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Placebo Response Persists in Depression

There has been considerable debate ever since PLoS Medicine published a study in February suggesting that antidepressants are largely no better than a placebo (sugar pill) for the treatment of depression. The only condition where the researchers found a significant difference was in severe depression, and this was only because the placebo response dropped off — not because the antidepressant medication’s response increased.

I commented on the study at the time suggesting that while adding to our understanding of antidepressant medications, it was hardly without faults. Other meta-analyses published since then support antidepressants’ effectiveness in older adults (Nelson et. al., 2008) and present a more mixed picture for long-term use (Deshauer et. al., 2008). With over 1,000 clinical studies conducted in the past few decades on the effectiveness of antidepressant medications, it’s hard to throw all that research out the window as “biased” or without value in adding to our knowledge and understanding.

However, one can’t argue with the finding from the PLoS February research showing how some research data is skewed toward the positive (Ioannidis, 2008):

“Negative” trials were either left unpublished or were distorted to present “positive” results. The average benefit of these drugs based on the FDA data was of small magnitude, while the published literature suggested larger benefits.

Indeed, if there’s one take-away from this controversy, it’s that research data will apparently always be portrayed in the best possible light by whoever is funding it. Negative results will be de-emphasized or simply ignored (even though they may still be found in the data), and positive results will often be raised up and highlighted.

So one of the questions being asked by researchers nowadays is, how long-lasting is this placebo response? In other words, if a person continues receiving a placebo instead of an antidepressant, does their depression get worse over time?

Khan and colleagues (2008) have an answer. They conducted a meta-analysis on 8 placebo-controlled antidepressant trials that included a total of 3,063 patients. They found research where patients were continued on placebo for more than 12 weeks and examined whether they relapsed back into depression or not.

The researchers found that 79% of those receiving placebo continued to be depression-free 4 months after their initial treatment (4 out of 5 people), compared with 93% of those taking an antidepressant medication. This study demonstrates that while placebos appear to still continue to work for most people taking them, they are still significantly less effective than an antidepressant.

I think that antidepressants remain an effective treatment modality for depression, although as STAR*D demonstrated, patients and their doctors will usually have to try multiple medications before finding one that works for them.


Deshauer D, Moher D, Fergusson D, Moher E, Sampson M, Grimshaw J. (2008). Selective serotonin reuptake inhibitors for unipolar depression: a systematic review of classic long-term randomized controlled trials. CMAJ, 178(10):1293-301.

Ioannidis JP. (2008). Effectiveness of antidepressants: an evidence myth constructed from a thousand randomized trials? Philos Ethics Humanit Med., 3:14.

Khan A, Redding N, Brown WA. (2008). The persistence of the placebo response in antidepressant clinical trials. J Psychiatr Res., 42(10):791-6.

Nelson JC, Delucchi K, Schneider LS. (2008). Efficacy of second generation antidepressants in late-life depression: a meta-analysis of the evidence. Am J Geriatr Psychiatry, 16(7):558-67.

Placebo Response Persists in Depression

John M. Grohol, Psy.D.

Dr. John Grohol is the founder of Psych Central. He is a psychologist, author, researcher, and expert in mental health online, and has been writing about online behavior, mental health and psychology issues since 1995. Dr. Grohol has a Master's degree and doctorate in clinical psychology from Nova Southeastern University. Dr. Grohol sits on the editorial board of the journal Computers in Human Behavior and is a founding board member of the Society for Participatory Medicine. You can learn more about Dr. John Grohol here.

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APA Reference
Grohol, J. (2018). Placebo Response Persists in Depression. Psych Central. Retrieved on September 28, 2020, from
Scientifically Reviewed
Last updated: 8 Jul 2018 (Originally: 5 Aug 2008)
Last reviewed: By a member of our scientific advisory board on 8 Jul 2018
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