What is the truth about anti-depression medication?
I was always very, very reluctant to take anti depression medication, although I didn’t have a fully articulated reason why.
Whilst I think I have benefited from anti-depressants, I’m still not convinced about how good they are for me overall, or on any kind of long-term basis. I’m therefore interested to see that there is a real debate currently taking place as to whether anti-depressants really are effective.
Does Anti-Depression Medication Work?
The case against is set out expertly and eloquently by Dr Marcia Angell, Senior Lecturer in Social Medicine at Harvard Medical School and former Editor in Chief of The New England Journal of Medicine, in a two part article in the New York Review of Books ( Part 1, Part 2).
Dr Angel’s piece in part focuses on the extremely worrying conclusion (for those being treated for depression) at the heart of Irving Kirsch’s book The Emperor’s New Drugs: Exploding the Antidepressant Myth. Kirsch conducted a meta-analysis of papers submitted by pharmaceutical companies to the US Federal Drug Administration (“FDA”) in relation to approval of 6 of the most prescribed anti-depressants. The analysis covered the period between 1987 and 1999 and placebo controlled trials on Effexor, Celexa, Zoloft, Paxil, Prozac and Serzone.
What was significant about the material Kirsch studied (apart from the fact that he had to use the Freedom of Information Act (“FOI”) to obtain it), was that it included studies with both positive and negative outcomes.
Apparently, and this in itself is an eye-opener, the pharmaceutical companies usually need only to show at least two trials which demonstrate that a product is more effective than a placebo to obtain approval to market the drug.
They can sponsor as many trials as they wish, the results of which all must be submitted to the FDA. But the fact that there may be studies with negative outcomes, and those negative outcomes themselves, will never normally be publicised. In fairness, it should be noted that negative trial outcomes may be for reasons connected with the trial process itself, rather than the efficacy of the drug.
Clearly, it is in the interests of the pharmaceutical companies to publish only the positive outcomes, whilst the FDA considers the material submitted to them to be confidential (hence the FOI application by Kirsch). The effect of this practice is what is called ‘publication bias’.
As Dr Angel reports:
“Altogether, there were forty-two trials of the six drugs. Most of them were negative. Overall, placebos were 82 percent as effective as the drugs, as measured by the Hamilton Depression Scale (HAM-D), a widely used score of symptoms of depression. The average difference between drug and placebo was only 1.8 points on the HAM-D, a difference that, while statistically significant, was clinically meaningless. The results were much the same for all six drugs: they were all equally unimpressive. Yet because the positive studies were extensively publicized, while the negative ones were hidden, the public and the medical profession came to believe that these drugs were highly effective antidepressants.”
Kirsch’s analysis led him to look carefully at the placebo effect. He examined studies where the placebo itself had side effects, as well as the drug being tested.
His conclusion was that the small difference in outcomes between placebo and drug may have been explained by the fact that, by noticing that they had experienced side effects, patients may have been able to tell whether they had received the placebo or the medication. In those cases, the reported improvement may have been an ‘enhanced placebo’ effect rather than a drug effect, so that overall, the FDA registered studies may not in fact demonstrate any effectiveness of drug over placebo.
Is this just about knocking Big Pharma?
Well, for a start, Kirsch’s is not a lone voice in all this.
A similar meta-analysis of FDA registered studies, by H Edmund Piggott and others, which was published in 2010 in Psychotherapy and Psychosomatics, reaches a similar conclusion:
“Meta-analyses of FDA trials suggest that antidepressants are only marginally efficacious compared to placebos and document profound publication bias that inflates their apparent efficacy.“
On the other hand, it seems like it is important to be clear about the type of depression that is under consideration. Another analysis of placebo-controlled trials of antidepressants approved by the FDA, published recently in the Journal of the American Medical Association in by Jay C. Fournier MA, (Department of Psychology, University of Pennsylvani) and others, found that:
“The magnitude of benefit of antidepressant medication compared with placebo increases with severity of depression symptoms and may be minimal or nonexistent, on average, in patients with mild or moderate symptoms. For patients with very severe depression, the benefit of medications over placebo is substantial.“
Fournier and others contend that due to the availability of additional material, their study method enabled a deeper level of scrutiny at patient level than Kirsch’s, so a more ‘fine-grained’ analysis was possible. Nevertheless, Fournier states that their findings were essentially consistent with Kirsch’s that anti-depression medication / placebo differences “increase as initial severity increases“.
A psychiatrist’s view
One of the other books reviewed by Dr Angell in her New York Review of Books piece was Unhinged: The Trouble with Psychiatry—A Doctor’s Revelations About a Profession in Crisis by Daniel Carlat.
Carlat is a psychiatrist himself and a proponent of anti-depressant use. Based on his own observations he is satisfied that anti-depressants work, in the sense that he sees patients improve all the time. Even so, he is much less certain why they work, or even if they work as a result of the pharmacological impact on the patient’s brain or some kind of placebo effect. Dr Angell quotes Carlat’s wonderfully and worryingly candid observation:
“Guided purely by symptoms, we try different drugs, with no real conception of what we are trying to fix, or how the drugs are working.“
This, it seems, is consistent with all the literature (see this for example, from the UK’s Royal College of Psychiatrists). Apparently, nobody really knows how or why anti-depressants work. Kirsch’s contribution takes matters further and raises the question of whether anti-depression medication works at all.
What is more, the idea that anti-depression medication corrects some kind of chemical imbalance in the brain (which was what I had always understood) seems itself to be discredited – Carlat calls it a “myth”, Kirsch, “simply wrong”.
So, what do we do about anti-depressants?
Frankly, I don’t know. But trying to work through it based upon my own experience and instincts, I come up with the following:
- I think anti-depressant medication helped me when I was seriously depressed – so that anecdotal evidence at least seems to accord with the latest research;
- Even so, I should be wary about taking any medication when there is no real scientific understanding of how it works;
- I should not take any medication (especially one which is not properly understood), for any condition where the medication is not shown to have any efficacy above placebo effect;
- Therefore, unless I am severely depressed, perhaps I should try to deal with my depression by means other than anti-depression medication, e.g. talking therapy, diet, exercise etc;
- However, I won’t stop taking medication without medical input and a gradual reduction in dosage.
That’s the best I can come up with for now. Does anybody out there have any other thoughts? Am I misinterpreting this information?
Dr Angell reviews:
The Emperor’s New Drugs: Exploding the Antidepressant Myth
by Irving Kirsch
Song of the Post
This is a hard one, especially as there is not much levity in this subject. I considered the Temptations “Ball of Confusion”, but I think the appropriate offering for this one is a message to all those out there in mental health land, including Big Pharma and their friends. I quote from it in the title of this piece – from John Lennon’s Imagine album, I commend to you his magnificently angry – “Gimme Some Truth”.