Adding to the literature
Andrews believes that this study adds to a body of literature that scientifically tests whether antidepressant medications are safe and effective.
“First, as a background point, clinicians have long known that most episodes of depression eventually resolve on their own, even without treatment,” Andrews says. “For instance, it is estimated that 20% to 35% of people will remit in a period of four to 20 weeks—this is usually the length of a single clinical trial—and in one year, it’s 53%.”
Second, research has consistently found that antidepressant medications are only modestly more effective than placebo in reducing depressive symptoms, Andrews says. Roughly 80% of the symptom reducing response to antidepressants can be attributed to placebo.
“Third, a related issue is what happens after you have gotten better on a treatment and decide to stop the treatment,” he says. “Research indicates that if you get better on an antidepressant, you have a much higher risk of relapse than if you got better on either placebo or on cognitive behavioral therapy.”
“Our study suggests that the risk of death associated with using antidepressants is greater than the risk of death associated with unmedicated depression, which contrasts previously held views that antidepressants lessen depression-related mortality by alleviating depressive symptoms” Andrews says.
Not all bad
However, the news about antidepressants is not all bad.
“Because commonly-used antidepressants—like SSRIs—have anti-clotting properties, they may normalize clotting processes in individuals where these processes are abnormally activated, like people with heart disease, diabetes, kidney disease and COPD," Andrews says. "In other words, because they reduce blood clotting, antidepressants may be beneficial for treating cardiovascular diseases, thereby offsetting their effects on mortality. This mechanism is speculative, and more empirical research is required to understand why antidepressants do not seem to affect mortality in these samples.”
A final point is that the reseachers found no evidence that newer or second-generation antidepressants (i.e., SSRI/SNRIs) are safer than older or first-generation antidepressants (i.e., TCAs). "The finding that SSRI/SNRIs and TCAs have similar effects on mortality is not consistent with widely-held views that TCAs are more harmful [perhaps because of their cardiotoxic side effects]," says Andrews. "However, SSRI/SNRIs and TCAs interfere with the functioning of important and evolutionarily ancient biochemicals (regardless of whether they selectively target serotonin, norepinephrine, or dopamine), and so it is perhaps not too surprising that their effects on all-cause mortality do not differ from one another."