- Email: [email protected]
The evaluation of depression in multiple sclerosis using the newly proposed Multiple Sclerosis Depression Rating Scale
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The evaluation of depression in multiple sclerosis using the newly proposed Multiple Sclerosis Depression Rating Scale L’évaluation de la dépression dans la sclérose en plaques par l’échelle MSDRS (Multiple Sclerosis Depression Rating Scale) U. Palm a,b , M.A. Chalah a,c , A. Créange a,d , J.-P. Lefaucheur a,c , S.S. Ayache a,c,e,∗ a
EA 4391, excitabilité nerveuse et thérapeutique, université Paris-Est-Créteil, 61, avenue du Général-de-Gaulle, 94000 Créteil, France Department of Psychiatry, Psychotherapy and Psychosomatics, Ludwig-Maximilian University, Geschwister-Scholl Platz 1, 80539 Munich, Germany c Service de physiologie–explorations fonctionnelles, hôpital Henri-Mondor, Assistance publique–Hôpitaux de Paris, 31, rue du Parc, 94000 Créteil, France d Service de neurologie, hôpital Henri-Mondor, Assistance publique–Hôpitaux de Paris, 31, rue du Parc, 94000 Créteil, France e Lebanese American University Medical Center, Rizk hospital (LAUMC-RH), Zahar street, Beirut, Lebanon b
a r t i c l e
i n f o
Article history: Received 21 August 2017 Accepted 29 November 2017 Available online xxx Keywords: Depression Fatigue Mood Multiple sclerosis MSDRS
a b s t r a c t Fatigue and depression are frequent symptoms in multiple sclerosis (MS). Both are overlapping and shadowing each other and may impair the quality of life. For detection of depression symptoms in MS, the Multiple Sclerosis Depression Rating Scale (MSDRS) has been proposed recently. Here, we compare the performance of MSDRS in MS patients with and without fatigue to that of established rating scales, i.e. Hospital Anxiety and Depression Scale and Beck Depression Inventory. Twenty-nine MS patients were screened for fatigue and depression symptoms. Patients with fatigue showed significantly higher depression scores compared to patients without fatigue, whereas the number of depressed patients did not differ between the two groups. MSDRS seems to have higher sensitivity to detect severe depression than established rating scales. However, one should keep in mind that such a finding might be due to an increase in false positive cases when using MSDRS. Implementing this scale in future studies might be of help to enhance the understanding of its potential utility. ´ Paris. © 2018 L’Encephale,
r é s u m é Mots clés : Fatigue Depression Humeur Sclérose en plaque MSDRS
Introduction. – La fatigue est l’un des symptômes les plus invalidants de la sclérose en plaque (SEP). Sur le plan étiologique, on peut distinguer la fatigue primaire, résultant de multiples atteintes corticosous-corticales générées par la SEP, de la fatigue secondaire consécutive à divers facteurs tels que la dépression, les carences vitaminiques et les troubles infectieux. Dans cette perspective, et en tenant compte de l’impact que pourrait avoir la dépression sur la qualité de vie, il est important de se procurer des moyens efficaces afin de mieux identifier ce symptôme chez les patients atteints de SEP. Or, les échelles standards dédiées à la dépression ne peuvent pas distinguer la fatigue de la dépression et donc sont incapables de confirmer ou infirmer l’identification de ce symptôme. Quanranta et ses collaborateurs ont proposé une nouvelle échelle de dépression destinée aux patients atteints de SEP. Il s’agit de la « Multiple Sclerosis Depression Rating Scale » ou la MSDRS. Cependant, l’intérêt de cette échelle n’a pas été évalué dans le contexte de la fatigue. Le but de ce travail est de comparer la performance de la MSDRS à celle de deux autres échelles de dépression chez deux groupes de patients SEP : fatigués et non fatigués. Méthodes. – Vingt-neuf patients ayant un diagnostic avéré de SEP, ont complété l’étude. Chez chaque patient, la fatigue a été évaluée en utilisant la version franc¸aise de l’échelle MFIS (Modified Fatigue Impact Scale). La dépression a été évaluée en utilisant trois auto-questionnaires : les versions franc¸aises de la MSDRS, la BDI-SF (French shortened version of the Beck Depression Inventory) et la HADS (Hospital Anxiety and Depression Scale). La dernière permet de calculer deux sous-scores, un pour la dépression
∗ Corresponding author. Service de physiologie, explorations fonctionnelles, hôpital Henri-Mondor, Assistance publique–Hôpitaux de Paris, 94010, Créteil, France. E-mail address: [email protected] (S.S. Ayache). https://doi.org/10.1016/j.encep.2017.11.004 ´ 0013-7006/© 2018 L’Encephale, Paris.
Please cite this article in press as: Palm U, et al. The evaluation of depression in multiple sclerosis using the newly proposed Multiple Sclerosis Depression Rating Scale. Encéphale (2017), https://doi.org/10.1016/j.encep.2017.11.004
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(HADSdepression ) et un pour l’anxiété (HADSanxiety ). Un score d’invalidité a été aussi calculé pour chaque patient selon l’échelle EDSS (Expanded Disability Status Scale). Le test de Kolmogorov-Smirnov a été utilisé pour étudier la normalité de distribution des données obtenues. Dans un premier temps, une analyse de comparaison entre les valeurs enregistrées dans les deux groupes (fatigués vs. non-fatigués) est réalisée au moyen du test exact de Fisher pour les variables catégorielles et du test de Mann-Whitney pour les variables quantitatives (puisque la distribution des données ne suivait pas une loi normale pour toutes les valeurs étudiées). Les études de corrélations ont été testées par l’intermédiaire des coefficients de corrélation de Spearman. La significativité de la valeur du p a été fixée à 0,05. Résultats. – Indépendamment des groupes, la MSDRS a identifié 17 patients déprimés, la HADS 11, et la BDI-SF 12. Cinquante-cinq pour cent des patients étaient fatigués. La comparaison entre les deux groupes (fatigués vs. non fatigués) n’a pas retrouvé de différence significative en ce qui concerne le nombre de patients déprimés. En revanche, par rapport aux patients non fatigués, ceux fatigués avaient des scores significativement plus élevés sur la MSDRS et la HADSdepression . L’étude de corrélation a retrouvé des corrélations similaires entre la MFIS et la MSDRS, la MFIS et la HADSdepression , et entre la MSDRS et la HADSdepression . Conclusion. – Cette étude confirme la relation étroite qui pourrait exister entre la fatigue et la dépression chez les patients atteints de SEP. Elle met également l’accent sur l’utilité potentielle de la nouvelle échelle MSDRS dans le dépistage des symptômes dépressifs chez cette population. Ces données nécessitent d’être confirmées dans des études ultérieures à plus grande échelle. ´ © 2018 L’Encephale, Paris.
1. Introduction Among patients with multiple sclerosis (MS), fatigue is a frequent and debilitating symptom that can be either “primary” attributed to the disease itself, or “secondary” due to various etiologies, such as depression [1]. In this perspective, clinical tools for identifying depression in fatigued MS patients are crucial, admitting the drastic impact of this symptom on the quality of life and the potential risk of suicide. However, standard depression rating scales might not detect the overlap between depressive symptoms and fatigue and therefore could bear a lack of diagnostic accuracy of both distinct etiologies. The Multiple Sclerosis Depression Rating Scale (MSDRS) has been recently proposed [2], but its relevance has not been evaluated in the context of MS fatigue. We hereby assessed the performance of MSDRS in fatigued (F-MS) and nonfatigued (NF-MS) MS patients, compared to Hospital Anxiety and Depression Scale (HADS) [3] and Beck Depression Inventory (BDI) [4].
2. Methods Thirty-five patients with definite diagnosis of MS according to the revised 2010 McDonald criteria and a stable treatment for at least one month were initially screened. Exclusion criteria were as follows: acute MS relapse within the last two months; intensive steroids treatment within the last trimester; clinical diagnosis of other psychiatric disorders prior to inclusion. Six of the screened patients were excluded and 29 patients agreed to participate and completed the study. The study protocol was approved by the local ethical committee and performed in compliance to the declaration of Helsinki. All participants received and signed informed consent prior to inclusion. Fatigue was assessed using the Modified Fatigue Impact Scale (MFIS) with a cutoff score ≥ 38 to differentiate F-MS from NF-MS patients [5]. The MSDRS (10 sections) was used as a semistructured, professional-guided interview according to a French translation made by U.P. and J.P.L. for this study, with a cutoff score ≥ 6 to include clinically meaningful symptom severity [2]. The French version of the HADS (14 items; two subscales: HADSanxiety and HADSdepression ) was used with a cut-off score ≥ 8 for each subscale [6,7]. The French shortened version of the BDI (BDI-SF, 13
items) was used with a cutoff score ≥ 7 [4]. Functional status was evaluated using the Expanded Disability Status Scale (EDSS) [8]. Nonparametric statistical tests were used since the data did not follow Gaussian distributions, as revealed by Kolmogorov-Smirnov test. Demographic and clinical data were compared between F-MS and NF-MS patient groups using Fisher’s test for categorical data and the Mann-Whitney test for numerical data. The relationship between the presence of depression/anxiety according to the different scales and the presence of fatigue (MFIS) was studied using Fisher’s test. Finally, Spearman’s test was used to assess the correlations between scales that differentiated F-MS from NF-MS patients. A p-value less than 0.05 was considered significant. Admitting the small sample size, our preliminary results are presented uncorrected for multiple comparisons.
3. Results Fifty-five % of patients had fatigue (n = 16; MFIS mean ± SD: 59.9 ± 10.8 vs. 28.8 ± 7.1; MFIS range: 44–76 vs. 10–36, in F-MS and NF-MS respectively). F-MS and NF-MS did not significantly differ in gender (F/M ratios: 13/3 vs. 9/4, P = 0.67), age (in years; mean ± SD: 49.5 ± 11.6 vs. 49.6 ± 11.4; range: 33–76 vs. 30–67, P = 0.95), MS type (relapsing-remitting: 10 vs. 8; primary progressive: 2 vs. 1; secondary progressive 4 vs. 4, P = 1), disease duration (in years; mean ± SD: 24.0 ± 10.3 vs. 21.2 ± 9.8; range: 12–34 vs. 10-30, P = 0.46), progressive phase duration (in years; mean ± SD: 13.0 ± 10.6 vs. 8.8 ± 3.8; range: 3–28 vs. 4-13, P = 0.18), and EDSS score (mean ± SD: 4.7 ± 1.5 vs. 4.3 ± 1.5; range: 2.5–7 vs. 3–7, P = 0.37). Regardless of the groups, MSDRS identified 17 depressed patients, HADS detected 11 depressed patients and 12 anxious patients, and BDI-SF revealed 12 depressed patients. Group comparisons have shown that F-MS patients had significantly higher MSDRS (mean ± SD: 9.8 ± 6.3 vs. 5.5 ± 3.0; range: 0–22 vs. 0–9; P = 0.047) and HADSdepression scores (mean ± SD: 7.6 ± 3.5 vs. 4.5 ± 2.8; range: 2–15 vs. 1–9, P = 0.019) than NFMS patients. They also tended to have higher HADSanxiety scores (mean ± SD: 8.4 ± 3.1 vs. 6.5 ± 2.0; range: 5–16 vs. 3–11, P = 0.062). However, no significant group difference was observed for BDISF scores (mean ± SD: 7.9 ± 4.8 vs. 5.4 ± 3.1; range: 2–20 vs. 1-10, P = 0.21). The number of depressed or anxious patients did not significantly differ between F-MS and NF-MS patient groups, whatever
Please cite this article in press as: Palm U, et al. The evaluation of depression in multiple sclerosis using the newly proposed Multiple Sclerosis Depression Rating Scale. Encéphale (2017), https://doi.org/10.1016/j.encep.2017.11.004
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Table 1 Demographic and clinical data of fatigued and non-fatigued MS patients.
Gender (f/m) Age (years, mean ± SD; range) Disease type (number and type) Total disease duration (years, mean ± SD; range) Progressive phase duration (years, mean ± SD; range) EDSS (mean ± SD; range) MSDRS (mean ± SD; range; [number of depressed patients]) HADSanx (mean ± SD; range; [number of anxious patients]) HADSdep (mean ± SD; range; [number of depressed patients]) BDI-SF (mean ± SD; range; [number of depressed patients])
F-MS patients (n = 16)
NF-MS patients (n = 13)
Statistics (P)
13/3 49.5 ± 11.6; 33–76 10 RR, 2 PP, 4 SP 24.0 ± 10.3; 12–34 13.0 ± 10.6; 3–28 4.7 ± 1.5; 3–7 9.8 ± 6.3; 0–22; [11] 8.4 ± 3.1; 5–16; [9] 7.6 ± 3.5; 2–15; [8] 7.9 ± 4.8; 2–20; [8]
9/4 49.6 ± 11.4; 30–67 8 RR, 1 PP, 4 SP 21.2 ± 9.8; 10–30 8.8 ± 3.8; 4–13 4.3 ± 1.5; 2.5–7 5.5 ± 3.0; 0–9; [6] 6.5 ± 2.0; 3–11; [3] 4.5 ± 2.8; 1–9; [3] 5.4 ± 3.1; 1–10; [4]
0.67 0.95 1 0.46 0.18 0.37 0.047 0.062 0.019 0.21
BDI-SF: shortened form of the Beck Depression Inventory; EDSS: Expanded disability status scale; HADSanx and HADSdep : anxiety and depression subscales of the Hospital Anxiety and Depression Scale; f: female; m: male; F-MS: fatigued patients; MFIS: Modified Fatigue Impact Scale; MS: multiple sclerosis; MSDRS: Multiple Sclerosis Depression Rating Scale; NF-MS: non-fatigued patients; PP: primary progressive; RR: Relapsing remitting; SD: standard deviation; SP: secondary progressive. Statistical analyses are performed using the Fisher test for categorical data and the Mann-Whitney test for numerical data.
the scale used (MSDRS: 11 vs. 6; HADSdepression : 8 vs. 3; HADSanxiety : 9 vs. 3; BDI-SF 8 vs. 4, P-values ranging from 0.13 to 0.45 using Fisher’s test). A summary of the data is displayed in Table 1. Correlation analysis has shown very similar correlations among MFIS, MSDRS and HADSdepression . The correlation ratio (r) was 0.43 between MFIS and MSDRS, 0.46 between MFIS and HADSdepression , and 0.47 between MSDRS and HADSdepression (i.e. corresponding Pvalues of 0.019, 0.011, and 0.010, respectively, Spearman’s test).
To conclude, the newly developed MSDRS might enhance the sensitivity in the screening of depressive disorders in MS patients before addressing them to psychiatrists for an appropriate treatment. It could therefore increase distinguishability between depressive and fatigue symptoms. This study shows the high interference between fatigue and depression in a small sample of MS patients and points out the need for further research on the interaction of both domains.
4. Discussion
Disclosure of interest
This small-sample study is the first to assess depression in fatigued and non-fatigued MS patients using the newly developed MSDRS. Our data confirm the significant association between fatigue and depression in MS patients, at least according to MSDRS and HADSdepression , which is in line with previous works [9]. F-MS patients showed higher scores of depression than NF-MS patients although other clinical data did not differ between both MS groups. This study confirms the usefulness of the recently introduced MSDRS as a screening tool for assessing depression specifically in MS patients. The latter finding was also highlighted by Quaranta et al., indicating a better detection of patients with severe depression. Although MSDRS was able to identify a larger number of depressed patients than the other two scales, our sample is too small to statistically corroborate this finding. This advantage of the MSDRS might be due to differences from the other depression scales at two points: first, it does not particularly consider fatigue or lack of concentration in MS patients since the latter symptoms can be due to the disease itself and not to a concomitant depression [10]. Second, MSDRS dedicates a section that investigates the emotional reactivity of MS patients against the aspects and consequences of their disease [2]. Therefore, these MSDRS characteristics might be beneficial in detecting a higher number of depressed MS patients among those who are presenting with secondary fatigue, and thus providing them with a better and more specific therapeutic management. However, one should keep in mind that such a finding might be due to an increase in false positive rates when using MSDRS. Another limitation of the current work would be that the used instruments might have contaminated each other. Furthermore, it remains to be elucidated, if in a larger sample of patients, the new questionnaire would provide better discrimination of depression and fatigue symptoms than the standard ones.
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. AC gave expert testimony for CSL Behring, Novartis, received grants from Biogen, Novartis, CSL Behring, GE Neuro, Octapharma, and gave lectures for Genzyme. SSA declares having received travel grants or compensation from Genzyme, Biogen, Novartis and Roche. The other authors declare that they have no competing interest. References [1] Chalah MA, Riachi N, Ahdab R, et al. Fatigue in multiple sclerosis: neural correlates and the role of non-invasive brain stimulation. Front Cell Neurosci 2015;9:460. [2] Quaranta D, Marra C, Zinno M. Presentation and validation of the Multiple Sclerosis Depression Rating Scale: a test specifically devised to investigate affective disorders in multiple sclerosis patients. Clin Neuropsychol 2012;26:571–87. [3] Snaith P, Zigmond AS. Anxiety and depression in general medical settings. BMJ 1988;297:1544. [4] Collet L, Cottraux J. Inventaire abrégé de la dépression de Beck (13 items) : étude de la validité concurrente avec les échelles de Hamilton et de ralentissement de Widlöcher. Encephale 1986;12:77–9. [5] Flachenecker P, Kümpfel T, Kallmann B, et al. Fatigue in multiple sclerosis: a comparison of different rating scales and correlation to clinical parameters. Mult Scler 2002;8:523–6. [6] Friedman S, Samuelian JC, Lancrenon S, et al. Three-dimensional structure of the Hospital Anxiety and Depression Scale in a large French primary care population suffering from major depression. Psychiatry Res 2001;104:247–57. [7] Watson TM, Ford E, Worthington E, et al. Validation of mood measures for people with multiple sclerosis. Int J MS Care 2014;16:105–9. [8] Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 1983;33:1444–52. [9] Téllez N, Río J, Tintoré M, et al. Does the Modified Fatigue Impact Scale offer a more comprehensive assessment of fatigue in MS? Mult Scler 2005;11:198–202. [10] Strober LB, Arnett PA. Assessment of depression in multiple sclerosis: development of a “trunk and branch” model. Clin Neuropsychol 2010;24:1146–66.
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The evaluation of depression in multiple sclerosis using the newly proposed Multiple Sclerosis Depression Rating Scale L’évaluation de la dépression dans la sclérose en plaques par l’échelle MSDRS (Multiple Sclerosis Depression Rating Scale) U. Palm a,b , M.A. Chalah a,c , A. Créange a,d , J.-P. Lefaucheur a,c , S.S. Ayache a,c,e,∗ a
EA 4391, excitabilité nerveuse et thérapeutique, université Paris-Est-Créteil, 61, avenue du Général-de-Gaulle, 94000 Créteil, France Department of Psychiatry, Psychotherapy and Psychosomatics, Ludwig-Maximilian University, Geschwister-Scholl Platz 1, 80539 Munich, Germany c Service de physiologie–explorations fonctionnelles, hôpital Henri-Mondor, Assistance publique–Hôpitaux de Paris, 31, rue du Parc, 94000 Créteil, France d Service de neurologie, hôpital Henri-Mondor, Assistance publique–Hôpitaux de Paris, 31, rue du Parc, 94000 Créteil, France e Lebanese American University Medical Center, Rizk hospital (LAUMC-RH), Zahar street, Beirut, Lebanon b
a r t i c l e
i n f o
Article history: Received 21 August 2017 Accepted 29 November 2017 Available online xxx Keywords: Depression Fatigue Mood Multiple sclerosis MSDRS
a b s t r a c t Fatigue and depression are frequent symptoms in multiple sclerosis (MS). Both are overlapping and shadowing each other and may impair the quality of life. For detection of depression symptoms in MS, the Multiple Sclerosis Depression Rating Scale (MSDRS) has been proposed recently. Here, we compare the performance of MSDRS in MS patients with and without fatigue to that of established rating scales, i.e. Hospital Anxiety and Depression Scale and Beck Depression Inventory. Twenty-nine MS patients were screened for fatigue and depression symptoms. Patients with fatigue showed significantly higher depression scores compared to patients without fatigue, whereas the number of depressed patients did not differ between the two groups. MSDRS seems to have higher sensitivity to detect severe depression than established rating scales. However, one should keep in mind that such a finding might be due to an increase in false positive cases when using MSDRS. Implementing this scale in future studies might be of help to enhance the understanding of its potential utility. ´ Paris. © 2018 L’Encephale,
r é s u m é Mots clés : Fatigue Depression Humeur Sclérose en plaque MSDRS
Introduction. – La fatigue est l’un des symptômes les plus invalidants de la sclérose en plaque (SEP). Sur le plan étiologique, on peut distinguer la fatigue primaire, résultant de multiples atteintes corticosous-corticales générées par la SEP, de la fatigue secondaire consécutive à divers facteurs tels que la dépression, les carences vitaminiques et les troubles infectieux. Dans cette perspective, et en tenant compte de l’impact que pourrait avoir la dépression sur la qualité de vie, il est important de se procurer des moyens efficaces afin de mieux identifier ce symptôme chez les patients atteints de SEP. Or, les échelles standards dédiées à la dépression ne peuvent pas distinguer la fatigue de la dépression et donc sont incapables de confirmer ou infirmer l’identification de ce symptôme. Quanranta et ses collaborateurs ont proposé une nouvelle échelle de dépression destinée aux patients atteints de SEP. Il s’agit de la « Multiple Sclerosis Depression Rating Scale » ou la MSDRS. Cependant, l’intérêt de cette échelle n’a pas été évalué dans le contexte de la fatigue. Le but de ce travail est de comparer la performance de la MSDRS à celle de deux autres échelles de dépression chez deux groupes de patients SEP : fatigués et non fatigués. Méthodes. – Vingt-neuf patients ayant un diagnostic avéré de SEP, ont complété l’étude. Chez chaque patient, la fatigue a été évaluée en utilisant la version franc¸aise de l’échelle MFIS (Modified Fatigue Impact Scale). La dépression a été évaluée en utilisant trois auto-questionnaires : les versions franc¸aises de la MSDRS, la BDI-SF (French shortened version of the Beck Depression Inventory) et la HADS (Hospital Anxiety and Depression Scale). La dernière permet de calculer deux sous-scores, un pour la dépression
∗ Corresponding author. Service de physiologie, explorations fonctionnelles, hôpital Henri-Mondor, Assistance publique–Hôpitaux de Paris, 94010, Créteil, France. E-mail address: [email protected] (S.S. Ayache). https://doi.org/10.1016/j.encep.2017.11.004 ´ 0013-7006/© 2018 L’Encephale, Paris.
Please cite this article in press as: Palm U, et al. The evaluation of depression in multiple sclerosis using the newly proposed Multiple Sclerosis Depression Rating Scale. Encéphale (2017), https://doi.org/10.1016/j.encep.2017.11.004
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(HADSdepression ) et un pour l’anxiété (HADSanxiety ). Un score d’invalidité a été aussi calculé pour chaque patient selon l’échelle EDSS (Expanded Disability Status Scale). Le test de Kolmogorov-Smirnov a été utilisé pour étudier la normalité de distribution des données obtenues. Dans un premier temps, une analyse de comparaison entre les valeurs enregistrées dans les deux groupes (fatigués vs. non-fatigués) est réalisée au moyen du test exact de Fisher pour les variables catégorielles et du test de Mann-Whitney pour les variables quantitatives (puisque la distribution des données ne suivait pas une loi normale pour toutes les valeurs étudiées). Les études de corrélations ont été testées par l’intermédiaire des coefficients de corrélation de Spearman. La significativité de la valeur du p a été fixée à 0,05. Résultats. – Indépendamment des groupes, la MSDRS a identifié 17 patients déprimés, la HADS 11, et la BDI-SF 12. Cinquante-cinq pour cent des patients étaient fatigués. La comparaison entre les deux groupes (fatigués vs. non fatigués) n’a pas retrouvé de différence significative en ce qui concerne le nombre de patients déprimés. En revanche, par rapport aux patients non fatigués, ceux fatigués avaient des scores significativement plus élevés sur la MSDRS et la HADSdepression . L’étude de corrélation a retrouvé des corrélations similaires entre la MFIS et la MSDRS, la MFIS et la HADSdepression , et entre la MSDRS et la HADSdepression . Conclusion. – Cette étude confirme la relation étroite qui pourrait exister entre la fatigue et la dépression chez les patients atteints de SEP. Elle met également l’accent sur l’utilité potentielle de la nouvelle échelle MSDRS dans le dépistage des symptômes dépressifs chez cette population. Ces données nécessitent d’être confirmées dans des études ultérieures à plus grande échelle. ´ © 2018 L’Encephale, Paris.
1. Introduction Among patients with multiple sclerosis (MS), fatigue is a frequent and debilitating symptom that can be either “primary” attributed to the disease itself, or “secondary” due to various etiologies, such as depression [1]. In this perspective, clinical tools for identifying depression in fatigued MS patients are crucial, admitting the drastic impact of this symptom on the quality of life and the potential risk of suicide. However, standard depression rating scales might not detect the overlap between depressive symptoms and fatigue and therefore could bear a lack of diagnostic accuracy of both distinct etiologies. The Multiple Sclerosis Depression Rating Scale (MSDRS) has been recently proposed [2], but its relevance has not been evaluated in the context of MS fatigue. We hereby assessed the performance of MSDRS in fatigued (F-MS) and nonfatigued (NF-MS) MS patients, compared to Hospital Anxiety and Depression Scale (HADS) [3] and Beck Depression Inventory (BDI) [4].
2. Methods Thirty-five patients with definite diagnosis of MS according to the revised 2010 McDonald criteria and a stable treatment for at least one month were initially screened. Exclusion criteria were as follows: acute MS relapse within the last two months; intensive steroids treatment within the last trimester; clinical diagnosis of other psychiatric disorders prior to inclusion. Six of the screened patients were excluded and 29 patients agreed to participate and completed the study. The study protocol was approved by the local ethical committee and performed in compliance to the declaration of Helsinki. All participants received and signed informed consent prior to inclusion. Fatigue was assessed using the Modified Fatigue Impact Scale (MFIS) with a cutoff score ≥ 38 to differentiate F-MS from NF-MS patients [5]. The MSDRS (10 sections) was used as a semistructured, professional-guided interview according to a French translation made by U.P. and J.P.L. for this study, with a cutoff score ≥ 6 to include clinically meaningful symptom severity [2]. The French version of the HADS (14 items; two subscales: HADSanxiety and HADSdepression ) was used with a cut-off score ≥ 8 for each subscale [6,7]. The French shortened version of the BDI (BDI-SF, 13
items) was used with a cutoff score ≥ 7 [4]. Functional status was evaluated using the Expanded Disability Status Scale (EDSS) [8]. Nonparametric statistical tests were used since the data did not follow Gaussian distributions, as revealed by Kolmogorov-Smirnov test. Demographic and clinical data were compared between F-MS and NF-MS patient groups using Fisher’s test for categorical data and the Mann-Whitney test for numerical data. The relationship between the presence of depression/anxiety according to the different scales and the presence of fatigue (MFIS) was studied using Fisher’s test. Finally, Spearman’s test was used to assess the correlations between scales that differentiated F-MS from NF-MS patients. A p-value less than 0.05 was considered significant. Admitting the small sample size, our preliminary results are presented uncorrected for multiple comparisons.
3. Results Fifty-five % of patients had fatigue (n = 16; MFIS mean ± SD: 59.9 ± 10.8 vs. 28.8 ± 7.1; MFIS range: 44–76 vs. 10–36, in F-MS and NF-MS respectively). F-MS and NF-MS did not significantly differ in gender (F/M ratios: 13/3 vs. 9/4, P = 0.67), age (in years; mean ± SD: 49.5 ± 11.6 vs. 49.6 ± 11.4; range: 33–76 vs. 30–67, P = 0.95), MS type (relapsing-remitting: 10 vs. 8; primary progressive: 2 vs. 1; secondary progressive 4 vs. 4, P = 1), disease duration (in years; mean ± SD: 24.0 ± 10.3 vs. 21.2 ± 9.8; range: 12–34 vs. 10-30, P = 0.46), progressive phase duration (in years; mean ± SD: 13.0 ± 10.6 vs. 8.8 ± 3.8; range: 3–28 vs. 4-13, P = 0.18), and EDSS score (mean ± SD: 4.7 ± 1.5 vs. 4.3 ± 1.5; range: 2.5–7 vs. 3–7, P = 0.37). Regardless of the groups, MSDRS identified 17 depressed patients, HADS detected 11 depressed patients and 12 anxious patients, and BDI-SF revealed 12 depressed patients. Group comparisons have shown that F-MS patients had significantly higher MSDRS (mean ± SD: 9.8 ± 6.3 vs. 5.5 ± 3.0; range: 0–22 vs. 0–9; P = 0.047) and HADSdepression scores (mean ± SD: 7.6 ± 3.5 vs. 4.5 ± 2.8; range: 2–15 vs. 1–9, P = 0.019) than NFMS patients. They also tended to have higher HADSanxiety scores (mean ± SD: 8.4 ± 3.1 vs. 6.5 ± 2.0; range: 5–16 vs. 3–11, P = 0.062). However, no significant group difference was observed for BDISF scores (mean ± SD: 7.9 ± 4.8 vs. 5.4 ± 3.1; range: 2–20 vs. 1-10, P = 0.21). The number of depressed or anxious patients did not significantly differ between F-MS and NF-MS patient groups, whatever
Please cite this article in press as: Palm U, et al. The evaluation of depression in multiple sclerosis using the newly proposed Multiple Sclerosis Depression Rating Scale. Encéphale (2017), https://doi.org/10.1016/j.encep.2017.11.004
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Table 1 Demographic and clinical data of fatigued and non-fatigued MS patients.
Gender (f/m) Age (years, mean ± SD; range) Disease type (number and type) Total disease duration (years, mean ± SD; range) Progressive phase duration (years, mean ± SD; range) EDSS (mean ± SD; range) MSDRS (mean ± SD; range; [number of depressed patients]) HADSanx (mean ± SD; range; [number of anxious patients]) HADSdep (mean ± SD; range; [number of depressed patients]) BDI-SF (mean ± SD; range; [number of depressed patients])
F-MS patients (n = 16)
NF-MS patients (n = 13)
Statistics (P)
13/3 49.5 ± 11.6; 33–76 10 RR, 2 PP, 4 SP 24.0 ± 10.3; 12–34 13.0 ± 10.6; 3–28 4.7 ± 1.5; 3–7 9.8 ± 6.3; 0–22; [11] 8.4 ± 3.1; 5–16; [9] 7.6 ± 3.5; 2–15; [8] 7.9 ± 4.8; 2–20; [8]
9/4 49.6 ± 11.4; 30–67 8 RR, 1 PP, 4 SP 21.2 ± 9.8; 10–30 8.8 ± 3.8; 4–13 4.3 ± 1.5; 2.5–7 5.5 ± 3.0; 0–9; [6] 6.5 ± 2.0; 3–11; [3] 4.5 ± 2.8; 1–9; [3] 5.4 ± 3.1; 1–10; [4]
0.67 0.95 1 0.46 0.18 0.37 0.047 0.062 0.019 0.21
BDI-SF: shortened form of the Beck Depression Inventory; EDSS: Expanded disability status scale; HADSanx and HADSdep : anxiety and depression subscales of the Hospital Anxiety and Depression Scale; f: female; m: male; F-MS: fatigued patients; MFIS: Modified Fatigue Impact Scale; MS: multiple sclerosis; MSDRS: Multiple Sclerosis Depression Rating Scale; NF-MS: non-fatigued patients; PP: primary progressive; RR: Relapsing remitting; SD: standard deviation; SP: secondary progressive. Statistical analyses are performed using the Fisher test for categorical data and the Mann-Whitney test for numerical data.
the scale used (MSDRS: 11 vs. 6; HADSdepression : 8 vs. 3; HADSanxiety : 9 vs. 3; BDI-SF 8 vs. 4, P-values ranging from 0.13 to 0.45 using Fisher’s test). A summary of the data is displayed in Table 1. Correlation analysis has shown very similar correlations among MFIS, MSDRS and HADSdepression . The correlation ratio (r) was 0.43 between MFIS and MSDRS, 0.46 between MFIS and HADSdepression , and 0.47 between MSDRS and HADSdepression (i.e. corresponding Pvalues of 0.019, 0.011, and 0.010, respectively, Spearman’s test).
To conclude, the newly developed MSDRS might enhance the sensitivity in the screening of depressive disorders in MS patients before addressing them to psychiatrists for an appropriate treatment. It could therefore increase distinguishability between depressive and fatigue symptoms. This study shows the high interference between fatigue and depression in a small sample of MS patients and points out the need for further research on the interaction of both domains.
4. Discussion
Disclosure of interest
This small-sample study is the first to assess depression in fatigued and non-fatigued MS patients using the newly developed MSDRS. Our data confirm the significant association between fatigue and depression in MS patients, at least according to MSDRS and HADSdepression , which is in line with previous works [9]. F-MS patients showed higher scores of depression than NF-MS patients although other clinical data did not differ between both MS groups. This study confirms the usefulness of the recently introduced MSDRS as a screening tool for assessing depression specifically in MS patients. The latter finding was also highlighted by Quaranta et al., indicating a better detection of patients with severe depression. Although MSDRS was able to identify a larger number of depressed patients than the other two scales, our sample is too small to statistically corroborate this finding. This advantage of the MSDRS might be due to differences from the other depression scales at two points: first, it does not particularly consider fatigue or lack of concentration in MS patients since the latter symptoms can be due to the disease itself and not to a concomitant depression [10]. Second, MSDRS dedicates a section that investigates the emotional reactivity of MS patients against the aspects and consequences of their disease [2]. Therefore, these MSDRS characteristics might be beneficial in detecting a higher number of depressed MS patients among those who are presenting with secondary fatigue, and thus providing them with a better and more specific therapeutic management. However, one should keep in mind that such a finding might be due to an increase in false positive rates when using MSDRS. Another limitation of the current work would be that the used instruments might have contaminated each other. Furthermore, it remains to be elucidated, if in a larger sample of patients, the new questionnaire would provide better discrimination of depression and fatigue symptoms than the standard ones.
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. AC gave expert testimony for CSL Behring, Novartis, received grants from Biogen, Novartis, CSL Behring, GE Neuro, Octapharma, and gave lectures for Genzyme. SSA declares having received travel grants or compensation from Genzyme, Biogen, Novartis and Roche. The other authors declare that they have no competing interest. References [1] Chalah MA, Riachi N, Ahdab R, et al. Fatigue in multiple sclerosis: neural correlates and the role of non-invasive brain stimulation. Front Cell Neurosci 2015;9:460. [2] Quaranta D, Marra C, Zinno M. Presentation and validation of the Multiple Sclerosis Depression Rating Scale: a test specifically devised to investigate affective disorders in multiple sclerosis patients. Clin Neuropsychol 2012;26:571–87. [3] Snaith P, Zigmond AS. Anxiety and depression in general medical settings. BMJ 1988;297:1544. [4] Collet L, Cottraux J. Inventaire abrégé de la dépression de Beck (13 items) : étude de la validité concurrente avec les échelles de Hamilton et de ralentissement de Widlöcher. Encephale 1986;12:77–9. [5] Flachenecker P, Kümpfel T, Kallmann B, et al. Fatigue in multiple sclerosis: a comparison of different rating scales and correlation to clinical parameters. Mult Scler 2002;8:523–6. [6] Friedman S, Samuelian JC, Lancrenon S, et al. Three-dimensional structure of the Hospital Anxiety and Depression Scale in a large French primary care population suffering from major depression. Psychiatry Res 2001;104:247–57. [7] Watson TM, Ford E, Worthington E, et al. Validation of mood measures for people with multiple sclerosis. Int J MS Care 2014;16:105–9. [8] Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 1983;33:1444–52. [9] Téllez N, Río J, Tintoré M, et al. Does the Modified Fatigue Impact Scale offer a more comprehensive assessment of fatigue in MS? Mult Scler 2005;11:198–202. [10] Strober LB, Arnett PA. Assessment of depression in multiple sclerosis: development of a “trunk and branch” model. Clin Neuropsychol 2010;24:1146–66.
Please cite this article in press as: Palm U, et al. The evaluation of depression in multiple sclerosis using the newly proposed Multiple Sclerosis Depression Rating Scale. Encéphale (2017), https://doi.org/10.1016/j.encep.2017.11.004