Are Antidepressant Medications Effective?
Newer antidepressant medications, including selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs), are some of the most commonly prescribed medications. Somewhere around 13% of adults in the United States are on antidepressant medication (Brody 2020).
And yet, ever since the launch of Prozac—the first SSRI—questions still remain around the efficacy of these drugs. SSRI and SNRI medications affect neurotransmitter levels in the brain. SSRI medications focus on serotonin, while SNRIs affect serotonin and norepinephrine. These neurotransmitters are signaling molecules that control aspects of brain functioning.
The overly simplistic idea is that depression is caused by a deficit of these brain chemicals. And with antidepressants, you can boost neurotransmitter levels and eliminate deficiencies. While this has produced highly effective marketing about “biochemical imbalances,” it is disingenuous at best to suggest that antidepressants normalize problematic brain functioning.
Effects of Antidepressants
Antidepressants change brain functioning by reducing the clearance of neurotransmitters used in transmitting signals throughout the brain. On a basic level, nerve cells communicate with other cells through neurotransmitters. To relay a signal, a nerve cell can release serotonin to communicate with a neighboring cell.
After the release of serotonin, the serotonin transporter, a kind of pump found on the surface of the cell, draws the serotonin back inside the cell. This eventually clears the serotonin signal. SSRI and SNRI medication partially block these pumps. When taking SSRI or SNRI medication, the serotonin signal stays around longer in an attempt to increase serotonin messaging.
Interestingly, this doesn’t necessarily translate into more serotonin long-term. In fact, early animal studies appear to indicate that long-term use of SSRI medication may actually cause decreased serotonin levels in multiple brain areas (Bosker 2010, Renoir 2013). These medications also decrease sensitivity of serotonin receptors.
The effects of these medications are complex, and to this day, not fully understood. And while the focus of SSRIs has been on serotonin, other neurotransmitters—including dopamine—are affected, adding additional layers of complexity (Renoir 2013).
Efficacy of Antidepressants
So if antidepressants change neurotransmitter signalling and receptor sensitivity, do these changes improve mood? Let’s see what the research shows.
One of the most recent meta-analyses from 2020 looked at the size of the benefit from antidepressant medication. The Hamilton Depression Rating Scale is a standard tool for evaluating the severity of depression. The maximum depression score is 52, with any score above 20 considered moderately severe depression or worse. Reductions of 3 points or more are considered clinically meaningful improvements.
Antidepressant medications, on average, were shown to reduce depression by 2 points (Volkmann 2020). Based on such poor performance, the authors called into question current prescribing practices. Unfortunately, earlier studies have come to similar conclusions. When compared to placebo, antidepressants are only slightly more effective and only in cases of severe depression (Kirsch 2008).
That doesn’t mean that people don’t feel improvements with medication. It just means that you could have given the patient an inert sugar pill and, on average, seen about the same level of benefit. Some people do have clinical improvements on these medications, but the average level of benefit across most patients is not impressive.
With such low levels of efficacy, side effects take on a greater level of concern. Are the small benefits seen with antidepressants worth the risks? Obviously, that’s an individual choice, but side effects with antidepressant medications are not insignificant.
Antidepressants carry a warning label for increased risk of suicide in adolescents and young adults. A recent analysis of antidepressants found that these medications double the risk for suicide (Kaminiski 2020). This is of obvious concern.
Sexual side effects are also common and problematic with antidepressant medication. Rates of sexual dysfunction range from 25 to 73% for individuals on SSRI medication (Higgins 2010). Even more concerning, data suggests that a small percentage of patients with sexual dysfunction will continue to have problems even after the discontinuation of the medication (Bala 2018).
Another well known side effect is weight gain. Patients on antidepressants have 1.29 times higher risk of weight gain than those not on these medications (Gafoor 2018). It’s probably fair to say that weight gain itself could add to a person’s low mood. There is evidence linking obesity to depressive symptoms, likely due to the increased inflammation found in obesity (Iodice 2021).
Withdrawal effects are symptoms caused by the body’s long-term adaptations to taking a substance followed by its subsequent removal. It’s been recognized for years that antidepressants can cause significant and acute withdrawal symptoms. Withdrawal effects from SSRI and SNRI medication can be painful and severe. In fact, a recent study found that SSRI and SNRI withdrawal can be persistent even after discontinuation (Cosci 2020). Some of the most commonly reported long-term symptoms include: poor mood, depression, emotional lability, moodiness, irritability, anxiety, poor sleep, problems concentrating and poor memory (Belaise 2012).
There are valid concerns around the efficacy of antidepressant medication, especially considering their side effect profile. Unfortunately, other than counseling, there aren’t readily available and accessible alternatives for most individuals. While natural treatments exist, some with good research support, they are often underutilized by clinicians in favor of standard medications.