The Puzzling Features of Fatigue

Fatigue, a sense of exhaustion, lack of energy, feeling “knackered” is a normal sensation for all of us. We feel it after working hard, or thinking hard (mental fatigue), but for many people it is condition they feel before they’ve put in any effort, and limits their ability to get things done, or even to put in the effort to do things they enjoy. It is an unfortunately common problem throughout the world, and appears to be increased in virtually every disorder known to man, Parkinson’s disease being no exception. Fatigue is one of the most common reasons for patients to see their primary care doctors around the world, and there is even a disorder, chronic fatigue syndrome, in which patients suffer from a severe, even incapacitating, level of fatigue with no apparent explanation being found.

In Parkinson’s disease, there is an explanation. In a study in Rhode Island, where I live and practice, one third of consecutive PD patients rated fatigue as their single worst problem associated with PD, more than tremor, slowness, speech problems, or anything else. One half rated fatigue as one of their three most bothersome PD problems. These staggering numbers were confirmed in numerous studies performed in different PD populations throughout the world, indicating that this is not simply a cultural issue. Yet, most people with PD (PWP), their families and their doctors are unaware that fatigue is related to the illness. One of the reasons for this under-appreciation is that fatigue is a normal part of life and distinguishing normal fatigue from “pathological” fatigue, that is, fatigue that is excessive for the situation, and that interferes with normal activities, is difficult. It is also impossible to see fatigue and it can only be measured by questionnaires.

One of the very puzzling features of fatigue in PD is that it does not correlate with motor severity. One third of PD patients entering a research study for newly diagnosed, untreated patients who were not taking any medications for PD, reported pathological fatigue. There does not seem to be a significant difference in fatigue severity or frequency in severely afflicted versus mildly afflicted PWP, which is highly counter-intuitive. This observation leads to the then not-surprising result that L-Dopa and other PD medications don’t help fatigue very much, even when they help mobility. One rigorous study did show an improvement in fatigue with L-dopa, but the effect was weak.1 Although fatigue is so common in PD, it has not been well studied, largely, I think, because it is so challenging. Fatigue, as noted above, is part of everyday life, and is increased in almost every illness, whether neurological or not. Making it more difficult in PD, is that fatigue is also significantly more common in people with depression and anxiety, which are very common in PD, as well. If a PWP has fatigue and depression, is the fatigue due to depression or to the PD? Or, is the depression due to the fatigue? Making this even more difficult to study, is the obvious fact that for many PWP, other illnesses are present, such as heart, lung, kidney and gastrointestinal diseases, diabetes and thyroid disorders, all of which may cause fatigue. So, how can we determine if the PWP with fatigue has fatigue from PD or from something else?

Unfortunately, we can’t. There is some research trying to tease out factors that might allow us to understand if there are any factors that distinguish one type of fatigue from another. For example, it has been noted that fatigued PD patients often report less fatigue after exercise, the opposite of what happens to people with normal fatigue. It will help develop treatment for PD fatigue if we can be sure that the fatigue is really from PD and not from depression, diabetes or something else.

We do not yet know how to treat fatigue. We try to eliminate any medications that might be contributing, encourage exercise, good sleep habits and treat other disorders, such as depression and anxiety. Some of us advocate trials of stimulant medications, but they may have side effects that prevent their use, and there have been no convincing studies showing that they work.

It is important to patients, families and doctors to recognize that fatigue is part of the disease, just like tremor, imbalance, constipation and sleep disturbances. It is NOT a moral failing. The PWP with fatigue is not guilty of “not trying.” Understanding the problem does not improve it, but certainly lessens the burden of living with it.

(1) Schifitto G, Friedman JH, Oakes D, Shulman L, Comella CL, Marek K, Fahn S; Parkinson Study Group ELLDOPA Investigators. Fatigue in levodopa-naive subjects with Parkinson disease. Neurology 2008 Aug 12;71(7):481-485.


Joseph H. Friedman, MD presented at the Third and Fourth World Parkinson Congresses in Montreal and Portland respectively, and was a member of the Third World Parkinson Congress program committee. He is currently Chief of Butler Hospital's Movement Disorders Program and Professor of Neurology at Brown University.

Ideas and opinions expressed in this post reflect that of the author(s) solely. They do not necessarily reflect the opinions of the World Parkinson Coalition®