Depression and Suicidality in Psoriasis and Clinical Studies of Brodalumab: A Narrative Review
Patients with psoriasis have high rates of depression and may be at increased risk for suicidal ideation and behavior (SIB). Attempted and completed suicides during clinical trials and other studies of psoriasis therapies, including brodalumab, highlight the importance of understanding psychiatric risk factors in patients with psoriasis. Recent meta-analyses, research studies, and published data from brodalumab clinical studies were reviewed. We also summarize research on effects of brodalumab on depression symptoms and occurrences of SIB in brodalumab clinical trials. Psoriasis elevates the risk for depression and possible suicide. Brodalumab has a boxed suicide warning; however, it states that there is no established causal association between treatment with brodalumab and increased risk for SIB. Clinicians are urged to evaluate patients with psoriasis for psychiatric risk factors regardless of their therapy and to consider the package insert and a comprehensive evaluation of relevant literature to make a well-balanced decision.
Practice Points
- Psoriasis elevates the risk for depression and possible suicide.
- Dermatologists should be aware that the brodalumab package insert has a boxed warning stating that there is no established causal association between treatment with brodalumab and increased risk for suicidal ideation and behavior.
- Clinicians are urged to evaluate patients with psoriasis for psychiatric risk factors regardless of their therapy.
Despite the boxed warning in the brodalumab package insert concerning suicidality, a causal relationship between brodalumab treatment and increased risk of SIB has not been firmly established.27 The US boxed warning is based on 3 completed suicides and 1 case adjudicated as indeterminate among more than 4000 patients who received at least 1 dose of brodalumab during global clinical trials (0.07% [3/4464]). Compliance in the Risk Evaluation and Mitigation Strategy (REMS) program is mandatory, and patient screening and counseling should not be minimized.27 The 3 completed suicides occurred in patients who reported a history of financial stressors, legal difficulties, or depression and anxiety, and they occurred at least 140 days after initiation of treatment with brodalumab, a chronology that does not support a strong association between brodalumab exposure and SIB.22 Taking into consideration the increased risk for depression among individuals with psoriasis and the details surrounding the 3 completed suicides, an evidence-based causal relationship between brodalumab and increased risk for suicidality cannot be concluded. However, physicians must assess risks and benefits of any therapy in the context of the individual patient’s preferences, risk factors, and response to treatment.
Dermatologists who are aware of the comorbidity between psoriasis and mood disorders play an important role in evaluating patients with psoriasis for psychiatric risk factors.30-32 The dermatologist should discuss with patients the relationship between psoriasis and depression, assess for any history of depression and SIB, and evaluate for signs and symptoms of depression and current SIB.33 Screening tools, including the HADS or the short, easily administered PHQ-234 or PHQ-4,35 can be used to assess whether patients have symptoms of depression.1,36,37 Patients at risk for depression or SIB should be referred to their primary care physician or a mental health care practitioner.37 Currently, there is a gap in knowledge in screening patients for psychiatric issues within the dermatology community33,38; however, health care providers can give support to help bridge this gap.
,Acknowledgments
This study was sponsored by Amgen Inc. Medical writing support was provided under the direction of the authors by Lisa Baker, PhD, and Rebecca E. Slager, PhD, of MedThink SciCom (Cary, North Carolina) and funded by Ortho Dermatologics, a division of Bausch Health US, LLC.
