Received: 2 June 2022 | Accepted: 22 August 2022 DOI: 10.1111/ane.13709 REVIEW ARTICLE Online psychological interventions to improve symptoms in multiple sclerosis: A systematic review Brenda Montañés-­Masias1 | Judit Bort-­Roig2 | Juan Carlos Pascual3,4,5 | Joaquim Soler3,4,5 | Laia Briones-­Buixassa1 1 Research group in Mental Health and Social Innovation (SaMIS), Centre The aim of this systematic review was to assess the effectiveness of Internet-­based for Health and Social Care Research, psychological interventions in the treatment of physical, socio-­affective and cognitive Universitat de Vic –­Universitat Central de Catalunya, Vic, Catalonia, Spain symptoms and quality of life (QoL) in people with multiple sclerosis (pwMS) to provide 2 Sport and Physical Activity Research currently available evidence. Group, Centre for Health and Social Care Research, Universitat de Vic –­Universitat Systematic searches for eligible studies were carried out in four databases (August Central de Catalunya, Vic, Catalonia, Spain 2021) using key words. Studies were screened, data extracted, quality appraised and 3 Department of Psychiatry, Hospital de la analysed by three independent reviewers, using predefined criteria and following Santa Creu i Sant Pau, Barcelona, Spain 4 the PRISMA rules. Study quality was assessed using Standard Quality Assessment Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Institut Criteria for Evaluating Primary Research Papers from a Variety of Fields QUALSYST de Recerca Biomèdica Sant Pau (IIB-­Sant tool. Physical, socio-­affective and cognitive symptoms and QoL were the primary Pau), Barcelona, Spain 5 Department of Psychiatry and Forensic outcomes. Medicine & Institute of Neurosciences, Thirteen studies were included. Two principal approaches were reported: Cognitive Universitat Autònoma de Barcelona, Bellaterra, Spain behavioural therapy (CBT) and mindfulness-­based interventions (MBI). Interventions varied from tailored versions to videoconference by a clinician, duration mean 8 weeks, Correspondence Judit Bort-­Roig, Sport and Physical delivered via individually and groups, all online. The review found that iCBT interven- Activity Research Group, Centre for tions were effective for improve depression, anxiety, fatigue and QoL, and slightly in Health and Social Care Research, Universitat de Vic –­Universitat Central de cognitive functioning in pwMS, whereas MBI interventions reported benefits in de- Catalunya Vic, Catalonia, Spain. pression, anxiety, stress and QoL, and less evidence in fatigue. Generally, study qual- Email: judit.bort@uvic.cat ity was acceptable in most studies; eleven of the studies scored a low risk of bias on all items in the Qualsyst Tool, whereas only two studies were considered unacceptable. Psychological online interventions may improve physical, socio-­affective and cog- nitive symptoms as well as QoL in pwMS, overcoming the face-­to-­face barriers (i.e. disability). Contact with the therapist and groups sessions have been identified as enablers of the online interventions. Nevertheless, the limited number of studies and the heterogeneity of health outcomes reported made difficult to afford robust con- clusions on psychological intervention effects in pwMS. KEYWORDS multiple sclerosis, online intervention, psychological therapy, quality of life, symptoms This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. © 2022 The Authors. Acta Neurologica Scandinavica published by John Wiley & Sons Ltd. 448 |  wileyonlinelibrary.com/journal/ane Acta Neurol Scand. 2022;146:448–464. MONTAÑÉS-­MASIAS et al. | 449 1 | I NTRO D U C TI O N Cognitive behavioural therapy (CBT) is the most commonly used approach and has shown effectiveness in reducing depression, anxi- Multiple sclerosis (MS) is a chronic and progressive inflammatory ety and stress, and improving cognitive functioning and the manage- autoimmune disorder of the central nervous system.1 MS is a rela- ment of symptoms such as pain and fatigue.12,13 tively common neurological disease that affects approximately 1–­2 Another psychological intervention that has shown encouraging per 1000 individuals. It usually begins between the ages of 20 and results and is in increasingly used healthcare is mindfulness-­based 40 and affects mostly women with a 3:1 ratio. 2,3 The clinical course interventions (MBIs),14 which are complex interventions based on of the disease is highly variable, although it is common to manifest paying attention to the present moment with a non-­judgmental at- as outbreaks associated with clinical signs of neurological dysfunc- titude.15 Several studies have reported that MBIs can help people tion with full or partial recovery. This type of MS is called relapsing–­ adjust to chronic illness and to relate to their symptoms more posi- remitting (RRMS) and affects 85%–­90% of people with MS (pwMS).4 tively.16,17 MBI have considerable evidence as a potential treatment After an average of 10–­20 years, most people transition to another for anxiety and depression, as well as fatigue, pain and improving type of MS called secondary progressive (SPMS), which is charac- QoL in pwMS.16,17 However, despite these promising results, many terized by a gradual worsening between relapses.4 There are also pwMS are unable to access these interventions due to limited mobil- two more types that represent around 15% of patients: primary ity, fatigue and related issues, costs associated with travel and lim- progressive MS (PPMS), which is characterized by experiencing dis- ited access to services.10 In addition, the ongoing global pandemic ability progression without relapses, and progressive relapsing MS makes it even more difficult to access psychological services and (PRMS), which combines relapses and disability progression from the receive support. In such circumstances, online intervention is good beginning.4 option to overcome many of these barriers.18 Several studies have MS patients suffer from a variety of physical, socio-­affective and evaluated Internet-­based interventions and suggest that they were cognitive symptoms. The main physical symptoms are fatigue, poor feasible and effective in various neurological disorders.19 balance, impaired speech, bladder and bowel dysfunction, chronic Some studies demonstrated that online psychological interven- pain and spasms,5 while the main socio-­affective symptoms are de- tions had potential benefits on physical, socio-­affective and cogni- pression, stress, anxiety and sleep disturbance, which are associ- tive symptoms in pwMS.7,20,21 However, less is known in pwMS with 6,7 ated with lower quality of life (QoL). Cognitive alterations are also respect to (a) their efficacy compared to face-­to-­face intervention; common, mainly in attention, memory, processing speed, executive (b) which psychological interventions (CBT, MBI) are more effective function and visuospatial processing.8 in Internet-­based format; (c) which symptoms improve; and (d) which To date, there is no cure for MS, but there are a number of treat- is the most efficient format (web-­based, video conferencing, app) to ments available. A recent review9 defended a multifaceted approach carry out the intervention. Therefore, the primary aim of this sys- for an effective management and recommend the use of drugs as tematic review was to examine the impact of online psychological first-­line treatment for many patients with early MS. In general, the interventions to improve physical, socio-­affective, cognitive symp- goals of the treatment are intended to accelerate recovery after an toms and QoL in pwMS. As a secondary aim, we analyse the mode of outbreak, slow disease progression down, manage symptoms and im- delivery of those interventions to explore the most efficient format 9,10 11 prove the QoL. In the same line, another review also defended to design online interventions in a future. medication are more effective in the early stages of disease, and the most used medication is disease-­modifying therapies (DMTs), which can reduce the number and severity of relapses, and slow down the 2 | M E TH O D S 11 damage caused by relapsing MS that builds up over time. Although MS drugs have shown reliable good results, they are 2.1 | Design not suitable for all the patients. A proper monitoring has to be pro- vided, and they have multiple side effects including chest pain, A systematic review was developed considering the PRISMA state- chills, cough, fever, flu-­like symptoms, headache, nausea, pain, ments. 22 The protocol has been registered in the National Institute 12 trouble breathing and unusual fatigue weakness, among others. for Health Research (NHS) on PROSPERO (International Prospective Moreover, the literature suggests that pwMS are not adequately Register of Systematic Reviews) database: CRD42021266181. treated for their mood disorders (i.e. anxiety and depression) and for other symptoms, such as fatigue and pain.13 In this regard, psy- chological interventions may improve the psychological and phys- 2.2 | Search strategy and selection criteria ical well-­being of pwMS by treating mood disorders, improving self-­management and adherence, reducing stress, and improving The search strategy was carried out in August 2021 (Pubmed, Web 13 coping skills to cope with emotions and thoughts, and QoL. In of Knowledge, Psycinfo and Scopus). Research for eligible studies addition, psychological group therapy may contribute to improving was conducted from the earliest available ones to the most re- acceptance, facilitating the expression of emotions related to the cent. We performed a keyword search using the terms (“Multiple disease and providing peer support. Sclerosis” OR “Disseminated Sclerosis” OR “MS” OR “Sclerosis, 450 | MONTAÑÉS-­MASIAS et al. Multiple” OR “Disseminated, Sclerosis”) AND (“therapy” OR “in- of disagreement, consensus was reached via discussion and a more tervention” OR “program” OR “treatment”) AND (“Mindfulness” conservative (the lowest score) approach was applied. A summary OR “CBT” OR “psychology” OR “Cognitive behavioural therapy” score was calculated for each paper by summing the total score ob- OR “mental health”) AND (“internet” OR “online” OR “website” OR tained across relevant items and dividing by the total possible score. “virtual”). Items not applicable to a particular study were excluded from the The eligibility of the studies was formulated according to the calculation of the summary score. following criteria: that (i) they were focused on the adult popula- tion (over 18 years); (ii) the participants were diagnosed with MS by a neurologist; (iii) they were psychological intervention studies; (iv) 3 | R E S U LT S the programme was mainly online (more than 50%); (v) they reported effectiveness on physical (e.g. pain), socio-­affective (e.g. depression 3.1 | Study selection and anxiety) and/or cognitive symptoms (e.g. attention) and/or QoL; and (vi) the language of the study was French, English or Spanish. The literature review retrieved 2211 articles. From these, 13 dupli- The exclusion criteria were studies (i) where participants had an- cate articles and 10 incomplete records were eliminated. Three more other physical or neurological disorder; (ii) in which interventions studies were added from checking reference lists from systematics were fully provided via telephone; (iii) that evaluated only accep- reviews. Subsequently, records were examined by title, a total of tance or satisfaction of the intervention; and (iv) grey literature (e.g. 258 full-­text articles were selected, and 43 full-­text articles were these editorials). Studies that involved participants with other diag- critically appraised for final eligibility. Twenty-­seven of these articles noses or neurological conditions where data were specifically pro- did not meet the inclusion criteria, the main reasons being: (a) the vided for pwMS were included. To attain additional eligible articles, intervention was not focused on psychological therapy (e.g. behav- reference lists of located studies and previous systematic reviews ioural change and physical activity); (b) they were not interventional were checked. studies (e.g. observational and protocol study); (c) the results were To identify potentially eligible studies, two reviewers inde- not specific on pwMS; and (d) they were systematic reviews. Finally, pendently performed the selection of articles. Any disagreements thirteen studies were included for the qualitative synthesis. were resolved through discussion among the reviewers. First, The flow diagram in Figure 1 shows the study selection process, B.M-­M identified records from the databases, and once duplicates and details from all studies were summarized in Table 1. and incomplete records were eliminated using management soft- ware (Mendeley), a list of articles that satisfied the eligibility criteria was compiled. Second, B.M-­M and L.B-­B performed the selection of 3.2 | Characteristics of included studies articles by examining abstracts and subsequently screening full-­text articles. Finally, a third author (J.B-­R) was available to resolve any Table 1 shows the main characteristics of the included studies. The disagreement and revised full-­text records that were in doubt. first article was published in 2011 and the most recent in 2021. A wide variety of countries were represented (e.g. the Netherlands, Germany, the UK, New Zealand, the United States and Australia). 2.3 | Data extraction Diagnosis was mainly performed by a specialized neurologist. The average time since diagnosis was 11.10 years (± 4.82), although two Extracted data included study characteristics (e.g. authors, age and studies did not provide this detail. 25,26 All studies were focused on country), diagnosis (e.g. type of MS and time since diagnosis), study the pwMS, although one study included participants with other design (e.g. RCT and pre–­post measures), sample (e.g. N, mean age neurological disorders reporting specific data for pwMS. 27 Six stud- and gender), intervention (e.g. type, time and follow-­up), main out- ies20,21,25,28,29,30 included all types of MS, while three studies31,32,33 comes and measurement tools, and findings. recruited only participants with diagnosis of RRMS and SPMS, and If relevant data were not included in the article, the authors of four studies did not report information about MS diagnosis/type. the study were contacted for further details. 23 Most participants had RRMS, and in only one study was SPMS the predominant type of MS. Most included studies were randomized controlled trials (RCT). 2.4 | Quality assessment Six of these studies20,23,25,28,29,30 employed a wait-­list control group; one study21 used usual care; two studies used comparison group in- Study quality was reported using the Standard Quality Assessment terventions such as CBT without therapeutic contact31 and online Criteria for Evaluating Primary Research Papers from a Variety of psychoeducation33; in one study26 the control group were partici- Fields QUALSYST tool. 24 Studies were scored on 14 items (e.g. eli- pants without MS; and one34 used a mixed-­methods design embed- gibility criteria, random allocation). Criteria can be answered as ‘yes’ ded within a three-­arm RCT of two different interventions against (2), ‘partial’ (1), ‘no’ (0) and ‘NA’. Three reviewers (B.M-­M, J.B-­R and a wait-­list control group. The remaining two studies27,33 used single L.B-­B) independently assessed the included studies by pairs. In case group pre–­post designs. MONTAÑÉS-­MASIAS et al. | 451 F I G U R E 1 Search and exclusion Identification of studies via databases and registers process flow diagram From: Page MJ, McKenzie JE, Bossuyt PM, et al. The Records identified from*: PRISMA 2020 statement: an updated Databases (n = 2211) Records removed before Identification guideline for reporting systematic Pubmed (n= 1281) screening: reviews. Bmj. 2021;372:71. Doi: 10.1136/ Psycinfo (n= 325) Duplicate records removed (n bmj.n71 WOS (n=171) = 207) Scopus (n= 434) Records removed for other reasons- incomplete (n = 23) Registers (n = 3) Records screened Records excluded (n = 1984) (n = 1723) Reports sought for retrieval Reports not retrieved (n = 261) (n = 215) Screening Reports assessed for eligibility Reports excluded: (n= 33) (n = 46) 1 the intervention was delivered via telephone 10 the intervention not being psychological therapy 3 the study design was correlational or qualitative 1 the results not specific for pwMS 4 protocol study 5 the study not finished yet Included Studies included in review 8 were narrative review or (n = 13) systematic review 1 full-text not available 3.3 | Quality assessment Nine studies21,23,25,2733 reported physical functioning and dis- ability. Five of these studies21,29,31,32,33 assessed disability using the The mean quality score was 87.77% (±9.81) with 15.38% of articles Expanded Disability Status Scale (EDSS: scores 0–­6.5); three stud- scoring below 75% (a ‘relatively’ conservative cut-­off for acceptable ies23,25,30 reported similar information using the Patient Determined 24 articles). The main reasons for lower scores were inappropriate Disease Steps (PDDS) scale; and one study27 used the World Health study design, robust measurement of outcome and estimate for vari- Organisation Disability Assessment Schedule (WHODAS 2.0). ance reported in insufficient detail, and lack of control for confound- ing variables. 3.5 | Intervention characteristics and delivery 3.4 | Sample characteristics In general, the included studies used Internet-­based psychological interventions that were based on contents of CBT and educational Samples sizes ranged from 24 to 275 participants. The age of the components: (a) Boeschoten et al. (2012)28 used problem-­solving participants ranged from 18 to 65 years old (mean = 47.80, ±5.65). therapy (PST) based on an online cognitive–­behavioural self-­help in- Most participants were females (75.42%). Almost half of the studies tervention that was modified and included additional information based participant recruitment on clinical cut-­off scores indicative of about MS and its psychosocial consequences; (b) Fischer et al. (2015)20 problematic fatigue, distress or depression from baseline self-­report, used an online programme based on principles of CBT (Deprexis); (c) clinical-­interview or both (7/13). 21,25,28,29,30,31,34 Moss-­Morris et al. (2012)21 and Van Kessel et al. (2015)31 examined 20,25,26,27,28,29,33,34 Eight studies provided information about psy- a programme based on CBT principles including psychoeducation 21,23,31,32,34 chotropic medication, while five studies did not report this. and self-­monitoring (Ms Invigor8: Breaking the Cycle of fatigue); (d) Most studies differentiated between disease-­modifying medication Pöttgen et al. (2018)25 explored a self-­guided, interactive, online fa- and medication for symptom relief (e.g. antidepressant and fatigue tigue management programme (ELEVIDA) also based on principles medication). of CBT; (e) Boeschoten et al. (2017)29 evaluated an Internet-­based TA B L E 1 Summary of included studies 452 | Intervention (type, Main outcomes, Authors, year, Criteria (type, time since frequency, time and measurement Quality assessment and country MS diagnosis) Study design Sample mode of deliverable) tools and periods Main findings (%) Finlayson et al., Self-­reported diagnosis RCT, two-­group time n = 181 6/w fatigue FIS Intervention group compared to wait list showed 92% 2011 of MS series design with (n = 89 intervention and 92 management FSS a significant reduction (mean difference) Selection strategies (USA)30 15 years since diagnosis a wait-­list control control group) program (CBT SF-­36 in all three FIS subscales: Cognitive (− were not ideal RRMS-­95 group Mean age = 56 contents), Secondary 3.12, p = .001); Physical (− 2.53, p = .014); but did not SPMS-­39 143 women, 38 males weekly 70-­min outcome: Social (− 6.01, p = .002); and a significant likely seriously PPMS –­16 FSS score of 4 or greater teleconference Self-­Efficacy improvement in the SF-­36 Role Physical distort the PRMS-­11 (i.e. moderate to severe calls via group for Energy subscale (18.06, p = .002). results Unknown 17 fatigue); and score 12 or Homework activities Conservation Intervention group compared to baseline scores, (telephone Missing 3 more on a short blessed Questionnaire after interventions showed (Cohen's D survey sampled test. Baseline, post, 3-­ effect) a large effect size in all FIS subscales from listed Mean PDSS = 4 and 6-­month at 3 months: Cognitive 0.58; Physical 0.68; phone numbers follow-­up Social 0.65 and 6 months: Cognition 0.55; only) and Physical: 0.61 and Social: 0.67; a significant comparability reduction in the FSS scores: at 3-­month: within groups (−0.38) and 6-­month (− 0.33). Significant at baseline improvement in the SF-­36 subscales insufficient except the physical functioning and body detailed pain subscales: Mental Health 5.78; Social Functioning 7.95; General Health 3.61; Role Physical 11.12. Significant improvement in Self-­Efficacy for Managing Fatigue Scale 0.51. Boeschoten, Diagnosis of MS confirmed Single group pre-­test/ n = 44 MS (23 intervention and 5/w web-­based iPST, Depression BDI-­II Depressive symptoms decreased a mean 68% et al., 2012 by a neurologist post-­test design 21 control group) 2 hours a week Secondary of 3.9 points in all patients (mean at Not used a (Netherlands)28 (>3 months ago) study Mean age = 45 years; 34 (5 modules), measures: baseline = 20.1, mean at post = 16.2; comparison Years since diagnosis, females individual, weekly HADS-­A d = 0.51, p = .01). There was a significant group and median = 5 (2 to 40) Scored 16 or higher on the e-mails support SF-­36 difference in BDI-­II change scores between sample size RRMS (48%) BDI-­II EQ -­5D completers (mean = −7.9) and non-­ reduced SPMS (23%) Medication: EQ-­VAS completers (mean = 0.61) (p = .001). PPMS (18%) • MS medication (disease SPSI-­R Completers analyses revealed a significant Not reported (11%) modifying and symptoms Baseline, post decrease on anxiety (mean at relief; n = 40, 90.90%) baseline = 9.4 ± 3.1; mean HADS-­A at post • Psychotropic medication 7.2 ± 3.1; d = 0.71, p = .004) and on negative (n = 21, 47.72%) problem orientation in whole sample (18.0 ± 5.4, 15.6 ± 6.3; d = 0.41; p = .004) larger for the patients who completed the intervention (mean at baseline 19.5 ± 4.8; mean at post 15.3 ± 6.0; d = 0.77, p = .001). MONTAÑÉS-­MASIAS et al. TA B L E 1 (Continued) Intervention (type, Main outcomes, Authors, year, Criteria (type, time since frequency, time and measurement Quality assessment and country MS diagnosis) Study design Sample mode of deliverable) tools and periods Main findings (%) Moss-­Morris, Diagnosis of MS from RCT, two arms n = 40 MS (intervention group 8-­10/w Internet-­based Fatigue scale The intervention group showed significant 85% et al., 2012 neurologist (intervention, usual 23, control group 17) CBT (MS Invigor8), MFIS reductions when compared to the control Sample size (England)21 Years since diagnosis: care) 32 females, mean age = 40 weekly sessions Secondary group on both the Fatigue Scale (mean insufficient and MONTAÑÉS-­MASIAS et al. intervention = 21 (9,05), Fatigue Scale score >4 (on average, measures: at baseline = 21.39 ± 4.30; mean at interventional control group = 16 Ambulation ability (self-­report sessions took 25 HADS post = 12.39 ± 6.84; d = 1.19, p < .001) and blinding of (7,88) EDSS): to 50 min) + three Baseline, post and the Modified Fatigue Impact Scale investigators MS type: • Able to walk 500 m or more telephone support (mean at baseline = 13.17 ± 3.81; mean at were not RRMS 22 without aid or rest (47.5%) sessions 30–­6 0′ post = 9.00 ± 3.75: d = 1.22, p < .001). reported SPMS 9 • Able to walk 100 m without Homework tasks There were significant differences between the PPMS 2 aid or rest 15% groups on anxiety at baseline (8.26 ± 4.31) Unsure 7 • Require unilateral or and at post (6.44 ± 3.91, p = ·001); and on bilateral aid to walk 20 to depression at baseline (7.96 ± 3.64) and at 100 m 32.5% post (5.18 ± 3.38, p = .001), with the MS • Missing data 5% Invigor8 group showing significantly greater reductions on both scales. Bogosian et al., Diagnosis of PPMS or SPMS RCT, two arms (CCBT n = 40 MS (19 intervention, 21 8/w MBCT GHQ -­12 Mean GHQ-­12 (distress) total scores were lower 96% 2015 PPMS = 17 (42%) online and wait list) control group) (Mindfulness), Secondary in the Mindfulness group compared to Exposure (England)32 SPMS = 23 (57,5%) Mean age = 52,7 (9,5), 22 once a week, measures: waiting-­list group at the post-­intervention measure(s) Median years since females 1 hour-­long HADS (−3,72 ± 1.76; d = −0.67, p = .035), and three-­ partial well diagnosis = 12 (1–­38) Mean EDSS = 6,5 (1,5) sessions, group MSIS-­29 month follow-­up (−5.45 ± 1.66, d = 0.97, defined Distress (GHQ-­12) score 3 or videoconference Pain intensity p = .005). (answer options greater (Skype) (0–­10) Significant reduction in the Mindfulness and number of Homework tasks FSS group compared to waiting-­list at items were not Baseline, post, post-­intervention on: HADS depression reported) 3-­month (mean at baseline = 6–­24 ± 3.51; follow-­up mean at post = 5.12 ± 3.20; p = .017), MSIS psychological (23.09 ± 6.39; at post = 19.19 ± 6.00; p = .000) and MSIS physical scores (mean at baseline = 64.52 ± 19.80; mean at post = 58.19 ± 17.56; p = .016); and three-­ month follow-­up on HADS depression (5.13 ± 4.27; p = .026). HADS anxiety (4.84 ± 3.21; p = .012), MSIS psychological (18.72 ± 6.31: p = .001), MSIS physical scores (60.54 ± 20.52; p = .005); and pain (1.73 ± 2.09; p = .034). | 453 (Continues) TA B L E 1 (Continued) 454 | Intervention (type, Main outcomes, Authors, year, Criteria (type, time since frequency, time and measurement Quality assessment and country MS diagnosis) Study design Sample mode of deliverable) tools and periods Main findings (%) Fischer Diagnosis MS RCT, two arms n = 90 MS (45 intervention 9/w online CBT Depression BDI Statistically significant treatment effect was 96% et al., 2015 Disease duration in (intervention and group and 45 control (‘Deprexis’), 10 Secondary showed in intervention group on BDI total Exposure (Germany)20 years = 8,30 wait list) group) modules, (60 min) measures: score (mean at baseline = 19.44 ± 9.02; measure(s) not RRMS 40 Intervention group: mean WHO-­QoL BREF mean at post 16.24 ± 8.66; p = .01) well defined SPMS 21 age = 45,36(12,64). 34 HAQUAMS and on BDI subscale subdomains of (Answer options Clinically isolated symptom females FSMC negative attitude towards self (mean and number of 6 Control group: mean Baseline, post, at baseline = 9.58 ± 5.47; mean at post items were not PPMS11 age = 45.20(810,56), 36 6-­month 7.83 ± 5.36; p = .03) and somatic symptoms reported) Unclear 12 females follow-­up (mean at baseline = 2.02 ± 1.56; mean at Medication: post 1.57 ± 1.07; p = 001). • Disease modifying There was statically significant difference treatment (68% none) on psychological well-­being subscale • Antidepressant treatment from WHO-­Q ol BREF (mean at (84.4% none) baseline = 47.13 ± 18.84; mean at post • Symptomatic treatment 52.22 ± 20.39; p = .04); and on motor (55.5% none, pain 7′8%, fatigue subscale from FSMC (mean at muscle relaxant 14.44%, baseline = 38.51 ± 6.82; mean at post bladder control 5.55%, other 36.17 ± 8.45; p = .03). 4.44%). At 6-­month follow-­up, mean BDI intervention group were lower than at baseline (mean BDI at baseline = 19·37 ± 9.59; mean BDI at 6 months = 14·80 ± 10.03; p = ·001). Van Kessel, et al., Diagnosis MS by neurologist RCT, two arms (grup n = 39 MS (20 MSInvigor8-­ 8-­10/w, weekly Chalder Fatigue The MSInvigor8-­Plus group showed significantly 77% 2015 RRMS-­26 MSInvigor8-­ Only, 19 MSInvigor8-­Plus) sessions, 25 to Scale greater reductions compared with the Study design partial (New Zealand)32 SPMS-­13 Only and group Mean age = 45 (8,1) 50 min Modified Fatigue MSInvigor8-­Only group on inappropriate Years since diagnosis: MSInvigor8-­Plus) MSInvigor8-­Only: mean MSInvigor8-­Only Impact Scale the Chalder Fatigue Scale (mean at (not used a MsInvigor8-­Only = 4,78 age = 42,95 (8,16), 18 (online CBT, Secondary baseline = 22.37 ± 4.39; mean at control group) (4,36); MsInvigor8-­ females without any outcomes: post = 11.37 ± 6.20; d = 0.99, p < .01) and method Plus = 5,12 (4,29) MsINvigor8-­Plus: mean therapeutic HADS and the Modified Fatigue Impact Scale of subject age = 45,70 (8,39), 11 contact) Baseline, post (mean at baseline = 13.58 ± 2.97; mean at selection and females MSInvigor8-­Plus post = 10.00 ± 2.71; d = 0.81, p < .02). comparison Chalder Fatigue Scale score of (online CBT with group was 4 or greater therapeutic inappropriate EDSS: contact 10 min Only: at week with • 0–­4: 10 (53,0) email support • 4,5-­5,5: 2 (10,0) from a clinical • 6–­6 ,5: 6 (31,5) psychologist) • NR-­1 (5,0) Both included Plus: homework tasks • 0–­4: 8 (40,0) • 4,5-­5,5: 7 (35,0) • 6–­6 ,5: 3 (15,0) NR-­2 (10,0) MONTAÑÉS-­MASIAS et al. TA B L E 1 (Continued) Intervention (type, Main outcomes, Authors, year, Criteria (type, time since frequency, time and measurement Quality assessment and country MS diagnosis) Study design Sample mode of deliverable) tools and periods Main findings (%) Boeschoten, Diagnosis MS (>3 months) RCT, two arms n = 171 MS (85 intervention 5/w iPST (‘Worry Depression BDI-­II Both groups showed a high within-­group 100% et al., 2017 Years since MS onset = 11,2 (intervention and and 86 wait list) Less’) Secondary effect size in depressive symptoms after (Netherlands)29 (8,1) wait list) Mean age = 48,9 ± 10,5 5 modules, once a measures: intervention (IPST = −7.9; wait list = −6.2), MONTAÑÉS-­MASIAS et al. Benign 2.3 Relapsing 137 females week HADS and at follow-­up (IPST = −7-­4: wait list remitting 55.0 EDSS: Contact therapeutic BAI control = − 7.1). Secondary progressive 28.1 0–­1.5 = 3.5 weekly via email FSS There was no difference between groups on Primary progressive 9.9 2–­4 = 50.0 MSNQ BDI-­II after intervention and at follow-­up. Relapsing progressive 3.5 4.5–­6 = 17.5 MSIS-­29 Missing 1.2 ⩾6.5 = 27.5 EQ -­5D Score BDI-­II (<20) SPSI-­R Medication: Pearlin Mastery • Disease modifying Scale treatment (32.9%) Baseline, post • Symptoms relief (52.0) (5–­10 weeks), Antidepressant (12.9%) 4-­month follow-­up, Alschuler et al., Self-­reported physician RCT, two arms n = 28 MS 6/w positive CD-­RISC Significant group effect in the treatment 95% 2018 diagnosis of MS (intervention, wait-­ (12 intervention and 16 control psychology Secondary group reporting higher resilience (mean Some estimate of (USA)23 Mean disease list control) group) intervention outcomes: at baseline = 25.70 ± 10.3 and at post-­ variance (e.g. duration = 20 years Intervention group: 10 females, (Everyday Matters Neuro-­Q oL test = 31.66 ± 2.26; d = 1.16, p = .02). confidence RRMS-­19 mean age = 59.8 (7.7); Intervention), SES Significant group effect in the intervention intervals, SPMS-­5 Control group: 16 females, 90-­min sessions, PROMIS group for satisfaction with social roles standard PPMS –­4 mean age = 59.8 (6.5) delivered SHS (mean PROMIS at baseline = 39.95 ± 9.44; errors) were PDDS: via group Baseline, post at post = 47.55 ± 2.92; d = 1.06, p = .02), insufficient • Mild disability 6 teleconference and a marginal effect for positive reported • Moderate disability 4 Private web-­based affect and well-­being (mean Neuro-­ for the main • Gait disability 3 group page among QoL at baseline = 50.01 ± 7.62; at results • Early cane 02 facilitators and post = 54.82 ± 3.45; d = 0.72, p = .09) • Late cane 4 participants and for depressive symptoms severity • Bilateral support 4 (57.43 ± 9.14 45.22 ± 3.93; d = 0.72, p = .09) • Wheelchair/scooter 5 | 455 (Continues) TA B L E 1 (Continued) 456 | Intervention (type, Main outcomes, Authors, year, Criteria (type, time since frequency, time and measurement Quality assessment and country MS diagnosis) Study design Sample mode of deliverable) tools and periods Main findings (%) Pöttgen, et al., Diagnosis MS confirmed by RCT, two arms n = 275 MS (139 intervention 12/w Internet-­based Chalder Fatigue Both groups showed a decreased in Chalder 100% 2018 neurologist (intervention, wait and 136 control group) CBT (ELEVIDA), Scale Scale, but this decline was more (England)25 RRMS 98 (70.5) list) Intervention group: mean once to twice a Secondary pronounced in the ELEVIDA group (mean SPMS 21 (15,1) age = 40,80(11,1), 114 week, modules measures: difference = −2.74, d = 0.53, p = .0007). PPMS 8 (5,8) females Included homework FSMC, HADS-­A , There were significant reductions in group Unknown 12 (8,6) Control group: mean tasks HADS-­D intervention on fatigue (FSMC: −3.47, RRMS 102 (75,0) age = 41,90 (9,4), 108 HAQUAMS p = .0034), as well as its subscales for motor SPMS 19 (14,0) females MSNQ fatigue (−1.71, p = .0064) and cognitive PPMS 3 (2.2) Unknown 12 FSMC (>43) FAI fatigue (−1.78, p = .0092), and on anxiety (8.8) Impairment (PDDS): Baseline, post, (HADSA-­A : −0.64, p = .0406). • Not impaired 9.81% 12-­week Domain-­specific QoL was significantly • Mild impairment 36.36% follow-­up increased for three of the HAQUAMS subscales: • Moderate impairment fatigue (−0.39, p = <.0001), thinking (−0.17, 17.81% p = .0458) and mobility lower extremities • Walking aid/ wheelchair (−0.13, p = .0397), favouring ELEVIDA. 28.36% Treatment effects remained statistically • Unclear 7.63% significant at 12-­week follow-­up on Chalder Medication: Fatigue scale (−2.19, p = .008). Group • Disease modifying differences also remained significant for treatment (24% none, 76% the secondary endpoints FSMC (−3.47, yes) p = .00049) and HAQUAMS subscales • Symptomatic therapies fatigue (−0.25, p = .01) and thinking (−0.19, (67.6% none, 22.1% p = .0459). antidepressant, fatigue medication 1.09%, other 9.09%) Tietjen et al., Diagnosis of MS RCT, two arms n = 47 participants (11 MS and 8/w CBT online PHQ -­8 Greater improvement in MS patients in 92% 2018 (intervention 36 others chronic diseases) program (‘Think Health Distress intervention group on depressive symptoms Study design (USA)26 MS, intervention MS group: 10 female, 1 male; Clearly About Scale (PHQ-­8) compared with control group inappropriate people with other mean age = 45 (10,07); Depression’), self-­ Self-­Rated Health (mean at baseline = 22.80 ± 3.63; at (not used a chronic diseases) Without MS group: 30 female, directed, contents Scale post = 15.20 ± 4.49), on health distress control group) 6 male; mean age = 47,15 in a web Chronic Disease scores (mean at baseline = 4.35 ± 0.72; and sample size (13,57). Homework tasks Self-­Efficacy at post = 3.25 ± 1.48), on self-­efficacy insufficient Antidepressant medication: Scales measures of exercising regularly (mean at 91% (10/11) Baseline, Week 4 baseline = 3.40 ± 3.00; at post = 4.67 ± 2.22), and Week 8 on social/recreational activities (mean at (post) baseline = 2.00 ± 1.84; at post = 5.50 ± 3.48; and on controlling/managing depression (mean at baseline = 1.40 ± 1.62; at post = 2.40 ± 1.70). MONTAÑÉS-­MASIAS et al. TA B L E 1 (Continued) Intervention (type, Main outcomes, Authors, year, Criteria (type, time since frequency, time and measurement Quality assessment and country MS diagnosis) Study design Sample mode of deliverable) tools and periods Main findings (%) Cavalera et al., Diagnosis of RR or SP MS by RCT, two arms: n = 121 MS (54 intervention 8/w online MSQ OL-­5 4 MSQOL-­5 4 was significantly higher in the 75% 2019 a neurologist intervention MSBR, and 67 active control Mindfulness-­ Secondary Mindfulness group at the post-­intervention No interventional (England) RRMS = intervention 51 active control group) based course outcomes: assessment (F[1110] = 4.68, p = .033), but and blinding of MONTAÑÉS-­MASIAS et al. (94%), control 62 (92%) group (online Mindfulness group: 36 females, (MSBR), once HADS no difference was found after 6 months investigators SPMS = intervention 3 (6%), psychoeducational) mean age = 42,26 (8,35); a week, group MOSS (F[1,95] = 0.018, p = .894). No blinding of control group 5 (8%) (Control group: 42 females, videoconference MFIS Anxiety and depression were significantly lower subjects Years since MS mean age) 43,19 (9,02) (Skype) Baseline, post, at the post-­intervention in the mindfulness Outcome and diagnosis = intervention EDSS median = 3 Active control group: 6-­month group compared to the psychoeducation exposure group 11,19 (8,0)/ Medication: online 8/w follow-­up one (respectively, F(1,111) = 3.96, p = .049; measure partial control group Disease modifying treatment psychoeducational F(1,111) = 5.56, p = .020), but the difference well defined 12,21(7,29) (85.95%) course and videos between the groups was not maintained at (information Antidepressant (4.13%) Both groups included the follow-­up (respectively, F(1,95) = 1.033, test missing) Anxiolytics (3.30%) home exercises p = .31; F(1, 95) = 0.169, p = .682). The mindfulness program showed a strong effect on sleep at the post-­intervention evaluation (F(1,111) = 16.257, p < .001) but no statistical difference between groups was found after 6 months (F(1,95) = 1.650, p = .202). Fatigue score differences at post-­intervention were borderline significant (F(1,111) = 3.674, p = .058) and non-­significant at the follow-­up (F(1,95) = 0.251, p = .617). Gandy et al., Formal diagnosis of Interventional study n = 29 participants with 10/w Internet-­ PHQ -­9 A significant effect was showed after 77% 2020 one of the targeted (pre–­post) MS of 105 adults with delivered GAD-­7 intervention for depression (mean at Study design (Australia)27 neurological disorders neurological disorders psychological WHODAS 2.0 baseline = 8.86 ± 5.28; at post = 5.07 ± 3.18; inappropriate (epilepsy, multiple Total sample: intervention based Secondary d = 0.94, p < .001); for anxiety (mean (not used sclerosis (MS), Mean age = 51.68 (12.07) on CBT and CRT measures GAD-­7 at baseline = 6.73 ± 5.49; at comparison Parkinson's disease 74 women; 31 men (six lessons in form PDQ post = 3.73 ± 3.50; d = 0.93, p < .001); group) and (PD), or acquired brain Medication (total sample): of slide show) FSS for disability (mean WHODAS method of injury (ABI)), with Neurology medication (81.9%) Weekly contact, via Baseline, post, 2.0 at baseline = 16.00 ± 8.29; at subject and clinical management by Antidepressant (41.9%) telephone or email 3-­month post = 11.31 ± 7.11; d = 0.69, p < .001). All comparison a GP or neurologist, Anxiolytics (7%) with a clinical follow-­up of these reductions remained at 3-­month group Duration neuro diagnosis: psychologist follow-­up, not prospective memory. selection were mean = 7.49, ±7.06 An overall time effects was revealed for insufficient perceived cognitive difficulties (mean described difference) on attention/concentration Confounding not (−0.17, d = 0.21, p < .01), planning/ controlled organization (−0.14, d = 0.17, p = .01) and and may had prospective memory (−0.16, d = 0.21, disturbed the p = .04); and for fatigue (−2.62, d = 0.21, results p < .05). | 457 (Continues) 458 | TA B L E 1 (Continued) Intervention (type, Main outcomes, Authors, year, Criteria (type, time since frequency, time and measurement Quality assessment and country MS diagnosis) Study design Sample mode of deliverable) tools and periods Main findings (%) Dunne et al., MS diagnosis ´ RCT, three arms n = 55 participants with MS 8/w M4MS program MSQ OL-­5 4 Significant marginal decrease after treatment in 92% 2021 Years since diagnosis (Mindfulness, Chair (n = 18) group Mindfulness (MBCT), weekly BPI M4MS group in two scales of the MSQoL-­5 4 Outcome and (Australia)34 (median [IQR]) = 8 (12) yoga and wait-­list M4MS, 18 Chair Yoga, 19 two-­hour Baseline, post (coefficient); sexual function (15.71, exposure control) control group Chair Yoga seated in p = .059); and role limitations emotional measure partial Mean age = 48,4 (±10,9) a chair (23.71, p = .036). well defined 45 women, 9 males Both programs were (information 1 missing delivered online test missing) Screened as not highly via live web Some estimate of distressed (Kessler sessions (Zoom) variance (e.g. Psychological Distress for one hour every confidence Scale K10 < 30) week for eight intervals, Psychotropic drugs (70.1%) weeks, group live standard sessions errors) were 10′ of home practice not reported and home tasks for the main results Abbreviations: BAI, Beck Anxiety Inventory; BDI-­II-­, Beck Depression Inventory Second Edition; BPI, Brief Pain Inventory; CBT, cognitive behavioural therapy; CD-­RISC, Connor-­Davidson Resilience Scale; CRT, compensatory cognitive rehabilitation therapy; CSRI, Client Service Receipt Inventory; EDSS, Expanded Disability Status Scale; EQ-­5D, EuroQol quality of life measure; EQ-­VAS, Visual analogue self-­ rating scale; FAI, Frenchay Activity Index; FIS, Fatigue Impact Scale; FSMC, Fatigue Scale For Motor And Cognitive Function; FSS, Fatigue Severity Scale; GAD-­7, Generalized Anxiety Disorder Scale; GHQ, General Health Questionnaire; HADS, Hospital Anxiety and Depression scale; HAQUAMS, Hamburg Quality of Life Questionnaire for Multiple Sclerosis; IPST, Internet-­based problem-­solving treatment; MFIS, Modified Fatigue Impact Scale; MOSS, Medical Outcomes Study Sleep; MS, Multiple Sclerosis; MSIS-­29, Physical and psychological impact of MS; MSNQ, Multiple Sclerosis Neuropsychological Screening Questionnaire; MSQOL-­54, Multiple Sclerosis Quality of Life-­54; NeuroQoL, Quality of Life in Neurological Disorders; PDDS, Patient Determined Disease Steps; PDQ, Perceived Difficulties Questionnaires; PHQ-­8, Personal Health Questionnaire Depression Scale; PPMS, primary progressive; PRMS, primary relapsing; PROMIS, Patient-­Reported Outcomes Measurement Information System; RRMS, relapsing remitting; SES, Self-­Efficacy Scale for MS–­Short Form; SF-­36, Medical Outcome Study Short Form 36; SHS, Subjective Happiness Scale; SPMS, secondary progressive; SPSI-­R , Social Problem-­Solving Inventory Revised; WHODAS (2.0), World Health Organisation Disability Assessment Schedule; WHO-­Q oL, WHO Quality of Life scale. MONTAÑÉS-­MASIAS et al. MONTAÑÉS-­MASIAS et al. | 459 problem-­solving treatment (IPST) (‘Worry Less’) that was adjusted for Only one study,32 of two that examined pain, showed a significant MS patients; (f) Gandy et al. (2020)27 examined an Internet-­delivered reduction of symptoms of pain through a MBI at 3-­month follow-­up psychological intervention tailored specifically for neurological disor- (1.73 ± 2.09; p = .034). Of eight studies that assessed fatigue, signifi- ders which integrates principles of CBT and compensatory cognitive cant changes were reported in all studies except three.29,31,33 Finlayson 26 rehabilitation therapy (CRT); (g) Tietjen et al. (2018) evaluated an et al. (2011)30 revealed a significant reduction of fatigue in the inter- Internet-­based CBT (iCBT), self-­directed programme for depressive vention group immediately after intervention compared to a waiting-­ symptoms; (h) Calavera et al (2018) used mindfulness-­based stress re- list control group [(Fatigue impact scale (FIS): Cognitive: −3.12 ± 6.10, duction (MSBR); (i) Bogosian et al. (2015)32 and Dunne et al. (2021)34 p = .001; Physical: −2.53 ± 6.47, p = .014; Social: −6.01 ± 12.06, used mindfulness-­based cognitive therapy (MBCT) which includes p = .002)]. These changes were maintained with large effect sizes in most of the MBSR syllabus with additional cognitive therapy exercises; all FIS subscales at the 3-­ and 6-­month follow-­up. Moss-­Morris et al. (j) Alschuler et al. (2018)23 used a positive psychology programme spe- (2012)21 revealed a similar improvement at post-­intervention iCBT 30 cific for pwMS; (k) while Finlayson et al. (2011) examined a group-­ in the fatigue score (Modified Fatigue Impact Scale) (MFIS) (mean at based, fatigue management programme based on CBT contents. baseline = 13.17 ± 3.81; at post = 9.00 ± 3.75; p < .001). Pöttgen et al. Most studies involved an individual format (8/13) and used time-­ (2012)25 using an iCBT programme showed a more pronounced de- limited interventions, whereas the remaining studies used a group cline in the intervention group compared with the waiting-­list control format (5/13). The individual treatments involved five to ten modules group (Chalder Fatigue Scale: −2.74, p = .0007) and a significant re- delivered on a weekly basis. Two of these studies20,25 used the tech- duction on the fatigue [(Fatigue Scale for motor and cognitive func- nique of a ‘simulated dialogue’, an interactive exercise that imitates a tion [FSMC]: −3.47, p = .0034)], as well as its subscales for motor real conversation and tailors the subsequent options to the patient's fatigue (−1.71, p = .006) and cognitive fatigue (−1.78, p = .009). Van responses. Two studies21,31 used a website with interactive sessions Kessel et al. (2015)31 compared CBT without any therapeutic contact and included self-­assessments to allow the intervention to be tailored (MSinvigor-­Only) and with therapeutic contact (MSinvigor-­Plus), the 26,27 to the individual user. Two studies used educational videos and latter receiving email support from a skilled clinical psychologist with interactive activities. Two other studies28,29 used an intervention with extensive CBT experience, and they reported significant reductions in modules containing text, exercises and examples. Group format trials both groups, although greater reductions were achieved in MSInvigor-­ (5/13) were conducted by an expert who was connected through a Plus (Chalder Fatigue Scale: mean at baseline = 22.37 ± 4.39; mean at 23,30,32,33,34 videoconference system to the group participants. post = 11.37 ± 6.20; p < .01) (MFIS: mean at baseline = 13.58 ± 2.97; at Group sizes ranged from five to seven participants, with one or post = 10.00 ± 2.71; p < .02). Gandy et al. (2020)27 found a significant two instructors. Most studies included homework tasks and thera- decrease in fatigue at both post-­intervention (−2.62, p < .05) and 3-­ peutic contact via e-mail or telephone, although three studies did month follow-­up [(Fatigue severity scale [FSS]: −2.5, p < .05)]. 20,25,26 not report therapist support. Duration of the studies ranged In reference to socio-­affective symptoms, that 11 studies that from five to 12 weeks, but the average was about 8 weeks, and the examined depressive symptoms, only three no reported significant sessions lasted between one and 2 h. All the studies assessed the reductions.25,29,31 Boeschoten et al. (2012)28 found a significant differ- 26 participants immediately after intervention, except for one study ence in change scores among completers and non-­completers using a that also includes an assessment at week four (middle of the inter- web-­based iPST (BDI-­II: −3.9, p = .001). Fischer et al. (2015)20 showed vention). Others’ follow-­up periods varied between trials. Long-­term a statistically significant treatment effect in the intervention group follow-­up was reported in seven trials and ranged between three [(Beck Depression Inventory [BDI]: mean at baseline = 19.44 ± 9.02; and 6 months. 20,25,27,29.30,32,33 mean at post 16.24 ± 8.66; p = .01)]. Moss-­Morris et al. (2012)21 found significantly greater reductions of 2.78 points of depressive and anxiety symptoms in the intervention group compared to a control 3.6 | Main outcomes and intervention group [(Hospital Anxiety and Depression Scale [HADS]: mean at base- effectiveness line = 7.96 ± 3.64; and at post = 5.18 ± 3.38, p = .001)]. Pöttgen et al. (2018)25 showed that an iCBT program reduced anxiety (HADS) in the 21,25,27,28,29,30,31,32,33 From 13 articles, nine studies examined physi- intervention group (−0.64, p = .0406). Bogosian et al. (2015)32 found 20,21,25–­3 4 cal functioning, which included pain and fatigue; 12 studies a significant reduction in the mindfulness group compared to the examined socio-­affective symptoms, specifically depression, anxiety waiting-­list control group at post-­intervention of depression (HADS: 25,27,29 and distress; three studies examined cognitive function and −1.12, p = .017), and at 3-­month follow-­up, the effect was also signifi- eight studies examined QoL. 20,23,25,28,29,33,34 Details about variables cant for anxiety (HADS: −2.12, p = .012). Cavalera et al. (2018) reported and measurement tools are shown in Table 1. that a MBI delivered via videoconference reduced depressive (HADS: Respect to physical functioning, one trial32 of four studies that spe- −3.46, p = .049) and anxiety symptoms (HADS: −5.56, p = .020) at the cifically assessed physical functioning reported significant reduction in end of the intervention compared to psychoeducation, but the differ- the mindfulness group compared to the waiting-­list control group on ence between the groups was not maintained at the follow-­up (respec- the physical scale [(Physical and psychological impact of MS [MSIS-­29]: tively, p = .312; p = .682). Tietjen et al. (2018)26 assessed depression 64.52 ± 19.80)] at post-­intervention (MSIS-­29: 58.19 ± 17.56, p = .016). and observed a significant reduction compared with the control group 460 | MONTAÑÉS-­MASIAS et al. [(Personal Health Questionnaire Depression Scale [PHQ] mean at and cognitive symptoms and to improve QoL in pwMS. This study 27 baseline = 22.80 ± 3.63; at post = 15.20 ± 4.49)]. Gandy et al. (2020) also explores the mode of delivery in order to know which the most reported an overall time effect for depressive and anxiety symptoms at efficient format is to design online interventions in a future. post-­intervention [(PHQ-­9: −9: −3.79, p = p < .001; GAD-­7: −3, p < .001)] Findings indicate that online-­based CBT and MBI used in pwMS and at follow-­up (PHQ-­9: −3.86, p < .001; GAD-­7; −3-­39, p < .001). may show changes in socio-­affective symptoms, QoL and physical Only one study32 evaluated distress (General Health Questionnaire: symptoms like fatigue, and slight changes in cognitive symptoms, GHQ-­12) and scores were lower in the mindfulness group compared specifically in executive functions. Moreover, data on how the inter- to the waiting-­list control group at the post-­intervention (−3,72 ± 1.76; vention was applied show two main enablers of online physiological p = .035) and three-­month follow-­up (−5.45 ± 1.66; p = .005). interventions: being in touch with the therapist and the importance 25,27,29 Of the three studies that assessed cognitive functions ; of group sessions (rather than individual ones). only one study27 showed a significant effect for difficulties in atten- tion/concentration (−0.17, p < .01), in planning/organization (−0.14, p < .01) and in prospective memory (−0.16, p = .04). Attention and 4.2 | Effectiveness of online psychological planning ability remained stable at three-­month follow-­up (−0.29; interventions p < .01; −0.23, p < .01, respectively). Of the eight studies that quantified health-­related QoL, seven The data reviewed suggest that iCBT interventions showed mainly indicated significant improvements in this domain. 20,23,25,28–­30,33,34 improvement in depression, anxiety, fatigue and QoL, and slight 20 Fischer et al. (2015) showed significant improvement in the psy- improvement in cognitive functioning in pwMS. Previous findings chological well-­being subscale measured (WHO-­Q ol BREF: mean at suggest that people with less severe depression could benefit baseline = 47.13 ± 18.84; mean at post 52.22 ± 20.39; p = .04) in the more from low-­intensity interventions than people with severe intervention group. Alschuler et al. (2012)23 found a significant im- depression. 28,29,35 However, most studies included in this review provement in satisfaction with social roles (mean PROMIS at base- were focused on mild-­to-­m oderate depression. Although no stud- line = 39.95 ± 9.44; at post = 47.55 ± 2.92; p = .02). Pöttgen et al. ies focused on anxiety symptoms, four studies assessed anxiety as (2018)25 revealed a significant increase in domain-­specific QoL in the a secondary outcome. In three of these studies, the interventions intervention HAQUAMS subscales: fatigue (−0.39, p < .0001), think- proved to be successful, showing a reduction in anxiety after the ing (−0.17, p = .046) and lower extremity mobility (−0.13, p = .004), intervention. It was unclear whether these benefits remained sig- and this difference remained statistically significant at a 12-­week fol- nificant at follow-­up. The moderate effect sizes of iCBT that we low-­up, except for lower extremity mobility. Finlayson et al. (2011),30 found were similar to those reported in other trials for depression found that a fatigue management programme significantly improved and anxiety for pwMS. 36 Also, iCBT interventions were effective QoL in the intervention group in the SF-­36 subscales (Mental Health: treating MS-­related fatigue. Besides, in most studies, this reduc- 5.32 ± 13.38, p = .012; Social Function: 7.54 ± 25.35, p = .05; Role tion maintained at follow-­up. Five studies showed that iCBT led to Physical: 18.06 ± 30.49, p = .000). Cavalera et al. (2018)33 observed clinically significant decreases in MS-­associated fatigue, whereas that the QoL (Multiple Sclerosis Quality of Life-­54: MSQOL-­54) was only one study failed to report a significant effect in fatigue This significantly higher in the mindfulness group at the post-­intervention result is in line with the findings from a meta-­analysis conducted (p = .033), but no difference was found after 6 months (p = .894). by Phyo et al. (2018), 37 who concluded that CBT was effective 34 Dunne et al. (2021) compared a MBI against Chair Yoga and against in the treatment of MS-­related fatigue but found moderate het- wait-­list control group found no statistically significant main effects erogeneity between studies. This might be associated with the for either intervention on any of the MSQoL-­54 scales, except two: ways in which CBT was delivered, as these were slightly different sexual function (15.71, p = .059) and role limitations emotional across the studies. Finally, iCBT-­b ased intervention also showed (23.71, p = .036) in favour of the mindfulness group. Boeschoten a significant improvement in QoL in most studies. However, it is et al. (2012)28 found a decrease of 2.4 points on negative problem important to analyse how QoL was measured, as it is a multidi- orientation in the whole sample (18.0 ± 5.4, 15.6 ± 6.3; p = .004) that mensional concept that encompasses several domains. It is usu- was larger for the patients who completed the intervention (mean at ally concerned with physical and mental well-­b eing, and thus was baseline 19.5 ± 4.8; mean at post 15.3 ± 6.0; p = .001). associated with depression, anxiety, fatigue and cognitive impair- ment. This is consistent with the systematic review conducted by Gil-­G onzález (2020), 38 which concluded that fatigue, cogni- 4 | DISCUSSION tive impairment and pain are associated with lower QoL.14,38,39,40 Cognitive functioning was not included in most CBT studies. Even 4.1 | Main findings though perceived cognitive difficulties were common in pwMS, only three of the studies reviewed took them in account.13 Only To our knowledge, this is the first systematic review that has com- one study reported benefits in some cognitive components such prehensively analysed online psychological interventions (13 stud- as attention, concentration, planification and organization, and all ies) and examined their impact on reducing physical, socio-­affective of these remained at 3 months after the intervention. This finding MONTAÑÉS-­MASIAS et al. | 461 suggests that attention and executive function were areas where in a blended-­care design and small group setting may have positive CBT could potentially benefit pwMS, which is also supported by effects on adherence and outcome of the psychological interven- other studies.41,42 tion.50 Moreover, in pwMS online interventions could help to over- With regard to MBIs, we found two different approaches, MBCT come disability physical barriers. (n = 2) and MBSR (n = 1), both of which reported benefits in de- Technological issues, such as slow Internet connections, interac- pression, anxiety, stress and QoL, and, to a lesser extent, in fatigue. tion with the computer interface and website bugs, and previous ex- MBSR intervention was associated with decreased depression and perience using the Internet programmes or videoconference, should anxiety and improvement in QoL, even though these changes did be considered as they can affect adherence. However, due to the not remain at follow-­up. MBCT intervention also showed an im- COVID-­19 pandemic, the use of video conferencing and calls related provement in depression, anxiety and QoL, but these effects also to health has become more widespread, and some of these techno- remained at follow-­up. The main results in depression are consistent logical issues have been solved or improved. with other findings.43–­47 Likewise, a meta-­analysis led by Simpson et al. (2019)14 concluded that MBIs were at least moderately effec- tive in treating depression in pwMS. However, there is low evidence 4.4 | Robustness of the evidence on the effectiveness of mindfulness interventions for anxiety re- duction.14 This is consistent with our review; although we found an Generally, study quality was acceptable in most studies. Moreover, apparent benefit for anxiety reduction, few studies examined this. some aspects that could influence the quality of evidence are con- Several previous trials of mindfulness interventions have shown sidered to be as limitations because they may influence the results: positive effects on stress-­management in pwMS.47 In our review, the lack of information related to the functional impairment, sever- only one trial focused on this through a mindfulness intervention, ity of symptoms, medication information, disease history and years but it reported a medium-­large effect post-­intervention and a large since diagnosis. Although most studies included data on disability or effect at 3 months. Therefore, more studies examining interven- functional impairment, few studies stipulated them as an inclusion tions for stress-­management for pwMS are needed, as this factor criterion. Furthermore, the severity of symptoms and associated im- has been related to a worsening or exacerbation of MS.48 In addi- pairment might influence the results. Some studies had only recruited tion, we only found one study that treated fatigue or chronic pain. patients with scores indicative of mild symptoms from baseline and Neither showed significant improvement after intervention, but im- excluded moderate or severe symptoms. Clinical cut-­off from base- provements in pain were significant at follow-­up. More studies with line could play a crucial role in the level of symptom changes during a robust methodology and greater sample size needed to verify the the intervention.38 Relatedly, five studies did not report medica- effect of mindfulness-­based interventions to manage chronic pain tion information. Also, few studies assessed whether participants 18 and fatigue in pwMS. In addition, the results of the reviewed stud- started any new or additional treatments (pharmacological or non-­ ies suggest that online mindfulness interventions may have signifi- pharmacological) after enrolment. In view with the evidence, disease cant though not large effects right after the treatment. Furthermore, history could be an important factor and could influence intervention long-­term psychological effects can disappear, at least if not prop- response.38,51 In patients with more years since diagnosis, neuro- erly supported.49 logical impairment and physical disability usually increased.52 In our review, years since diagnosis differ among studies, and it was under- valued in many of the studies when analysing results. 4.3 | Mode of delivery: characteristics, Moreover, some interventions include a large social compo- barriers and enablers nent, which can promote well-­being and could influence the results. Consequently, social components should be evaluated separately be- Findings suggest that offering a website alone without support or cause they may lead to improvements in some parameters, such as therapeutic contact may contribute to less adherence and probably depression and anxiety. Another important feature is related to the a higher dropout rate. Therapeutic contact via telephone, mail or fact that all the sessions in most studies were delivered by the same videoconference was seen as a key component of the interventio therapist, which could represent a risk of bias because the therapist's n. 20,21,23,28–­34 Dropout probably had an influence on the efficacy of skill may influence treatment effect and intervention adherence.21 the intervention, and the absence of regular contact with a ‘thera- pist’ may have contributed to low levels of engagement. Besides, it was seen that contact with a therapist encouraged socialization 4.5 | Strengths and limitations and was instrumental in prompting participants to engage in the sessions. Thus, wordance with previous studies, we also observed In conducting the systematic review, we adopted rigorous search, that group intervention approaches could be more successful than appraisal and analysis strategies, using various reviewers for data ex- individual self-­management.38 Adherence rates in online-­based in- traction, and our methods were guided by the PRISMA checklist. 22 terventions were substantially lower compared with face-­to-­face However, this systematic review has several limitations. The treatments. Furthermore, adding short face-­to-­face consultations limited number of studies (n = 13) and the heterogeneity of health 462 | MONTAÑÉS-­MASIAS et al. outcomes reported across studies made it difficult to provide a met- PEER REVIEW analysis that produced robust conclusions on the effect of online The peer review history for this article is available at https://publo​ psychological intervention in pwMS. Nevertheless, relatively few ns.com/publo​n/10.1111/ane.13709. studies met the inclusion criteria. In addition, practically all the stud- ies were carried out in women with RRMS or SPMS, so despite being DATA AVA I L A B I L I T Y S TAT E M E N T 4 the most common profile of pwMS the results extracted may not be Data sharing is not applicable to this article as no new data were cre- representative for the whole population. It could be useful to carry ated or analyzed in this study. out more studies with a sample of men. 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