No new data
An umbrella review is supposed to be of the highest quality and should entail “taking out the studies and analysing them yourself,” but here, “all they have done is put a synthesis forward of other people’s reviews, so essentially there’s no new data there,” said Dr. Jauhar.
And sometimes the review’s findings differ from the original research. “When you have people who haven’t conducted original research themselves quoting someone else’s work and ignoring what those people say, we’re all in trouble,” said Dr. Jauhar.
In an additional commentary also published in Molecular Psychiatry, Jacob Pade Ramsøe Jacobsen, Evecxia Therapeutics, Durham, N.C., also criticized the review by Dr. Moncrieff and colleagues.
Its authors appear unfamiliar with serotonin biology and pharmacology, Dr. Jacobsen wrote.
“The review contains factual errors, makes conclusions serotonin neurobiology may not support, and quotes the cited literature in a selective manner,” he added.
“Most troubling, they misinterpret some data reviewed and intimate that serotonin reuptake inhibitor antidepressants, e.g., SSRIs, may decrease, rather than increase, serotonin function.”
If accepted by general practitioners and the public, the review’s conclusions “could lead to reduced use of antidepressants among patients in need and increased morbidity related to depression.”
Dr. Moncrieff pushes back
Responding to the torrent of criticism of her study, Dr. Moncrieff told this news organization via email that they stand by the review, adding that Dr. Jauhar and others “don’t want to let the cat out of the bag” that there’s no good evidence to support the hypothesis that low serotonin causes depression because it challenges antidepressant use.
“The idea that antidepressants work by correcting an underlying chemical imbalance or serotonin abnormality has led research up a blind alley and meant scientists have not taken the harmful effects of these drugs seriously enough.”
These critics, she added, “want business as usual – which means people will continue to be misinformed and exposed to harmful effects of drugs that have minimal and uncertain benefits.”
In a letter to the editor of Molecular Psychiatry, Dr. Moncrieff and her fellow authors maintain that they used approved and well-accepted methods for the umbrella review, including preregistering the protocol and using recommended search methods and quality assessments, and that they did not miss certain studies, as has been claimed.
In her blog, Dr. Moncrieff wrote that the “marginal differences between antidepressants and placebo that are apparent in clinical trials are likely to be produced by alternative, more plausible mechanisms like the emotional blunting effects of the drugs or by amplified placebo effects, rather than by targeting underlying biological mechanisms (since these have not been demonstrated).”
It also highlights “how we don’t know what antidepressants do to the brain exactly, which is a cause for concern,” she adds.
Dr. Jauhar has received honoraria for nonpromotional educational talks on antipsychotics from Janssen, Sunovion, and Lundbeck and on causes of schizophrenia for Boehringer-Ingelheim. He has also received honoraria for consulting on antipsychotics for LB Pharmaceuticals. He sits on Council for the British Association for Psychopharmacology and was a recent panel member for the Wellcome Trust.
A version of this article originally appeared on Medscape.com.