Review of suicide and depression in psoriasis and management of suicide warnings in patients treated with psoriasis drugs

Main Article Content

Emily Lebowitz
Mark Lebwohl

Keywords

Psoriasis, depression, suicide, apremilast, brodalumab

Abstract

Patients with psoriasis are thought to be at increased risk of depression, anxiety and suicidality predominantly as a result of the psychosocial impact of this disease. Studies have shown that the pro-inflammatory cytokines that are elevated in psoriasis and targeted by biologics have also been identified in patients with depression. It is therefore thought that anti-cytokine therapies may improve patients’ quality of life not only by reducing their disease burden but also by modulating the inflammatory pathways implicated in depression. While depression is mentioned in the package inserts of brodalumab and apremilast, only brodalumab has a black box warning requiring discussion of suicidality prior to prescribing the drug. In clinical trials, the majority of patients receiving brodalumab experience a reduction in symptoms of depression and anxiety. The package insert for brodalumab points out that no causal association has been established between brodalumab and suicide, and the FDA-mandated Risk Evaluation and Mitigation Strategies (REMS) program for brodalumab takes only minutes to complete. Brodalumab and apremilast may therefore be considered for patients in whom depression is caused by psoriasis, provided that patients and their providers have a mutual understanding of the risks and benefits of these therapies and the REMS program is followed. 

References

1. Kurd SK, Troxel AB, Crits-Christoph P, Gelfand JM. The risk of depression, anxiety, and suicidality in patients with psoriasis: a population-based cohort study. Arch Dermatol. 2010;146(8):891-895.

2. Dowlatshahi 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.

3. Dommasch ED, Li T, Okereke OI, Li Y, Qureshi AA, Cho E. Risk of depression in women with psoriasis: a cohort study. Br J Dermatol. 2015;173(4):975-980.

4. Cohen BE, Martires KJ, Ho RS. Psoriasis and the Risk of Depression in the US Population: National Health and Nutrition Examination Survey 2009-2012. JAMA Dermatol. 2016;152(1):73-79.

5. Egeberg A, Thyssen JP, Wu JJ, Skov L. Risk of first-time and recurrent depression in patients with psoriasis - a population-based cohort study. Br J Dermatol. 2018.

6. Wu JJ, Penfold RB, Primatesta P, et al. The risk of depression, suicidal ideation and suicide attempt in patients with psoriasis, psoriatic arthritis or ankylosing spondylitis. J Eur Acad Dermatol Venereol. 2017;31(7):1168-1175.
7. Devrimci-Ozguven H, Kundakci TN, Kumbasar H, Boyvat A. The depression, anxiety, life satisfaction and affective expression levels in psoriasis patients. J Eur Acad Dermatol Venereol. 2000;14(4):267-271.

8. Patel N, Nadkarni A, Cardwell LA, Vera N, Frey C, Feldman SR. Psoriasis, Depression, and Inflammatory Overlap: A Review. Am J Clin Dermatol. 2017;18(5):613-620.

9. Langley RG, Feldman SR, Han C, et al. Ustekinumab significantly improves symptoms of anxiety, depression, and skin-related quality of life in patients with moderate-to-severe psoriasis: Results from a randomized, double-blind, placebo-controlled phase III trial. J Am Acad Dermatol. 2010;63(3):457-465.

10. Krishnan R, Cella D, Leonardi C, et al. Effects of etanercept therapy on fatigue and symptoms of depression in subjects treated for moderate to severe plaque psoriasis for up to 96 weeks. Br J Dermatol. 2007;157(6):1275-1277.

11. Menter A, Augustin M, Signorovitch J, et al. The effect of adalimumab on reducing depression symptoms in patients with moderate to severe psoriasis: a randomized clinical trial. J Am Acad Dermatol. 2010;62(5):812-818.

12. Griffiths CEM, Fava M, Miller AH, et al. Impact of Ixekizumab Treatment on Depressive Symptoms and Systemic Inflammation in Patients with Moderate-to-Severe Psoriasis: An Integrated Analysis of Three Phase 3 Clinical Studies. Psychother Psychosom. 2017;86(5):260-267.

13. Feldman SR, Gottlieb AB, Bala M, et al. Infliximab improves health-related quality of life in the presence of comorbidities among patients with moderate-to-severe psoriasis. Br J Dermatol. 2008;159(3):704-710.

14. Johnston A, Fritz Y, Dawes SM, et al. Keratinocyte overexpression of IL-17C promotes psoriasiform skin inflammation. J Immunol. 2013;190(5):2252-2262.

15. Lowes MA, Kikuchi T, Fuentes-Duculan J, et al. Psoriasis vulgaris lesions contain discrete populations of Th1 and Th17 T cells. J Invest Dermatol. 2008;128(5):1207-1211.

16. Papp KA, Leonardi C, Menter A, et al. Brodalumab, an anti-interleukin-17-receptor antibody for psoriasis. N Engl J Med. 2012;366(13):1181-1189.

17. Papp KA, Reich K, Paul C, et al. A prospective phase III, randomized, double-blind, placebo-controlled study of brodalumab in patients with moderate-to-severe plaque psoriasis. Br J Dermatol. 2016;175(2):273-286.

18. Lebwohl MG, Papp KA, Marangell LB, et al. Psychiatric adverse events during treatment with brodalumab: Analysis of psoriasis clinical trials. J Am Acad Dermatol. 2018;78(1):81-89.e85.

19. Chiricozzi A, Romanelli M, Saraceno R, Torres T. No meaningful association between suicidal behavior and the use of IL-17A-neutralizing or IL-17RA-blocking agents. Expert Opin Drug Saf. 2016;15(12):1653-1659.

20. Schafer PH, Parton A, Gandhi AK, et al. Apremilast, a cAMP phosphodiesterase-4 inhibitor, demonstrates anti-inflammatory activity in vitro and in a model of psoriasis. Br J Pharmacol. 2010;159(4):842-855.

21. Papp K, Cather JC, Rosoph L, et al. Efficacy of apremilast in the treatment of moderate to severe psoriasis: a randomised controlled trial. Lancet. 2012;380(9843):738-746.

22. Papp K, Reich K, Leonardi CL, et al. Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, in patients with moderate to severe plaque psoriasis: Results of a phase III, randomized, controlled trial (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM] 1). J Am Acad Dermatol. 2015;73(1):37-49.

23. Stein Gold L, Bagel J, Lebwohl M, et al. Efficacy and Safety of Apremilast in Systemic- and Biologic-Naive Patients With Moderate Plaque Psoriasis: 52-Week Results of UNVEIL. J Drugs Dermatol. 2018;17(2):221-228.

24. Crowley J, Thaçi D, Joly P, 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.e311.

25. Ighani A, Georgakopoulos JR, Shear NH, Walsh S, Yeung J. Long-term 52-week trends in apremilast safety outcomes for treatment of psoriasis in clinical practice: a multicentre, retrospective case series. Br J Dermatol. 2018.

26. Lee EB, Amin M, Egeberg A, Wu JJ. Adverse events associated with apremilast use and withdrawal for psoriasis in a real-world setting. J Eur Acad Dermatol Venereol. 2018;32(10):e393-e394.

27. Papadavid E, Rompoti N, Theodoropoulos K, Kokkalis G, Rigopoulos D. Real-world data on the efficacy and safety of apremilast in patients with moderate-to-severe plaque psoriasis. J Eur Acad Dermatol Venereol. 2018;32(7):1173-1179.

28. Tohid H, Aleem D, Jackson C. Major Depression and Psoriasis: A Psychodermatological Phenomenon. Skin Pharmacol Physiol. 2016;29(4):220-230.

29. Koo J, Marangell LB, Nakamura M, et al. Depression and suicidality in psoriasis: review of the literature including the cytokine theory of depression. J Eur Acad Dermatol Venereol. 2017;31(12):1999-2009.

30. Brustolim D, Ribeiro-dos-Santos R, Kast RE, Altschuler EL, Soares MB. A new chapter opens in anti-inflammatory treatments: the antidepressant bupropion lowers production of tumor necrosis factor-alpha and interferon-gamma in mice. Int Immunopharmacol. 2006;6(6):903-907.

31. Jha MK, Minhajuddin A, Gadad BS, Greer TL, Mayes TL, Trivedi MH. Interleukin 17 selectively predicts better outcomes with bupropion-SSRI combination: Novel T cell biomarker for antidepressant medication selection. Brain Behav Immun. 2017;66:103-110.

32. Kappelmann N, Lewis G, Dantzer R, Jones PB, Khandaker GM. Antidepressant activity of anti-cytokine treatment: a systematic review and meta-analysis of clinical trials of chronic inflammatory conditions. Mol Psychiatry. 2018;23(2):335-343.

33. Kannan S, Heller MM, Lee ES, Koo JY. The role of tumor necrosis factor-alpha and other cytokines in depression: what dermatologists should know. J Dermatolog Treat. 2013;24(2):148-152.

34. Tyring S, Gottlieb A, Papp K, et al. Etanercept and clinical outcomes, fatigue, and depression in psoriasis: double-blind placebo-controlled randomised phase III trial. Lancet. 2006;367(9504):29-35.

35. Gordon KB, Armstrong AW, Han C, et al. Anxiety and depression in patients with moderate-to-severe psoriasis and comparison of change from baseline after treatment with guselkumab vs. adalimumab: results from the Phase 3 VOYAGE 2 study. J Eur Acad Dermatol Venereol. 2018;32(11):1940-1949.

36. Kimball AB, Leonardi C, Stahle M, et al. Demography, baseline disease characteristics and treatment history of patients with psoriasis enrolled in a multicentre, prospective, disease-based registry (PSOLAR). Br J Dermatol. 2014;171(1):137-147.

37. Strober B, Gooderham M, de Jong EMGJ, et al. Depressive symptoms, depression, and the effect of biologic therapy among patients in Psoriasis Longitudinal Assessment and Registry (PSOLAR). J Am Acad Dermatol. 2018;78(1):70-80.

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