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Letter to the Editor

Antidepressants Added Nothing to Mood Stabilizers Alone: Reply to Terao

S. Nassir Ghaemi, MD, MPHa,*

Published: June 22, 2021

J Clin Psychiatry 2021;82(4):21lr13919a

To cite: Ghaemi SN. Antidepressants added nothing to mood stabilizers alone: reply to Terao. J Clin Psychiatry. 2021;82(4):21lr13919a.
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© Copyright 2021 Physicians Postgraduate Press, Inc.

aDepartment of Psychiatry, Tufts University School of Medicine, and Department of Psychiatry, Harvard Medical School, Boston, Massachusetts
*Corresponding author: S. Nassir Ghaemi, MD, MPH, Department of Psychiatry, Tufts Medical Center, 800 Washington St, Boston, MA 02111 (



See letter by Terao, reply by Goldberg, and article by Ghaemi et al

To the Editor: Dr Terao’s letter commenting on our study1 makes an excellent observation. Indeed, we wanted to see if antidepressants were effective when combined with mood stabilizers, versus mood stabilizers alone. If we had not allowed patients to enter the study unless they already were taking mood stabilizers, as is commonly the case, then the study would have been biased against mood stabilizers. In that case, since all patients had to be depressed, they would have failed their mood stabilizers already, and the resulting study would have been a study of bipolar depression that was treatment-resistant to mood stabilizers. Most clinicians do not practice this way and instead either use antidepressants alone or give antidepressants plus mood stabilizers together. The study design was left flexible so as to be generalizable to this treatment setting. The “placebo” group reflects “mood stabilizer plus placebo,” and thus the study results answer the practical question whether antidepressants should be given with mood stabilizers in clinical practice, or whether mood stabilizers alone are just as effective. The answer was that mood stabilizers alone were just as effective, and adding antidepressants provided no further benefit. Whether that benefit from mood stabilizers is a pharmacologic effect, or a natural history effect, or another placebo-based effect is irrelevant. The randomized trial provides causal evidence that adding antidepressants to mood stabilizers, contrary to long-standing and difficult-to-change popular belief, does not provide further meaningful clinical benefit.

Published online: June 22, 2021.
Potential conflicts of interest: From October 2017–June 2021, Dr Ghaemi was an employee of Novartis Institutes for Biomedical Research (NIBR), Cambridge, MA. The study discussed in this letter was funded by the National Institute of Mental Health (NIMH) in 2007, with Dr Ghaemi as the principal investigator, and was conducted and completed in 2007–2016, before Dr Ghaemi’s employment at NIBR.
Funding/support: The study discussed in this letter was funded by NIMH grant 5R01MH078060-05.
Role of the sponsor: The NIMH had no role in the conduct or publication of the study.

Volume: 82

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