Attenuation of response to antidepressants in animals induced by reduction in food intake.

A salient feature of depression is eating disorders (reduced appetite and caloric intake) and/or weight loss. In the present study, reduction in food intake in rats, resulting in moderate weight loss, markedly attenuated the ability of various antidepressant drugs to reverse depressive-like behaviors: escape deficits provoked by previous exposure to uncontrollable stress. Further data support the notion that hypofunctioning of central noradrenergic processes, perhaps linked to reduced thyroid hormone levels, might contribute to such an altered response to antidepressants. These findings suggest that current nutritional status, even with marginal weight loss, could be an intervening factor in the delayed therapeutic response to antidepressants and/or in drug-resistant depression.