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Placebo as Good as Paxil, Tofranil for Most Depression

Placebo as Good as Paxil, Tofranil for Most DepressionFrom the “What the…?!” file, new research we reported on today found that two antidepressants — Paxil (still commonly prescribed) and Tofranil (not commonly prescribed) — seem to only really work for the most severe kind of depression. When prescribed for mild to moderate — the vast majority of depression diagnosed today — these two antidepressants did not any better than a sugar pill placebo.

The researchers for this new study pooled together the results of six previously published research studies that compared the effects of antidepressants to placebo for 718 adults with varying levels of depression — from very severe depression, to moderate depression, to mild depression.

Three of the studies looked at paroxetine (Paxil) and the others looked at imipramine (Tofranil). Paxil is an antidepressant known as an SSRI (selective serotonin reuptake inhibitor), while Tofranil is an older medication, known as a tricyclic antidepressant.

The researchers were looking for clinically significant differences in the rating scales used to measure depression, typically of 3 or more points. They found that for mild, moderate and even severe depression, both the sugar pill and the antidepressant were about equally effective. That is, they both helped relieve a person’s depression (suggesting that it’s the act of treating someone — not the drug itself — that is actually helping the person feel better). Only for very severe depression was there a clinically significant difference in rating scale scores for antidepressants.

One of the limitations of the study is obvious — it looked at only two specific antidepressant medications, one of which is not commonly prescribed in the U.S. However, since Paxil is in a class of similar SSRI antidepressants, it would not be unreasonable to suggest that other SSRI antidepressants are likely to suffer from the same issues.

The upshot is simple — doctors and psychiatrists should think twice before prescribing one of these two antidepressants for the vast majority of patients who present with mild to severe depression. This doesn’t mean no treatment is available for such patients — other types of antidepressants are available that weren’t included in this study, and psychotherapy has been shown quite effective in the treatment of mild to moderate depression alone, without any medication.

Will these results hold up in future studies? Time will tell. This is the first study to come to this surprising conclusion and it’s likely more research — and more robust research — is needed before we have the final word on the matter.

Read the full story: Antidepressants Work Better than Placebo for Severe Depression

Placebo as Good as Paxil, Tofranil for Most 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 as Good as Paxil, Tofranil for Most Depression. Psych Central. Retrieved on October 1, 2020, from
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Last updated: 8 Jul 2018 (Originally: 6 Jan 2010)
Last reviewed: By a member of our scientific advisory board on 8 Jul 2018
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