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The truth behind the Prozac headlines

The research about antidepressants not working was massively picked up by the media earlier this year. But mental health treatment is more complex than just prescribing a pill …

Raj Persaud
BSc MSc MB BS MPhil FRCPsych
Consultant Psychiatrist  The Maudsley Hospital London
Emeritus Gresham Professor for Public Understanding of Psychiatry

In February newspaper headlines screamed and got agitated about mood disorders; "Prozac, used by 40 million people, does not work say scientists" was one example from a broadsheet newspaper.
The story that was picked up so massively by the media was based on a paper in an otherwise rather obscure academic journal, PLoS Medicine, which published an analysis that had for the first time combined the results of 47 trials on some antidepressant drugs, including Prozac, and found only minimal benefits over placebo, except for the most depressed patients.
The significance of the analysis was not that it was comprehensive (in fact it didn't look at any of the research done over the most recent years); instead this was the data set that US regulators were supposed to have been paying attention to when they decided to license newer drugs for the treatment of depression back in the 1990s.

However, it appeared that some of this vital data might have been less accessible than others, and furthermore it may have been that pharmaceutical companies have actively suppressed the less flattering studies on the benefits of antidepressants. Therefore there was the suggestion of a distortion in the scientific data on which doctors and regulators are supposed to make treatment decisions, introduced by an industry that has a vested interest in getting as much medication as possible prescribed.

Unfortunately the media missed several vital points if the truth of the treatment of mood disorders is to be properly communicated to the public, patients, therapists and doctors. No one who knows anything about psychiatric illness could ever have suggested that prescribing a pill was ever going to be the definitive treatment of anything in the mental health field. Psychological problems are complex and usually require a sophisticated approach that combines treatment modalities and tailors them to the specific needs of a particular patient, so no one should be surprised at the idea that studies that merely look at whether antidepressants are superior to placebos find that the medication doesn't do that well. That's because the treatment of mood problems is always about much more than just taking a pill. It should involve a range of interventions including psychotherapeutic, behavioural, family, social and stress management.

Given these facts, what we really need are studies that compare patients having psychological therapies combined with medication against patients having only psychological approaches and patients having only medication.

Martin Keller and colleagues at the Department of Psychiatry and Human Behavior, Brown University in the USA, published such a study in the New England Journal of Medicine. Among the 519 subjects who completed the study, the rates of successful response to treatment were 55% in the nefazodone (antidepressant) group and 52% in the psychotherapy group, compared with 85% in the combined treatment group - which was a highly statistically significant finding.

We need more research like this on the effect of combining treatments compared with just having one treatment element alone, but this kind of investigation is much more difficult to undertake. As a consequence we don't have nearly as many studies of this kind as we need to come to a definitive conclusion about what really works with mood disorders.

The second point is that medication in these studies is often prescribed at a standard dose in order to facilitate comparison with other medications also being trialled at the same time. These doses are rarely the effective dose that most clinicians end up using.
The prescribing of a tablet requires expert supervision. The way a medication is prescribed, what dose, how side-effects are monitored and dealt with, how the particular medication is selected and how it might be changed depending on patient response - these are all delicately handled issues that dramatically alter the impact of the pill.
This issue of physician expertise is not adequately examined in most randomised controlled trials where one standard dose or a limited range of doses tend to be deployed. For this reason antidepressants are not likely to fare well in the laboratory and benefit from an interaction effect. The right drug in the right hands for the right patient is likely to have a much more massive effect than the wrong drug, prescribed by someone who doesn't know what they are doing, to a patient who may not suit it.