Are Antidepressant Drugs Effective?
Major depression is a serious disease. In 2005, The New England Journal of Medicine (NEJM) published Dr. J. John Mann’s excellent review “The Medical Management of Depression.” In this piece, Dr. Mann states: “major depressive disorder accounts for 4.4% of the global disease burden, a contribution similar to that of ischemic heart disease…” Equally concerning is that: “Patients who have diabetes, epilepsy, or ischaemic heart disease with concomitant major depression have poorer outcomes than do those without depression.”
One would think, therefore, that those concerned with medical care would be grateful for the availability of drugs to treat depression. Yet, there are many who challenge the value and the need for antidepressants. Dr. John Abramson, author of Overdosed America and my verbal sparring partner on The Dr. Oz Show, says the following in his book: “…new antidepressants were found to be not even 10% more effective than placebos: symptoms of depression improved by 30.9% in the people who took placebos and by 40.7% of people who took the newer antidepressants.” Dr. Abramson’s implication is that these drugs offer little value over sugar pills.
Dr. Marcia Angell, a noted pharmaceutical industry critic and a former editor of the NEJM, has also expressed a number of concerns about antidepressants, not the least of which is that drug companies rarely publish negative data on these drugs. In her article “The Epidemic of Mental Illness – Why?” which appeared in the June 23rd edition of The New York Review of Books, Dr. Angell states the following:
“When drug companies seek approval from the FDA to market a new drug, they must submit to the agency all clinical trials they have sponsored… If two trials show that the drug is more effective than a placebo, the drug is generally approved. But companies may sponsor as many trials as they like, most of which could be negative – that is, fail to show effectiveness… For obvious reasons, drug companies make very sure that their positive studies are published in medical journals and doctors know about them, while the negative ones often languish unseen within the FDA…”
Factually speaking, Dr. Abramson and Dr. Angell are correct. Antidepressant drug trials usually show only modest superiority of the experimental drug over the placebo. And yes, drug trials where there is no difference in the efficacy of the drug vs. the placebo normally aren’t published. However, such statements don’t tell the whole story in the battle to treat psychiatric disorders.
In doing clinical studies, there are some medical areas where it is easy to measure whether a drug is working or not. If you have a new antibacterial to treat an infection, you can take blood samples to measure the effect that the drug is having on the eradication of the bacteria from the patient. Similarly, with a drug to treat high blood pressure, you can treat a patient with a new drug and take real-time blood pressure measurements to quantify the drug’s effects.
Psychiatric diseases are different. In clinical studies, patients are given a standardized test, such as the Hamilton Rating Scale for Depression (HRSD), which involves answering a variety of questions about a patient’s mood, anxiety, ability to sleep, etc. The patients are then randomized to receive either the placebo or the test drug. Each week, the patient returns and is seen by the psychiatrist to determine if any improvements are evident. Generally, these studies last for about two months. Such studies are notorious for the high efficacy response rates seen in patients who turn out to be taking the placebo. In an excellent 2002 NEJM paper on this subject, “Placebo Response in Depression Studies” by Timothy Walsh, Stuart Seidman, Robyn Sysko and Madelyn Gould, analysis of 75 clinical trials showed that the response to the placebo across the trials ranged from 10% to more than 50%. While the authors couldn’t point to one definitive reason why such high placebo rates occur, they offered a few possibilities:
1) patients in these trials, whether on the placebo or on the drug, are usually allowed to take sedatives and anti-anxiety medication, so the placebo responses encompasses the effects of these drugs;
2) the weekly physician visits contribute to the patient’s great sense of improvement;
3) it’s likely that these studies included patients with milder, briefer, and more responsive forms of depression thereby enhancing the chances of either the placebo or the drug being effective.
Thus, it is well-established that there are high placebo efficacy rates in clinical trials in psychiatric disorders. As a result, studies where the efficacy of the placebo is equal to that of the drug being tested are rarely published. It is not that companies are hiding data. Rather, such a result is of little interest. Most skilled in the science behind the results realize that seeing the benefit of a placebo over an experimental drug is a hazard of this type of study. However, it is big news when a new antidepressant does, in fact, show statistically significant efficacy over the placebo. This instance is deemed very important by the scientific community and, therefore, medical journals are very willing to publish such results. In other words, there is a very simple explanation to Dr. Angell’s concern.
Dr. Abramson and Dr. Angell’s position that companies try to bury negative data is simply not true. For almost a decade, the US National Institutes of Health has logged and published the results of EVERY federally and privately supported clinical trial on the website http://clinicaltrials.gov. When each trial is completed, the sponsoring organization is required to summarize its results for all to see – favorable or unfavorable.
Still, Dr. Angell’s article has spurred a tremendous debate not just in New York Review of Books, but also in places like The New York Times (NYT). On July 9th, the NYT published an opinion piece by Dr. Peter Kramer titled, “In Defense of Antidepressants.” Kramer, a clinical professor of psychiatry at Brown, provided a spirited defense of the current methodology in treatment paradigms. As one would expect, the debate continued a week later with a number of letters to the NYT not just from Dr. Angell, but also from a number of heads of important psychiatric associations as well as psychiatry professors from major universities. However, the letters that made the biggest impression on me were the ones from actual patients. One in particular stood out.
“As a professional ethicist, I share… concerns about the medical-pharmaceutical complex and how the obsession with ever-greater profits can hinder, not promote, ethically intelligent patient care. But, as someone who has been using antidepressants successfully for many years, I can say from experience that some of that concern is misplaced. My life is richer and infinitely more satisfying because of this medication. I offer my profound gratitude to the dedicated researchers and conscientious clinicians who have made this possible.”
These are important drugs. They add value to society. Yes, they need to be prescribed appropriately. But to impugn the motives of the people and companies working to discover drugs to ease the pain of depression or the psychiatrists and physicians who prescribe them is irresponsible.