Can Systemic Inflammation Influence Mood?

Rheumatologists routinely deal with mood issues that may shroud the benefits of the drugs we prescribe.
Image Credit: Bruce Rolff/shutterstock.com

The Friday night press release: When a politician or any public figure needs to disclose unfavorable news, chances are they will release it sometime on a late Friday afternoon or evening, hoping that nobody is paying attention. In fact, this behavior was coined “the take out the trash day” on the television political drama, The West Wing. The likelihood of a press release fading into oblivion gets even better whenever it is disclosed on the Friday before a long weekend break. Guaranteed to achieve complete obscurity, or so claim the consultants who specialize in these sorts of things.

The press release dated Friday, May 22, 2015, at the start of the Memorial Day long weekend was decidedly low key.¹ Most of its 1,200-plus words consisted of boilerplate jargon, but the first sentence said it all: “Amgen today announced (it) has commenced termination of its participation in the co-development and commercialization of brodalumab with AstraZeneca. Brodalumab, an investigational IL-17 inhibitor, is in development for patients with moderate-to-severe plaque psoriasis, psoriatic arthritis and axial spondyloarthritis. The decision was based on events of suicidal ideation and behavior in the brodalumab program, which Amgen believes likely would necessitate restrictive labeling.”

Have I read this correctly? Do we have our drug classes confused? As rheumatologists, we are accustomed to dealing with mood issues that may shroud the benefits of some of the drugs that we prescribe: Pain-modifying medicines, such as pregabalin and tramadol, are frequent offenders, and rarely, antimalarial agents, such as hydroxychloroquine, precipitate nightmares. Of course, corticosteroids are the greatest mood-offending drugs we prescribe. How often have we witnessed a troubling steroid-induced mood swing or, even worse, the unmasking of an underlying psychosis? Even lower doses of steroids are not immune, because they too can create feelings of anxiety or depression in some individuals.

In contrast, scant evidence implicates biological therapies as drivers of mood disorders. One exception may be belimumab. The data submitted to the Food and Drug Administration (FDA) by its manufacturer included information on a total of seven suicide attempts that were recorded in the various study protocols of this anti-B cell therapy.² To use drug-study parlance, three were completed suicides. In contrast, data derived from the FDA’s spontaneous report system concluded that the rate of suicide and depression among users of TNF-inhibiting drugs was not disproportionate to the frequency of their use.³ This latter observation is in keeping with what we see in clinical practice. If anything, because biological therapies frequently enhance the quality our patients’ lives, they may indirectly improve their mood.