INTRODUCTION
Psoriasis is a chronic, immune-mediated, inflammatory skin condition that affects 2-3% of the world’s population.1,2 Plaque psoriasis is the most common form of the disease, characterized by the presence of well-demarcated, erythematous, and scaly plaques. Several co-morbid conditions are linked to psoriasis, including inflammatory arthritides, inflammatory bowel disease, and cardio-metabolic disease.3 Importantly, studies have shown that psoriasis patients suffer from a multitude of psychological stressors, as the disease burden can lead to functional disability, social stigmatization, and poor self-image.4 Compared to the general population, patients with psoriasis are at an increased risk of depression—a risk factor for suicidality—even after controlling for other comorbidities.5-8 The presence of systemic inflammation may also contribute to depression and psychological symptoms due to pro-inflammatory cytokines such as tumor necrosis factor(TNF)-α, which are increased in both major depressive disorder and psoriasis.9,10 Over one quarter of psoriasis cases are categorized as moderate-to-severe, with the disease severity often necessitating systemic treatment agents.11 The development of biologic therapies has vastly improved the treatment outlook for these patients, and research continues to explore increasingly specific disease mediators and targeted approaches. In particular, the identification of interleukin (IL)-17 as a fundamental component in the pathogenesis of psoriasis has led to the approval of several new biologics. The currently approved anti-IL-17 agents are secukinumab (COSENTYX®, Novartis, East Hanover, New Jersey), ixekizumab (TALTZ®, Eli Lily, Indianapolis, Indiana), and brodalumab (SILIQ®, Valeant, Bridgewater, New Jersey).Notably, brodalumab carries a boxed warning regarding possible increases in suicidal ideation and behavior (SIB). However, brodalumab demonstrated higher rates of clinical response relative to both placebo and ustekinumab.12 Given the significant capacity of brodalumab to improve disease states in psoriasis patients, there has been close evaluation of the nature and validity of its SIB warning. In this article, we explore the possible link between brodalumab and SIB in the context of its clinical trial data as well as data from other recently approved agents.Psychiatric Co-morbidity in PsoriasisOver the past decade, the risk of psychiatric disease in psoriasis patients has been increasingly recognized and explored. Given the complexity in identifying psychiatric disorders, the most applicable data can be garnered from large scale epidemiological studies.A population-based study from the National Health and Nutrition Examination Survey examined the association between psoriasis and major depression in 12,382 US citizens.5 Among patients with self-reported psoriasis (2.8% of the study population), 16.5% met the criteria for major depression, which was over double the 7.8% prevalence found in the general study population. Psoriasis was significantly associated with major depression even after adjustment for sex, age, race, body mass index (BMI), physical activity, smoking history, alcohol use, history of myocardial infarction, history of stroke, and history of diabetes mellitus (OR 2.09, 95% CI 1.41-3.11).
