Should Package Insert Warnings Deter Prescribing in Psoriasis Patients with Depression?

Main Article Content

Graham H Litchman DO, MS
Quinn Thibodeaux
Ryan Rivera-Oyola
John Koo
Rick Fried
Gary Goldenberg
George Han
Sylvia Hsu
Leon Kircik
Melissa Knuckles
Andrea Murina
Jashin Wu
Mark Lebwohl

Keywords

Psoriasis, Suicidality, Depression, Apremilast, Brodalumab

Abstract

Introduction: Psoriasis, an immune-mediated disease that manifests cutaneously with possible arthritic complications, affects millions of people in the United States and worldwide. Depression and suicidal ideation and behavior (SIB) are two prevalent comorbidities associated with psoriasis, due to the chronic nature of the disease, lack of a cure, as well as social stigma, all of which are detrimental to quality of life. Among the options available for management of moderate-severe psoriasis, apremilast and brodalumab represent recent additions to the therapeutic armamentarium for managing psoriasis. It has been suggested that the aforementioned drugs can lead to depression and possibly increase the risk for SIB. Furthermore, a black box warning was issued for brodalumab. This review challenges opinions that the drugs are solely responsible for exacerbating depression and SIB, when in fact it could be psoriasis itself.


Methods: An extensive search of available literature linking cytokines to suicidal behavior was performed. After filtering for relevance, 22 articles were reviewed in detail.


Results: Brodalumab and apremilast, both molecularly and clinically, do not objectively increase the risk for depression and/or suicidal ideation and behavior.


Conclusion: After careful review of the appropriate studies and relevant literature, patients with moderate-severe psoriasis, including those that experience depression resulting from their chronic condition, would likely benefit from early, rather than delayed initiation of effective medications like apremilast and brodalumab. The speed of response and high level of efficacy of brodalumab make it an ideal intervention for patients suffering depression caused by their psoriasis.

References

1. Parisi R, Symmons DP, Griffiths CE, Ashcroft DM; Identification and Management of Psoriasis and Associated ComobidiTY (IMPACT) project team. Global epidemiology of psoriasis: a systematic review of incidence and prevalence. J Invest Dermatol. 2013 Feb;133(2):377-85.

2. Foulkes AC, Warren RB. Brodalumab in psoriasis: evidence to date and clinical potential. Drugs Context. 2019 Apr 17;8:212570.

3. Stern RS, Nijsten T, Feldman SR, Margolis DJ, Rolstad T. Psoriasis is common, carries a substantial burden even when not extensive, and is associated with widespread treatment dissatisfaction. J. Investig. Dermatol. Sympos. Proc. 2004 Mar;9(2):136-139.

4. Lebwohl, MG, Papp KA, Marangell LB, Koo J, Blauvelt A, Gooderham M, Wu JJ, Rastogi S, Harris S, Pillai R, Israel RJ. Psychiatric adverse events during treatment with brodalumab: Analysis of psoriasis clinical trials. J Am Acad Dermatol. 2018 Jan;78(1): 81-89.

5. Ganança L, Ouquendo MA, Tyrka AR, Cisneros-Trujillo S, Mann JJ, Sublette ME. The role of cytokines in the pathophysiology of suicidal behavior. Psychoneuroendocrinology. 2016;63:296-310.

6. Davami MH, Baharlou R, Ahmadi Vasmehjani A, Ghanizadeh A, Keshtkar M, Dezkham J, ATashzar MR. Elevated IL-17 and TGF- serum levels: a positive correlation between T-helper 17 cell-related pro-inflammatory responses with major depressive disorder. Basi Clin. Neurosci. 2016 Apr;7(2):137-142.

7. Nadeem A, Ahmad SF, Al-Harbi NO, Fardan AS, EL-Sherbeeny AM, Ibrahim KE, Attia SM. IL-17A causes depression-like symptoms via NFB and p38MAPK signaling pathways in mice: implications for psoriasis associated depression. Cytokine. 2017 Sept;97:14-24.

8. Tsuboi H, Sakakibara H, Minamida Y, Tsujiguchi H, Matsunaga M, Hara A, Nakamura H. Elevated levels of serum IL-17A in community-dwelling women with higher depressive sumptoms. Behav. Sci. (Basel). 2018 Nov;8(11):102-108.

9. Raison CL, Capuron L, Miller AH. Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol. 2006 Jan;27(1):24-31.

10. Schafer P. Apremilast mechanism of action and application to psoriasis and psoriatic arthritis. Biochem. Pharmacol. 2012;(83(12):1583-1590.

11. European Medicines Agency. (2014). Assessment Report: Otezla. Retrieved from https://www.ema.europa.eu/en/documents/assessment-report/otezla-epar-public-assessment-report_en.pdf.

12. Crowley J, Thaçi D, Joly P, Peris K. et al. Long-term safety and tolerability of apremilast in patients with psoriasis: Pooled safety analysis for ≥ 156 weeks from 2 phase 3, randomized, controlled trials (ESTEEM 1 and 2). J Am Acad Dermatol. 2017;77(2):310-317.

13. Gooderham M, Papp K. Selective phosphodiesterase inhibitors for psoriasis, focus on apremilast. Biodrugs. 2015;29(5):327-339.

14. Dowlayshahi EA, Wakkee M, Arends LR, Nijsten T. The prevalence and odds of depressive symptoms and clinical depression in psoriasis patients: a systematic review and meta-analysis. J Invest Dermatol. 2014;134(6):1542-1551.

15. Kavanaugh A, Gladman DD, Edwards CJ, Schett G, Guerette B, Delev N, Teng L, Paris M, Mease PJ. Long-term experience with apremilast in patients with psoriatic arthritis: 5-year results from a PALACE 1-3 pooled analysis. Arthritis Res. Ther. 2019;21(118).

16. Menter A, Strober BE, Kaplan DH, Kivelevitch D et al. Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with biologics. J. Amer. Acad. Dermatol. 2019 Apr;80(4):1029-1072.

17. European Medicines Agency. (2016). Assessment Report: Taltz. Retrieved from https://www.ema.europa.eu/en/documents/assessment-report/taltz-epar-public-assessment-report_en.pdf.

18. Pan W, Kastin, AJ. Changing the chemokine gradient: CINC1 crosses the blood-brain barrier. J. Neuroimmunol. 2011;115(1-2):64-70.

19. Banks WA. Characteristics of compounds that cross the blood-brain barrier. BMC Neurology. 2009;9(Suppl. 1):S3.

20. Papp KA, Reich K, Paul C, Blauvelt A, Baran W, Bolduc C, Toth D, Langley RG, Cather J, Gottlieb AB, Thaçi D, Kreuger JG, Russell CB, Milmont CE, Li J, Klekotka PA, Kricorian G, Nirula A. A prospective phase III, randomized, double-blind, placebo-controlled study brodalumab in patients with moderate-to-severe plaque psoriasis. Br J Dermatol. 2016 Aug;175(2):273-286.

21. Kaushik SB, Lebwohl MG. Psoriasis: Which Therapy for Which Patient:
Psoriasis comorbidities and preferred systemic agents. J Am Acad Dermatol. 2019;80(1):27-40.

22. Kaushik SB, Lebwohl MG. Psoriasis: Which Therapy for Which Patient. Focus on special populations and chronic infections. J Am Acad Dermatol. 2019;80(1):43-53.

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