The use of antidepressants has soared in recent years. It is currently estimated that 1 in 10 people in the United States rely on antidepressants. Additionally, 1 in 4 women in their 40s and 50s are reported to take the drugs.
People with depression have reduced levels of serotonin, so by blocking this reuptake, the drugs enable patients to make the best of what they have. But the long-term effects of these drugs are subject to controversy.
This prompted a team of researchers - led by scientists from McMaster University in Ontario, Canada - to study the link between antidepressant use and mortality risk.
As the authors of the new study write, antidepressants "disrupt multiple adaptive processes regulated by evolutionarily ancient biochemicals, potentially increasing mortality." Such a biochemical is serotonin.
The first author of the study - which is published in the journal Psychotherapy and Psychosomatics - is Marta Maslej, from McMaster University, and the lead investigator is Paul Andrews, who is an associate professor at McMaster University.
Death risk raised by 33 percent
Prof. Andrews and his team conducted a meta-analysis of existing research from various medical databases, looking for a link between mortality and antidepressant use. The analysis comprised 16 studies, summing up approximately 375,000 participants.
The researchers pulled out data on cardiovascular diseases, cardiovascular risk, and the class of antidepressants. They looked at SSRIs, tricyclic antidepressants, and others.
They used a so-called mixed-effects model to conduct their meta-analysis, controlling for depression and other diseases.
Maslej spoke to Medical News Today about the methodology, reassuring us of its strength. "We made sure to only include studies that did a good enough job controlling for important variables (like depression and other illnesses)," she said, "and so we have attempted to statistically rule out other factors that could contribute to mortality."
The analysis found that in the general population, those taking antidepressants had a 33 percent higher risk of dying prematurely than people who were not taking the drugs. Additionally, antidepressant users were 14 percent more likely to have an adverse cardiovascular event, such as a stroke or a heart attack.
As Maslej explained to us, "We also ensured that our findings weren't related to confounding by indication. This means that people who have more severe depression could be more likely to take antidepressants, and if that's the case, we could not be sure whether the increase in risk of death is due to using antidepressants or having more severe depression."
"To address this issue, we re-ran our analysis on only the studies that assessed depression in participants before they began using antidepressants," Maslej explained. "When we re-ran this analysis, the risk of mortality remained high which suggests that confounding by indication wasn't an issue in our study."
No significant differences were noted between SSRIs and tricyclic antidepressants, which are widely perceived as the first generation of antidepressants.
The findings did not seem to suggest a negative effect of antidepressant medication on those with cardiometabolic conditions such as heart disease and diabetes.
This is consistent with the hypothesis that, due to their anticoagulant properties, antidepressants may be helpful for people with cardiovascular diseases but harmful to those who are healthy.
Disrupting serotonin may have side effects
Prof. Andrews and team warn that the findings should urge the research community to investigate deeper into how antidepressants work.
"We are very concerned by these results. They suggest that we shouldn't be taking antidepressant drugs without understanding precisely how they interact with the body."
Prof. Paul Andrews
Study co-author Benoit Mulsant, at the University of Toronto in Canada, also expresses his concern, saying, "I prescribe antidepressants even though I do not know if they are more harmful than helpful in the long-term."
"I am worried that in some patients they could be, and psychiatrists in 50 years will wonder why we did not do more to find out," he adds.
As this was an observational study, the researchers could not draw any conclusions about causality.
However, speaking to MNT about the possible mechanisms that could explain the findings, Maslej said, "Antidepressants disrupt the functioning of monoamines (important biochemicals such as serotonin and dopamine), and these monoamines have important functions not only in the brain, but all over the body."
"For example," she added, "serotonin affects growth, reproduction, digestion, immune function, and many other processes, and it is found in almost every major organ."
"Disrupting the functioning of serotonin can therefore have different adverse effects, which can contribute to a risk of death in many different ways."