Increased monoaminergic neurotransmission improves compliance with physical activity recommendations in depressed patients with fatigue

Med Hypotheses. 2013 Jan;80(1):47-9. doi: 10.1016/j.mehy.2012.10.007. Epub 2012 Nov 2.


Clinical studies have shown that moderately intense physical activity effectively treats various types of depression. Beneficial effects have been reported in the acute phase of the disease as well as in a long-term perspective. In addition, epidemiological studies have shown that inactivity increases the risk of depression and that exercise prevents relapse. Depressed patients are often prescribed antidepressants, with or without psychotherapy. Some studies have, however, suggested that the most frequently used antidepressants, selective serotonin reuptake inhibitors (SSRIs), contribute to fatigue, which is a common residual symptom associated with depression and the target of the proposed study. Profound fatigue may in turn decrease the ability and motivation to perform the beneficial physical activity, e.g. via executive dysfunction. Fatigue and impaired executive function are commonly linked to disturbed cerebral dopaminergic and noradrenergic neurotransmission. This kind of dysfunction is hard to overcome, even when the major symptoms of depression are alleviated. Interestingly, physical activity has been suggested to improve the dopamine and norepinephrine neurotransmission. Furthermore, the favorable effects may be reciprocal; improved dopamine and norepinephrine transmission in the brain may hypothetically increase the ability and motivation to exercise, since some parts of the brain (e.g. the prefrontal cortex, striatum and cerebellum) that control movement and initiative receive dopaminergic and noradrenergic projections. Based on these findings and assumptions, our hypothesis is that increased dopaminergic and noradrenergic neurotransmission, via intake of a dopamine- and norepinephrine-enhancing agent, improves the compliance with prescribed physical activity in patients with depression and residual fatigue. We also believe that the increased physical activity can prevent relapse into depression, even after interruption of medication. Since increased physical activity also has been shown to improve executive cognitive function, we suggest that executive function should be examined as a secondary outcome together with other possibly related variables such as quality of life, sick leave and BMI.

MeSH terms

  • Depression / drug therapy*
  • Depression / therapy*
  • Dopamine / metabolism
  • Executive Function / physiology*
  • Exercise Therapy*
  • Fatigue / chemically induced
  • Fatigue / physiopathology*
  • Humans
  • Models, Biological
  • Motivation / drug effects
  • Norepinephrine / metabolism
  • Selective Serotonin Reuptake Inhibitors / adverse effects*
  • Selective Serotonin Reuptake Inhibitors / therapeutic use
  • Synaptic Transmission / physiology*


  • Serotonin Uptake Inhibitors
  • Dopamine
  • Norepinephrine