With nearly 40 million Americans taking some kind of antidepressant medication — the vast majority selective serotonin reuptake inhibitors (SSRIs) — you’d think we would at least know the mechanism of action of these drugs. But you’d be wrong.

The theory is that depression is an imbalance of the neurotransmitter serotonin and the drugs block its uptake, leaving more serotonin active to benefit mood. If only it were that easy.

A systemic review looked at medical literature that analyzed the link between serotonin and depression. Seventeen studies and 12 other reviews and meta-analyses were analyzed. The authors concluded, “The main areas of serotonin research provide no consistent evidence of there being an association between serotonin and depression, and no support for the hypothesis that depression is caused by lowered serotonin activity or concentrations. Some evidence was consistent with the possibility that long-term antidepressant use reduces serotonin concentration.”

In other words, here we are more than three decades after its introduction, and we’re still unsure of how this whole class of widely prescribed medications actually work.

In fact, there are no good data indicating that depression is caused by an imbalance of any neurotransmitter, including serotonin.

We’ve all been duped into believing that depression has been proven to be a biochemical problem. This is a perfect example of the kind of slick marketing that convinces physicians to write millions of prescriptions for medications that have not been properly studied. Simply stated, there’s no proof that SSRIs relieve depression.

But knowing this has not changed much in the world of psychiatry. Antidepressants are still overprescribed and deliver underwhelming benefits.

Do I think antidepressants should be pulled from the market? No. I’ve seen them help people, especially those with major depression, which is defined as suffering for at least two weeks loss of interest or pleasure in activities, having feelings of worthlessness or guilt, and suicidal thoughts. Patients suffering from this type of depression often require drug therapies.

However, for mild or moderate depression — which are much more common — the one therapy that has consistently proved effective is exercise.

This is not to say that people suffering mild to moderate depression might not benefit from medication. Some do. But SSRIs and other antidepressants are not without serious adverse effects, including nervousness, restlessness, and agitation to the point of developing suicidal thoughts.

Furthermore, patients who take SSRIs often have a very difficult time coming off the medications. Doing so can also lead to inappropriate thoughts, including suicidal ideation.