Chronic fatigue: What causes it?

A 37 year-old man with hypertension reports fatigue since mid-adolescence, and a depressive episode one year earlier. He did not do well with serotonin reputake inhibitors and amphetamines only helped briefly. MRI showed white matter periventricular hyperintensities, which was read as unrelated to fatigue. Other workup, including sleep study and endocrine labs, were mainly normal. He sought consultation on further treatment.

Fatigue is a nonspecific symptom, like fever. It often is an effect of another condition, not an illness by itself. The most common cause is clinical depression, which is defined as being very low in mood and motivation and energy and activity for weeks to months. During those periods a person would be more tired. Sometimes people have depressive symptoms as part of their personality, called “mood temperaments”. If one is mildly depressed all the time, it is called “dysthymic” temperament. If no other cause can be identified, one's condition could be part of a dysthymic temperament as part of one's personality. It’s notable that the patient was diagnosed also with anxiety, which can cause fatigue, but his fatigue did not improved when anxiety improved. Anxiety also can be part of a chronic mild depressive state, which used to be called “neurotic depression,” but which was replaced with phrases like dysthymia and in the official US textbooks of the “DSM” diagnostic labels, the constant anxiety as part of one’s personality is called “generalized anxiety disorder” (GAD). The PL view is that these labels do not add any new information and are not based on scientific evidence that they are meaningful beyond what is described above, i. e., that anxiety is present as part of your personality.

If fatigue is part of dysthymia as a temperament, the problem with any medication treatment is that it will have to be long-term, but it will only help symptomatically to mild to moderate degree. This is because a mood temperament is not something you can take away; you can decrease it but you cannot completely change a personality trait. Thus, benefit will be moderate at best, but patients still will have long-term side effects, like withdrawal syndrome risks with serotonin reuptake inhibitors. Amphetamines can increase energy symptomatically, as this patient experienced, but they are like Tylenol for unexplained fever, and thus do not solve the problem long-term. They also have long-term risks including cardiac arrhythmias and neurotoxicity in animals.

If patients have a mood illness, like recurrent severe unipolar depressive episode, then they might improve more with medications, but this patient did not.

The most notable finding in this workup is the brain MRI. It is abnormal, but not in an extreme way, but rather in a way that also occurs in normal variation in healthy individuals. These kinds of white matter and periventricular hyperintensities often are viewed as variants of normal by radiologists and neurologists, but they are not normal when they occur in people with depression, often called vascular depression.

This patient is quite young for vascular depression and hypertension, both of which tend to occur in middle age, but since he has hypertension, which is unusual in one's thirties, it may indicate that you are especially vulnerable for some reason to small vessel cerebrovascular disease, which means basically that small blood vessels in the brain close off, which is caused by hypertension, with diabetes as another risk factor.

Such small vessel vascular disease is commonly associated with depression, and it doesn’t tend to improve much with standard antidepressant medications. It doesn’t tend to produce fatigue as an isolated symptoms, but since you have had depression, it could be consistent with depression along with fatigue. Earlier symptoms would be more consisent with baseline dysthymia.

Treatment recommendations included assertive antihypertensive treatment to prevent further progression of vascular disease. Symptomatic benefit for current fatigue with medications would be difficult to achieve.

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