This might be a hard pill to swallow for both those in treatment for depression and those giving treatment to clients: both psychotherapy and antidepressant medications are beginning to be considered to have rather limited contributions to the effectiveness of treating depression. Some researchers and clinicians alike are considering that for some, the placebo effect might be the most powerful treatment of all.

A series of both research and opinion-based articles are suggesting that we may have been focussing on the wrong thing all along. Research into the placebo effect and spontaneous recovery from depression, and indeed other mental health problems, may be the way forward for both pharmacotherapy and psychotherapy.

Hot in the news at the moment is a position emission tomography (PET) study suggesting that some people are indeed more responsive to the intention to treat their depression, as opposed to the treatment itself.

The results indicate that those who can muster their brain’s own chemical forces against depression when receiving a placebo, also appear to have a head start in overcoming its symptoms with help from an approved antidepressant.

But those whose brain chemistry didn’t react as much to the placebo pill given in the study, struggle even after getting an official antidepressant. Although unexplored this could involve internal positive or negative beliefs about treatment, either promoting or inhibiting the placebo effect respectively.

The findings support scientific perspectives and opinions discussed in a series of placebo effect articles published in World Psychiatry, including highly acclaimed scientists such as the President of the European College of Neuropsychopharmacology, Dr. Stuart Montgomery, who authored the article “Antidepressants or antidepressants plus placebo?”

While public opinion is certainly suspicious about the ability of antidepressants to treat depression, as well as the pharmaceutical industry’s intentions in finding rewarding outcomes in efficacy studies, researchers have also grown increasingly skeptical regarding treatment efficacy studies over the years.

There is a realization that the we need even greater accuracy in distinguishing treatment effects from placebo in order to determine the true efficacy of the treatment. Our current general standard of randomized, placebo-controlled trials just doesn’t quite cut it.

In one article entitled, “What if a placebo effect explained all the activity of depression treatments?” the key problem is posed:

“Due to the discrepancy between the relatively high rate of spontaneous remission and the low additional value of specific (pharmacological and psychological ) treatments, several important issues arise. One question is whether these treatments do in fact have any effects.”

This may initially sound absurd to some, but there are sound arguments behind this line of thinking, only some of which are mentioned in this article.

Some of the most recent meta-analyses reveal relatively small effect sizes of 0.30 for antidepressants and 0.25 for psychotherapies, with only the highest quality of studies being able to show these small effects. This roughly equates to only 15% of the variance in treatment outcome being a result of the treatment itself, which is in the same range as many accepted treatments in general medicine.

Dr. Montgomery suggests that even though these studies aim to remove all biases, many may still remain. He used an example supported by a recent article exploring differences between active placebos (those that produce side-effects) and antidepressants for depression. A placebo pill that does not produce noticeable side-effects may make the test subject aware that they are indeed receiving placebo and reduce their expectations of success, thus biasing results in favor of the treatment being assessed.

With further advancements in the tweaking of methodologies to remove remaining biases, perhaps there is almost no effect from the actual treatment itself.

Indeed, there has been a constant increase in placebo response to fake antidepressants in efficacy trials over the last decade, especially in the US. This is thought to be due to many combinatorial factors, such as more effective and intensified marketing of antidepressants and the increased contact between study participants and clinical staff in more modern and rigorous studies where participants are closely monitored. This enhanced placebo effect may in fact be making it hard to differentiate placebo from drug responses, and make antidepressants appear to have a small effect size when they may be greater.

While research has been fervently focusing on the neurological and psychological changes in response to various therapies, perhaps research into spontaneous remission and the placebo effect should at least be of equal importance.

As put by Dr. Marta Pecina, lead author of the PET study and research assistant professor in the U-M Department of Psychiatry:

“We can envision that by enhancing placebo effects, we might be able to develop faster-acting or better antidepressants.”

The same can be said for psychotherapy treatments, were aspects of interventions that facilitate the placebo effect, on top of any true treatment effects, may be more effective than current treatments.

References

Cuijpers P, & Cristea IA (2015). What if a placebo effect explained all the activity of depression treatments? World psychiatry : official journal of the World Psychiatric Association (WPA), 14 (3), 310-1 PMID: 26407786

Cuijpers P, Turner EH, Mohr DC, Hofmann SG, Andersson G, Berking M, & Coyne J (2014). Comparison of psychotherapies for adult depression to pill placebo control groups: a meta-analysis. Psychological medicine, 44 (4), 685-95 PMID: 23552610

Khan A, & Brown WA (2015). Antidepressants versus placebo in major depression: an overview. World psychiatry : official journal of the World Psychiatric Association (WPA), 14 (3), 294-300 PMID: 26407778

Montgomery SA (2015). Antidepressant or antidepressant plus placebo effect? World psychiatry : official journal of the World Psychiatric Association (WPA), 14 (3), 303-4 PMID: 26407781

Peciña, M., Bohnert, A., Sikora, M., Avery, E., Langenecker, S., Mickey, B., & Zubieta, J. (2015). Association Between Placebo-Activated Neural Systems and Antidepressant Responses JAMA Psychiatry DOI: 10.1001/jamapsychiatry.2015.1335

Walsh BT, Seidman SN, Sysko R, & Gould M (2002). Placebo response in studies of major depression: variable, substantial, and growing. JAMA, 287 (14), 1840-7 PMID: 11939870

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