Milder Depressions Don't Appear to Benefit From Antidepressant Treatment
Major newspapers today, including the New York Times, are reporting on a study published in this month's Journal of the American Medical Association titled “Antidepressant Drug Effects and Depression Severity”. You can read the abstract here. The full article is behind a pay-wall. This work was led by graduate student Jay Fournier and psychologist and professor Robert DeRubeis of the University of Pennsylvania with multiple other prominent psychologists and psychiatrists as co-authors.
These authors did a meta-analysis of depression treatment outcome studies, looking at how well treatment of depression with antidepressant drugs worked in terms of reducing patients' overall depression. The term meta-analysis is perhaps not clear to all readers, so I'll take a moment to define it. A meta-analysis is an archival research technique. No actual new data collection occurs in a meta-analysis. Instead, researchers go to the “library” and compare data from past published and unpublished research to see how consistent they were. It is expected that there will always be some variability or difference in outcome across studies conducted at different times, in different locations, with different people, etc. However, it is sometimes the case that some studies produce outcomes that are very different than other studies. In such cases, it is not easy to understand whether these differences are simply random occurrences or whether they mean something. Meta-analytic techniques were designed to help researchers make better sense out of conflicting multiple data sets like this. In essence, the technique involves finding the average treatment outcome (or “effect size”) across the multiple studies. Because the averaged treatment outcome is based on multiple sources of input, it is probably more stable and reliable than any singular observation.
In the current work, then, multiple studies examining depression treatment effects were looked at. The studies shared features in common which enabled them to be compared. All of the studies measured depression severity in the same way, using a standardized interview known as the Hamilton. They all also compared an antidepressant drug treatment to placebo. Two seperate antidepressant drugs were looked at - Paroxetine (aka Paxil - a classic SSRI or second-generation antidepresant) and Imipramine (a classic tricyclic or first generation antidepressant). Placebos, of course, are things that look like drugs but actually aren't. They are “sugar pills” designed to provide all of the experience of taking a medication save for delivering the actual active ingredient. Studies of this type are known as “double blind” because neither the patients receiving the drugs or placebos, nor the medical staff providing the pills to the patients know which contains the drug and which is the placebo. It's tempting to think that a placebo is inert and offers no benefits to patients, but this is generally not the case. In taking a placebo, patients get a lot of attention, and they generally believe that they have taken something which will help them. These factors (a little care and suggestion) do help people to get better, so placebos are not in fact completely inert. Because they offer the same psychological benefits as real drugs, placebos are good “masks” against which to isolate the pure treatment effects of drugs (subtracting out the role of care and belief).
When the studies were looked at through the lens of the meta-analysis, it was clear that the antidepressant drugs (both of them were about the same) really were not offering benefits beyond those due to placebo effects for mildly depressed people. Clear treatment effects were only present (beyond that associated with placebo alone) when people were severely depressed.
This finding is important because we live in a world where antidepressant drugs are very widely prescribed, and not just to people who are severely depressed, but to people with mild and moderate depressions as well. If the finding is solid and reliable – and the averaged nature of the study (that it is a sort of summary of many studies all put together) pulls in that direction – it suggests that antidepressants are routinely over-prescribed and should be instead prescribed a lot less often, only when someone's depression is moderate to severe in intensity. To prescribe the drugs to mildly depressed people is perhaps not going to help them (more than placebo anyway), and will add to their burden the various unpleasant side effects commonly associated with antidepressants. If doctors were to take this study seriously, it would cut into prescriptions for antidepressants, and thus into the profits of pharmaceutical companies.
While this is an important study it is not definitive or the last word on the subject. There is the matter of the placebo effect for one thing. Namely, that in cases of mild depression antidepressant drugs did not offer people better symptom relief than did placebo. Placebo, being comprised of positive expectation that something good is being done and attention or care is not the same thing as nothing at all. This study cannot answer questions about whether mildly depressed people who do nothing at all to help themselves will tend to do as well as similarly mildly depressed people who take antidepressants. The study highlights the powerful role of placebo-like effects which instill into people a belief that they will get better, and provide them with attention in helping people to recover from milder forms of depression but does not speak to how this might be best done in the absence of actually providing a placebo. Fortunately, this part is easier to speak to as numerous other studies have pointed out the efficacy of various specific forms of psychotherapy (namely, cognitive-behavioral therapy and interpersonal therapy), and other interventions that promote exercise and socialization in helping people recover from depression. There are lots of well-known, easy to access non-drug treatments out there today.
The most interesting part of this study for me is not the study itself, but that its publication was notable enough for national newspapers to want to write about it. The average archival research project does not get this sort of attention. My personal theory is that there's a lot of resentment, anger and distrust in the popular culture today for the pharmaceutical companies and anyone closely aligned with them. This study is newsworthy precisely because it is a minor blow to the message that pharmaceutical marketing is continually pushing out towards consumers – that there is a pill to solve your problem you should ask your doctor about …
What are your thoughts on the issue? Please leave a comment if you have an opinion or thought you'd care to share.
2010-01-11 Update: There was a wonderful Op/Ed by Judith Warner in the New York Times from the 9th titled, "The Wrong Story About Depression" which is worth reading. The money quote from that piece follows:
This is the big picture of mental health care in America: not perfectly healthy people popping pills for no reason, but people with real illnesses lacking access to care; facing barriers like ignorance, stigma and high prices; or finding care that is ineffective.
2010-01-13 Update: A further follow-on op/ed was published in the Times the other day by Richard Friedman, MD titled "Before You Quit Antidepressants...". The piece is essentially a defense of the use of Antidepressants. Worth reading if this area is of interest to you. My first impulse was to think that Dr. Friedman was probably in the employ of the pharmas, but the Times says this is not the case (in the comments section). A quote from this essay (making a good point) follows:
... the real test of an antidepressant is not just whether it can lift someone out of depression; it is whether it can keep depression from returning. For a vast majority of people with depression, the illness is chronic. Relapses and low-level symptoms between episodes are common.
of course, Cognitive Behavioral Psychotherapy for Depression can accomplish this goal as well or better than antidepressants in many cases if people are up for that sort of thing.
Anti depressants not effective on low level depression - dasha - Jan 15th 2010
I have to disagree. In my case, as well as in others I know of, certain medications work well. In my case, I tried many many different meds until my doctor put me on Cymbalta for the Dysthemia I have had for years. It saved my life