, prior investigations of therapies for IBS have demonstrated robust positive influences of practitioner-patient relationships for producing clinically significant outcomes, Benninga and Mayer note. An intriguing explanation for placebo effects in children may relate to the fact that, in contrast to straightforward physician-patient interactions in the adult, the healthcare provider exerts a dual effect on the pediatric patient: one directly on the child, the other on the parent–child “dyad” — that is, the child's response to therapy is influenced by changing parents' attitudes and expectations. There apparently can be a close correlation between parental anxiety and pain sensitivity in the child; in brief, if the parents believe in a treatment and/or practitioner, and act less anxious about the child’s symptoms, it can increase placebo effects in the child.

Benninga and Mayer observe that most children with functional abdominal pain have mild symptoms that are usually of short duration and are easily managed in primary care. Current practice typically involves support and empathy for the family with assurances that no serious disease is present and that the child will likely outgrow it — all of which might enhance the placebo power of the practitioner-family-patient interaction. The primary goal is not complete eradication of pain, but resumption of a normal lifestyle with regular school attendance, participation in desired extracurricular activities, and a normal sleep pattern. With this approach, approximately 40%–70% of the children may have complete resolution of their complaints. The study by Saps et al. might be viewed as an important contribution to the pediatric literature, emphasizing the vital importance of supportive practitioner-family-patient interactions and perhaps inspiring new studies of placebo effects in children with other GI disorders, such as gastroesophageal reflux disease and constipation.

> Benninga MA, Mayer EA. The power of placebo in pediatric functional gastrointestinal disease. Gastroenterology. 2009(Oct);137(4):1207-1210 [see
full article here].
> Saps M, Youssef N, Miranda A, et al. Multicenter, randomized, placebo-controlled trial of amitriptyline in children With functional gastrointestinal disorders. Gastroenterology. 2009(Oct);137(4):1261-1269 [
see abstract].