By Laura Bush, DMSc, PA-C, DFAAPA
Laura Bush, DMSc, PA-C, DFAAPA, is a dermatology physician assistant at Fayette Area Dermatology in Fayetteville, Georgia. She is a graduate of Emory University in Atlanta, Georgia, and a recent graduate of the University of Lynchburg Doctor of Medical Science program in Lynchburg, Virginia. She has also served on the board of professional societies at both the state and national level.
Disclosures: The author has disclosed no potential conflicts of interest, financial or otherwise, relating to the content of this article.
The purpose of the article is to explain the role of inflammation in psoriasis and its connection to comorbid depression, expand on recognition of depression in psoriasis patients, and explain efficient screening tools, diagnosis, and treatment options for physician assistants.
CME Credit Available. This program has been reviewed and is approved for a maximum of .5 hours of AAPA Category I CME credit by the Physician Assistant Review Panel. Approval is valid for 1 year from the issue date of October 26, 2020. Participants may submit the self-assessment exam at any time during that period. This program was planned in accordance with AAPA’s CME Standards for Enduring Material Programs and for Commercial Support of Enduring Material Programs. SDPA members may access the post-test at https://www.dermpa.org/JDPA_Exams
- Describe the pathophysiology of psoriasis and how the inflammatory process seen in patients with psoriasis may also contribute to comorbidities such as depression.
- Summarize available screening tools designed to help healthcare providers determine if a patient is suffering from depression and list considerations in implementing these into practice.
- Discuss available treatment options that support treating psoriasis and depression concurrently
Psoriasis is a chronic, autoimmune systemic disease affecting roughly 7.5 million people in the United States and more than 125 million worldwide.1-3 Although psoriasis is visualized externally, it is important that healthcare providers are educated on internal processes that contribute to the inflammatory state seen in patients with psoriasis as well as known psoriasis-related comorbidities, such as depression.
Psoriasis can begin with a trigger or injury causing keratinocytes to respond by proliferating at an accelerated rate, causing neovascularization, and recruiting T cells which produce cytokines.4 These cytokines are an active component in the inflammatory process and may play a significant role in associated comorbid conditions.5-8 An elevation of proinflammatory cytokines exists in both psoriasis and depression.5,7,9 Both this potential link with proinflammatory cytokines and the psychosocial effects of such a visible disease can result in the development of depression for those who have psoriasis.3,7,9
Depression, a comorbid condition of psoriasis, can lead to overall adverse health, impacting sleep, sexual function, and increased psychiatric morbidity and mortality.3,8,10,11 Depression can also be associated with anxiety, and possibly give rise to suicidal ideation or suicide.7 Depression associated with psoriasis warrants recognition, screening, diagnosis, treatment, and prevention. Comorbid depression is often under-diagnosed because of a lack of screening and awareness. Without adequate resources, knowledge of available screening tools, and straightforward treatment guidelines, the dermatology clinician caring for patients with psoriasis might face challenges in diagnosing and treating comorbid depression. Streamlining the process of recognizing depression will equip the busy clinician with efficient options for evaluation and treatment.
Although psoriasis is common, there is still much to learn about the cause, pathophysiology, methods to evaluate, and treatment of associated conditions. Psoriasis appears to begin with a stressor that causes an increase in tumor necrosis factor-? (TNF-?), a signaling protein, and release of cytokines Interleukin (IL)-6, IL-12, and IL-23 that activate the naïve T cells to convert to T helper 1 cells (TH-1) and TH-17.4,5,7,9 This cascade causes a release of IL-17 and interferon-ɣ, stimulating rapid keratinocyte proliferation and a flood of immune cells.4,7 The result is an inflamed, thick psoriasis plaque. Although not proven, cytokines and the inflammatory process may play a role in the association of depression and psoriasis.7,8
SCREENING FOR DEPRESSION IN PATIENTS WITH PSORIASIS
Psoriasis-associated depression often goes unrecognized and untreated, which can negatively affect patients. One systematic review and meta-analysis study found that 28 percent of psoriasis patients had symptoms of depression, while 12 percent had clinical depression.12 If clinicians have neither formal psychological training nor expanded knowledge of depression symptoms and treatment, addressing a patient’s mental health state might be uncomfortable for clinician and patient alike.13 Having a quick and simple screening tool available may make the process of screening for depression easier for both the provider and the patient. Screening tools help determine if a patient is suffering from depression and monitor their improvement in treatment. Several easy-to-use options for screening are readily available in print or as computer-generated tools.
The Patient Health Questionnaire. The Patient Health Questionnaire (PHQ) has credible reliability and validity in screening for depression.10,11,14,15 One version of the PHQ, the PHQ-9, demonstrates high validity (area under receiver operating characteristic curve [AUROC] 0.85, 95% confidence interval [CI] 0.82-0.88]) with 49 percent sensitivity and 94 percent specificity.15 At the same time, the PHQ-2 was also valid (AUROC 0.76, 95% CI 0.73-0.79), although to a lesser degree, with sensitivity 60 percent and specificity 84 percent.15 In comparison, the PHQ-2 has only two questions, while the PHQ-9 is more comprehensive with nine questions.15 The PHQ-2 has the advantage of being very quick to complete.15,16 However, if positive, the patient may be given the PHQ-9 for confirmation.
The Patient-Reported Outcomes Measurement Information System-Depression. The Patient-Reported Outcomes Measurement Information System-Depression (PROMIS-D) developed by the National Institutes of Health (NIH), is patient-reported. In a recent article published in the British Journal of Dermatology, Gaufin et al found that the PROMIS-D was significantly better at identification than PHQ-9 (p<0.01).16 In comparison, the PROMIS-D is longer than the PHQ-9 but can be done at home and has a built-in system to flag patients screening positive for moderate to severe depression.16 Every practice is different; factors to consider might be location, language barriers, and time available when choosing the right screening tool. PROMIS-D is advantageous as it is reliable, convenient, and accessible in many languages.16 It is patient-reported electronically; therefore, the PROMIS-D can be done at home and integrated digitally into a patient’s chart.16
Other Tools and Considerations for Use. The Hospital Anxiety and Depression Scale (HADS) is frequently used in research but would not be as useful in a dermatology care setting because it is provider-driven and has associated costs to administer. The Beck Depression Inventory-Second Edition (BDI-II), with sensitivity 88 percent and specificity 92.1 percent, is a valid and reliable tool comparable to the PHQ-9, but the PHQ-9 is free, shorter, and easier to use.13,14 Therefore, a reasonable choice would be a printed PHQ-2, PHQ-9, or an electronic PROMIS-D, which are all patient-driven. It is best to have a consistent procedure for evaluation and follow up with whichever screening tool is used. The screening tools are summarized in Table 1.
TREATING PSORIASIS FROM THE INSIDE OUT
The treatment options for psoriasis have grown and improved over the past decade. In dermatology, we often appropriately reach for a topical steroid or a vitamin D analog to treat the skin; however, when considering inflammation-driven comorbidities, drug choice should focus on the internal process of psoriasis. Patients’ skin often flares when under stress, supporting treatment of both psoriasis and depression concurrently.17
Biologics. Multiple studies report the improvement of depression using biologic therapies.8,17 TNF inhibitors and IL-12/23 blockers have shown to improve depression in several randomized controlled studies.8,17,18 This improvement may be partially due to the biologics targeting the inflammatory cytokines resulting in skin clearance, leading to improved self-image and quality of life.8,9,17,18
TNF inhibitors. The TNF inhibitors are a class of biologic medication that block TNF-?.19 These include etanercept, adalimumab, infliximab, and certolizumab.19 They were often first-line agents in psoriasis unless otherwise contraindicated, however, as more treatment options are available, this is changing. Most research on treatment with biologics has been with the anti–TNF-?. Etanercept, adalimumab, and a small case study on infliximab all show improvement in psoriasis and depressive symptoms.8,17-19
IL-12/23, IL-17, and IL-23. The next biologic proven to be effective in treating moderate-severe psoriasis as well as decreasing comorbid depressive symptoms is ustekinumab, an IL-12/23 blocker.8,10,18,19 High IL-17 levels are present in patients with major depression.9 Secukinumab, ixekizumab, and brodalumab are three available IL-17 blockers indicated for the treatment of psoriasis.19 Because of observed suicidal behavior in subjects treated with brodalumab, it is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS). Given the potential risks and benefits of biologic use in patients with a history of depression and/or suicidal ideation or behavior, IL-17 blockers warrant further investigation in the treatment of psoriasis with comorbid depression.9,19
The newer IL-23 class, including guselkumab, tidrakizumab, and risankizumab, improve psoriasis, and although not studied in depression, could, in theory, result in improvement, from clearance of skin lesions and improved psychosocial implications.19 When selecting a biologic, the provider must consider the patient’s comorbidities and their overall medical condition.
Biosimilars. Biosimilars have recently become available as an alternative for many psoriasis biologic medications. They are complex proteins produced to be highly similar in function to traditional biologic medication.20 Many steps are involved in the production of biosimilars, therefore, variations in manufacturing result in different biosimilar batches.20 Each batch is unique but similar to other batches and other biologics.20 Biosimilars are not identical copies of a biologic medication and are not considered generics.20 Although not yet commonly used, these biosimilars will likely become a popular and lower-cost option to traditional biologics for psoriasis treatment along with other autoimmune inflammatory disorders.
IDENTIFYING AND TREATING PATIENTS WITH PSORIASIS-ASSOCIATED DEPRESSION
Education. It is essential to discuss significant psoriasis comorbidities, including the elevated risk of anxiety and depression.18 Patients might feel the stigma associated with depression or be unaware that they are experiencing depressive symptoms.18 Thus, the use of a screening tool at this juncture can help the clinician identify those at risk for depression and provide an opportunity for treatment discussion, ultimately serving as a preventative measure. Once a patient is identified as having depressive symptoms, counseling, support groups, or referral to psychiatry may be warranted.11,13 Several agents can also be considered for treating depression, such as selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitor (SNRIs), or tricyclic antidepressants (TCAs).11
SSRIs. SSRIs are both effective and tolerable antidepressants, making them a favorable first choice, with fluoxetine and sertraline most commonly used.11,13 Sertraline proved to be the best first option, starting at 50 mg each day and increasing 25 mg weekly if needed to a max dose of 200 mg daily.13 Venlafaxine, a serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant medication, is another option.13
TCAs. TCAs are one of the first classes of medication used to treat depression. When a patient’s depressive symptoms center around itching and sleep disturbances, the tricyclic antidepressant doxepin is an option.13 Doxepin dosing starts at 25 mg titrating up every week to 100 to 150 mg per day.13 TCAs have a lethal dose, contradicting their use if any suicide risk exists.13
At this time, the cytokine association with depression is theory. Future studies on the connection may lead to a better understanding of the association. Since current studies on psoriasis patients are not consistent in the screening instruments used to diagnose depression, a more standardized method in studying depression with consistent tools could yield a better comparison.
Psoriasis is a disease that encompasses more than what is visible on the skin. When caring for patients with psoriasis, it is equally important to consider what is happening inside along with outside the body. Treating the internal factors associated with the inflammation, as well as the outside factors, like the skin, is vital to the comprehensive care of patients with psoriasis. Dermatology physician assistants should educate patients on the association of depression with psoriasis, screen the patient with one of the available patient-driven screening tools, such as the PHQ-2, PHQ-9, or PROMIS-D, and observe them for any signs and symptoms of depression during the exam as patients often do not report symptoms because of fear or stigma. The inflammatory process as well as the psychosocial aspects of having psoriasis are implicated in depression.5,7,8,13,18 Multiple studies favor using a biologic medication to manage psoriasis and depression with referral to psychiatry or adding antidepressant medicines if needed.8,11,13,18 Recognizing comorbid depression and choosing the right treatment plan, including medication, counseling, and referrals, are essential to decreasing morbidity and mortality associated with psoriasis.
- Takeshita J, Grewal S, Langan SM, et al. Psoriasis and comorbid diseases part I. epidemiology. Journal of the American Academy of Dermatology. 2017;76(3):377. Accessed Aug 18, 2019. doi: 10.1016/j.jaad.2016.07.064.
- Rachakonda TD, Schupp CW, Armstrong AW. Psoriasis prevalence among adults in the united states. Journal of the American Academy of Dermatology. 2014;70(3):512-516. Accessed August 20, 2019. doi: 10.1016/j. jaad.2013.11.013.
- Mahmutovic J, Zukic M, Pasalic A, Brankovic S, Jaganjac A, Katana B. Correlation between quality of life and depression among persons suffering from psoriasis. Medical Archives. 2017;71(5):341. Accessed Sep 1, 2019. doi: 10.5455/medarh.2017.71.341-346.
- Baliwag J, Barnes DH, Johnston A. Cytokines in psoriasis. Cytokine. 2015;73(2):342-350. Accessed Oct 24, 2019. doi: 10.1016/j.cyto.2014.12.014.
- Farzanfar D, Dowlati Y, French LE, Lowes MA, Alavi A. Inflammation: A contributor to depressive comorbidity in inflammatory skin disease. Skin pharmacology and physiology. 2018;31(5):246-251. doi: 10.1159/000490002.
- Aleem D, Tohid H. Pro-inflammatory cytokines, biomarkers, genetics and the immune system: A mechanistic approach of depression and psoriasis. Revista Colombiana de Psiquiatría. 2018;47(3):177-186. doi: 10.1016/j. rcp.2017.03.002.
- 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. Accessed August 18, 2019. doi: 10.1111/jdv.14460.
- González-Parra S, Daudén E. Psoriasis and depression: The role of inflammation. Actas Dermo-Sifiliográficas (English Edition). 2019;110(1):12-
19. doi: 10.1016/j.ad.2018.05.009.
- Patel N, Nadkarni A, Cardwell L, et al. Psoriasis, depression, and inflammatory overlap: A review. American Journal of Clinical Dermatology. 2017;18(5):613-
620. doi: 10.1007/s40257-017-0279-8.
- Korman AM, Hill D, Alikhan A, Feldman SR. Impact and management of depression in psoriasis patients. Expert Opin Pharmacother. 2016;17(2):147-152. doi: 10.1517/14656566.2016.1128894
- Kolli SS, Amin SD, Pona A, Cline A, Feldman SR. Psychosocial impact of psoriasis: A review for dermatology residents. Cutis. 2018;102(5S):21-25. https://pubmed.ncbi.nlm.nih.gov/30566553/. Accessed Feb 23, 2020.
- 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. Journal of Investigative Dermatology. 2014;134(6):1542-1551. doi: 10.1038/jid.2013.508.
- Connor CJ. Management of the psychological comorbidities of dermatological conditions: Practitioners’ guidelines. Clinical, Cosmetic and Investigational Dermatology. 2017;10:117. Accessed Dec 4, 2019. doi: 10.2147/CCID.S111041.
- Smarr KL, Keefer AL. Measures of depression and depressive symptoms: Beck depression inventory-II (BDI-II), center for epidemiologic studies depression scale (CES-D), geriatric depression scale (GDS), hospital anxiety and depression scale (HADS), and patient health questionnaire-9 (PHQ-9). Arthritis Care Res. 2011;63:S454-S466. doi: 10.1002/acr.20556.
- Bhana A, Rathod SD, Selohilwe O, Kathree T, Petersen I. The validity of the patient health questionnaire for screening depression in chronic care patients in primary health care in South Africa. BMC Psychiatry. 2015;15:118. Accessed May 31, 2020. doi: 10.1186/s12888-015-0503-0.
- Gaufin M, Hess R, Hopkins ZH, Biber JE, Secrest AM. Practical screening for depression in dermatology: Using technology to improve care. Br J Dermatol. 2020;182(3):786-787. doi: 10.1111/bjd.18514.
- Elmets CA, Leonardi CL, Davis DMR, et al. Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with awareness and attention to comorbidities. Journal of the American Academy of Dermatology. 2019;80(4):1073-1113. doi: 10.1016/j.jaad.2018.11.058.
- Fleming P, Roubille C, Richer V, et al. Effect of biologics on depressive symptoms in patients with psoriasis: A systematic review. J Eur Acad Dermatol Venereol. 2015;29(6):1063-1070. doi: 10.1111/jdv.12909.
- Mikhaylov D, Hashim PW, Nektalova T, Goldenberg G. Systemic psoriasis therapies and comorbid disease in patients with psoriasis: A review of potential risks and benefits. The Journal of Clinical and Aesthetic Dermatology. 2019;12(6):46. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6624011/6624011/. Accessed Feb 23, 2020.
- Yamauchi P, Crowley J, Kaur P, Spelman L, Warren R. Biosimilars: What the dermatologist should know. J Eur Acad Dermatol Venereol. 2018;32(7):1066-1074. doi: 10.1111/jdv.14812.