Treatment of chronic fatigue with analgesics

Bruce Charlton

Bruce G Charlton MD
Reader in Evolutionary Psychiatry
Department of Psychology
University of Newcastle upon Tyne

Editor-in-Chief, Medical Hypotheses


Fatigue is a form of generalized pain whose function is to signal the need for rest and recuperation. But chronic fatigue is usually a misleading signal that does more harm than good, and needs treatment. Since it is a type of pain, analgesics/ pain-killers may be an effective treatment of fatigue.

What is fatigue?

Fatigue is an emotion - and an emotion is a body state as perceived by the brain. For example, anxiety is the brain’s perception of the body’s physical state of arousal and preparedness for action (hair on end, thumping heart etc). Similarly, fatigue is the brain’s perception of a state of physical exhaustion of the body induced by excessive activity. The brain interprets these body signals of fatigue as indicating a need to stop activity. Fatigue is therefore an emotion that signals the need for rest, for physical recuperation.

So fatigue can be considered a negative-feedback signal, which limits the amount of physical activity. The more prolonged and vigorous the activity, the more powerful becomes the signal of fatigue which tends to stop the activity. In a nutshell, fatigue prevents the body harming itself by excessive activity. (This can happen - before modern treatments were available, psychiatric patients with mania would be hyper-active for so long that they sometimes would literally die of exhaustion)

Many people complain of ‘tiredness’ or being ‘tired all the time’, but fatigue is not the same as sleepiness. Of course, both may occur together. But when someone complains of tiredness they are not necessarily drowsy, nor is their sleep necessarily disturbed - they may be complaining of fatigue.

Fatigue as generalized pain

When we are overactive, eventually fatigue catches up with us and we stop, rest, and sleep. So although fatigue is a subjectively unpleasant feeling, like pain; fatigue is also an evolved, biological adaptation, just like pain. Indeed, it may be reasonable and useful to think of fatigue as a form of generalized pain.

Removal of normal fatigue might be damaging or dangerous because it would allow activity to continue when it ought to stop. For instance, fatigue-reducing drugs such as the amphetamines can be dangerous (even fatal) when used to allow athletes to push their bodies beyond the limits of human endurance.

So under normal circumstances, acute fatigue therefore performs the useful function of ensuring a short rest. A more prolonged form of fatigue occurs when the immune system is activated - this is part of the syndrome of ‘sickness behaviour’ which has evolved to ensure that sick animals (including humans) will rest and fight infections. Such fatigue may be useful over a time span of a few days - which is the normal duration for acute infectious disease. But if fatigue is prolonged much beyond a few days it becomes harmful rather than beneficial. Eventually animals must (if possible) get on with the biologically necessary business of finding food, finding a mate, and performing their social roles. The same applies to people.

The biochemical basis of chronic fatigue is probably therefore related to a class of immune chemicals called the cytokines which are secreted during activation of the immune system by infection. There is a substantial literature documenting significant immune activation in chronic fatigue, with a wide range of abnormalities in cytokines. Whatever the reason for this immune activation, the chronic fatigue it produces is a symptom that does more harm than good.

Hyper-algesia - a false signal of pathology

Cytokines produce hyper-algesia or increased sensitivity to pain. Ordinary bodily sensations, which would usually be ignored, may rise above the threshold of awareness when cytokines are circulating. These aversive sensations - which really have no pathological significance, are then perceived as pains, aches, heaviness and fatigue.

Like all aversive biological signals, these are hard to ignore since the body interprets them as a warning of pathology, usually altering the motivational state in the direction of rest and immobilization. But these signals may be misleading, a functionless by-product of immune activation - in which case it would be better if these misleading signals of ‘generalised pain’ were eliminated. Appropriate analgesic drugs may be able to do this job of eliminating misleading pain signals - as when aspirin is used to treat a tension headache. The pain of a tension headache does not signify any significant pathology - furthermore pain tends to increase the tension in a vicious cycle. Treating the headache with an analgesic not only makes people feel better, it may also break the vicious cycle of pain and tension.

Similarly, treating chronic fatigue symptoms is almost certainly beneficial. In the first place chronic fatigue serves no useful biological purpose, secondly treatment of fatigue would make people feel better so that they can get on with life, thirdly treatment of fatigue would tend to break a vicious cycles of excessive lethargy leading to weakness and more lethargy.

Treatment of fatigue with analgesics

Substances that remove aversive sensations of pain are called analgesics. I suggest that conventional analgesics may also act to remove those aversive sensations we term fatigue. What kinds of drugs? This would depend on individual responsiveness and susceptibility to side effects. The best way to find out would be careful ‘self-experimentation’ in close consultation with a trusted and expert physician.

Perhaps it would be sensible to start with the mildest and safest pain-killers such as those available over the counter: paracetamol, codeine, and either aspirin or ibuprofen. These could be tried individually and in combination. It may also be worth trying supplementation with caffeine in the mornings (caffeine is also a painkiller). More powerful NSAIDs (such as diclofenac) and opiate analgesics are available on prescription.

Opiates, of course, may be addictive. But it is generally believed that when used appropriately as analgesics, in minimum effective doses, and in the form of slowly-absorbed tablets, opiate dependence is unlikely to become a problem.

The tricyclic ‘antidepressants’ are another group of powerful painkillers, being increasingly used in the management of chronic pain, neurogenic pain, migraine, chronic fatigue, cancer pain, AIDS and arthritis. Indeed, I have argued that the antidepressant action of tricyclics depends mainly on their analgesic properties. It seems probable that it is the painkilling effect of tricyclics which explains why some chronically fatigued patients seem to benefit from ‘antidepressants’.

Of course, treatment of fatigue with analgesics - even when effective - may not be the whole answer. And the underlying problem leading to the chronic fatigue may well remain - so that people would only benefit for as long as they continue to take regular pain killers. But as long as people feel significantly better, and side effects from drugs are not problematic, then treatment of fatigue with analgesics would seem justified.

The above notes bring together some ideas scattered through my book Psychiatry and the Human Condition - this book may be referred-to for background. It is important to acknowledge that my specific knowledge of Chronic Fatigue and its syndromes is purely theoretical, and I have no relevant clinical experience in this field. Although this paper is (I believe) scientifically plausible and coherent - it should be read as no more than a tentative contribution to the debate on the causes and treatments of a sub-group of people suffering from chronic fatigue. See also Malaise theory of depression and Pharmacology and personal fulfillment.



also by Bruce Charlton
The Malaise Theory of Depression
Public Health and Personal Freedom
Psychiatry and the Human Condition
Pharmacology and Personal Fulfillment
Awareness, Consciousness and Language
Injustice, Inequality and Evolutionary Psychology