Antidepressant MedGuide Arouses Controversy

October 1, 2007

The FDA is considering changes to the Patient Medication Guides (MedGuides), which must now accompany about 65 drugs, including those in 2 major classes, one of which is antidepressants. MedGuides provide information about potential adverse reactions and are considered a warning of sorts.

The FDA is considering changes to the Patient Medication Guides (MedGuides), which must now accompany about 65 drugs, including those in 2 major classes, one of which is antidepressants. MedGuides provide information about potential adverse reactions and are considered a warning of sorts. They are supposed to be distributed by pharmacists when a customer receives his or her prescription.

The FDA first ordered MedGuides for antidepressants in 2005 based on concerns about suicidal ideation in children and adolescents. At the same time, and as part of a broad action plan, the agency ordered antidepressant labeling to include a black-box warning. There has been some subsequent evidence, however, that primary care physicians, because of concern for professional liability, have been unwilling to prescribe antidepressants during the past few years with the result that suicide rates have begun to rise. "It is impossible to develop a direct cause and effect relationship [between the black-box warning and the drop in prescriptions], but the association is striking," states Darrel Regier, MD, research director, American Psychiatric Association (APA) and executive director of the APA's American Psychiatric Institute for Research and Education.

That striking association led the FDA's Psychopharmacologic Drugs Advisory Committee to recommend to the FDA in December 2006 that the agency eliminate some language in the antidepressant MedGuide and add language on the benefits of the drugs. The agency ordered drug companies to do just that in May 2007.

Those changes, however, did not go quite far enough for many psychiatrists. Regier said, "I would like the Med-Guide to say a whole lot more about what depression is, and how it can ruin your life if you don't get treatment, and the risk of suicide if depression goes untreated." But Regier added that he is more impressed by the changes the FDA ordered in May than critical of the additional material they did not add.

The major change the FDA made was dropping a monitoring schedule to which physicians were supposed to adhere. "It was a barrier to primary care physicians, particularly," Regier explained. What he would like to have seen included in the MedGuide, but what the FDA declined to order, was a more explicit endorsement of measurement-based care. For example, it could recommend that primary care physicians use the Patient Health Questionnaire 9 (PHQ-9), a 27-point self-report tool that allows a physician to score a patient on 9 measures, with the total indicating where that patient is on the depression continuum.

About a month after ordering the antidepressant changes last May, the FDA held a 2-day workshop to hear public suggestions for broader changes to all MedGuides, which have come under fire from pharmacy, physician, and consumer groups for a number of reasons. The FDA is under a congressional mandate to determine whether 95% of prescriptions dispensed to patients in the United States are accompanied by useful medication information. That determination was supposed to have been made in 2006. The FDA missed that deadline but is expected to propose changes in the MedGuides sometime soon.

Complaints about the shortcomings of antidepressant MedGuides dominated the 2-day FDA workshop in June. Rep Mike Ferguson (R, NJ), the only member of Congress who appeared, said, "Specifically, I want to register my concerns that FDA-approved medication guides are not being distributed to patients and parents when antidepressant medications are being prescribed." Ferguson went on to say that neither the FDA nor the state boards of pharmacy have the authority to insure that manufacturers are providing MedGuides to pharmacies and that pharmacists are distributing them.

Consumer groups argued that the MedGuides that accompany antidepressants are unclear. David Fassler, MD, a clinical professor of psychiatry at the University of Vermont who represented the American Academy of Child & Adolescent Psychiatry (AACAP) at the FDA workshop in June, said, "It was also clear from the testimony that there's significant room for improvement in terms of design, format, style, language, and layout. The goal is not just to distribute accurate information, but to see that it's actually read and understood. Patients and family members need and deserve as much information as possible in order to make fully informed decisions about treatment options."

However, Fassler's strong backing at the June meeting for additional benefit information in the antidepressant Med-Guides was met with skepticism by a top FDA official, Joseph Temple, MD, director of the office of medical policy at the FDA's Center for Drug Evaluation and Research. "Let me tell you what our problem in this case is," Temple replied. "It's not that we don't suspect that they have major benefits, too, but nobody has ever shown that any use of these drugs improves survival or anything like that. So here you have something you're worried about, which is that kids are thinking about suicide, and you can say in the other part, well, it does treat acute depression."

Fassler responded that SSRIs prevent relapse and reduce the risk of relapse in adolescents by approximately 50%. "To me, if I was a parent of a child with depression, that would be extremely significant data, which I would want to have. So I agree, certainly, we don't have all of the data or all of the information that we want and we need more funding and we need more long-term studies. But we do have important data."

In part because of the antidepressant MedGuides' shortcoming with regard to benefit information, the APA, AACAP, and other physician groups have developed an alternative antidepressant MedGuide, which is available at www.parentsmedguide.org.