The hypothesis that cytokines play a key role in the pathophysiology of depression implies that antidepressant treatments should exert their effects by interfering with cytokine production and action. Antidepressants are usually not considered as anti-inflammatory drugs even if some psychopharmacologists have proposed that they behave as central inhibitors of prostaglandins (Leonard, 1987). However, if one goes beyond such general statements to investigate in details the ability of antidepressants to affect cytokine production and action, many surprising effects can be found. The ability of antidepressants to impair the release of proinflammatory cytokines from activated monocytes and macrophages, act as inhibitors of chemotaxis, and enhance the expression of anti-inflammatory cytokines is reviewed by Neveu and Castanon in their chapter. Yirmiya et al (this volume) go one step further by demonstrating that chronic but not acute antidepressant treatment abrogates symptoms of LPS-induced sickness behavior in rats, specially the decreased preference for saccharin that mimics anhedonia. This effect is probably mediated by a decreased ability of monocytes and macrophages to produce proinflammatory cytokines.
Although pharmacologists are prompt to jump from such positive results to pathophysiological interpretations, there is still a long way to go. The preliminary results obtained in animals should encourage more systematic studies on the effects of various classes of antidepressants and non pharmacological treatments of depression (e.g., electroshock) on the different components of sickness induced by LPS or recombinant cytokines. If these effects are confirmed, their mediating mechanisms should then to be elucidated. At the clinical level, this effort should be accompanied by investigation of the effects of antidepressant treatment on immune activation in depressed patients and the temporal relationship between these effects and mood changes.
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Are You Depressed? Heard the horror stories about anti-depressants and how they can just make things worse? Are you sick of being over medicated, glazed over and too fat from taking too many happy pills? Do you hate the dry mouth, the mania and mood swings and sleep disturbances that can come with taking a prescribed mood elevator?