In response to critics arguing that placebo controls are never ethical when treatments are shown to be effective for a particular disorder, a consensus panel consisting of 33 patient advocates and leading researchers in the study of mood disorders reported that placebo is, in fact, appropriate for use in clinical trials. The National Depressive and Manic-Depressive Association’s report, “Consensus Statement on the Use of Placebo in Clinical Trials of Mood Disorders,” stated that “placebo has a definite role in mood disorder studies.” Because “patients with mood disorders have inherently high placebo response rates, without placebo or a valid alternative method, most study findings are difficult to interpret, and the risks associated with research cannot be justified.... Findings of equivalence between a new drug and standard treatment in active control studies is not evidence of efficacy unless the new drug is also significantly more effective than placebo,” the authors asserted.

“Patients with mood disorders will benefit from clinical trials that include a placebo element, because trials without placebo may yield unreliable results or lead to false claims about drug performance,” added Dennis Charney, MD, Chief of the Mood and Anxiety Disorder Research Program at the National Institute of Mental Health. Dr. Charney was Chairman of the Consensus Development Panel and coauthor of the report.

PLACEBO PRINCIPLES

Published in the March Archives of General Psychiatry, the consensus ruled that use of placebo is also ethical when there is no existing treatment—or when a newer class of drugs is being studied, if the sample population is closely monitored, controlled, and screened for suicidal ideation. “This statement underscores that the patient’s safety and well-being must come first, while at the same time stressing the importance of placebo in developing new treatment options,” Dr. Charney said. “Placebos in a drug trial don’t cause harm in the great majority of cases if there’s adequate monitoring and high-risk patients are removed from the study.”

Further evidence for maintaining the role of placebo in mood disorder trials was generated out of logistical and pragmatic considerations. According to the authors, clinical trials without placebo controls require large sample populations to show significant differences between groups, unnecessarily exposing a large number of people to medications that may be ineffective, poorly tolerated, or toxic. Such trials can also increase the time of developing a drug that may be helpful in alleviating the suffering of people with mood disorders, they observed.

TO PROTECT AND SERVE

Throughout the consensus, there is abundant emphasis placed on the fact that the role of the researchers as overseers is vital to ensuring the safety of patients in clinical trials. “Placebo-controlled trials are not ethical when patients are inadequately protected from serious risk, permanent disability, or death,” reiterated Lydia Lewis, Executive Director of the National Depressive and Manic-Depressive Association and coauthor of the consensus statement. “High-risk patients should not take part in them—the trial’s design should call for a patient’s withdrawal from the study if they are doing poorly or if they turn suicidal.”

Another safety measure Ms. Lewis identified was limiting the length of the patient’s exposure to placebo. “That’s very important to ensure a patient’s protection,” she said. “In addition, when patients in a trial respond exceptionally well to a drug, it should be made available [to them] at an affordable cost after they withdraw from the study.”

Finally, the statement calls for more documentation in future studies about the use of placebo and urges improvements in informed consent. “The professionals who administer these trials need to be vigilant about informed consent,” said Ms. Lewis. “This is an absolute requirement to ensure that patients truly understand the risks and implications of participating in a study. Patients need to be informed that there is no guarantee that the treatment will help them,” she concluded.

Suggested Reading
Charney DS, Nemeroff CB, Lewis L, et al. National Depressive and Manic-Depressive Association consensus statement on the use of placebo in clinical trials of mood disorders. Arch Gen Psychiatry. 2002;59:262-270.

Return to table of contents