Do Antidepressants Actually Work?

August 3, 2018

The use of antidepressant medications, particularly the selective serotonin reuptake inhibitors (SSRIs) such as Prozac and Zoloft, have skyrocketed in the past thirty years. If you’re reading this column, then there is an excellent chance that you have either taken an antidepressant medication or know someone who has. The latest data shows that in the U.S., almost 14 percent of adolescents and adults are actively prescribed these medications, with several other countries not far behind that number. This is an increase of approximately 450 percent since the late 1980s based on Center for Disease Control statistics (Table 80).

The Prevalence of Mood Disorders

Given that the anxiety and mood disorders (which are those that these medications reportedly help with) are the most frequently diagnosed difficulties in the U.S., one would expect the increased prescription rates to correspond with a decline in the number of people struggling with disability status due to mental health issues. Unfortunately, when we look at the numbers this is not the case. In the United States, disability rates due to mental illness have doubled since 1987 (when fluoxetine, one of the first “blockbuster” antidepressants, came to market), to about one in every seventy Americans). In fact, the category “mood disorders” accounts for about 14 percent of all people who are on disability, second only to “Musculoskeletal system and connective tissues” diagnoses (Table 6 here). This pattern of increases is not unique to the United States either, with similar trends in many Western nations with high rates of antidepressant use (see Whitaker’s article in the October 2015 issue of The Behavior Therapist for exact numbers).

So what exactly is happening? Why do we not see a lowering of such numbers? Numerous pieces of recent research provide at least a partial answer: only a small number of people prescribed antidepressants actually benefit from them.

What Do the Clinical Trials Say?

Setting up, running, and interpreting clinical trials can be very complicated. In general, when we test the effectiveness of a medication or therapy on a particular health condition we have to be very careful that we attribute change to the effect of the drug and not to other potential causes, such as the placebo effect and regression to the mean. The best way to do this is to conduct a randomized, placebo controlled, double blinded trial (RPCDP). These trials control both for expectancy effects (that is, placebo effects) and for natural changes in symptoms across time (that is, regression to the mean). A RPCDP trial is considered the gold standard when it comes to evaluation of treatment effects, but even their results cannot be considered as definitive evidence.

Instead, we try to rely on large scale, meta-analytic studies that help to remove and control for potential biases that can so easily creep into research studies. A meta-analysis is essentially a “study of studies,” in which you combine the results of lots of smaller scale studies into a larger study. This helps to increase the power of a study, or the chance that what you find is actually there and not due to random chance.

Two recent, large scale meta-analyses of antidepressant data provide some of the best evidence to date regarding how well antidepressants work in adolescents and adults. In a 2016 study, Dr. Andrea Cipriani and his colleagues surprisingly found no evidence that most antidepressants were more effective than placebos in relieving depressive symptoms in children and adolescents. The only exception was the drug fluoxetine (trade name Prozac), and even then the effects were mild at best.

Evidence is slightly more promising in adult populations, with Dr. Cipriani again leading the charge with a 2018 meta-analysis. In it, the various antidepressants were found to be better than placebos but still not an amazing cure. The study’s results indicated that people taking an antidepressant were at maximum twice as likely to see results than someone taking a placebo.

Sadly, these unimpressive results are consistent with other findings that show that an average of 30 percent of people who take placebos will have depressive symptom improvement while maybe 50 percent of people who take an actual antidepressant will show the same improvement. To put it plainly, taking antidepressants probably improves symptoms of depression in about one out of every five people who take them.

Who Actually Benefits from Taking Antidepressants?

Most people who find this out—that 80 percent of people who take antidepressants do not actually benefit from them—are shocked. Given how widespread these drugs are, and how much advertising there has been over the past twenty-five years spreading the notion that depression and other mental health difficulties are the result of a “chemical imbalance,” most laypersons assume that these drugs are safe and effective at treating depression. The data, however, tell a much different story.

It is important to note that even though most people don’t benefit from taking antidepressants, there are a significant minority of people who will benefit from taking these drugs to at least some degree. That’s led to increasing amounts of research attempting to identify this population. Recently published results from Dr. Christian Webb and colleagues at McLean Hospital focused on trying to predict treatment response prior to people actually taking these drugs.


Overall, the study’s conclusions fit with prior research finding little overall difference between people with depression who took a placebo versus the actual antidepressant. However, Webb’s research led to the development of an algorithm to help identify those most likely to benefit from antidepressants. Those participants who were older, employed, had worse depressive symptoms, and better cognitive control were much more likely to respond positively to the antidepressants. This represented about a third of the total sample, and they were found to have a much greater response to the medications.

Combined with other research, these findings point to a strong need for physicians to not just dole out antidepressant prescriptions to anyone coming in and complaining of common depressive symptoms such as feeling down or sad, loss of interest in activities, sleeping problems, and the like. Instead, working to identify if someone is actually likely to benefit needs to be the first step, given how many people these drugs do not work for. For those unlikely to benefit, referring them to evidence-based psychological providers using cognitive behavior therapy (CBT), interpersonal therapy, or behavioral activation may result in a greater chance of improvement.