April 15, 2002

CHICAGO: A consensus panel of patient advocates and the nation’s leading scientists studying mood disorders report that placebo is appropriate for use in clinical trials. The report, "Consensus Statement on the Use of Placebo in Clinical Trials of Mood Disorders," states that placebo can be used in studies for new psychotropic drugs, if the sample population is highly-monitored, controlled, and screened for suicidal ideation.

The Depression and Bipolar Support Alliance's (formerly National Depressive and Manic-Depressive Association) (DBSA) consensus statement says that the use of placebo is ethical when there is no existing treatment, or a newer class of drugs is being studied. The statement was published in the March Archives of General Psychiatry.

"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," said Dennis Charney, M.D., Chief, of the Mood & Anxiety Disorder Research Program at the National Institute of Mental Health, chairman of the study panel, and co-author. "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."

"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 drugs performance," said Charney, who also serves as chairman of DBSA’s 65-member Scientific Advisory Board (SAB).

Arguments Pro and Con

The panel studied the issues in response to critics who argue that placebo controls are never ethical when treatments are shown to be effective for a particular disorder. Other critics of psychiatric research mistakenly assume that patients are overly compliant and over eager to participate, and therefore patients with incorrect criteria will be part of the study.

However, the statement says that placebo use is justified in the case of disaffective disorders where there is no evidence for irreversible harm associated with placebo assignment. Clinical trials without placebo controls also require large sample populations to show significant differences between groups. That, noted the authors, unnecessarily exposes a large number of people to medications that may be ineffective, poorly tolerated, or toxic. It can also increase the time of developing a drug that may be helpful to alleviate the suffering of people living with mood disorders.

Comprehensive Safeguards Needed

The authors, a group of 33 patients and scientists, emphasized that oversight is vital to ensure 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," said Lydia Lewis, Executive Director of DBSA and a statement co-author. "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 is to shorten the length of a patient’s exposure to placebo," said Lewis. "That’s very important to ensure a patient’s protection. In addition, when patients in a trial respond exceptionally well to a drug, it should be made available at an affordable cost after they withdraw from the study."

Greater Vigilance about Informed Consent

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 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 said.

More Mood Disorders Research Needed

In the trials studied, the authors report that depressed patients with mood disorders have inherently high placebo response rates of up to 70%, with a mean between 30 and 40%.

The statement reported that bipolar disorder is "inherently variable, complex, and clinically challenging, and research is in the early stages." Bipolar disorder in adults is "remarkably understudied" and "studies in adolescents, children, and elderly persons are virtually non-existent."

Incorporated in 1986 and based in Chicago, DBSA is the nation’s largest patient-directed, illness specific organization. It is governed by a 15-member board of directors and has more than 1000 support groups across the United States and Canada.