Many researchers believe antidepressants in development should be tested in clinical trials against other antidepressants because they feel it is unethical to give participants treatment with a placebo. But other investigators say placebo controls in antidepressant research remain important because placebos provide the best contrast to measure the effectiveness of a new drug.
Spurred by this debate, Dr. B. Timothy Walsh, the William and Joy Ruane Professor of Pediatric Psychopharmacology at P&S, and colleagues at P&S and the New York State Psychiatric Institute reviewed the medical literature to investigate how placebo control groups in antidepressant drug trials have changed during the past 20 years.
The researchers searched for trials of antidepressant medications published between 1981 and 2000 and found 75 had adult outpatients with major depressive disorder who were randomly assigned to receive medication or placebo. They found the response to placebo on average increased about 7 percent a decade, but the response varied widely.
Our finding means that a trial of a new drug against an older, established drug should still include a placebo control group because a researcher cannot assume that the accepted level of effectiveness for the older drug is still valid, since its relationship to the placebo has probably changed, Dr. Walsh says. Use of a placebo control group seems to be the only way to test if study participants are getting better because of the antidepressant or the placebo. Their findings were reported in the Journal of the American Medical Association on April 10.
But it remains unclear why the placebo response rate is rising. Senior author Dr. Walsh and his colleagues speculate the response rates to placebo and medication (response rate to medication is increasing by approximately 7 percent a decade) are most likely due to differences, which are hard to detect, in the study population over time. Today, for example, people with milder depression may be included in antidepressant trials, skewing the results for both the placebo and drug arms of the trials.
More research is needed to understand why the response rates to placebo and medication are increasing, Dr. Walsh says.
The increasing numbers of premature births in the United Statesup 23 percent since the early 1980sis linked to increasing rates of obesity among women, according to a report from the March of Dimes Task Force on Nutrition and Optimal Human Development. Dr. Richard Deckelbaum, director of the Institute of Human Nutrition and the Robert R. Williams Professor of Nutrition and Pediatrics at P&S, initiated and chaired the task force, which published its report in February.
Babies from overweight/obese women also have a higher risk of neural tube, heart, and other malformations. Dr. Deckelbaum says these links have been underappreciated even among health professionals.
The task force also reported on health problems associated with micronutrient deficiency, low birth weight, and suboptimal growth of children more common in developing countries. Undernourished women are more likely to have smaller babies who are more prone to death, infection, and learning disabilities.
To improve health in both developing and developed countries, the report says nutrition programs must pay special attention to young women and children under age 2. Nutrition problems before and during pregnancy and during the first two years of life can have permanent effects on the health of the child and impair cognitive development.
Generic implementation templates provided in the report will be utilized in Asia, Africa, South America, and the United States. Because certain genes strongly influence responses to nutrients, Dr. Deckelbaum plans to bring genomics and new molecular markers into the projects to tailor strategies to different populations.
Andrea Yates killing her five children made postpartum depression front-page news. But women who have severe depression before delivery are the most likely to have depression after giving birth. Treating those 5 percent of women during pregnancy could possibly prevent postpartum depression in some cases.
If we can nip antepartum depression in the bud, we will improve the prognosis for an uneventful postpartum year, says Dr. Michael Terman, P&S professor of clinical psychology (in psychiatry).
So Dr. Terman and colleagues at Columbia Health Sciences, Yale University, and Case Western Reserve University decided to test in a small study whether bright light therapy could help pregnant depressed women. Light therapy has been successful at treating major depression and seasonal affective disorder. Light has advantages for pregnant women because antidepressants might hurt the fetus and psychotherapy alone might not be sufficient.
The investigators tested the value of morning bright light therapy with 16 pregnant women diagnosed with major depression. The women received either three or five weeks of treatment, after a week or two of baseline assessment without treatment. Participants sat in front of a light box for one hour daily, starting within 10 minutes upon waking.
After three weeks of treatment, depression scores decreased by an average of 49 percent. After seeing these benefits, the study was extended to five weeks. The seven women who received five weeks of treatment showed a 59 percent improvement. The study's results were reported in the April American Journal of Psychiatry.
To follow up on this study, Dr. Terman and his colleagues have begun a randomized, controlled trial, using two levels of light therapy with the lower, less intense light exposure serving as the control. The new study aims to determine if the positive results of the pilot study were due to the light treatment and not a placebo effect. He and his colleagues are recruiting more women for the study.