Psychosomatics 46:131-134, April 2005
© 2005 The Academy of Psychosomatic Medicine
Predictive Value of the CES-D in Detecting Depression Among Candidates for Disease-Modifying Multiple Sclerosis Treatment
Rupang Pandya, B.Sc., M.D.,
Luanne Metz, M.D., F.R.C.P.(C), and
Scott B. Patten, M.D., F.R.C.P.(C), Ph.D.
Received July 21, 2003; revision received March 29, 2004; accepted May 12, 2004. From the Departments of Psychiatry, Clinical Neurosciences, and Community Health Sciences, University of Calgary; and the Alberta Heritage Foundation for Medical Research, Calgary. Address correspondence and reprint requests to Dr. Pandya, Psychiatry Administration, Department of Psychiatry, University of Calgary, 1403 29th St., NW, Calgary, ALB T3H 2R9, Canada; ruppandya{at}hotmail.com (e-mail).
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ABSTRACT
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The presence of depression is an important concern for patients with multiple sclerosis who are candidates for disease-modifying treatment, since depression may affect treatment adherence. The authors evaluated the positive predictive value of the Center for Epidemiologic Studies Depression Rating Scale (CES-D) in detecting depression among patients who were candidates for disease-modifying multiple sclerosis treatment. Of 47 patients who scored  16 on the CES-D, 74.5% (N=38) were found to have a depressive disorder. The results of the study indicate that case-finding for depressive disorders among multiple sclerosis patients can be facilitated by use of the CES-D scale.
Key Words: Major Depression • Depressive Disorder • Multiple Sclerosis • Psychiatric Symptom Rating Scales
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INTRODUCTION
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Depressive disorders are common in patients with multiple sclerosis, with prevalence estimates ranging between 23% and 54%.1–5 Depression is a particularly important concern in candidates for disease-modifying treatment of multiple sclerosis, since depression may affect treatment adherence.6
A previous trial of intramuscular interferon beta-1a initiated during an initial demyelinating event reported depression as a side effect in 20% of patients treated.7 On the other hand, two other studies failed to confirm that interferon beta-1a was associated with an elevated risk of depression.8,9 In any case, depression is important to detect because of its impact on quality of life, adherence, and suicide risk. The University of Calgary Multiple Sclerosis Clinic screens all candidates for disease-modifying treatments (interferon beta or glatiramer acetate) with the Center for Epidemiologic Studies Depression Rating Scale (CES-D).10,11 This scale is widely used in medically ill populations because it does not over-emphasize physical symptoms such as fatigue, which could falsely elevate the symptom ratings. However, in populations with multiple sclerosis, several symptoms (most notably fatigue and deficits in memory and concentration) overlap with the syndrome of depression, and false positive ratings may occur. As such, it is possible that a large number of false positives could translate into a low positive predictive value when symptom scales are used for case finding.
The CES-D has been demonstrated to measure depressive symptoms and not merely general psychological distress.11 The CES-D is a self-report scale with 20 items, each of which is rated on a 4-point scale, with a minimum score of zero and a maximum score of 60. Individuals are asked to report the frequency of how they felt in the previous week on parameters such as crying spells, loneliness, self-esteem, sleep, etc. Scores of 16 or greater on the CES-D are traditionally interpreted as suggestive of clinically significant depression.12 It is not clear whether the traditional cutoff score for the CES-D is the best one for medically ill populations.13
The objective of this study was to evaluate the positive predictive value of the CES-D rating scale, across a range of possible cutoff scores, in detecting depression among persons with multiple sclerosis who were considered candidates for disease-modifying treatments.
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METHOD
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The study group consisted of a consecutive series of 47 patients with multiple sclerosis who were referred for psychiatric assessment on the basis of scoring 16 or greater on the CES-D either before or during treatment with a disease-modifying agent. All patients attending the University of Calgary Multiple Sclerosis Clinic are screened prior to initiating treatment, and psychiatric assessment is sought for all who exceed the cutoff point. The University of Calgary Multiple Sclerosis Clinic is the only regional resource for specialized multiple sclerosis care in southern Alberta and is the only regional center for government-reimbursed multiple sclerosis therapy (interferon beta-1a, interferon beta-1b, and glatiramer acetate). At the time this study group was acquired, diagnoses were made by neurologists specializing in multiple sclerosis; Poser criteria were used. All patients had relapsing/remitting multiple sclerosis with a minimum of two relapses in the previous 2 years, and all were at least minimally ambulatory. The assessments consisted of a detailed psychiatric interview (conducted by R.P., S.B.P., or Christine Mason, M.D.) that led to application of DSM-IV criteria.14 Age, sex, multiple sclerosis subtype (relapsing/remitting, primary progressive, or secondary progressive), and CES-D score were also recorded.
The predictive value of the CES-D ratings and associated confidence intervals (for the entire sample) were calculated by identifying the proportion of subjects with various DSM-IV diagnoses. Subsequent analyses explored the impact of various cutoff scores on the predictive value. Mann-Whitney U tests and t tests were used to compare median and mean CES-D ratings, respectively. The Mann-Whitney test was used whenever fulfillment of the t test normality assumption was questionable. Confidence intervals for the predictive value were calculated using exact binomial techniques. Statistical analysis was performed with STATA version 7.0.15
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RESULTS
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The study group comprised a consecutive series of patients referred for psychiatric assessment because of an elevated CES-D score. The group predominantly consisted of women (72.3%, N=34 of 47). The mean age was 39.3 years (range=18–56). In order to supplement the available data, additional clinical information was sought from the multiple sclerosis clinic database. Detailed demographic and illness data were available for 37 of 47 patients. The median duration of symptoms was 5.8 years (interquartile range: 3.3–11.5 years). The mean score on the Expanded Disability Status Scale16 was 3.0. Regarding education, 8.1% had less than a high school education; 13.5% had graduated high school; 56.8% had some post-grade 12 education (trade certificate, diploma); and 16.2% had a minimum of a bachelor’s degree. Marital status was as follows: 56.8% were married or in a common-law relationship, 18.9% were widowed/divorced/separated.
The vast majority of patients had relapsing/remitting multiple sclerosis (93.6%, N=44 of 47), with the remaining three patients having early secondary progressive multiple sclerosis. This high percentage is consistent with the clinical indications for disease-modifying treatments, which are considered most efficacious in persons with relapsing/remitting multiple sclerosis. Since most of the subjects were referred for evaluation before initiation of treatment (89.4%, N=42 of 47), only two subjects (4.3%) were receiving interferon at the time of assessment.
The CES-D scores at the time of referral were approximately normally distributed, with a range of 18 to 52. The mean score was 32.6 (95% CI=30.1%–35.1%). The CES-D scores were not correlated with age (rs=0.19, p<0.20). The median CES-D ratings were 32 and 33 in men and women, respectively. This difference was not statistically significant (Mann-Whitney  2=0.44, df=1, p=0.50).
Twenty-eight of the 47 patients (59.6%) were diagnosed with major depression. An additional seven (14.9%) were diagnosed with dysthymic disorder. The latter condition is characterized by at least a 2-year period of depressed mood with two or more of the following symptoms: appetite disturbance, sleep disturbance, low energy, low self-esteem, poor concentration, and hopelessness.14 Thus, a total of 35 patients (74.5%) were found to have a depressive disorder (no subjects had a bipolar disorder diagnosis). As such, the positive predictive value associated with a score of 16 or greater on the CES-D was 59.6% (95% CI=45.0%–74.1%) for major depression and 74.5% (95% CI=61.5%–87.4%) for any depressive disorder. Figure 1 presents the predictive value for diagnosis of major depressive disorder and any depressive disorder by cutoff score.
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FIGURE 1. Predictive Value of CES-D, by Cutoff Scores, for Diagnosis of Major Depressive Disorder and Any Depressive Disorder in Patients With Multiple Sclerosis
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Of the 47 patients with scores 16 on the CES-D, positive predictive value was calculated for the following DSM-IV diagnoses: major depressive disorder (60%); dysthymic disorder (15%); adjustment disorder (13%); and bipolar disorder (0%). The zero positive predictive value for bipolar disorder is predictable, since the base rate in this population was zero. Only six of the 47 subjects (12.8%) received no axis I diagnosis. Subjects with major depression had a higher median CES-D score (36.5) than subjects without this diagnosis (26.0). This difference was statistically significant (Mann-Whitney 2=12.1, df=1, p= 0.0005).
The University of Calgary Multiple Sclerosis Clinic has access to psychiatric as well as psychological consultation. One methodological concern is that individuals with more severe depression might be preferentially referred for psychiatric consultation. In turn, this might have introduced bias into the estimates of predictive value. To evaluate this possibility, we determined the CES-D scores of patients referred to a psychologist (N=17). The mean score of those referred to the psychologist (32.1) closely resembled that of the psychiatric referrals (32.9), and the small differences did not approach statistical significance (t=0.30, df=45, p=0.77).
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DISCUSSION
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The traditional CES-D cutoff score (16 or greater) was approximately 75% predictive of having a depressive disorder in this population of multiple sclerosis patients. The predictive value for major depression was approximately 60%. Adopting a higher cutoff for screening purposes will increase the positive predictive value but will also result in some false negative results. Ideally, a study of the validity of a screening instrument should include a random sample of the population being screened. In such circumstances it would be possible to calculate sensitivity, specificity, and positive and negative predictive values. Since in the current investigation we had access only to a series of screen-positive patients, we were only able to determine positive predictive value. As such, we can conclude that a large proportion of people screening positive on the CES-D (using the 16 or greater threshold) have clinically significant disorders. However, an important unanswered question concerns the sensitivity of the CES-D. Some proportion of those with scores below 16 may also have had depressive disorders, and such persons would not have entered the series evaluated here. A substantial false negative rate could limit the usefulness of the CES-D as a screening tool.
In the population studied, a clinical database of CES-D scores is kept, which does provide an estimate of the base-rate for this threshold. At the University of Calgary Multiple Sclerosis Clinic, 25% of subjects considered appropriate for treatment with interferon or glatiramer acetate exceed the CES-D threshold.
A potential limitation of this study is the reliance on an unstructured diagnostic interview. Generally, a structured or semistructured diagnostic interview would offer superior reliability and validity. However, it may be noted that no structured or semistructured diagnostic interviews have been specifically validated (or their reliability tested) using subjects with multiple sclerosis.
In summary, 75% of those referred because they exceeded the traditional cutoff score indicating possible depression were found to have diagnosable depressive disorders. To the extent that the DSM-IV categories identify patients with psychiatric treatment needs, the traditional CES-D cutoff of 16 or greater appears to identify persons with a high probability of benefiting from psychiatric consultation. Additional studies are needed to determine the false negative rate associated with this screening process and also to determine whether these results can be generalized beyond the subset of subjects under consideration for disease-modifying treatments.
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ACKNOWLEDGMENTS
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The authors thank Drs. Christine Mason and Nandini Singh (Medical Staff, Consultation-Liaison Psychiatry, Peter Lougheed Centre, Calgary, Alberta, Canada) for reviewing the manuscript and Dina Lavorato (Research Assistant) for data analysis.
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ABSTRACT
INTRODUCTION
