Lupus (2017) 0,
1–6
journals.sagepub.com/home/lup
CONCISE REPORT
Medication adherence, depression and disease activity among patients with systemic lupus erythematosus N Alsowaida1, M Alrasheed2, A Mayet3, A Alsuwaida4 and MA Omair5 1
Pharmacy Services, King Saud University Medical City, Riyadh, Saudi Arabia; 2College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; 3Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; 4Division of Nephrology, Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia; and 5Division of Rheumatology, Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia
Introduction: Medication non-adherence is an important cause of treatment failure among patients with systemic lupus erythematosus (SLE). Depression is a common neuropsychiatric disorder associated with SLE. The aims of this study are to assess the prevalence of both medication non-adherence and depressed mood among Saudi patients with SLE by using validated tools and to explore the impact of both depressive symptoms and disease activity on medication non-adherence. Methods: A cross-sectional study was conducted in outpatients with SLE. Medication non-adherence was assessed by using the Morisky Medication Adherence Scale, and the severity of depressed mood was evaluated with the Beck’s Depression Inventory. Disease activity was measured using the SLE Disease Activity Index (SLEDAI). Multiple logistic regression models were used to identify the multivariate predictors of medication non-adherence. Results: Out of 140 patients, 134 (95.7%) were females with a mean (SD) age of 35.6 (11.3) years and a disease duration of 8.8 (6.7) years. Medication non-adherence and depressed mood were detected in 62.1% and 35% of the patients, respectively. A moderate or severe depressed mood was significantly associated with medication non-adherence (p ¼ 0.04). There was a significant correlation between disease activity and the severity of depressed mood (r ¼ 0.31, p ¼ 0.003). Disease activity did not correlate with medication non-adherence. Logistic regression demonstrated that moderateto-severe depressed mood increased the probability of medication non-adherence (OR 2.62; 1.02–6.71). Conclusion: Medication non-adherence and depressive symptoms are highly prevalent among Saudi SLE patients. Routine screening could facilitate the early detection and management of depression and medication adherence. Lupus (2017) 0, 1–6. Key words: Systemic lupus erythematosus; depression; adherence
Introduction The current management of systemic lupus erythematosus (SLE) has led to improved quality of life and survival.1 Treatment regimens are usually complex and long-term, which can predispose patients to medication non-adherence. Similar to other chronic conditions,2 the presence of depression may aggravate medication non-adherence in patients with SLE and may lead to disease flares, a decreased quality of life and increased healthcare system costs.3 There are many tools used in the Correspondence to: Mohammed A. Omair, Division of Rheumatology, Department of Medicine, King Saud University, Riyadh, Saudi Arabia, P.O. Box 2925 Riyadh 11321. Email: [email protected] Received 4 September 2016; accepted 18 July 2017 ! The Author(s), 2017. Reprints and permissions: http://www.sagepub.co.uk/journalsPermissions.nav
literature to assess patient adherence to medications. The Morisky Medication Adherence Scale-4 (MMSA4) is a self-reported scale used widely in research since it has been validated in a wide range of diseases, especially for patients with chronic conditions. In Saudi Arabia, the Morisky Scale has been used in liver transplant patients,4 patients with depression5 and patients on warfarin therapy.6 It has the advantage of ease of administration and a short duration to complete the questionnaire. However, the most important disadvantage is its inability to identify barriers to adherence. Similar to many other aspects of the disease, differences in ethnicity may affect the barriers to medication adherence.7,8 In two retrospective studies, neuropsychiatric manifestations were detected in 27.6% and depression was detected in 15.2% of Saudi Arabian 10.1177/0961203317725585
Medication Adherence and Depression in Lupus N Alsowaida et al.
2
patients with SLE.9,10 The retrospective nature of these studies may underestimate neuropsychiatric manifestations, especially milder forms that do not require treatment. There are no current data on medication non-adherence in our patient population. The aims of this study are to assess the prevalence of both medication non-adherence and depressive symptoms among Saudi patients with SLE by using validated tools and to explore in these patients the impact of both a depressed mood and disease activity on medication nonadherence. All medications were available through the government-funded healthcare system.
Materials and methods Study subjects This was a cross-sectional study of SLE patients. Subjects were enrolled between May 2015 and February 2016 from the rheumatology and nephrology outpatient clinics. The inclusion criteria were age 18 years, Saudi nationality, fulfilment of the Systemic Lupus International Collaborating Clinics (SLICC) classification criteria,11 a disease duration of 24 weeks, and ability to complete the questionnaire. The exclusion criteria were pregnancy, a confirmed diagnosis of malignancy or the presence of endstage organ disease. Informed consent was obtained before study inclusion. The study was approved by the Institutional Review Board (IRB) of the College of Medicine. Healthcare is provided to all Saudi Arabian citizens by the government through a national healthcare system, which covers all costs including medications. All medication refills were provided through the hospital pharmacy. Patients’ data were collected through a standardized data collection sheet that included demographics, marital status, education level, initial clinical presentation at diagnosis, disease duration and medication profile. The validated Arabic version of Beck’s Depression Inventory (BDI)12 was used to measure the severity of current depressive symptoms. The tool consists of 21 questions (a total of 63 points), with score categories that range from an absence of depression (0–13 points) to mild (14–19 points), moderate (20–28 points) or severe depression (29–63 points). The validated Arabic version of the Morisky Medication Adherence Scale-4 items (MMAS-4) tool was used to assess treatment regimen Lupus
adherence.10 The MMAS-4 consists of four questions with a score that begins at 0, which indicates high adherence.12 SLE Disease Activity Index (SLEDAI) and SLE International Collaboration Clinics/ACR (SLICC/ ACR) index were calculated for all patients. The assessment of disease activity was performed by using the SLEDAI, with a scoring system that ranges from 0 to 105 points.11 Based on the score, the patients were classified as inactive (0–4 points) or having mild-to-moderate (5–12 points) or severe disease activity (>12 points). Data analysis Descriptive statistics were used for the demographics and patient characteristics. The categorical data were summarized as numbers and percentages, whereas the continuous data were summarized as the mean, standard deviation, median and interquartile range. Comparison between the groups for categorical variables was performed by using a Chi-square test or Fisher’s exact test, whereas for the continuous data, the Student t-test or MannWhitney test were used as appropriate. Multiple logistic regression models were used to identify the multivariate predictors of low and medium adherence. To quantify the strength of the multivariate association, we used odds ratios with 95% confidence intervals. An association with a p-value 0.05 was considered statistically significant. All analyses were performed by using SAS version 9.2 (SAS Institute, Inc., Cary, NC). The reporting of the study results was performed by using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: Guidelines for reporting observational studies.13
Results One hundred and forty consecutive patients were included in this study. Of these, 134 (95.7%) were females, and 78 (55%) were married. The mean (SD) age was 35.6 (11.3) years, and the mean disease duration was 8.8 (6.7) years. The sociodemographic characteristics, clinical manifestations, immune profile and disease activity are presented in Table 1. According to the SLEDAI score, 31 patients (22%) had mild-to-moderate disease activity, whereas 37 patients (24%) had severe disease activity. The SLICC/ACR damage index was greater than 0 in 63.8% of patients with a median value of 2 [interquartile range (IQR); 1-3].
Medication Adherence and Depression in Lupus N Alsowaida et al.
3
Table 1 Demographic characteristics and clinical manifestations of the patient population Characteristics
No. (%)
Gender Female Male Age (years) 40 Marital status Unmarried Married Widow Education High school Bachelor Other Obesity Normal Overweight Obese Laboratory data Serum creatinine Urine protein Medications Prednisolone Hydroxychloroquine Mycophenolate mofetil Azathioprine Tacrolimus ACE/ARB Clinical presentation at diagnosis (%) Arthritis Malar rash Oral ulcer Renal Photosensitivity Serositis Haematological Discoid rash Cerebral Positive SLEDAI components No. (%) Arthritis Proteinuria Low complement Pyuria New rash Alopecia Haematuria Mucosal ulcers Others anti-dsDNA ANA
anti-dsDNA: Anti-double Antinuclear antibody
stranded
134 (95.7%) 6 (4.3%) 49 (35%) 41 (29.2%) 50 (35.7%) 53 (37%) 78 (55%) 9 (6.4%) 36 (25.7%) 66 (47.1%) 38 (27.1%) 55 (39.2%) 66 (47.1%) 18 (12.8%) 95 127 mmol/L 0.9 g/day 0.5 91 (65%) 123 (87.8%) 29.2 (41%) 20 (28%) 4.2 (6%) 48 (34.2%) 71.4 41.4 34.3 24.3 29.3 2.1 17.1 14.3 5.7
Discussion
40 (29) 35 (25) 25 (17.8) 23 (16.4) 21 (15) 20 (14.2) 15 (10.7) 11 (7.9) 29 (20.7) 140 (100) 140 (100)
DNA;
20 (14.3%) and six (4.3%) patients, respectively. Patients with minimal or mild depressive symptoms (n ¼ 114) had an average SLEDAI score of 5.16 SD, whereas patients with moderate or severe symptoms (n ¼ 26) had an average SLEDAI score of 9.96 SD. A strong correlation between disease activity and severity of depressed mood was found (r ¼ 0.31, p ¼ 0.003). Univariate analyses showed that being married (p ¼ 0.01), having a low level of education (p ¼ 0.05), a higher SLEDAI score (p < 0.001), and a longer disease duration (p ¼ 0.05) were associated with the presence of moderate-to-severe depressed mood. In the multivariate analysis, only disease activity was associated with a depressed mood (the odds ratio is 1.12 for every one-unit increase in the SLEDAI score (CI 1.04–1.21, p ¼ 0.004)). Other details are presented in Table 2. Medication non-adherence was reported in 87 (62.1%) patients according to the MMAS-4. Low and medium medication adherence were noted in 16.4% and 45.7%, respectively. The number of medications did not impact the adherence rate. The mean number (SD) of medications were 3.5 (1.6), 2.8 (1.5) and 3.4 (1.7) in the low, medium and high adherence groups, respectively (p ¼ 0.8). Logistic regression revealed that a younger age and a moderate-to-severe depressed mood were associated with non-adherence (OR 2.62; 1.02–6.71). However, no significant effect on medication non-adherence was found regarding disease duration, steroid use, marital status, educational level or SLEDAI score (Table 3).
ANA:
Forty-nine (35%) patients had evidence of current depressive symptoms, according to their BDI score. Mild, moderate and severe forms of depressed mood were identified in 23 (16.4%),
Depression and medication non-adherence were prevalent in our study population. According to the Hopkins Lupus cohort, the incidence of depression is 29.7/1000 person-years.14 In the systematic review by Palagini et al.,15 the rate of depression ranged between 17% and 75%. Van Exel reported that the prevalence of depression in lupus patients was triple the prevalence of depression in the normal European population.16 Our study indicates that one-third of our patients have some form of depression. Many patients’ depression had not been clinically detected or managed appropriately. Many risk factors for depression were identified. These included female gender,17 higher steroid use,14 neurological involvement,14 and the presence of fatigue.16 Our study could not detect a difference in gender because of the small male Lupus
Medication Adherence and Depression in Lupus N Alsowaida et al.
4
Table 2 Logistic regression for the predictors of depression among patients with SLE Depression
Covariate
Statistics
level
Gender
N (Col %) N (Col %) N (Col %) N (Col %) N (Col %) N (Col %) N (Col %) N (Col %) N (Col %) N (Col %) N (Col %) N (Col %) N (Col %) N (Col %) N (Col %) N (Col %) N (Col %) N (Col %) N (Col %) N (Col %) N Mean Median Std. Dev QRANGE N Mean Median SD IQR N Mean Median SD IQR N Mean Median SD IQR
Male Female
1–6
journals.sagepub.com/home/lup
CONCISE REPORT
Medication adherence, depression and disease activity among patients with systemic lupus erythematosus N Alsowaida1, M Alrasheed2, A Mayet3, A Alsuwaida4 and MA Omair5 1
Pharmacy Services, King Saud University Medical City, Riyadh, Saudi Arabia; 2College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; 3Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; 4Division of Nephrology, Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia; and 5Division of Rheumatology, Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia
Introduction: Medication non-adherence is an important cause of treatment failure among patients with systemic lupus erythematosus (SLE). Depression is a common neuropsychiatric disorder associated with SLE. The aims of this study are to assess the prevalence of both medication non-adherence and depressed mood among Saudi patients with SLE by using validated tools and to explore the impact of both depressive symptoms and disease activity on medication non-adherence. Methods: A cross-sectional study was conducted in outpatients with SLE. Medication non-adherence was assessed by using the Morisky Medication Adherence Scale, and the severity of depressed mood was evaluated with the Beck’s Depression Inventory. Disease activity was measured using the SLE Disease Activity Index (SLEDAI). Multiple logistic regression models were used to identify the multivariate predictors of medication non-adherence. Results: Out of 140 patients, 134 (95.7%) were females with a mean (SD) age of 35.6 (11.3) years and a disease duration of 8.8 (6.7) years. Medication non-adherence and depressed mood were detected in 62.1% and 35% of the patients, respectively. A moderate or severe depressed mood was significantly associated with medication non-adherence (p ¼ 0.04). There was a significant correlation between disease activity and the severity of depressed mood (r ¼ 0.31, p ¼ 0.003). Disease activity did not correlate with medication non-adherence. Logistic regression demonstrated that moderateto-severe depressed mood increased the probability of medication non-adherence (OR 2.62; 1.02–6.71). Conclusion: Medication non-adherence and depressive symptoms are highly prevalent among Saudi SLE patients. Routine screening could facilitate the early detection and management of depression and medication adherence. Lupus (2017) 0, 1–6. Key words: Systemic lupus erythematosus; depression; adherence
Introduction The current management of systemic lupus erythematosus (SLE) has led to improved quality of life and survival.1 Treatment regimens are usually complex and long-term, which can predispose patients to medication non-adherence. Similar to other chronic conditions,2 the presence of depression may aggravate medication non-adherence in patients with SLE and may lead to disease flares, a decreased quality of life and increased healthcare system costs.3 There are many tools used in the Correspondence to: Mohammed A. Omair, Division of Rheumatology, Department of Medicine, King Saud University, Riyadh, Saudi Arabia, P.O. Box 2925 Riyadh 11321. Email: [email protected] Received 4 September 2016; accepted 18 July 2017 ! The Author(s), 2017. Reprints and permissions: http://www.sagepub.co.uk/journalsPermissions.nav
literature to assess patient adherence to medications. The Morisky Medication Adherence Scale-4 (MMSA4) is a self-reported scale used widely in research since it has been validated in a wide range of diseases, especially for patients with chronic conditions. In Saudi Arabia, the Morisky Scale has been used in liver transplant patients,4 patients with depression5 and patients on warfarin therapy.6 It has the advantage of ease of administration and a short duration to complete the questionnaire. However, the most important disadvantage is its inability to identify barriers to adherence. Similar to many other aspects of the disease, differences in ethnicity may affect the barriers to medication adherence.7,8 In two retrospective studies, neuropsychiatric manifestations were detected in 27.6% and depression was detected in 15.2% of Saudi Arabian 10.1177/0961203317725585
Medication Adherence and Depression in Lupus N Alsowaida et al.
2
patients with SLE.9,10 The retrospective nature of these studies may underestimate neuropsychiatric manifestations, especially milder forms that do not require treatment. There are no current data on medication non-adherence in our patient population. The aims of this study are to assess the prevalence of both medication non-adherence and depressive symptoms among Saudi patients with SLE by using validated tools and to explore in these patients the impact of both a depressed mood and disease activity on medication nonadherence. All medications were available through the government-funded healthcare system.
Materials and methods Study subjects This was a cross-sectional study of SLE patients. Subjects were enrolled between May 2015 and February 2016 from the rheumatology and nephrology outpatient clinics. The inclusion criteria were age 18 years, Saudi nationality, fulfilment of the Systemic Lupus International Collaborating Clinics (SLICC) classification criteria,11 a disease duration of 24 weeks, and ability to complete the questionnaire. The exclusion criteria were pregnancy, a confirmed diagnosis of malignancy or the presence of endstage organ disease. Informed consent was obtained before study inclusion. The study was approved by the Institutional Review Board (IRB) of the College of Medicine. Healthcare is provided to all Saudi Arabian citizens by the government through a national healthcare system, which covers all costs including medications. All medication refills were provided through the hospital pharmacy. Patients’ data were collected through a standardized data collection sheet that included demographics, marital status, education level, initial clinical presentation at diagnosis, disease duration and medication profile. The validated Arabic version of Beck’s Depression Inventory (BDI)12 was used to measure the severity of current depressive symptoms. The tool consists of 21 questions (a total of 63 points), with score categories that range from an absence of depression (0–13 points) to mild (14–19 points), moderate (20–28 points) or severe depression (29–63 points). The validated Arabic version of the Morisky Medication Adherence Scale-4 items (MMAS-4) tool was used to assess treatment regimen Lupus
adherence.10 The MMAS-4 consists of four questions with a score that begins at 0, which indicates high adherence.12 SLE Disease Activity Index (SLEDAI) and SLE International Collaboration Clinics/ACR (SLICC/ ACR) index were calculated for all patients. The assessment of disease activity was performed by using the SLEDAI, with a scoring system that ranges from 0 to 105 points.11 Based on the score, the patients were classified as inactive (0–4 points) or having mild-to-moderate (5–12 points) or severe disease activity (>12 points). Data analysis Descriptive statistics were used for the demographics and patient characteristics. The categorical data were summarized as numbers and percentages, whereas the continuous data were summarized as the mean, standard deviation, median and interquartile range. Comparison between the groups for categorical variables was performed by using a Chi-square test or Fisher’s exact test, whereas for the continuous data, the Student t-test or MannWhitney test were used as appropriate. Multiple logistic regression models were used to identify the multivariate predictors of low and medium adherence. To quantify the strength of the multivariate association, we used odds ratios with 95% confidence intervals. An association with a p-value 0.05 was considered statistically significant. All analyses were performed by using SAS version 9.2 (SAS Institute, Inc., Cary, NC). The reporting of the study results was performed by using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: Guidelines for reporting observational studies.13
Results One hundred and forty consecutive patients were included in this study. Of these, 134 (95.7%) were females, and 78 (55%) were married. The mean (SD) age was 35.6 (11.3) years, and the mean disease duration was 8.8 (6.7) years. The sociodemographic characteristics, clinical manifestations, immune profile and disease activity are presented in Table 1. According to the SLEDAI score, 31 patients (22%) had mild-to-moderate disease activity, whereas 37 patients (24%) had severe disease activity. The SLICC/ACR damage index was greater than 0 in 63.8% of patients with a median value of 2 [interquartile range (IQR); 1-3].
Medication Adherence and Depression in Lupus N Alsowaida et al.
3
Table 1 Demographic characteristics and clinical manifestations of the patient population Characteristics
No. (%)
Gender Female Male Age (years) 40 Marital status Unmarried Married Widow Education High school Bachelor Other Obesity Normal Overweight Obese Laboratory data Serum creatinine Urine protein Medications Prednisolone Hydroxychloroquine Mycophenolate mofetil Azathioprine Tacrolimus ACE/ARB Clinical presentation at diagnosis (%) Arthritis Malar rash Oral ulcer Renal Photosensitivity Serositis Haematological Discoid rash Cerebral Positive SLEDAI components No. (%) Arthritis Proteinuria Low complement Pyuria New rash Alopecia Haematuria Mucosal ulcers Others anti-dsDNA ANA
anti-dsDNA: Anti-double Antinuclear antibody
stranded
134 (95.7%) 6 (4.3%) 49 (35%) 41 (29.2%) 50 (35.7%) 53 (37%) 78 (55%) 9 (6.4%) 36 (25.7%) 66 (47.1%) 38 (27.1%) 55 (39.2%) 66 (47.1%) 18 (12.8%) 95 127 mmol/L 0.9 g/day 0.5 91 (65%) 123 (87.8%) 29.2 (41%) 20 (28%) 4.2 (6%) 48 (34.2%) 71.4 41.4 34.3 24.3 29.3 2.1 17.1 14.3 5.7
Discussion
40 (29) 35 (25) 25 (17.8) 23 (16.4) 21 (15) 20 (14.2) 15 (10.7) 11 (7.9) 29 (20.7) 140 (100) 140 (100)
DNA;
20 (14.3%) and six (4.3%) patients, respectively. Patients with minimal or mild depressive symptoms (n ¼ 114) had an average SLEDAI score of 5.16 SD, whereas patients with moderate or severe symptoms (n ¼ 26) had an average SLEDAI score of 9.96 SD. A strong correlation between disease activity and severity of depressed mood was found (r ¼ 0.31, p ¼ 0.003). Univariate analyses showed that being married (p ¼ 0.01), having a low level of education (p ¼ 0.05), a higher SLEDAI score (p < 0.001), and a longer disease duration (p ¼ 0.05) were associated with the presence of moderate-to-severe depressed mood. In the multivariate analysis, only disease activity was associated with a depressed mood (the odds ratio is 1.12 for every one-unit increase in the SLEDAI score (CI 1.04–1.21, p ¼ 0.004)). Other details are presented in Table 2. Medication non-adherence was reported in 87 (62.1%) patients according to the MMAS-4. Low and medium medication adherence were noted in 16.4% and 45.7%, respectively. The number of medications did not impact the adherence rate. The mean number (SD) of medications were 3.5 (1.6), 2.8 (1.5) and 3.4 (1.7) in the low, medium and high adherence groups, respectively (p ¼ 0.8). Logistic regression revealed that a younger age and a moderate-to-severe depressed mood were associated with non-adherence (OR 2.62; 1.02–6.71). However, no significant effect on medication non-adherence was found regarding disease duration, steroid use, marital status, educational level or SLEDAI score (Table 3).
ANA:
Forty-nine (35%) patients had evidence of current depressive symptoms, according to their BDI score. Mild, moderate and severe forms of depressed mood were identified in 23 (16.4%),
Depression and medication non-adherence were prevalent in our study population. According to the Hopkins Lupus cohort, the incidence of depression is 29.7/1000 person-years.14 In the systematic review by Palagini et al.,15 the rate of depression ranged between 17% and 75%. Van Exel reported that the prevalence of depression in lupus patients was triple the prevalence of depression in the normal European population.16 Our study indicates that one-third of our patients have some form of depression. Many patients’ depression had not been clinically detected or managed appropriately. Many risk factors for depression were identified. These included female gender,17 higher steroid use,14 neurological involvement,14 and the presence of fatigue.16 Our study could not detect a difference in gender because of the small male Lupus
Medication Adherence and Depression in Lupus N Alsowaida et al.
4
Table 2 Logistic regression for the predictors of depression among patients with SLE Depression
Covariate
Statistics
level
Gender
N (Col %) N (Col %) N (Col %) N (Col %) N (Col %) N (Col %) N (Col %) N (Col %) N (Col %) N (Col %) N (Col %) N (Col %) N (Col %) N (Col %) N (Col %) N (Col %) N (Col %) N (Col %) N (Col %) N (Col %) N Mean Median Std. Dev QRANGE N Mean Median SD IQR N Mean Median SD IQR N Mean Median SD IQR
Male Female
