When drug trials are conducted, the gold standard (and requirement for FDA approval) is a double-blind placebo-controlled study. In this kind of drug study participants are randomly assigned to receive either the medication or an inert (does nothing) pill known as a placebo. Neither the doctor not the patient knows whether they are getting the placebo or the real drug.
The study then compares what happens to those who received the real drug versus those who received the placebo and determines the efficacy of the real drug.
The Placebo Effect
This is critical because of something known as the “placebo effect.” The placebo effect is this odd scenario where people get better just because you give them a pill, even if the pill does nothing. Doctors and scientists don’t understand the placebo effect but not only will people get better on a placebo, but they will even experience side effects – something that isn’t possible given that the placebo is inert. But the brain is a powerful thing and something we don’t fully understand.
And one of the problems with antidepressants (and many medications) is that sometimes they aren’t better than the placebo. Additionally, sometimes when they are better than the placebo, it’s only by a small margin. Drug companies have to prove that their drug is statistically significantly better than a placebo in order to get FDA approval but even this statistically significant amount can be very small.
However, this isn’t a piece about how effective are when antidepressants are compared to placebos. This is a piece about how effective antidepressants are compared to no treatment.
Depression Treatment vs. No Treatment
Now, each disorder would have to be studied individually, but basically the question is, if you put treatment vs. placebo vs. no treatment, what would happen? ^
I can tell you what would happen – the people who received no treatment would do worse than those who received a placebo.
To the best of my knowledge there is no exact study like this, likely because it wouldn’t make it past an ethics board. If you determine a person is ill and needs treatment it is unethical to offer them none.
There is, however, a comparison of treatment vs. no treatment that I’m aware of. Here, they study people who have received treatment vs. those who have not. (They break down those who have not into three additional groups: those that don’t think they need treatment, those who think they need treatment but don’t get it, and those that don’t need treatment.) Note that “treatment” isn’t specified so it could be of any kind.
What they find for depression is that those who receive treatment go from around 30 to 24 on a depression scale in one year and those that need treatment but don’t get it go from about a 27 to 23 in one year (in both cases a higher number indicates greater depression).
So, treatment moves them 6 points and no treatment moves them 4 points. Approximately.*
No Big Deal?
Well, it depends if you’re the one depressed.
Firstly, it’s important to note that those in treatment were more depressed than those who weren’t. This should be noted as those people would likely have worse outcomes in one year. (The study wasn’t designed to take this into account but does note that symptom severity at outset is the biggest predictor of poor outcomes.)
Secondly, it’s worth noting that 2 points on a 35-point scale can lead to a significantly greater quality-of-life for the person in general. Many people with treatment-resistant depression I know would kill for that kind of improvement.
Thirdly, this improvement marker isn’t the only relevant one; it’s just the only one I have to go on.
Numbers on the kind of improvement seen in treatment versus no treatment vary, but everyone agrees that no treatment is worse. (The above estimate is rather conservative.)
What, No Placebo?
Unfortunately, no. There is no placebo in this study. Sorry.
But as we do know that people on a placebo do almost as well, and sometimes better, than those on the drug, we can guess (yes, guess; again, sorry) that people on a placebo would land somewhere in between the two above outcomes.
Question: How Do We Improve Outcomes without Giving a Placebo?
So the question is, if people on a placebo do better than no treatment (but not as well as those treated) then is there a way to preserve that gain? Doctors can’t prescribe placebos, it’s unethical.
Or is the placebo effect when being given an antidepressant such a bad thing? If, really, you respond to a real medication because of the placebo effect (and you wouldn’t know the difference, no one would) is that really all that bad? Does that not have a value?
People decry the placebo effect saying it proves that antidepressants are worthless. But I say how would all those people benefiting from them, even from the placebo effect, get better without them?
^ See the comment Placebo Effect in Depression as well.
* In case you were wondering, people who were depressed but didn’t think they had a problem were less depressed than those that perceived a need for treatment; however, they only moved down the scale from about 18 to 16 in one year.
From what I understand, if a person does require treatment, the placebo effect will only work temporarily anyway.
Placebos … ain’t they called homeopathic medicines? :¬)
Oh sure, open up _that_ can of worms…
– Natasha Tracy
Good one!!! Hahahaha!
Some time ago I found on the web a report of a study that suggested placebo’s tend to work best with people who have been diagnosed as being “mildly” affected by BP Disorder, not so much those who are more seriously ill.
It is also worth noting that drug trials probably do not show the full potential of a drug, for good or ill, because the trials are conducted over the shortest time possible. As soon as a statistically significant result is obtained, the companies stop the trials and apply for authorisation to sell them, because the development on the drugs are so very expensive, they want to begin generating an income a.s.a.p. to get a return on that investment. Longer trials would be likely to offer more data and might demonstrate greater effectiveness. (Prozac is one example. Trials show it to be better than a placebo but not much; however, practitioners and patients report a greater level of effectiveness than the trials predicted.)
Also, it should be remembered that the trials require volunteers to take the drugs and for the subjects of the trials to cooperate from beginning to end of the process. The trials tend to have patients drop out of the studies and, with mental health treatments, those who drop out tend to be those who are most unwell. Indeed, the original samples for the trials will probably be biased towards patients who are least unwell anyway because the more severely affected are less likely to volunteer in the first place. So, the results of trials will probably tend to under estimate the effectiveness of the drugs in treating those who are more severely affected by the illness, where their potency would have been most likely to be observed.
(Note, I have no connection with any drug companies.)
Hi Graham,
You bring up many fine points and I don’t disagree. I’m not trying to suggest that antidepressants don’t work, I believe that they do and I believe that they data supports this, I just wanted to comment on placebos and how to produce a response if, in fact, placebos can’t be prescribed (which they can’t). It’s just an interesting phenomenon. No one wants to take a pill if they don’t have to (obviously) but if it helps them, even through the placebo effect, then they might have to.
And you’re right, the evidence even in the study I mentioned suggests that those who respond to placebos are less sick.
I have no connection to drug companies either :)
– Natasha Tracy