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Nearly half a century ago, in 1965, the Rolling Stones wrote a song called Mother’s Little Helper. The words went:
Kids are different today, I hear ev’ry mother say
Mother needs something today to calm her down
And though she’s not really ill, there’s a little yellow pill
She goes running for the shelter of a mother’s little helper
And it helps her on her way, gets her through her busy day…
They continued:
And if you take more of those
You will get an overdose
No more running for the shelter of a mother’s little helper
They just helped you on your way
Through your busy dying day…
The pill was valium (diazepam) and the yellow pill was 5 milligrams – as it still is. White is 2 milligrams and blue is 10.
The song was not great poetry, perhaps, but for pop music it was prescient pharmacovigilance, the epidemiological study of the adverse effects of drugs: though strictly speaking overdoses of diazepam are not dangerous. Many thousands of people have taken overdoses of diazepam in attempts to kill themselves with it, but few have succeeded unless they took something else with it.
However, it has long been known that diazepam and other similar drugs cause falls in the elderly, and such falls are often the precursor of death. It has also been suspected that, by some unspecified mechanism, diazepam (and sleeping draughts of all kinds) promote death.
A paper in a recent edition of the British Medical Journal compares the death rates of primary care patients who were prescribed diazepam-like medicines and hypnotics with those who never were prescribed them more than once (they excluded patients who had been prescribed them only once because it was possible that they had never taken them, which was unlikely if they were prescribed them twice). The authors compared the records of 37,000 of the former with 63,000 of the latter. They attempted to match them for such variables as age, social class, sex, and medical and psychiatric history. They followed the patients for an average of 7.6 years.
Overall the death rate from all causes was twice as high in those who had been prescribed the drugs, and because the authors had matched the patients for psychiatric histories the difference was not attributable to the fact that those who took them suffered from the kind of psychiatric disorders associated with a reduced life expectancy (as many of them do). They were, however, unable fully to control for the severity of psychiatric disorder, which might have affected the result.
The effect size increased with age: that is to say, the older the patient the bigger effect the drugs had on the death rate. Another reason for thinking the effect was real and not just an artefact was that there was a dose-response effect: the more of the drugs the patients took, the higher the rate of excess death.
What the paper does not do (and other papers like it that found similar results) is suggest a mechanism by which all causes of death are increased by taking these drugs. There being many variables for which a study like this cannot possibly control, it is possible that one or several of them are responsible for the result: in other words, like is not being compared with like, which would invalidate the result. The strange thing is that these drugs do not kill directly, as, say, cyanide does.
Nevertheless, it is curious that a pop song should have spotted so long ago what doctors at the time almost certainly would have denied, namely that…
They just helped you on your way
Through your busy dying day…
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