Prevalence and concurrence of anxiety, depression and fatigue over time in multiple sclerosis
Open accessAbstract
Background: Anxiety, depression and fatigue are commonly reported by persons with multiple sclerosis (PwMS). Objectives: We estimated the prevalence of each factor in a representative sample of PwMS, and in subgroups defined by age, sex and disease duration, at cohort entry and over time. We further examined whether and how these factors clustered together. Methods: A population-based longitudinal cohort of 198 PwMS was followed 6-monthly for 2.5 years. The Hospital Anxiety and Depression Scale (HADS) was used to measure anxiety (cut-point >7) and depression (>7) and the Fatigue Severity Scale (FSS) to measure fatigue (≥5). Results: At cohort entry, prevalence of anxiety was 44.5% (95%CI 37–51%), depression 18.5% (95%CI 12.6–23.4%), and fatigue 53.7% (95%CI 47–61%). Fatigue was more common in males than females (RR 1.29, p =0.01), with attenuation of the effect after adjustment for Expanded Disability Status Scale (adjusted RR 1.18, p =0.13). Prevalence of anxiety (but not depression or fatigue) decreased by 8.1% per year of cohort observation (RR 0.92, 95%CI 0.86–0.98, p =0.009), with the effect more pronounced in women (14.6%, RR 0.85, 95%CI 0.79–0.93, –<0.001) than men (2.6%, RR 1.03, 95%CI 0.90–1.17, p =0.77). There was no apparent seasonal variation in the prevalence of any of the three factors ( p >0.05). All three factors occurred contemporaneously at cohort entry in a higher proportion of the cohort than expected by chance ( p <0.001). Conclusions: Anxiety, depression and fatigue are common in PwMS and tend to cluster together. The findings are important for clinical management of PwMS and to the exploration of possible shared causal biological pathways.
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The lifetime prevalence of anxiety disorders in MS ranges from 20% to 45% throughout the course of MS.
“The lifetime prevalence of anxiety disorders ranges from 20% to 45% throughout the course of MS,1”
From EMDR treatment for anxiety in MS patients: A pilot study (2020) · cites this paper as [1]
Patients with multiple sclerosis (MS) suffer from high levels of anxiety.
“Multiple sclerosis (MS) patients suffer from high levels of anxiety.”
From EMDR treatment for anxiety in MS patients: A pilot study (2020) · cites this paper as [1]
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“In line with these findings, clinical studies have shown that anxiety and depression are often considered the most common neuropsychological disorders influencing MS patients (Wallin et al., 2006, Wood et al., 2012).”
InfluentialTaylor, E. C., & Taylor‐Piliae, R. E. (2017) · Complementary Therapies in Medicine · doi:10.1016/j.ctim.2017.03.001 · Cited by 59 · see citing works
Anxiety, depression and fatigue at 5‐year review following CNS demyelination
Simpson, S., Tan, H., Otáhal, P., Taylor, B. V., Ponsonby, A., Lucas, R. M., Blizzard, L., Valery, P. C., Lechner‐Scott, J., Shaw, C., et al. (2016) · Acta Neurologica Scandinavica · doi:10.1111/ane.12554 · Cited by 57 · see citing works
“65 times that expected under statistical independence (26).”
BackgroundResultInfluentialSelf-citationBattalio, S. L., Huffman, S. E., & Jensen, M. P. (2020) · Health Psychology · doi:10.1037/hea0000848 · Cited by 56 · see citing works
“For example, research has found significant associations between anxious and depressive symptoms and pain, fatigue, physical functioning, self-reported and objective cognitive function, and social functioning (Asmundson & Katz, 2009; Battalio et al., 2018; Korostil & Feinstein, 2007; Lester, Stepleman, & Hughes, 2007;…”
BackgroundAnxiety disorder among rheumatoid arthritis patients: Insights from real-life data
Watad, ., Bragazzi, N. L., Adawi, M., Aljadeff, G., Amital, H., Comaneshter, D. S., Cohen, A. D., & Amital, D. (2017) · Journal of Affective Disorders · doi:10.1016/j.jad.2017.02.007 · Cited by 55 · see citing works
Valentine, T. R., Alschuler, K. N., Ehde, D. M., & Kratz, A. L. (2022) · Multiple Sclerosis Journal · doi:10.1177/13524585211023352 · Cited by 55 · see citing works
Mental Health Comorbidity in MS: Depression, Anxiety, and Bipolar Disorder
Turner, A., Alschuler, K., Hughes, A., Beier, M., Haselkorn, J., Sloan, A., & Ehde, D. (2016) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-016-0706-x · Cited by 49 · see citing works
Ohle, L.-M., Ellenberger, D., Flachenecker, P., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-92722-x · Cited by 53 · see citing works
Jiang, J., Chu, C., Wu, C., Wang, C., Zhang, C., Li, T., Zhai, Q., Yu, L., Tian, F., & Chen, W. (2021) · Food & Function · doi:10.1039/d0fo03203d · Cited by 52 · see citing works
Cognitive Impairment in Multiple Sclerosis: A Review of Neuropsychological Assessments
Korakas, N., & Tsolaki, M. (2016) · Cognitive and Behavioral Neurology · doi:10.1097/wnn.0000000000000097 · Cited by 52 · see citing works
Sexual dysfunction levels in iranian women suffering from multiple sclerosis
Nayeri, N. D., Khakbazan, Z., Ghafoori, F., & Nabavi, S. M. (2017) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2017.01.005 · Cited by 51 · see citing works
Kiropoulos, L. A., Kilpatrick, T., Holmes, A., & Threader, J. (2016) · BMC Psychiatry · doi:10.1186/s12888-016-1152-7 · Cited by 50 · see citing works
“Similarly, anxiety affects between 16 and 45% of the MS population [7, 8] and has been associated with younger age of onset, disease severity, fatigue [9] and severity of depressive symptoms [10].”
BackgroundNakazawa, K., Noda, T., Ichikura, K., Okamoto, T., Takahashi, Y., Yamamura, T., & Nakagome, K. (2018) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2018.08.023 · Cited by 50 · see citing works
Predictors of anxiety in multiple sclerosis.
Hartoonian, N., Terrill, A. L., Beier, M. L., Turner, A. P., Day, M. A., & Alschuler, K. N. (2014) · Rehabilitation Psychology · doi:10.1037/rep0000019 · Cited by 47 · see citing works
“…greater MS-related disability (Jones et al., 2012), higher levels of fatigue (Beiske et al., 2008), MS exacerbations (rapid onset or an increase in symptoms; Burns, Nawacki, Siddique, Pelletier, & Mohr, 2013; Feinstein et al., 1999), and depression (Garfield & Lincoln, 2012; Wood et al., 2013).”
InfluentialFatigue, Depression, and Anxiety Among Ambulating Multiple Sclerosis Patients
AlSaeed, S., Aljouee, T., Alkhawajah, N. M., Alarieh, R., AlGarni, H., Aljarallah, S., Ayyash, M., & Abu-Shaheen, A. K. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.844461 · Cited by 53 · see citing works
“Depression and anxiety have an unpredictable disease nature and are considered to be the most disabling symptoms that affect the QoL and general health in MS patients (11, 12).”
BackgroundResultInfluentialChen, M. H., DeLuca, J., Genova, H. M., Yao, B., & Wylie, G. R. (2020) · Diagnostics · doi:10.3390/diagnostics10110930 · Cited by 45 · see citing works
“Fatigue is one of the most prevalent symptoms of multiple sclerosis (MS) [1,2], an immunemediated, neurodegenerative disorder characterized with demyelination, axonal injury, and brain atrophy.”
BackgroundWilliams, A., Vietri, J., Isherwood, G., & Flor, A. (2014) · Multiple Sclerosis International · doi:10.1155/2014/203183 · Cited by 46 · see citing works
“Indeed, research has documented that fatigue, depression, and anxiety are observed together at higher-than-chance levels among individuals with multiple sclerosis (MS) and vary together [2, 3].”
BackgroundQuality of life and coping strategies in Lebanese multiple sclerosis patients: a pilot study
Farran, N., Ammar, D., & Darwish, H. (2016) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2015.12.003 · Cited by 42 · see citing works
Metacognition and self-awareness in Multiple Sclerosis
Mazancieux, A., Souchay, C., Casez, O., & Moulin, C. J. A. (2018) · Cortex · doi:10.1016/j.cortex.2018.11.012 · Cited by 45 · see citing works
Kos, D., Duportail, M., Meirte, J., Meeus, M., D'hooghe, M. B., Nagels, G., Willekens, B. M. P., Meurrens, T., Ilsbroukx, S., & Nijs, J. (2016) · International Journal of Rehabilitation Research · doi:10.1097/mrr.0000000000000178 · Cited by 44 · see citing works
“Introduction Fatigue is one of the most common and bothersome symptoms in multiple sclerosis (MS) patients and is reported in 50–92% of the MS population (Wood et al., 2013; Patti and Vila, 2014).”
BackgroundAnxiety in multiple sclerosis is related to depressive symptoms and cognitive complaints
Wallis, O. C., Bol, Y., Köhler, S., & Heugten, C. M. V. (2019) · Acta Neurologica Scandinavica · doi:10.1111/ane.13191 · Cited by 43 · see citing works
McKay, K. A., Tremlett, H. L., Fisk, J. D., Patten, S. B., Fiest, K. M., Berrigan, L. I., Marrie, R. A., & for the CIHR Team in the Epidemiology and Impact of Comorbidity on Multiple Sclerosis (ECoMS) (2015) · Multiple Sclerosis Journal · doi:10.1177/1352458515599073 · Cited by 42 · see citing works
Third wave cognitive behavioural therapies for people with multiple sclerosis: a scoping review
Zarotti, N., Eccles, F., Broyd, A., Longinotti, C., Mobley, A., & Simpson, J. (2023) · Disability and Rehabilitation · doi:10.1080/09638288.2022.2069292 · Cited by 40 · see citing works
Psychometric properties of the Hamilton Depression Rating Scale in multiple sclerosis
Raimo, S., Trojano, L., Spitaleri, D. L. A., Petretta, V., Grossi, D., & Santangelo, G. (2015) · Quality of Life Research · doi:10.1007/s11136-015-0940-8 · Cited by 40 · see citing works
“[2–5]), for reasons likely related to divergent criteria for patient selection, and to the different measures used to”
BackgroundAlsaadi, T. M., Hammasi, K. E., Shahrour, T. M., Shakra, M., Turkawi, L., Mudhafar, A., Diab, L., & Raoof, M. (2015) · Multiple Sclerosis International · doi:10.1155/2015/487159 · Cited by 41 · see citing works
“Indeed, a recent study has shown that patients with EDSS scores less than 3, similar to our cohorts, were at least twice less likely to suffer from depression and/or anxiety [26].”
BackgroundRecovery From COVID-19 in Multiple Sclerosis
Garjani, A., Middleton, R. M., Nicholas, R. S., & Evangelou, N. (2021) · Neurology Neuroimmunology & Neuroinflammation · doi:10.1212/nxi.0000000000001118 · Cited by 38 · see citing works
Ensari, I., Sandroff, B. M., & Motl, R. W. (2015) · International Journal of MS Care · doi:10.7224/1537-2073.2014-104 · Cited by 38 · see citing works
Barakou, I., Hackett, K. L., Finch, T. L., & Hettinga, F. J. (2023) · Annals of Medicine · doi:10.1080/07853890.2023.2270688 · Cited by 42 · see citing works
“More specifically, in multiple sclerosis, depression and anxiety are considered as highly debilitating symptoms that significantly impact individuals’ quality of life while pain and fatigue have also been associated with anxiety [166,167].”
BackgroundPoint prevalence and correlates of depression in a national community sample with multiple sclerosis
Viner, R., Fiest, K. M., Bulloch, A. G. M., Williams, J. V. A., Lavorato, D. H., Berzins, S. A., Jetté, N., Metz, L. M., & Patten, S. B. (2014) · General Hospital Psychiatry · doi:10.1016/j.genhosppsych.2013.12.011 · Cited by 36 · see citing works
“5% was reported, approximately twice the reported prevalence in an otherwise comparable non-MS population [3].”
BackgroundMethodBahrani, S., Zargar, F., Yousefipour, G., & Akbari, H. (2017) · Iranian Red Crescent Medical Journal · doi:10.5812/ircmj.44566 · Cited by 36 · see citing works
“Depression is one of the most common psychiatric symptoms diagnosed in patients with MS (10), the prevalence of which was reported to be 23.7% in a recent review study (11).”
BackgroundInfluentialDepression and anxiety in multiple sclerosis. Review of a fatal combination
Jellinger, K. A. (2024) · Journal of Neural Transmission · doi:10.1007/s00702-024-02792-0 · Cited by 41 · see citing works
“…more frequent (AlSaeed et al. 2022; Jones et al. 2012; Koltuniuk and Rosinczuk 2021; Mustac et al. 2021 ; Shafiee et al. 2023; Simpson et al. 2016; Wood et al. 2013) or less frequent than depression (Alharbi et al. 2022; Alswat et al. 2023; Bamer et al. 2008; Boeschoten et al. 2017; Marrie et al.…”
InfluentialFatigue in multiple sclerosis: A UK MS-register based study
Moore, H., Nair, K. P. S., Baster, K., Middleton, R., Paling, D., & Sharrack, B. (2022) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2022.103954 · Cited by 37 · see citing works
Is Personality Profile a Relevant Determinant of Fatigue in Multiple Sclerosis?
Schreiber, H., Lang, M., Kiltz, K., & Lang, C. (2015) · Frontiers in Neurology · doi:10.3389/fneur.2015.00002 · Cited by 35 · see citing works
“A recent study has emphasized that the prevalence of the three factors is high in MS, with depression rarely occurring alone or without concurrent anxiety and/or fatigue (27).”
Backgroundvan Gorp, D. A. M., van der Hiele, K., Heerings, M. A. P., Jongen, P. J., van der Klink, J. J. L., Reneman, M. F., Arnoldus, E. P. J., Beenakker, E. A. C., van Eijk, J. J. J., Frequin, S. T. F. M., et al. (2019) · Neurological Sciences · doi:10.1007/s10072-019-03999-w · Cited by 36 · see citing works
Fatigue and Affective Manifestations in Multiple Sclerosis—A Cluster Approach
Ayache, S., & Chalah, M. A. (2019) · Brain Science · doi:10.3390/brainsci10010010 · Cited by 28 · see citing works
Zanten, J. V., Douglas, M. R., & Ntoumanis, N. (2020) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2020.102602 · Cited by 35 · see citing works
Intensity of treadmill walking exercise on acute mood symptoms in persons with multiple sclerosis
Ensari, I., Sandroff, B. M., & Motl, R. W. (2016) · Anxiety Stress & Coping · doi:10.1080/10615806.2016.1146710 · Cited by 34 · see citing works
“The average disease duration was 8.1 ± 6.8 years and the median EDSS was 3.0, which indicates that on average, the sample was fully ambulatory with mild-to-moderate disability (Kurtzke, 1983).”
BackgroundResultInfluentialThe relationship between cognitive fusion, stigma, and well-being in people with multiple sclerosis
Valvano, A., Floyd, R. M., Penwell-Waines, L., Stepleman, L., Lewis, K., & House, A. (2016) · Journal of Contextual Behavioral Science · doi:10.1016/j.jcbs.2016.07.003 · Cited by 32 · see citing works
Zhang, X., Song, Y., Wei, Z., Chen, X., Zhuang, X., & Li, Y. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1120541 · Cited by 37 · see citing works
Negaresh, R., Motl, R. W., Mokhtarzade, M., Ranjbar, R., Majdinasab, N., Khodadoost, M., Zimmer, P., Baker, J. S., & Patel, D. I. (2018) · EXPLORE · doi:10.1016/j.explore.2018.07.007 · Cited by 33 · see citing works
“, interferon beta).(3,6) Fatigue and depression are commonly accompanied by disability progression,(2,7) and fatigue and depression symptoms may reduce physical activity and quality of life in persons with MS.”
BackgroundHistory of fatigue in multiple sclerosis is associated with grey matter atrophy
Palotai, M., Nazeri, A., Cavallari, M., Healy, B. C., Glanz, B. I., Gold, S. M., Weiner, H. L., Chitnis, T., & Guttmann, C. R. G. (2019) · Scientific Reports · doi:10.1038/s41598-019-51110-2 · Cited by 33 · see citing works
Chalah, M. A., Grigorescu, C., Padberg, F., Kümpfel, T., Palm, U., & Ayache, S. S. (2020) · Journal of Neural Transmission · doi:10.1007/s00702-020-02166-2 · Cited by 33 · see citing works
Sparasci, D., Gobbi, C., Castelnovo, A., Riccitelli, G. C., Disanto, G., Zecca, C., & Manconi, M. (2022) · Journal of Neurology · doi:10.1007/s00415-022-11143-6 · Cited by 35 · see citing works
Askey-Jones, S., David, A. S., Silber, E., Shaw, P., & Chalder, T. (2013) · Behaviour Research and Therapy · doi:10.1016/j.brat.2013.04.001 · Cited by 32 · see citing works
Gavrilov, Y. V., Shkilnyuk, G. G., Valko, P. O., Stolyarov, I. D., Ивашкова, Е. В., Ilves, A. G., Nikiforova, I. G., Shchelkova, O. Y., Wasserman, L. I., Vais, E. E., et al. (2018) · Acta Neurologica Scandinavica · doi:10.1111/ane.12993 · Cited by 32 · see citing works
Vesić, K., Tončev, G., Drakulić, S. M., & Borovčanin, M. (2018) · Acta Neurologica Belgica · doi:10.1007/s13760-018-1015-8 · Cited by 31 · see citing works
Mayo, C. D., Miksche, K., Attwell-Pope, K., & Gawryluk, J. R. (2019) · Journal of Clinical and Experimental Neuropsychology · doi:10.1080/13803395.2019.1614535 · Cited by 32 · see citing works
“…& Zivadinov, 2011; Chiaravalloti & DeLuca, 2008; Planche et al., 2016); up to 50% of individuals diagnosed with MS have experienced depression (Feinstein, Magalhaes, Richard, Audet, & Moore, 2014) and 50% to 80% of individuals with MS experience fatigue (Wood et al., 2012; Zajicek et al., 2010).”
BackgroundMS Energize: Field trial of an app for self-management of fatigue for people with multiple sclerosis
Babbage, D. R., van Kessel, K., Drown, J., Thomas, S., Sezier, A., Thomas, P., & Kersten, P. (2019) · Internet Interventions · doi:10.1016/j.invent.2019.100291 · Cited by 31 · see citing works
Simpson, R., Simpson, S., Wasilewski, M., Mercer, S., & Lawrence, M. (2022) · Disability and Rehabilitation · doi:10.1080/09638288.2021.1964622 · Cited by 30 · see citing works
Battalio, S. L., Glette, M., Alschuler, K. N., & Jensen, M. P. (2018) · Rehabilitation Psychology · doi:10.1037/rep0000231 · Cited by 30 · see citing works
Butchard-MacDonald, E., Paul, L., & Evans, J. J. (2017) · Journal of the International Neuropsychological Society · doi:10.1017/s1355617717000947 · Cited by 28 · see citing works
“Estimated prevalence rates for depression range from 10% to 41.8%; anxiety 23.5% to 41%, which are considerably higher than in the general population (Wood et al., 2012).”
BackgroundInfluentialSkorve, E., Lundervold, A. J., Torkildsen, Ø., & Myhr, K. (2020) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2020.102577 · Cited by 30 · see citing works
Simpson, R., Posa, S., Langer, L. K., Bruno, T. R., Simpson, S., Lawrence, M., Booth, J., Mercer, S. W., Feinstein, A., & Bayley, M. T. (2022) · Journal of Neurology · doi:10.1007/s00415-022-11451-x · Cited by 29 · see citing works
“Common symptoms include stress [3], anxiety [4], depression [5], fatigue [6], spasticity [7], pain [8], temperature sensitivity [9], cognitive difficulties [10], sleep impairment [11], bowel [12], bladder [13] and sexual dysfunction [14].”
BackgroundMood and coping in clinically isolated syndrome and multiple sclerosis
Bianchi, V., Giglio, L. D., Prosperini, L., Mancinelli, C. R., Angelis, F. D., Barletta, V. T., & Pozzilli, C. (2013) · Acta Neurologica Scandinavica · doi:10.1111/ane.12194 · Cited by 29 · see citing works
“Strong associations have been observed between depression and anxiety (12).”
BackgroundConnaughton, J., & Gibson, W. (2016) · Physiotherapy Canada. Physiothérapie Canada · doi:10.3138/ptc.2015-66 · Cited by 26 · see citing works
- Authors
- Wood, B., van der Mei, I., Ponsonby, A.-L., Pittas, F., Quinn, S., Dwyer, T., Lucas, R., & Taylor, B.
- Affiliations
- University of Tasmania (AU)
- Menzies Research Institute Tasmania, University of Tasmania, Tasmania, Australia
- The University of Melbourne (AU)
- Flinders University (AU)
- National Centre for Epidemiology and Public Health, The Australian National University, Canberra, Australia
- Venue
- Multiple Sclerosis Journal
- Publisher
- SAGE Publications
- Published
- 2012-06-22
- Volume
- 19
- Issue
- 2
- Pages
- 217-224
- ISSN
- 1352-4585 (ISSN-L)
- 1477-0970
- OpenAlex
- W1973836236
- Cited by
- 294
- References
- 41
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 17 · 2023: 15 · 2022: 24 · 2021: 36 · 2020: 21 · 2019: 19 · 2018: 25 · 2017: 22 · 2016: 24 · 2015: 25 · 2014: 28 · 2013: 19 · 2012: 1
- FWCI
- 16.84
- Type
- journal article
- Language
- en
- Open access
- green
- figshare.com
- Locations
- Multiple Sclerosis Journal (publishedVersion)
- PubMed (publishedVersion)
- eCite Digital Repository (University of Tasmania) (submittedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- ANU Open Research (Australian National University) (submittedVersion)
- Swinburne figshare (Swinburne University of Technology) (submittedVersion)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Oncology › Cancer survivorship and care
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Keywords
- multiple sclerosis, anxiety, depression, fatigue, comorbidities, prevalence, longitudinal cohort, sex differences, disease duration, Expanded Disability Status Scale, seasonal variation, Hospital Anxiety and Depression Scale, Fatigue Severity Scale
- MeSH terms
- Adult, Age Factors, Antidepressive Agents, Anxiety, Depression, Disability Evaluation, Educational Status, Fatigue, Female, Humans, Immunologic Factors, Longitudinal Studies, Male, Middle Aged, Multiple Sclerosis, Seasons, Sex Characteristics, Tasmania, Cohort Studies, Disease Progression
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