Clinical Review

Depression and Suicidality in Psoriasis and Clinical Studies of Brodalumab: A Narrative Review

Cutis. 2019 December;104(06):361-365

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.

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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.

References

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Psoriasis is a chronic inflammatory skin disorder that affects patients’ quality of life and social interactions.^¹ Several studies have shown a strong consistent association between psoriasis and depression as well as possible suicidal ideation and behavior (SIB).^{^1-13} Notable findings from a 2018 review found depression prevalence ranged from 2.1% to 33.7% among patients with psoriasis vs 0% to 22.7% among unaffected patients.^⁷ In a 2017 meta-analysis, Singh et al^² found increased odds of SIB (odds ratio [OR], 2.05), attempted suicide (OR, 1.32), and completed suicide (OR, 1.20) in patients with psoriasis compared to those without psoriasis. In 2018, Wu and colleagues^⁷ reported that odds of SIB among patients with psoriasis ranged from 1.01 to 1.94 times those of patients without psoriasis, and SIB and suicide attempts were more common than in patients with other dermatologic conditions. Koo and colleagues^¹ reached similar conclusions. At the same time, the occurrence of attempted and completed suicides among patients in psoriasis clinical trials has raised concerns about whether psoriasis medications also may increase the risk for SIB.^⁷

We review research on the effects of psoriasis treatment on patients’ symptoms of depression and SIB, with a focus on recent analyses of depressive symptoms and SIB among patients with psoriasis who received brodalumab in clinical trials. Finally, we suggest approaches clinicians may consider when caring for patients with psoriasis who may be at risk for depression and SIB.

MATERIALS AND METHODS

We reviewed research on the effects of biologic therapy for psoriasis on depression and SIB, with a primary focus on recent large meta-analyses. Published findings on the pattern of SIB in brodalumab clinical trials and effects of brodalumab treatment on symptoms of depression and anxiety are summarized. The most recent evidence (January 2014–December 2018) regarding the mental health comorbidities of psoriasis was assessed using published English-language research data and review articles according to a PubMed search of articles indexed for MEDLINE using the following terms: depression, anxiety, suicide, suicidal ideation and behavior, SIB, brodalumab, or psoriasis. We also reviewed citations within articles to identify relevant sources. Implications for clinical care of patients with psoriasis are discussed based on expert recommendations and the authors’ clinical experience.

RESULTS

Effects of Psoriasis Treatment on Symptoms of Depression and Suicidality

Occurrences of attempted suicide and completed suicide have been reported during treatment with several psoriasis medications,^7,9 raising concerns about whether these medications increase the risk for depression and SIB in an already vulnerable population. Wu and colleagues⁷ reviewed 11 studies published from 2006 to 2017 reporting the effects of medications for the treatment of psoriasis—adalimumab, apremilast, brodalumab, etanercept, and ustekinumab—on measures of depression and anxiety such as the Beck Depression Inventory, the Hospital Anxiety and Depression Scale (HADS), and the Patient Health Questionnaire (PHQ) 8. In each of the 11 studies, symptoms of depression improved after treatment, over time, or compared to placebo. Notably, the magnitude of improvement in symptoms of depression was not strongly linked to the magnitude of clinical improvement.⁷ Other recent studies have reported reductions in symptoms of depression with biologic therapies, including adalimumab, etanercept, guselkumab, ixekizumab, secukinumab, and ustekinumab.^14-21

With respect to suicidality, an analysis of publicly available data found low rates of completed and attempted suicides (point estimates of 0.0–0.15 per 100 patient-years) in clinical development programs of apremilast, brodalumab, ixekizumab, and secukinumab. Patient suicidality in these trials often occurred in the context of risk factors or stressors such as work, financial difficulties, depression, and substance abuse.⁷ In a detailed 2016 analysis of suicidal behaviors during clinical trials of apremilast, brodalumab, etanercept, infliximab, ixekizumab, secukinumab, tofacitinib, ustekinumab, and other investigational agents, Gooderham and colleagues⁹ concluded that the behaviors may have resulted from the disease or patients’ psychosocial status rather than from treatment and that treatment with biologics does not increase the risk for SIB. Improvements in symptoms of depression during treatment suggest the potential to improve patients’ psychiatric outcomes with biologic treatment.⁹

FDA approves infliximab-axxq for numerous indications

Depression and Suicidality in Psoriasis and Clinical Studies of Brodalumab: A Narrative Review

References

MATERIALS AND METHODS

RESULTS

Effects of Psoriasis Treatment on Symptoms of Depression and Suicidality

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