Impact and management of depression in psoriasis patients

1. Introduction

Psoriasis causes emotional and social burdens [1,2]. Psoriasis patients are 1.5 times more likely to experience depression compared to those without psoriasis (odds ratio 1.57; 95% confidence interval 1.40–1.76) [3]. The proportion of psoriasis patients who have depressive symptoms ranges from 9% to 55%, likely due to differences in screening methods and study populations (Table 1).

Table 1. Most common questionnaires and clinical tools used to screen for depression in psoriasis patients.

Screening tool	Number of items	Number of studies analyzed	Psoriasis patients with depressive symptoms (%)
Clinical judgment	-	1	26
ICD-codes	-	10	12
Antidepressant use	-	10	9
Patient Health Questionnaire-9	9	1	16.5
DSM-IV criteria	9	4	19
Hospital Anxiety and Depression Scale*	14	19	23
Zung Self-Rating Depression Scale	20	2	37
Center for Epidemiologic Studies Depression Scale	20	3	55
Beck Depression Inventory	21	10	36
Hamilton Rating Scale for Depression	21	2	25

Questionnaires and clinical tools vary in their estimates of the proportion of psoriasis patients with depression. *Most commonly used. ICD: International Classification of Disease; DSM: Diagnostic and Statistical Manual of Mental Disorders.

Estimated adherence to therapies is 40–50% [4,5]. Psychiatric comorbidity is a strong predictor of poor adherence [6,7]. Depression in psoriasis patients may reduce adherence to treatment, resulting in worse psoriasis and more depression [7].

Managing depression may improve adherence and outcomes. To treat depression, it must be detected. Dermatologists’ clinical judgment has a sensitivity and specificity of 60% and 21% for detecting depression [8]. Clinical judgment of depression in psoriasis patients, unaided by formal measures, is poor.

This study reviews factors relating to depression in psoriasis patients, estimates the proportion of psoriasis patients with depression and the effect depression has on adherence in psoriasis patients, and discusses management of depression in psoriasis patients. The study also proposes an algorithm for detecting and managing depression in psoriasis patients using two easy-to-use, validated questionnaires.

2. Methods

2.1. Determination of factors relating to depression in psoriasis

PubMed was systematically searched using the terms ‘depression and psoriasis’ and ‘factors and depression and psoriasis’ to identify six critical factors that were frequently cited as associated with depression in psoriasis patients.

2.2. Assessment, management, and impact of managing depression in psoriasis

PubMed and Google Scholar were systemically searched using the terms ‘assessment and depression and psoriasis’ and ‘management and depression and psoriasis’ for the latest literature on assessing, managing, and the impact of managing depression in psoriasis patients.

2.3. Algorithm design

An algorithm to help physicians screen for depression in psoriasis patients was designed using published data on appropriate score cut-offs used in the Patient Health Questionnaire-2 (PHQ-2) and Patient Health Questionnaire-9 (PHQ-9) for detecting depression.

3. Results

3.1. Factors caused by depression in psoriasis

3.1.1. Sexual dysfunction

Psoriasis patients experience sexual dysfunction at higher rates than the general population, with 53.7% versus 17.5% affected, respectively (P < .001) [9]. Psoriasis patients with depression have higher rates of sexual dysfunction than psoriasis patients without depression [9].

3.1.2. Suicidal ideation

Psoriasis patients experience suicidal ideation more than twice as much as the general population, with 17.3% versus 8.2% affected, respectively (P < .001).[10] Additionally, the incidence of suicidality is 44% higher in psoriasis patients than the general population [11].

3.1.3. Sleep disturbances

Psoriasis patients experience sleep disturbances significantly more often than the general population, with 81.8% versus 59.1% affected, respectively (P = .008).[12]

Importantly, the association of these disorders with psoriasis cannot be definitively attributed to depression.

3.2. Factors that contribute to depression in psoriasis

3.2.1. Pruritus

Pruritus is a prominent symptom of psoriasis. The severity of pruritus in psoriasis patients positively correlates with the severity of depression (P = .034) [13]. A post-hoc analysis of a randomized, double-blind trial of etanercept in 270 patients with moderate-to-severe plaque psoriasis found that clinically apparent improvement in pruritus led to a 42% reduction in depression as measured by the Hospital Anxiety and Depression Scale [13].

3.2.2. Stigmatization

Psoriasis patients often feel stigmatized due to the presence of visible psoriatic lesions and the resulting reactions of disgust and/or fear from other people. The severity of stigmatization in psoriasis patients is significantly positively correlated with the severity of depression.[14]

3.2.3. Psoriatic arthritis

Psoriatic arthritis, which is characterized by pain, swelling, tenderness, and possibly destruction of the joints, occurs in up to 30% of psoriasis patients with up to 15.5% of psoriasis patients having undiagnosed psoriatic arthritis [15]. Psoriasis patients with psoriatic arthritis have significantly increased rates of depression compared to those without psoriatic arthritis (P = .002) [16].

3.3. Assessment of depression in psoriasis

Depression in psoriasis patients can be assessed by dermatologist-subjective clinical judgment, questionnaires, International Classification of Disease codes, and DSM-IV/V criteria; the most common method in clinical practice is clinician judgment, while the most common method in research studies is questionnaire use [3]. About one in four psoriasis patients has depression by dermatologists’ judgment (Table 1) [8]. Questionnaires and clinical tools find depressive symptoms in 9–55% of psoriasis patients (Table 1) [3,17]. Depression detection in psoriasis patients is currently limited by three factors: variability of detection by the currently available questionnaires, no questionnaire has been designed and validated for dermatologic populations, and limited use and familiarity of questionnaires among dermatologists [3].

3.4. Impact of treating depression in psoriasis patients

The treatment of depression in psoriasis includes both nonpharmacologic and pharmacologic options. Nonpharmacologic modalities, including cognitive behavioral therapy and other techniques used to reduce stress, have had promising results, reducing anxiety, depression, stress, and clinical severity of psoriatic lesions [18].

The data supporting pharmacologic options are more limited. In a study of 60 patients with mild-to-moderate plaque psoriasis, moclobemide treatment led to a 14% reduction in depressive symptoms (P < 0.05) [19]. Paroxetine use helped resolve psoriatic lesions [20]. In a retrospective study, escitalopram reduced depressive and physical symptoms 78% in 38 patients with moderate-to-severe psoriasis compared to a 22% reduction with placebo as measured by the Hamilton Rating Scale for Depression. Furthermore, there was a statistically significant reduction in pruritus with escitalopram (35%) versus the control group (11% increase) [21].

Other reports on Selective Serotonin Reuptake Inhibitors find efficacy in treating depression but with a negative effect on psoriatic lesions. One study found that paroxetine led to the worsening of psoriasis lesions [22]. Two patients using fluoxetine for depression had worsening of psoriasis [23].

3.5. Impact of treating psoriasis on depression

Three biologic drugs improve depression in psoriasis (Table 2). Etanercept reduced depression 29% in psoriasis patients with minimal depression [24]. Ustekinumab reduced depression 55%; 27% and 12% of patients reported depression before and after treatment, respectively [25]. Adalimumab reduced depression 18.5% [26]. Apremilast was associated with a small risk of depression in psoriasis patients (1.3% versus 0.4% in placebo) [27]. Brodalumab was associated with suicidal ideation, but the risk of suicidal attempts is exceedingly low [28].

Table 2. Effect of biologic drugs on depression in psoriasis patients.

Lead author, year	Drug	Number of psoriasis patients	Tool for measuring depression	Results
Gelfand, 2008	Etanercept	2546	Beck Depression Inventory	29% reduction in depression
Langley, 2010	Ustekinumab	1230	Hospital Anxiety and Depression Scale-Depression	55% relative reduction in depression
Menter, 2010	Adalimumab	96	Zung Self-rating Depression Scale	18.5% relative reduction in depression

Effect of biologic drugs on depression in psoriasis patients as assessed by various tools is compared.

4. Expert opinion

Psoriasis impairs social, physical, and emotional functioning [2]. The impact on the quality of life may cause depression, which in turn negatively affects adherence to treatment. Based on a meta-analysis, the prevalence of depression in patients with psoriasis is 20–30% [3,29]. Severity of psoriasis was unrelated to depression risk [17].

In several studies considering hopelessness to be a surrogate for depression, out of 10 nonadherent psoriasis patients, two to three were found to be nonadherent due to depressive symptoms [30–33]. About 27% of patients appeared to be nonadherent due to belief that the medication would never work, and 22% of patients appeared to be nonadherent due to being fed up.

There is a need for a validated, user-friendly questionnaire for depression screening in psoriasis patients. The PHQ-9 is a questionnaire developed for screening depression based on DSM-IV criteria (Table 3). These criteria remain unchanged in the DSM-V. The PHQ-9 consists of 9 items, requiring about 1–3 minutes; in comparison, the Hamilton Rating Scale for Depression requires 15–30 minutes, as well as special training to administer [34]. The PHQ-2 is a shorter version of the PHQ-9, consisting of the first two questions (Table 3). At a score of 2 or greater, the PHQ-2 has a sensitivity and specificity of 86% and 78%, respectively, for detecting depression [35]. At a score of 15 or greater, the PHQ-9 has a sensitivity and specificity of 45% and 97%, respectively [35]. Several studies of the general population have recommended initial screening with the PHQ-2 for high sensitivity, followed by positive result screening with the PHQ-9 [35,36].

Table 3. Patient health questionnaire-9.

Over the last 2 weeks, how often have you been bothered by any of the following problems?	Not at all	Several days	More than half the days	Nearly every day
1. Little interest or pleasure in doing things	0	1	2	3
2. Feeling down, depressed, or hopeless	0	1	2	3
3. Trouble falling or staying asleep, or sleeping too much	0	1	2	3
4. Feeling tired or having little energy	0	1	2	3
5. Poor appetite or overeating	0	1	2	3
6. Feeling bad about yourself—or that you are a failure or have let yourself or your family down	0	1	2	3
7. Trouble concentrating on things, such as reading the newspaper or watching television	0	1	2	3
8. Moving or speaking so slowly that other people could have noticed? Or the opposite—being so fidgety or restless that you have been moving around a lot more than usual	0	1	2	3
9. Thoughts that you would be better off dead or of hurting yourself in some way	0	1	2	3

The Patient Health Questionnaire-9 consists of 9 items derived from the DSM-IV criteria for depression. The Patient Health Questionnaire-2 consists of the first two questions of the Patient Health Questionanire-9.

A recent study used receiver operating curve analysis to show that the PHQ-9 had a good discriminant ability in detecting depression (area under curve: 0.81, standard error = 0.04, 95% CI = 0.72–0.89) in psoriasis patients [37]. That is, 81% of patients with depression were identified by the PHQ-9. The PHQ-9 was able to detect depression in psoriasis patients, with an estimated prevalence of 16.5% [17].

Screening for depression could be considered for every psoriasis patient using the PHQ-2 (Figure 1). With a score ≥2, the PHQ-9 could be administered for confirmation of depression. With a score <2, rescreening with the PHQ-2 in a year could be considered. With a score ≥15 on the PHQ-9, the patient could be referred to a psychiatrist for evaluation: if diagnosed with depression, treatment could be initiated with rescreening in a year; if not diagnosed, the screening could be performed again at the following visit(s). With a score ≤10, the patient could be rescreened in a year. With a score of 11–14, the patient could be rescreened at the following visit(s). In order to make this screening process more widely accepted, validation of the PHQ-2 and PHQ-9 in psoriasis patients would be an appropriate first step.

Figure 1. Algorithm for screening psoriasis patients for depressive symptoms.

The algorithm helps guide physicians on which actions could be taken based on the scores of the Patient Health Questionnaires-2 and -9.

Declaration of interest

The Center for Dermatology Research is supported by an unrestricted educational grant from Galderma Laboratories, L.P. M Alikhan is a speaker for Celgene and Valeant, has served on advisory boards for Novartis and Valeant, and serves as a consultant for Prasco. S R Feldman is a speaker for Janssen and Taro. He is a consultant and speaker for Galderma, Stiefel/GlaxoSmithKline, Abbott Laboratories and Leo Pharma Inc. He has received grants from Galderma, Janssen, Abbott Laboratories, Amgen, Stiefel/GlaxoSmithKline, Celgene and Anacor. He is a consultant for Amgen, Baxter, Caremark, Gerson Lehrman Group, Guidepoint Global, Hanall Pharmaceutical Co Ltd, Kikaku, Lilly, Merck & Co Inc, Merz Pharmaceuticals, Mylan, Novartis Pharmaceuticals, Pfizer Inc, Qurient, Suncare Research and Xenoport. He is on an advisory board for Pfizer Inc. S R Feldman is the founder and holds stock in Causa Research and holds stock and is majority owner in Medical Quality Enhancement Corporation. He receives Royalties from UpToDate and Xlibris. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.