When it comes to antidepressant prescribing, less may be more, new research suggests.
A new review suggests antidepressants are overprescribed and that the efficacy of these agents is questionable, leading researchers to recommend that, when physicians prescribe these medications, it should be for shorter periods.
“Antidepressants have never been shown to have a clinically significant difference from placebo in the treatment of depression,” study co\investigator Mark Horowitz, GDPsych, PhD, division of psychiatry, University College London, said in an interview.
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He added antidepressants “exert profound adverse effects on the body and brain” and can be difficult to stop because of physical dependence that occurs when the brain adapts to them.
“The best way to take people off these drugs is to do so gradually enough that the unpleasant effects are minimized and in a way that means the reductions in dose get smaller and smaller as the total dose gets lower,” Dr. Horowitz said.
However, at least one expert urged caution in interpreting the review’s findings.
“The reality is that millions of people do benefit from these medications, and this review minimizes those benefits,” Philip Muskin, MD, chief of consultation-liaison for psychiatry and professor of psychiatry, Columbia University Medical Center and New York–Presbyterian Hospital, said when approached for comment.
The findings were published online Dec. 20, 2021, in the Drug and Therapeutics Bulletin.
Personal experience
Prescribing of newer-generation antidepressants, such as SSRIs and serotonin and norepinephrine reuptake inhibitors (SNRIs), is increasing, with an estimated one in six adults in the United Kingdom receiving at least one prescription in 2019-2020, the investigators noted.
Dr. Horowitz noted a personal motivation for conducting the review. “As well as being an academic psychiatrist, I’m also a patient who has been prescribed antidepressants since age 21, when my mood was poor, due to life circumstances.”
The antidepressant “didn’t have particularly helpful effects,” but Dr. Horowitz continued taking it for 18 years. “I was told it was helpful and internalized that message. I came to understand that much of the information around antidepressants came from the drug companies that manufactured them or from academics paid by these companies.”
Dr. Horowitz is currently discontinuing his medication – a tapering process now in its third year. He said he has come to realize, in retrospect, that symptoms not initially attributed to the drug, such as fatigue, impaired concentration, and impaired memory, have improved since reducing the medication.
“That experience sensitized me to look for these symptoms in my patients and I see them; but most of my patients were told by their doctors that the cause of those problems was the depression or anxiety itself and not the drug,” he said.
Dr. Horowitz collaborated with Michael Wilcock, DTB, Pharmacy, Royal Cornwall Hospitals, NHS Trust, Truro, England, in conducting the review “to provide an independent assessment of benefits and harms of antidepressants.”
“Much of the evidence of the efficacy of antidepressants comes from randomized placebo-controlled trials,” Dr. Horowitz said. Several meta-analyses of these studies showed a difference of about two points between the agent and the placebo on the Hamilton Depression Rating Scale (HAM-D).
“Although this might be statistically significant, it does not meet the threshold for a clinical significance – those aren’t the same thing,” Dr. Horowitz said. Some analyses suggest that a “minimally clinically important difference” on the HAM-D would range from 3 to 6 points.
The findings in adolescents and children are “even less convincing,” the investigators noted, citing a Cochrane review.
“This is especially concerning because the number of children and adolescents being treated with antidepressants is rapidly increasing,” Dr. Horowitz said.
Additionally, the short duration of most trials, typically 6-12 weeks, is “largely uninformative for the clinical treatment of depression.”