The management of treatment-resistant depression in disorders on the interface of psychiatry & medicine. Fibromyalgia (FM), Chronic Fatigue Syndrome (CFS), migraine, irritable bowel syndrome, atypical facial pain, & premenstrual dysphoric disorder

We have reviewed studies examining the efficacy of various

psychotropic medications, primarily antidepressant agents, in

the treatment of a group of disorders that appear to exhibit

some phenomenologic and genetic relationship to major

depression. These disorders all appear to benefit (albeit to

varying degrees) from antidepressant medications of several

different chemical families. This observation has important

theoretical and clinical implications. From a theoretical

perspective, these results invite the hypothesis that these

various disorders may share some particular etiologic “step”

in common with major depression-and that the various

antidepressant classes benefit these various disorders and

major depression via a common action at this hypothetical

“step”. Although there is an appealing parsimony to this

hypothesis, several reservations must be considered. First, it

must be recognized that the quality of the available studies

varies widely. As noted in the text, these studies used

numerous different designs, varying diagnostic criteria for

the disorders under study, and diverse methods of rating

outcome. Interpretation is further complicated by the fact

that many studies included other concomitant medications or

therapeutic interventions in addition to the psychotropic

drugs administered. Also, the dose of antidepressant

medications administered in many of these studies, especially

those using TCAs, was often much less than that normally

administered in the treatment of major depressive disorder

itself. Finally, many of the studies did not systematically

evaluate improvement in both the physical and psychological

symptoms of a given disorder. For all of these reasons, any

theoretic discussion of the results must be tentative.

Nevertheless, the overall tally of results strongly favors the

hypothesis that antidepressant agents, regardless of their

chemical class, are generally useful in the treatment of these

disorders. At a minimum, therefore, we can conclude that

antidepressant treatment in these disorders deserves

aggressive further investigation in studies with modern,

rigorous designs. Second, even allowing that multiple

antidepressant agents are effective in these various

disorders, it still may be premature to conclude that these

disorders are related to major depressive disorder. In

particular, many of the studies found little correlation

between improvement in psychological symptoms and physical

symptoms of a given disorder. This observation would seem to

argue against a relationship with major depressive disorder.

The alternative hypothesis, however, namely, that these

disorders do not share a common etiologic “step,” seems even

less attractive. It would be a remarkable coincidence if, say,

fluoxetine possessed an antidepressant property, an

independent antimigraine property, and a third, independent,

antipremenstrual dysphoric disorder property. And it would be

even more peculiar if various other antidepressant medications

chemically unrelated to fluoxetine also, by chance alone,

benefited all of these same disorders via still other

independent mechanisms.

Although we cannot, of course, rule

out the possibility of multiple mechanisms and multiple

causes, the experience of scientific research often has been

that the simpler explanation of a phenomenon has proved to be

correct. Therefore, the possibility of a link among these

various antidepressant-responsive disorders deserves

investigation. From a clinical perspective, too, these results

are important. They suggest that trials of antidepressant

medications should be strongly considered in patients with

these disorders. Furthermore, other types of psychotropic

medication appear to have a role in the treatment of

individual disorders, as discussed in the corresponding

sections. In summary, the management of patients with

fibromyalgia, chronic fatigue syndrome, migraine, irritable

bowel syndrome, atypical facial pain, and premenstrual

dysphoric disorder is often d [References: 79]

Gruber AJ, Hudson JI, Pope HG Jr

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