Are Antidepressants Performance-Enhancing Drugs?

Doping scandals continue to rock endurance athletics. Discoveries, admissions, or allegations of EPO microdosing, abuse of therapeutic use exemptions, and the use of other performance enhancing substances have dominated headlines in cycling and distance running. Athletes and spectators use online forums to debate the ‘who’, ‘what’, ‘when’, and ‘how’ of doping in both professionals and amateurs.

As a professional triathlete and soon-to-be pharmacist reading these forums, I couldn’t help but notice the surprisingly high number of forum posts debating the effects that antidepressants may or may not have on athletic performance.

In online forums, individuals with personal experience comment on their perceptions of how particular antidepressants influenced their performance – positively or negatively. Most of these athletes are taking antidepressants for diagnosed mental illnesses, particularly depression and anxiety. After all, research suggests that athletes are at least as likely as nonathletes to experience depression.

A number of studies among NCAA athletes suggest that as many as 1 in 5 college athletes may be depressed. And while the traditional stoicism of athletes to hide perceived weaknesses may prompt athletes to hide their depressive symptoms, the media coverage of the 2014 suicide of University of Pennsylvania runner Madison Holleran highlighted the unseen weight of depression in high-achieving athletes. If efforts to reduce the stigma associated with mental illness are successful, more athletes may feel empowered to seek help for their illnesses, which may include starting an antidepressant.

At the same time as depressed athletes seek appropriate treatment for their illness, non-depressed athletes may question whether they could benefit from a dose or two of Prozac.  The potential use of antidepressants in athletes who are not depressed raises concerns about whether these drugs could offer an unfair performance advantage.  The underlying question here is this: Are Antidepressants Performance-Enhancing Drugs?

Improved athletic performance with SSRIs? 

The most commonly prescribed antidepressants are in a class of medications known as Selective Serotonin Reuptake Inhibitors (SSRI). This group includes drugs like Prozac (Fluoxetine), Zoloft (Sertraline), Lexapro (Escitalopram), Celexa (Citalopram), and Paxil (Paroxetine), among others. These drugs improve symptoms of depression by altering the amount and functioning of serotonin, a signaling molecule in the brain.

The idea that SSRIs improve athletic performance in athletes who are not depressed has its basis in studies linking positive emotional states with enhanced athletic performance. This idea was popularized in the media following NFL running back Ricky Williams’ breakout season. Prior to the season, he initiated SSRI treatment for an anxiety disorder. A New York Times article commenting on his improved performance asked,

“What if a few Paxils in the Gatorade cooler could give a team that extra edge?”

A medical professor at the University of Colorado, San Diego asked in a commentary in the journal Psychiatry whether athletes could unfairly improve their ability to compete in high-stress competitions by using antidepressants. An article in Psychology Today stated,

“SSRIs are boosting [athletes’] performance on the field.”

Despite these possible advantages, others theorize that SSRIs negatively impact performance because serotonin may. Additionally, paroxetine, the first SSRI on the market, is often associated with weight gain, which may negatively impact athletic performance. Newer SSRIs, however, are much less likely to cause weight gain. 

Evidence: Antidepressant Use in Healthy Athletes 

Do SSRIs Directly Improve Performance in Healthy Athletes?

The bottom line: No. Three studies in male cyclists – the results of which are highlighted in the table below – specifically investigated questions surrounding the impacts of SSRIs on athletic performance.

# of doses of an SSRI Measure of Performance Change in athletic performance
2 doses Time trial
1 dose Anaerobic power, fatigue index, V02 max
2 doses Time Trial
Two weeks Anaerobic power, fatigue index, V02 max

These studies aren’t perfect: they are all small, included only male cyclists, and studied SSRI use for 2 weeks or less. As a bit of context: the benefits of SSRIs for anxiety or depression are usually seen after much longer times – four to six weeks. Nevertheless, all three studies come to the same conclusion: SSRI use does not impact athletic performance in healthy athletes positively or negatively.

Do SSRIs Indirectly Improve Performance in Healthy Athletes by Improving Mood?

The bottom line: No, because SSRIs do not improve mood in individuals without depression or anxiety. The researchers who analyzed sixty-five published articles on antidepressant use in individuals without a psychiatric condition sum up what we know about SSRIs and mood in healthy people:

 “In summary, no consistent evidence for enhancing effects of antidepressants could be found. There is little evidence so far to support the popular opinion that antidepressants have a positive effect on the mood of healthy individuals after repeated administration.”

SSRI use is thereby different from other medications that are abused by healthy athletes. Thyroid hormone and testosterone, for example, directly increase hormone levels in the body regardless of whether the levels were low to start with – hence the ability for a healthy athlete to use the drugs for an unfair advantage. Since SSRIs do not improve mood in healthy athletes (or directly improve performance through some other mechanism), they offer little incentive for abuse.

Drug SSRI Testosterone Thyroid Hormone
Positively impacts people with illness?
Positively impacts people without illness?

Do SSRIs impact perceptions of exhaustion?

The bottom line: The scientific community isn’t sure. Recall that serotonin may increase a person’s perceptions of physical and mental fatigue. This is a distinct disadvantage to athletes who are training and competing at their physical and mental limits. If SSRIs make athletes feel MORE fatigue, abuse of them by healthy athletes would HINDER success rather than promote it! Several studies have looked at whether SSRIs impact healthy male cyclists’ perceptions of exhaustion.

In these studies, cyclists are given either an SSRI or a placebo. They are then asked to ride to exhaustion, and researchers measure how long they ride before stopping from exhaustion. Of the four studies conducted in this way, two reported that athletes receiving one dose of an SSRI , and two reported that athletes receiving one dose of an SSRI did not feel exhausted sooner. While the jury is still out on this question, we know that SSRIs do not reduce perceptions of exhaustion (aka they do not provide a potentially performance-enhancing benefit by allowing athletes to train or compete for longer before feeling exhausted).

Do Other Commonly Prescribed Antidepressants Impact Athletic Performance in Healthy Individuals?  

The bottom line: Probably not. SSRIs are the most commonly prescribed antidepressants, but two additional types of drugs are often prescribed for depression: the serotonin/norepinephrine reuptake inhibitors (SNRIs) and bupropion.

The SNRIs include Effexor (venlafaxine), Cymbalta (duloxetine), Pristiq (Desvenlafaxine), and others. Like SSRIs, these drugs impact serotonin, but they also impact another brain signaling molecule – norepinephrine. Norepinephrine is similar in structure and effect to epinephrine, a hormone that is on the World Anti-Doping Agency banned substances list because it increases heart rate, glucose availability, and blood flow to muscles.

The SNRIs are also used to treat some chronic pain conditions. In theory, an improvement in pain tolerance could improve performance. Again, we don’t see a lot of studies on the effects of SNRIs on athletic performance, but the evidence we do have says that Effexor does not improve cycling time trial performance. And while the SNRIs may help some chronic pain conditions, they haven’t been shown to help acute pain like the pain you’re going to feel during the power test on your training plan next week. Therefore, based on the available evidence, SNRIs get the same assessment as SSRIs: no impact on performance.

Bupropion (Wellbutrin, Zyban) is a different kind of antidepressant that, at the risk of oversimplifying, impacts both norepinephrine, the hormone that’s similar to epinephrine, and dopamine, which is part of the brain’s reward system. Bupropion is in the WADA 2015 Monitoring Program, which monitors substances “in order to detect patterns of misuse in sport.” WADA lists bupropion as a stimulant along caffeine, nicotine, and phenylephrine (a decongestant that is less stimulating – and less effective – than the pseudoephedrine found in Sudafed).

Bupropion does have some stimulating action. It is, after all, structurally similar to Ritalin, amphetamine (Adderall), and cocaine! But does that mean that bupropion is enough of a stimulant to improve performance?  The two studies on bupropion in cycling time trial performance at moderate temperatures say “no”. In hotter temperatures, the link between bupropion and performance is murkier. One study reported that bupropion improved performance; another found that it did not. The inclusion of bupropion in the WADA Monitoring Program likely reflects both its stimulant structure and the conflicting findings regarding performance improvement in hot conditions.

Conclusion

The bottom line: Despite popularized speculations of SSRIs as doping agents, SSRIs and SNRIs do not directly or indirectly improve athletic performance in healthy athletes. To go one step further, they may or may not put a healthy athlete at a disadvantage by making her feel exhausted more easily. If you are thinking about using an SSRI (Prozac, Zoloft, Lexapro, etc.) or an SNRI (Effexor, Cymbalta, etc.) to boost your performance, think again. It’s not going to work. Do not pass go. Do not collect $200.

photo-1434543177303-ef2cc7707e0d

 

What does the Evidence Say About Antidepressant Use in Athletes with Depression and/or Anxiety? 

Do Antidepressants Directly or Indirectly Improve Performance in Healthy Athletes?

The bottom line: maybe, maybe not, but it shouldn’t matter. Based on forum testimonials, an athlete’s performance may improve if, as her depression improves, she regains her baseline motivation to train that was previously reduced by depression. Remember here that an antidepressant will restore the athlete’s baseline personality and ability to function but not will improve her motivation or drive beyond her normal, healthy state.

Conversely, she may feel that, as her anxiety improves, her “edge” softens, compromising her intensity in training. She may feel less tired if fatigue was a symptom of her depression, but she may feel more tired if she experiences fatigue as a side effect of the antidepressant. Similarly, she may gain or lose weight and sleep more or less after she starts an antidepressant, depending on her symptoms of depression and the medication side effects. Physicians and athletic patients with depression will need to work together to find a therapeutic regimen that improves symptoms while minimizing side effects that may impact performance. 

What’s Your Point?

SSRIs and SNRIs do not impact performance in healthy athletes. That is, if an athlete without depression or anxiety starts on these antidepressants, performance will not improve. So, if an athlete WITH depression or anxiety starts on these antidepressants and performance subsequently improves, that improvement can be attributed to the effective treatment of the underlying illness. This is analogous to a legitimately hypothyroid patient experiencing a performance boost with an appropriate dose of thyroid hormone (emphasis on legitimate and appropriate given recent allegations about illegitimate hypothyroidism diagnoses and inappropriate dosing). I fervently hate doping and the way it degrades our sport as much as you. But treating a legitimate medical illness with a drug that does not provide an unfair advantage in healthy athletes should not be considered doping.

Most importantly, depressed athletes should not forgo treatment out of concerns that their performance will be negatively impacted, that they will be gaining an “unfair” advantage, or that they will be perceived as “weak” amongst their peers a result of their illness. I can personally testify to the burden of depression in elite athletes, as I recently sought help for a relapse of major depression.

Many have commended the “strength” I displayed in making it to the start line at Timberman 70.3 after fracturing two ribs the day before. Those who have not experienced or loved someone through depression may have a hard time understanding that the strength required to race with fractured ribs paled in comparison to the strength required to fight the burden of depression on a daily basis. I battled depression alone for months because I was worried that my doctor would not believe that a successful graduate student and professional athlete could be depressed (he did) and was afraid that an antidepressant would negatively impact my performance (it didn’t).

Those of us struggling with depression face enough barriers to getting the help we need.  Let’s not let unfounded concerns about antidepressants as doping agents get in the way of treating a legitimate and already unjustifiably stigmatized illness.

About the Author

Julie Patterson is a professional triathlete with Maverick Multisport and a fifth year graduate student at Virginia Commonwealth University in Richmond, VA.  She is pursuing a Doctor of Pharmacy degree and a PhD in Pharmacoeconomics and Outcomes Science. She lives in Richmond, VA with her husband, Tim, the all-star of non-triathlete Sherpa spouses, and her dog, Soller, who is always the fastest dog at the dog park.

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