A new large-scale analysis found that the short-term cardiovascular and metabolic side effects of antidepressants vary widely by drug, but the ones most commonly prescribed in the United States are linked to relatively mild issues.
Tens of millions of U.S. adults take antidepressants for mental health conditions such as depression and anxiety. Like any medication, antidepressants have well-established side effects for some people. Researchers at institutions including King’s College London and the University of Oxford wanted to better understand just how much those side effects differed from drug to drug.
The new study, published Tuesday in The Lancet, is among the largest meta-analyses to compare some of the short-term side effects of antidepressants. The findings may help millions of doctors work with their patients to determine the right choice for them in a sea of options.
The researchers looked at 30 antidepressants, using data from more than 58,000 participants across 151 studies and 17 Food and Drug Administration reports. A wide variety of drugs were reviewed, including selective serotonin reuptake inhibitors (S.S.R.I.s) like sertraline (Zoloft) and fluoxetine (Prozac); serotonin-norepinephrine reuptake inhibitors (S.N.R.I.s) like duloxetine (Cymbalta) and venlafaxine (Effexor); and norepinephrine-dopamine reuptake inhibitors (N.D.R.I.s) like bupropion (Wellbutrin).
Dr. Andrew J. Gerber, a psychiatrist and the president and medical director of Silver Hill Hospital in New Canaan, Conn., who was not involved in the study, said it was the most “comprehensive and carefully done” review on the subject that he had ever seen.
The researchers focused on changes to weight, cholesterol and heart rate, as well as other cardiovascular and metabolic indicators, and found they varied markedly by antidepressant. The research generally looked at side effects over the short-term — the median length of treatment was only eight weeks — and noted that they may look different long-term.
Some drugs, such as fluoxetine, were associated with increases in systolic blood pressure, while others, like citalopram, also sold as Celexa, were not. Some, including venlafaxine, were linked to increases in heart rate, while those who took paroxetine, which can be sold as Paxil, saw no change in heart rate.
The effects on weight were also mixed. There was strong evidence for weight gain in participants taking less commonly prescribed antidepressants such as mirtazapine, sold as Remeron. But the antidepressants more commonly prescribed in the United States, including fluoxetine, bupropion and sertraline, were associated with weight loss in the short-term trials included in the analysis.
Sertraline was linked to an increase in a liver enzyme that can be an indication of abnormal liver function; that association was also found with the medication desvenlafaxine. And three S.N.R.I.s — duloxetine, venlafaxine and desvenlafaxine — were associated with increases in total cholesterol.
Outside experts said the results were useful, but not concerning, as the fluctuations were fairly small.
“Not everything that’s statistically significant is clinically meaningful,” said Dr. Jonathan Alpert, who chairs the psychiatry department at Montefiore Einstein.
Dr. Frank Moriarty, an associate professor at the Royal College of Surgeons in Ireland who was not involved with the study, similarly said that the analysis did not show major new physical side effects of antidepressants. He added there might be differences between individuals in their experience of using a specific medicine.
A key limitation of the analysis is that the trials it analyzed were relatively short. The median length of treatment analyzed was far shorter than the length of time that most people take antidepressants. And the research did not look at other side effects of some antidepressants, including common ones like sexual dysfunction, headache, upset stomach and, in rare cases, agitation and suicidal behavior.
Still, experts said that the study could provide useful information for conversations between medical providers and patients.
“It helps us know where to guide the flashlight,” Dr. Alpert said.
Experts also emphasized that the benefits of antidepressants make the side effects a worthy trade-off for many patients.
“The health risks of untreated depression are far larger than any of the health risks associated with the treatments themselves,” Dr. Gerber said.
The authors of this analysis plan to further study the effects over longer periods of time, as well as the effects of particular dosages.
Chloe W. Shakin is a social media editor for The Times, based in London.
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