IFN-induced depression: a role for NSAIDs.

Interferon-alpha (IFN) is widely used for the treatment of viral illnesses and other chronic diseases, though its usefulness is hampered by a problematic side-effect profile. In particular, IFN-alpha induces neuropsychiatric and neurotoxic side effects, including depression, anxiety, insomnia, lethargy, confusion, and psychosis. Of particular interest, a number of patients develop full psychiatric syndromes, particularly depressive disorders. Recent evidence suggests that conventional antidepressants (especially selective serotonin reuptake inhibitors) are effective in preventing or reducing IFN-induced side-effects, but even these compounds are not 100% effective in preventing these symptoms. As such, alternative treatments must be considered. Non-steroidal anti-inflammatory drugs (NSAIDs) are known to counteract a number of IFN-induced side effects, including cytokine activation, stress hormone release, and neurochemical alterations (reduced 5-HT [serotonin]). NSAIDs are widely recommended for various aspects of flu-like symptoms or sickness behaviors in humans, including those induced specifically by IFN. In addition, NSAIDs appear to be effective in treating premenstrual dysphoric disorder. These data indirectly specify a role for NSAIDs in syndromes with a prominent depression component. Drawing from an extensive pre-clinical and clinical research base, we hypothesize that pretreatment with NSAIDs will not only reduce the incidence of flu-like symptoms, but also prove effective for the prevention or reduction of IFN-induced depression.