How's this for a dilemma: you are running a clinical trial and two of your patients have died in circumstances that suggest suicide. And you know that, to improve your understanding of what's going on, not only do you have to repeat the trial but you have to increase the risk of the same thing happening again. Who'd be a scientist?
The study in question, led by a team at the University Health Network in Toronto, Canada, looked into a promising way of treating severe depression. Deep-brain stimulation involves a surgical procedure in which electrodes are inserted into specific regions of the brain. The patient carries a battery-powered signal generator that pumps electrical pulses into the brain.
A paper published in the 1 February edition of the American Journal of Psychiatry shows that this method is far more effective than any other treatment for severe, long-term depression. The researchers tracked 20 patients with implants over a six-year period. While two of the patients died by presumed suicide, 12 experienced a lifting of depression with no relapse.
The type of depression being addressed here is so severe that, without medical intervention, between 15 and 30 per cent of patients commit suicide. The 10 per cent suicide rate in the study can therefore be seen as an improvement. The lack of relapse is also a good sign: relapse is a permanent fixture in chemical-based treatments.
Overall, deep-brain stimulation seems to be a huge breakthrough in the medical struggle against depression. But there's a catch - this study had no placebo arm.
In a standard "double-blind" clinical trial, some patients are given a placebo treatment. The placebo is a sham that has no medical value, apart from raising hopes of feeling better. The researchers don't know which treatments are placebos or who is getting them; nor do the patients.
To be scientifically valid, trials must account for placebos. Studies show that a well-administered sham treatment can stimulate chemical responses in a patient's body and that these responses are powerful enough to relieve symptoms. In some cases, notably irritable bowel syndrome, a good placebo can be as effective as the market-leading drug.
Trial and tribulations
A number of researchers are now running placebo-controlled studies on deep-brain stimulation for the treatment of depression. In such cases, some of the patients will have no power delivered to their implanted electrodes.
Here lies the danger of the new trials. To be valid, they need to give some people a false hope of their depression lifting. These patients may have their depression relieved through a placebo response - but only for a short while; the effect does not last. That is why the placebo phase will go on for just a few months; after a certain time, all of the patients will have their electrodes switched on.
Even so, it could be a risky few months. Everyone taking part in the trial will give their full, informed consent; they will be told about the process and that they may be in the placebo arm and thus receive no treatment.
With something as delicate as human brain chemistry, however, the false hope poses a significant risk. Raising the possibility of relief without delivering it, regardless of how well-informed the patient may be, makes suicide more likely.
Is it worth it? Discuss.