New Study: SSRI Antidepressants ‘Clinically Insignificant’ For Most People
A new study published today is sure to set off another storm in the ongoing debate about the widespread prescription of antidepressants. Professor Irving Kirsch at the University of Hull and colleagues in the US and Canada report that new generation 'SSRI' antidepressants like Prozac or Seroxat mostly fall, "below the recommended criteria for clinical significance" (Kirsch et al. 2008). In other words, the most modern drugs prescribed for depression generally don't work.
The study was particularly interested in whether the drugs had different effects on people with different levels of depression. Here is what they found:
- Mild depression: not tested as mild depression is usually treated with a 'talk therapy' rather than antidepressants.
- Moderate depression: antidepressants made "virtually no difference".
- Severe depression: antidepressants had a "small and clinically insignificant" effect.
- Most severe depression: antidepressants had a significant clinical benefit - but see below...
Effectiveness limited even for severe depression
When Professor Kirsch and colleagues looked more closely at the data for those who were most severely depressed they uncovered more bad news for drug manufacturers. The antidepressant effect the drugs appeared to have, though small, was largely due to differences in the effects that the placebo had on the control group rather than better response to the drug.
Let's unpack this a little.
The placebo effect means that even when you give someone a 'fake' antidepressant they still improve a little, simply because they expect to. This effect is so powerful and reliable that to be taken seriously drug studies have to compare depressed people taking an antidepressant to a control group taking a placebo.
What Professor Kirsch and colleagues found was that while the placebo effect was present for moderately depressed people, it disappeared for those who were the most severely depressed. This meant that antidepressants weren't having any more effect on those who were more depressed, it's just that in comparison to the control group that's how it appeared. In reality what was happening was that the control group weren't responding to the placebo.
The authors, therefore, conclude that there's no point prescribing SSRI antidepressants to anyone but the most severely depressed people, unless other treatments have been tried and have failed.
Can we believe this study?
So the question is: can we believe the results? Well, the study used data from 47 clinical trials that had been submitted to the US Food and Drugs Administration (FDA). The FDA already has a rigorous set of criteria for including studies, so this suggests only quality studies were included.
The data from all these studies were then combined using a statistical technique called 'meta-analysis'. This means all the studies were collected together and analysed as though they were all one huge study. By doing this you can increase the power of the study significantly.
Like many statistical techniques, though, there is some debate about the use of meta-analyses. For example it is often argued that they lump together studies with different protocols so that effectively you end up comparing apples with oranges. Whether this sort of criticism is valid depends on the study's nitty-gritty details.
High stakes
More broadly, we have to be careful about drawing conclusions from a single piece of work. There's no doubt how high the stakes are for everyone: Professor Irving Kirsch has built a career on showing the power of the placebo effect, pharmaceutical companies have built their fortunes on studies proclaiming the benefits of SSRI antidepressants, while patients are stuck in the middle.
Despite this, the evidence does seem to be mounting up against SSRI antidepressants. Although previous studies seemed to show SSRIs were effective, recent work has suggested this might be due to a bias in the way research is reported (Turner et al., 2008). Studies which show no effect have a tendency to be 'filed' rather than being submitted for publication. This can result in a much more rosy picture being painted of a drug's effectiveness than is really the case.
Either way, considering the number of people worldwide currently taking SSRI antidepressants, we can be sure this isn't the end of the story.
» Read some of the strong reactions to the antidepressant study.
[Image credit: selva]
References
Kirsch, I., Deacon, B. J., Huedo-Medina, T. B., Scoboria, A., Moore, T. J., & Johnson, B. T. (2008). Initial severity and antidepressant benefits: a meta-analysis of data submitted to the food and drug administration, PLoS Medicine, 5(2), e45 EP
Turner, E. H., Matthews, A. M., Linardatos, E., Tell, R. A., & Rosenthal, R. (2008). Selective publication of antidepressant trials and its influence on apparent efficacy, New England Journal of Medicine, 358(3), 252-260.
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I began taking SSRIs for depression in my mid 30's (15 years ago). I had been clinically depressed for several years but had resisted using a "chemical" approach to feeling better. When I finally relented and began on Paxil, the effect was tremendous. I had been in counseling for a couple of years at that point, and while helpful, it was the SSRI that made the difference. I have experimented with going off medication a few times - all with the same negative effect: the return of the darkness of depression. I guess it is possible that this is a placebo effect, but my experience suggests that at least in my case, SSRIs have been a godsend.
My wholly unscientific observations support the effectiveness of SSRIs.
I've seen them save marriages. I've seen them take angry, difficult people and make the much more bearable.
I would imagine that the effectiveness varies highly from individual to individual.
Everyone's aware of publication bias in the results of clinical trials and other forms of research. But this paper included some pretty interesting examples of the lengths people (ok, people funded by Big Pharma) go to to stack the research itself in favour of a "positive" outcome.
When I took SSRIs for depression, it sure seemed like they worked better than a placebo... but then again, a few years later I was able to go off of them and my depression was gone. So maybe it was me all along after all!
One question that this brings to my mind (without having read the report) is: If this meta-analysis can cast doubt on the effectiveness of SSRIs, what other drugs are we routinely prescribing and taking that may be equally ineffective?
Working in research this is something that people have suspected for some time...that SSRIs don't tend to help much more than placebo unless the depression was severe, and even then Psychiatrists nowdays are more likely to go back to the old standbys such as TCAs and MAOIs because they don't get referred any patients who haven't been on a bunch of them already.
I think at least in the US and UK that the real difference the study will make is to lessen the degree that GPs prescribe SSRIs as first line for depression; rather they may be more inclined to refer for psychotherapy first and then refer to a Psychiatrist if the patient does not have clinical improvement. Prozac and it's ilk are not going anywhere, but I think a more balanced view of their benefits will lead to more responsible prescribing, which will ultimately benefit patients and clinicians alike (though not without some controversy).
I'm sorry to say, but as far as I'm aware the argument that anti-depressants are little more than symptom suppressors and are overall ineffective has been argued long before. I am glad at least now it's become a major news story, people should take notice now.
This chart is one of the things that makes me skeptical of the study. It's clearly curve-fitting to an outlier that strongly affects the curve. The conclusion would be different without the outlier.
Felix - although that one outlier could have altered the results somewhat, this is not the first piece of research to show that anti-depressants are not more effective than placebos. It's quite angering to know that research was done two-three years earlier, but ultimately ignored.
http://eprints.ucl.ac.uk/archive/00001963/01/155.pdf
http://www.soteria.freeuk.com/JoCan.pdf
I think there's no doubt that too much significance has been put into the SSRIs, mostly by media, getting people's hopes up about the remarkable effect they're supposed to have, only to disappoint them when they're not "cured" instantly. I believe people in general don't understand the drugs, they don't know what they can expect. Not even physicians/GPs understand them and hand them out like candy to get rid of patients with problems beyond the physician's competence - rather than getting people good help.
On the other hand, I have been taking them myself since 2003 and I believe I can feel a difference. Not a huge difference, it hasn't changed my life completely or made everything better, but it helps me to the extent I need to even begin working with the things I know are causing these troubles in my life. Before the pills I couldn't even get out the door to even go see my therapist...
It makes me sad that some people's only goal in life seems to be to disprove the effect of medicine, whatever kind it may be. It's a slap in the face for all of us who actually are (feeling) helped by them and with the way my "issues" work, it makes me feel even more worthless, insignificant and waste of space being told I'm just being a gullible victim of a high-level scam. So, personally I think dr Kirsch should find a new life purpose and stop persecuting me. He's welcome to cure me from my problems any day though - if he decides to do something useful like figuring out how to!
Will, you stated that you're depression subsided after several years. That is wonderful. However, it's important to note that the elimination of depression may not have been due to the SSRIs. Clinical depression, by nature, has the tendency to "go away" in most people with no treatment whatsoever.
Also, I think regardless of the implications of the study and its strength, it highlights one important point: for most people (those with mild to moderate depression) , psychotherapy will not onlyb perform as well, if not better, than anti-depressants, but the effects are longer lasting. It's the ol' "teach a man to fish" theory. If taught how to restructure negative and dysfunctional thinking instead of being given a pill, an individual is more likely to cope and deal with depression if it comes about again in the future.
Psychlaw, that was exactly my point. It's impossible for me to say what the cause of the change might have been. My thoughts about the effectiveness of the medicine were cast into doubt because it seemed to "go away" on its own as you say.
I agree with your point about competent therapy. I would even go so far as to say that lifestyle change and improved outlook could help combat almost all depression. Jeremy has already posted about the effectiveness of group therapy on treating mild depression. Having an active social life (which group therapy can be part of), staying fit, getting good rest, and knowing how to maintain a positive outlook and handle stress - these are all things that we tend to sacrifice in the name of modern efficiency which probably contribute strongly to depression and other problems.
What everyone needs to keep in mind is that it is impossible to generalize about these things. Whether antidepressants are effective on any one individual is dependant on many different factors.
For some they will have little or no effect. For others they can be life changing or life saving.
And there are many other results in between.
For me personally, they have been life changing.
After 17 years of intensive analytical psychotherapy which although it gave me great insight and understanding of my condition, didn't really help much to alleviate my depression, I started taking antidepressants with an almost instant (within the first hour) relief from my depression.
After several years on them I am still going strong and am finally living some sort of "normal" life.
By the way, somthing I forgot to add in my previous post....
I do agree that antidepressants are too easily prescribed to people. The medical profession should be held more accountable here.
The fact that anyone can go to a GP and spin a line about feeling down and walk away with a prescription is wrong. GP's are not psychologists and are not equipped to properly assess a persons mental condition.
I personally know several people who are on antidepressants and in my opinion don't need them. In fact some of these people treat them as an adjunct to their recreational drug use.
The use of antidepressants needs to be more strictly controlled.
As a GP I agree that antidepressants are over-prescribed, but do believe that there is a case for at least trying them in some patients. I am saddened that despite the increasingly strong evince for counselling and psychotherapy to treat depression it's availability is so limited in the UK. Counselling on the NHS is frequently restricted to a 6 session limit with a long waiting list or not available at all.
I find the above comment that 'GP's are not psychologists and are not qualified to assess mental illness' very insulting. GP's are doctors with a minimum of 10 years training and that includes psychiatry. We use accepted depression scales to assess the severity of a patient's depression. We are also trained in trying to identify the 'high'risk' suicidal patients.
I use Zoloft. I don't know how I'd be without it. I have been diagnosed with clinical depression. I would like to see what those of you posting against SSRIs would say, if someone you loved started sleeping all day, cutting themselves, and hating themselves. You'd want to help them of course. Why is it such a big deal if that help should come in a pill?
The problem with the suicide risk isn't the SSRIs themselves, it's unprofessional people prescribing them. Like doctors instead of Psychatrists, who have to legally check in with the patient to assess how they feel on the medication.
I think people who are saying to get rid of SSRIs, clearly have never been touched by depression. Perhaps they should be greatful, instead of seeking to make life more difficult for those who have depression.