Therapeutic responses to tricyclic antidepressants and related drugs in non-affective disorder patient populations.

Although therapeutic responsiveness to tricyclic antidepressants has been primarily associated with the affective disorders, clinical investigations in the last decade have suggested that non-affective disorders such as panic disorder, obsessive-compulsive disorder, anxiety disorder, bulimia, enuresis, migraine, and the chronic pain syndrome may also respond to tricyclics and other antidepressants. This therapeutic responsiveness may sometimes be related to improvement in secondary depressive symptoms, but may also clearly occur in the absence of secondary depression; in particular, improvement in the core symptoms of at least some of these disorders may occur without a change in mood. Furthermore, many patients with these disorders display psychobiologic abnormalities that show many similarities, but also some differences, compared to those observed in patients with affective disorders, despite the frequent absence of affective symptoms. While an improvement in subclinical or "masked" depression remains one hypothesis linking tricyclic responsiveness and shared biological abnormalities in this diverse group of diagnostic entities, an alternative hypothesis (the "ven disorder" hypothesis) is presented, suggesting the possibility that tricyclic and other antidepressant-responding patients have a core disorder with common psychobiologic abnormalities but multiple clinical and diagnostic presentations. An alternative hypothesis (the "shotgun" hypothesis) suggests that the multiple actions of tricyclics (e.g. on adrenergic receptors vs. muscarinic receptors vs. serotonin system changes) may each be differentially important in the therapeutic outcome in patients with specific or predominant problems in one or another of these areas. An examination of both the similarities and differences among the non-affective, tricyclic-responsive disorders and the affective disorders may provide clues about the important psychobiologic elements in these disorders, and to the mode of action of tricyclic antidepressants and related drugs across the psychiatric disorder spectrum.