Exercise / Psychosocial / running

Pill, Placebo and Performance: Exercise for the Treatment of Depression

Several people sent me this article from the New York Times today, which described one woman’s use of running as therapy following several stressful occurrences in her life.  The author isn’t alone; when asked why they exercise, many avid athletes mention stress relief, mood elevation and psychological well-being among their top reasons for being physically active. But can exercise be used to treat clinical depression? If so, is it as effective as our best drugs?

Graphic take from Kirsch et al. 2005Well, the difficulty in answering this question begins with the understanding that our best drugs may not be all that great at treating clinical depression. This study made headlines in 2008 when it provided a comprehensive analysis of 35 randomized clinical trials involving SSRIs (selective serotonin reuptake inhibitors such as Prozac).  As represented by the accompanying graphic, researchers demonstrated that “there was virtually no difference in the improvement scores for drug and placebo in patients with moderate depression and only a small and clinically insignificant difference among patients with very severe depression.” In other words, SSRIs may only be really effective (i.e., better than placebo) for severely depressed patients. The graphic demonstrates this well as the red line shows the average trajectory for improvement in drug groups and the dashed blue line the similar trajectory for placebo groups. Only the shaded green area, which occurs in severely depressed patients with a high Hamilton Rating Scale of Depression, models a substantial clinical impact of SSRIs (which are the standard of care for treatment of clinical depression).  Graph taken from Archives of General Psychiatry 2011Now, in 2011, a revamped analysis of SSRI data provided some greater insight into what was seeming, well, very depressing about the efficacy of treatment for depression.  The new statistical models showed that there are trajectories of response to antidepressants such that approximately 75% of patients may be responders (i.e., doing better than placebo) and 25% of patients are non-responders (i.e., doing worse than placebo). This trend is modeled in the accompanying graph, with non-responders, placebo group, and responders graphed from top to bottom against changes in depression scores over time. So, in other words, antidepressants may work, but not for everyone.

So now that we’ve navigated through that puzzle, let’s turn to exercise.  In general, here’s what is known about using exercise to treat depression:

  • Exercise therapy is feasible and has a significant therapeutic benefit, especially when it is continued over time
  • Although pharmacologic antidepressants may elicit a more rapid onset in their therapeutic effect, exercise training “catches up” in effectiveness after about 4 months
  • Graph taken from Hoffman et al. 2011Long-term exercise appears to support the short-term benefits of exercise on depression and may also augment the benefits of antidepressant use. This point is illustrated by the graph on the right, which models minutes of self-reported exercise per week against depression scores (left) and probability of depression remission (right) one year after patients completed an intervention study of exercise training alone or in combination with sertraline (Zoloft)
  • The most recent meta-analysis of 2326 patients in 39 randomized clinical trials concluded that “exercise is moderately more effective than a control intervention for reducing symptoms of depression… and when compared to psychological or pharmacological therapies, exercise appears to be no more effective, though this conclusion is based on a few small trials.”  In other words, exercise may not fully replace or exceed pharmacotherapy, but is relatively equal in effectiveness.

As most of the studies to date have involved a standard aerobic training program, many questions remain regarding frequency, intensity, duration and type of exercise necessary to optimally treat depression. Regardless, though, it appears that for most patients with clinical depression, exercise is an important complement to standard antidepressant therapy. And for certain patients– those who do not respond to standard pharmacologic therapy, for example– an Rx for exercise may be as, if not more, important than a prescription for a pill.


3 thoughts on “Pill, Placebo and Performance: Exercise for the Treatment of Depression

  1. Great post. I had no idea that the SSRI data was so poor for treatment of depression. So why are they prescribed like candy? It would be interestng to see more data on mood effects in running. I find mood elevation higher if I do a tough run (but not too tough) almost like a buzz. But there’s also a long term, more subtle elevator I feel just by runnng a few times each week. I wonder if these are due to different physiological mechanisms.

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