Factors influencing quality of life in multiple sclerosis patients: disability, depressive mood, fatigue and sleep quality

OBJECTIVES: In a series of 504 patients with multiple sclerosis (MS), quality of life (QOL) and its main clinical and demographic determinants were assessed in comparison with healthy individuals. MATERIALS AND METHODS: A postal questionnaire with self-completed measures of disability (Expanded Disability Status Scale, EDSS), QOL (Quality of Life Index, QLI), depressive mood (Self-rating Depression Scale, SDS), fatigue severity (Fatigue Severity Scale, FSS) and sleep quality (Pittsburgh Sleep Quality Index, PSQI) was sent to this sample of MS patients. RESULTS: Most patients were severely disabled; almost half were mildly to severely depressed, suffering from reduced sleep quality and/or fatigue. The multiple sclerosis patients had significantly lower QLI scores than healthy controls. EDSS and SDS scores were found to be predictors of global QLI score. Regarding the different QLI domains, mean SDS scores remained predictive for all QLI items, while mean EDSS, PSQI and FSS scores were only predictive for physical domains. CONCLUSION: Our study clearly demonstrates that depressive mood is the main factor influencing QOL. The disability status, fatigue and reduced sleep quality have an impact mainly on physical domains of life quality.     

Fatigue in multiple sclerosis and its relationship to depression and neurologic disability

We studied multiple sclerosis fatigue (MSF) and its relationship to depression and disability. Seventy-one patients [50 relapsing-remitting, 21 secondary progressive] were grouped by Fatigue Severity Scale (FSS) into MS-fatigue (MSF) (FSS>/=5; n=46) or MS-nonfatigue (MSNF) (FSS相似文献   

Neuropsychiatric manifestations in multiple sclerosis: correlation of fatigue and depression with disease progression

Abstract

Fatigue is one of the most common disabling symptoms in multiple sclerosis (MS) with significant impact on daily life. The aim of this study is to explore the association among MS fatigue, clinical disability and depression. Fifty-seven patients were assessed by fatigue severity scale (FSS), expanded disability status scale (EDSS) and Beck depression inventory (BDI). Mean FSS score was 4·1 ± 1·6. Based on FSS scores, patients were divided into three groups: Patients with FSS score >5 (n = 10, 32%) were evaluated to present with fatigue symptoms, patients with borderline fatigue (n = 29, 50%) had an FSS score between 4 and 5 and patients with no fatigue (n = 18, 18%) had an FSS<4. When the patients were compared according to the presence of fatigue symptoms, patients with fatigue had significantly higher EDSS scores (p = 0·03). BDI evaluation revealed that 33 (57%) patients had a score 11. MS patients with fatigue showed significantly higher BDI scores when compared to patients without fatigue (p = 0·0002). A significant relationship among fatigue, disease disability and depression was observed in our study, implying the complex interplay of fatigue and depression with disability.     

Depression, disability and cognitive impairment in multiple sclerosis: a cross sectional Italian study

The disability, cognitive impairment, fatigue and depression are interacting features in multiple sclerosis (MS), whose relation is still unclear. The objective of this study was to evaluate in a sample of MS patients, the frequency of depressive symptoms, its predicting factors and relation with cognitive impairment, fatigue and disability. 255 consecutive MS patients and 166 healthy subjects were assessed for the presence of depressive symptoms with the Beck Depression Inventory-Fast Screen (BDI-FS). Patients with BDI-FS ≥4 were further investigated for the presence of neuropsychological impairment. Depressive symptoms were significantly more frequent and severe in patients than in controls. EDSS score was the only predicting factor of depression (3.5 = threshold EDSS score for depressive symptoms) in patients, whereas neuropsychological impairment was not correlated with BDI-FS and fatigue was found to be significantly correlated with attention, executive function and memory test scores, as well as with BDI-FS score in patients.     

Apolipoprotein E polymorphism interacts with cigarette smoking in progression of multiple sclerosis

Background and purpose:  The influence of apolipoprotein E (ApoE) polymorphism on clinical severity of multiple sclerosis (MS) is still controversial. Cigarette smoking has been suggested to influence the progression of disability in these patients. In this study, we aimed to investigate whether an interaction of smoking with the ApoE polymorphism influences the progression of disability in MS patients.
Methods:  Smoking history from 205 female patients with MS was obtained. Clinical data collected include age at onset, disease duration, annual relapse rate, the Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Severity Score (MSSS). ApoE polymorphism was examined in all patients and stratified according to smoking status and associations with the clinical data investigated.
Results:  There were no significant associations between cigarette smoking and any of the clinical characteristics in the whole group of patients. In women carrying the ApoE E4 isoform, smokers had a lower EDSS ( P  = 0.033) and MSSS ( P  = 0.023) in comparison with non-smokers.
Conclusion:  Our data suggest that in women with MS carrying the ApoE E4 isoform, cigarette smoking may have a protective influence on disease progression and accumulation of disability. These findings need to be confirmed by future large longitudinal studies.     

Fatigue in multiple sclerosis: relationship with disease duration, physical disability, disease pattern, age and sex

To evaluate the relationship between disease duration, disability, disease pattern, age and sex with fatigue in MS patients. One hundred and seventy-three clinically definite MS patients and 87 age-matched healthy controls enrolled in this cross sectional study. Demographic data (sex, age), duration of the disease and disease pattern extracted from patient’s files and Kurtzke Expanded Disability Status Scale (EDSS) were recorded for each patient by an expert neurologist. Participants were asked to answer the validated and reliable Persian version of beck depression inventory (BDI) and FSS (fatigue severity score) questionnaires. Mean FSS and BDI scores were significantly different between patients and controls (p < 0.001). Patients with longer disease duration, higher EDSS and progressive type of disease had significantly higher FSS and BDI scores. Although men had higher EDSS, FSS and BDI scores were similar in both sex groups. FSS was significantly correlated with age, disease duration, BDI and EDSS. The analysis of covariance revealed that there is no difference in the covariance-adjusted means for fatigue among two disease groups (relapsing remitting and secondary progressive) except for EDSS. MS patients with longer disease duration, higher EDSS and progressive type of disease suffer from fatigue more than cases with lower EDSS, duration of disease and relapsing type of the disease.     

Fatigue and its association with sleep disorders,depressive symptoms and anxiety in patients with multiple sclerosis

Background and purposeThe aetiopathogenesis of fatigue in multiple sclerosis (MS) is not clear. It could be associated with structural changes of the central nervous system, but also with mood and sleep disorders. The purpose of the study was to evaluate frequency of fatigue and its association with sleep and mood disorders in MS patients.Material and methodsThe examined group consisted of 122 MS patients (mean age 37.7 ± 10.8 years). The following questionnaires were used: Fatigue Severity Scale (FSS), Epworth Sleepiness Scale (ESS), Athens Insomnia Scale (AIS), Montgomery-Asberg Depression Rating Scale (MADRS), and Hospital Anxiety and Depression Scale (HADS).ResultsFatigue was present in 75 MS patients (61.5%). Excessive daytime sleepiness was observed in 25 (20.5%), insomnia in 73 patients (59.8%). According to MADRS, depressive symptoms were present in 33 (27%), according to HADS in 15 people (12.3%). Anxiety was present in 32 patients (26.2%). We observed an association between fatigue (FSS) and sleep disorders (ESS, AIS) and also between fatigue and either depression (MADRS, HADS-D) or anxiety (HADS-A). The FSS score was not associated with age, sex, disease course and duration, Expanded Disability Status Stage (EDSS), treatment or level of education in MS patients. In inactive professionally people we noted significantly higher FSS scores (44.8 ± 13.8) in comparison with active individuals (37.2 ± 14.9; p = 0.0053).ConclusionsFatigue is a very common symptom in MS, sometimes associated with sleep disorders, depressive symptoms or anxiety. The treatable causes of fatigue in MS such as sleep and mood disturbances should be identified and treated.     

Quality of life in patients with multiple sclerosis: the impact of fatigue and depression

Quality of Life (QOL) is impaired in multiple sclerosis (MS) in part due to physical disability. MS-associated fatigue (MSF) and depression (MSD) are common and treatable features of MS, which could also impact on QOL, independent of physical disability. We prospectively studied 60 consecutive patients with MS. QOL was assessed using Multiple Sclerosis Quality of Life (MSQOL)-54. Group differences in QOL scores were assessed after adjusting for Expanded Disability Status Scale (EDSS), Fatigue Severity Scale (FSS) and Hamilton Depression Inventory scores. MS patients were grouped into relapsing-remitting (RR) or secondary-progressive (SP), MSF (FSS> or =5) or MS-nonfatigue (MSNF) (FSS< or =4), and MSD or MS-nondepression (MSND). After accounting for disability and depression, fatigue was associated with impaired QOL with respect to health perception (p=0.03) and limitations due to physical dysfunction (p=0.008). After accounting for disability and fatigue, depression was associated with lower QOL with respect to health perception (p=0.02), sexual dysfunction (p=0.03), health distress (p=0.03), mental health (p=0.006), overall QOL (p=0.006), emotional dysfunction (p=0.04), and limitations due to emotional dysfunction (p=0.03). This study demonstrates that fatigue and depression are independently associated with impaired QOL in MS, after accounting for physical disability, suggesting that their recognition and treatment can potentially improve QOL.     

多发性硬化患者生活质量评估及其影响因素探讨

目的评估多发性硬化患者生活质量水平,并探讨其影响因素。方法收集2012年7月~2016年12月就诊于河南省人民医院复发缓解型多发性硬化患者(relapsing-remitting MS,RRMS)36例,继发进展性多发性硬化患者(secondary progressive MS,SPMS)21例作为研究对象。采用多发性硬化生活质量54项评分(Multiple Sclerosis Quality of Life-54 instrument,MSQo L-54)测试MS患者的生活质量;对所有研究对象进行认知功能、抑郁状态、疲劳、睡眠质量及日常生活能力评估。结果 (1)RRMS组及SPMS组患者躯体生活质量(RRMS组58.62±16.32;SPMS组28.77±15.99,P=0.000)、精神生活质量(RRMS组57.33±16.72;SPMS组36.27±23.50,P=0.000)均有下降,SPMS组下降更明显。多元逐步回归法分析,与MS生活质量相关因素中,Hamilton抑郁量表评分处于第一位(β=-0.516,P<0.001),其次为反应躯体化残疾程度的EDSS评分(β=-0.372,P<0.001),第三位为疲劳评分(β=-0.250,P=0.002)。结论 MS患者有不同程度的生活质量下降,SPMS患者更明显。EDSS评分、抑郁、疲劳影响患者生活质量,早期干预抑郁及疲劳,对于改善MS患者生活质量有益。     

Alexithymia in multiple sclerosis: relationship with fatigue and depression

Objective –  The aim of this study was to investigate the prevalence of alexithymia in a sample of patients with multiple sclerosis (MS) and to further evaluate the association between alexithymia and the occurrence of common disabling MS-related symptoms such as fatigue and depression.
Methods –  Fifty-eight relapsing–remitting MS patients treated with interferon (IFN)-beta-1a underwent a complete neurological evaluation, including Expanded Disability Status Scale score assessment. Alexithymia, depressive symptoms and fatigue were assessed using the 20-item Toronto Alexithymia Scale, Beck Depression Inventory and Fatigue Severity Scale.
Results –  Prevalence of alexithymia was 13.8%, with 27.6% of patients presenting borderline alexithymia. Sixty-seven per cent of the patients complained of fatigue while 29.3% of them were depressed. Higher levels of fatigue and depression were found in alexithymic patients when compared with non-alexithymic patients. Results from logistic regressions showed that alexithymia significantly contributes to the severity of fatigue and depression.
Conclusions –  Alexithymia was associated with increased severity of fatigue and depression.     

Does the Modified Fatigue Impact Scale offer a more comprehensive assessment of fatigue in MS?

BACKGROUND: As a symptom of multiple sclerosis (MS), fatigue is difficult to manage because of its unknown etiology, the lack of efficacy of the drugs tested to date and the absence of consensus about which would be the ideal measure to assess fatigue. OBJECTIVE: Our aim was to assess the frequency of fatigue in a sample of MS patients and healthy controls (HC) using two fatigue scales, the Fatigue Severity Scale (FSS) and the Modified Fatigue Impact Scale (MFIS) with physical, cognitive and psychosocial subscales. We also studied the relationship fatigue has with depression, disability and interferon beta. METHODS: Three hundred and fifty-four individuals (231 MS patients and 123 HC) were included in this cross-sectional study. Fatigue was assessed using the FSS and MFIS. Depression was measured by the Beck Depression Inventory (BDI), and disability by the Expanded Disability Status Scale (EDSS). A status of fatigue was considered when the FSS > or =5, of non-fatigue when the FSS < or =4, and scores between 4.1 and 4.9 were considered doubtful fatigue cases. RESULTS: Fifty-five percent of MS patients and 13% of HC were fatigued. The global MFIS score positively correlated with the FSS in MS and HC (r =0.68 for MS and r =0.59 for HC, p <0.0001). Nonetheless, the MFIS physical subscale showed the strongest correlation score with the FSS (r =0.75, p <0.0001). In addition, a prediction analysis showed the physical MFIS subscale to be the only independent predictor of FSS score (p <0.0001), suggesting other aspects of fatigue, as cognition and psychosocial functions, may be explored by the FSS to a lesser extent. Depression also correlated with fatigue (r =0.48 for the FSS and r =0.7 for the MFIS, p <0.0001) and, although EDSS correlated with fatigue as well, the scores decreased after correcting for depression. Interferon beta showed no relationship with fatigue. CONCLUSIONS: Fatigue is a frequent symptom found in MS patients and clearly related with depression. Each fatigue scale correlates with one another, indicating that they are measuring similar constructs. Nevertheless, spheres of fatigue as cognition and psychosocial functions are probably better measured by the MFIS, although this hypothesis will need to be confirmed with appropriate psychometrical testing.     

Physical dimension of fatigue correlated with disability change over time in patients with multiple sclerosis

To determine the value of fatigue in predicting the change in disability status in patients with multiple sclerosis (MS), we realized a prospective population-based cohort study of 196 patients with clinically definite MS. In 2002, baseline data were collected on fatigue (Modified Fatigue Impact Scale), health-related quality of life (SF-36), and disability status (EDSS score). The EDSS scores were determined again at least three years later. Univariate and multivariate analysis were performed to determine the predictive value of different dimensions of fatigue and other variables (depression and SF- 36) on the change in disability status. Of the 196 patients, 106 (54%) patients had an unchanged status or improvement and 90 (46%) showed a worsening of disability. After three years, with control for gender, age, and baseline disability status, a high baseline level of physical fatigue was associated with a worsening of disability status, whereas a low baseline level of physical fatigue was associated with the absence of worsening of the EDSS score. Other dimensions of fatigue, depression and SF-36 were not associated with a worsening of disability.A patient's perceived fatigue may be not only a clinically and psychosocially meaningful outcome but also a predictor of objective outcomes such as changes in disability status at three years.     

Predictive value of health-related quality of life in progression of disability and depression in persons with multiple sclerosis: a 3-year study

In our study, we examined whether health-related quality of life (HRQoL) could predict changes in disability, depression, and fatigue in patients with multiple sclerosis (MS) over a 3-year follow-up period. A group of 109 consecutive MS patients (McDonald’s criteria) referring to the Institute of Neurology, Belgrade were enrolled in the study. At two time points during the study (baseline, and after a 3-year period) an HRQoL (measured by MSQoL-54), EDSS, Hamilton Rating Scale for Depression (HDRS) and Fatigue Severity Scale (FSS) were assessed. At the end of a 3-year follow-up, 12 out of 109 patients (11 %) had dropped out. Multiple linear regression analysis showed that Physical Health scale of MSQoL-54 is significant independent predictor of change in EDSS after 3 years (p = 0.035). Mental health composite score of MSQoL-54 was predictor of change in HDRS score (p = 0.049). In separate regression analysis, only social function was independent predictor of the development of depression (p = 0.041). None of the HRQoL domains had predictive effect on the change of FSS. Our study suggests that baseline HRQoL scores, measured by MSQoL-54, could be applied as a prognostic marker for progression of both, disability, and severity of depressive symptoms in MS.     

Fatigue in multiple sclerosis is related to disability, depression and quality of life

Fatigue in multiple sclerosis is a frequent and disabling symptom that can interfere in daily functioning. The aim of this study is to demonstrate the relationship between fatigue and disability, disease course, depression and quality of life. We administered French valid versions of the Fatigue Impact Scale (EMIF-SEP), the short form of the Beck depression inventory (13 items) and the SF-36 to 237 out of 312 patients with clinically definite multiple sclerosis with EDSS相似文献   

Sleep disturbances in patients with multiple sclerosis

Sleep disturbances constitute one of the important yet underestimated aspects of functioning of patients with multiple sclerosis (MS). The objective of this study was to evaluate sleep disturbances in patients with MS, with regard to demographic factors, disease-related variables, co-existing conditions and fatigue. In 100 MS patients, Epworth Sleepiness Scale (ESS) and a questionnaire about sleep disturbances (SlD) were implemented. ESS and SlD results were analyzed with regard to age, gender, duration of MS, type of its course, degree of disability in Expanded Disability Status Scale (EDSS), MS therapies, coexisting diseases, results of Fatigue Severity Scale (FSS) and Modified Fatigue Impact Scale (MFIS). ESS score indicated increased daytime sleepiness in 19 patients. In SlD, 49 subjects reported sleep disturbances and 35 more than one of their kind (most commonly terminal and middle insomnia). No relationships were found between ESS and SlD scores and age, gender, MS duration, type of its course, EDSS or coexisting diseases. In 36 patients, somatic complaints interfered with sleep. The patients with depression had significantly lower ESS result and those currently treated with immunomodulation had significantly lower SlD score. SlD score correlated positively with FSS and MFIS. Sleep disturbances in MS patients may occur independently from demographic and disease-related variables, but they are often influenced by the symptoms of MS and therapies used. Sleep disturbances may contribute to fatigue in the course of MS.     

Fatigue, depression and progression in multiple sclerosis

OBJECTIVE: To investigate the effect of fatigue and depression on disease progression in multiple sclerosis (MS), and the long-term prognosis of these symptoms. METHODS: 228 patients with MS were investigated for fatigue and depression with the Fatigue Severity Scale (FSS) and Center for Epidemiologic Studies Depression Scale (CES-D). These patients regularly attended the MS clinic, where disability scores and the development of secondary progression were monitored. After 10 years, the 149 patients remaining from the original cohort were asked to participate in a repeat assessment of fatigue and depression and 96 (64%) could be re-evaluated. In relapsing-remitting patients, the influence of baseline fatigue and depression on the risk of secondary progression during the following 10 years was assessed with survival analyses. In the whole patient group, we investigated the influence of baseline fatigue and depression on progression of disability at 10 years. We also investigated differences in fatigue, depression and disability scores between baseline and 10 years. RESULTS: Fatigue and depression at baseline did not predict the development of secondary progression or progression of disability. Most patients who were fatigued or depressed at baseline remained so at 10 years, and the majority of patients not experiencing these symptoms remained free of them. FSS and CES-D scores were not significantly different between baseline and 10 years, while disability scores significantly increased. CONCLUSION: Our data suggest that fatigue and depression in MS are unrelated to disease progression in MS. Fatigue and depression tend to persist at roughly the same levels over time.     

Selective Cerebellar Atrophy Associates with Depression and Fatigue in the Early Phases of Relapse-Onset Multiple Sclerosis

Cerebellar dysfunctions have been associated to depressive disorders and cognitive impairment in neurodegenerative diseases. The objective is to analyze the associations between cerebellar atrophy, depression, and fatigue in the early phases of relapse-onset multiple sclerosis (RRMS). Sixty-one RRMS patients and 50 healthy controls (HC) were enrolled and clinically evaluated by means of expanded disability status scale (EDSS), Rao’s brief repeatable battery of neuropsychological tests (BRB-NT), Delis-Kaplan executive function system sorting test, beck depression inventory II (BDI-II), and fatigue severity scale (FSS). The relationships between MRI variables and clinical scores were assessed. Depressed RRMS (dRRMS) had significantly lower Vermis Crus I volume compared with not depressed RRMS (ndRRMS) (p?=?0.009). Vermis Crus I volume was lower in dRRMS suffering from fatigue than in ndRRMS without fatigue (p?=?0.01). The hierarchical regression models which included demographic and clinical data (age, sex, and disease duration, FSS or BDI-II) and cerebellar volumes disclosed that cerebellar lobule right V atrophy explained an increase of 4% of the variability in FSS (p?=?0.25) and Vermis Crus I atrophy explained an increase of 6% of variability in BDI-II (p?=?0.049). Since clinical onset, atrophy of specific cerebellar lobules associates with important clinical aspects of RRMS. Cerebellar pathology may be one of the determinants of fatigue and depression that contribute to worsen disability in RRMS.

     

A prospective study of patterns of fatigue in multiple sclerosis

We sought to identify clinical characteristics and socio-demographic variables associated with longitudinal patterns of fatigue in multiple sclerosis (MS) patients. A questionnaire including the Fatigue Severity Scale (FSS) was mailed to a community sample of 502 MS patients three times 1 year apart. Three patterns of fatigue were defined: persistent fatigue (PF) (mean FSS score ≥5 at all time-points), sporadic fatigue (SF) (mean FSS score ≥5 at one or two time-points) and no fatigue (mean FSS score <5 at all time-points). Among the 267 (53%) patients who responded at all time-points, 101 [38%, 95% confidence intervals (CI) 32–44] had persistent, 98 (37%, 95% CI 31–43) sporadic and 68 (25%, 95% CI 20–31) no fatigue. Persistent and sporadic fatigue were more common in patients with, increased neurological impairment ( P  < 0.001), primary progressive MS ( P  = 0.01), insomnia ( P  < 0.001), heat sensitivity ( P  < 0.001), sudden-onset fatigue ( P  < 0.001) or mood disturbance ( P  < 0.001) compared with patients without fatigue. Multivariable analysis showed that depression (PF P  = 0.02, SF P  < 0.001), heat sensitivity (PF P  = 0.04, SF P  = 0.02) and physical impairment (PF P  = 0.004, SF P  = 0.01) were associated with both sporadic and persistent fatigue. About 75% of the patients had persistent or sporadic fatigue over a 2 years observation period. Multivariable analyses confirmed a significant association between levels of depression, physical impairment and persistent fatigue.     

Depressive symptoms and severity of illness in multiple sclerosis: epidemiologic study of a large community sample

OBJECTIVE: Previous research has shown high prevalence rates of depression in multiple sclerosis patients seen in specialty clinics. The relationships among depressive symptoms and severity, duration, and course of multiple sclerosis are controversial. METHOD: A survey was mailed to members of the Multiple Sclerosis Association of King County (Wash.). Of the 1,374 eligible participants, 739 returned the survey, a response rate of 53.8%. Data about demographic characteristics, employment, and duration and course of multiple sclerosis were collected. Severity of multiple sclerosis was determined by the Expanded Disability Status Scale, self-report version. Severity of depressive symptoms was evaluated with the Center for Epidemiologic Studies Depression Scale (CES-D Scale). Analysis of covariance was used to compare mean CES-D Scale scores across categories of multiple sclerosis, and logistic regression was used to identify variables associated with clinically significant depression. RESULTS: Clinically significant depressive symptoms (CES-D Scale score > or =16) were found in 41.8% of the subjects, and 29.1% of the subjects had moderate to severe depression (score > or =21). Subjects with advanced multiple sclerosis were much more likely to experience clinically significant depressive symptoms than subjects with minimal disease. Shorter duration of multiple sclerosis was associated with a greater likelihood of significant depressive symptoms, but the pattern of illness progression was not. CONCLUSIONS: In this large community sample, the severity of multiple sclerosis was more strongly associated with depressive symptoms than was pattern of illness. Clinicians should evaluate depression in patients with recent diagnoses of multiple sclerosis, major changes in functioning, or limited social support.     

Fatigue in multiple sclerosis: multidimensional assessment and response to symptomatic treatment

Sixty relapsing remitting multiple sclerosis (MS) patients were selected on the basis of their score on the Fatigue Severity Scale (FSS) and formed two groups: 40 patients (fatigued MS; MSf) scored above the 75th percentile of a previously assessed representative MS sample (100 patients), and 20 age- and sex-matched patients (nonfatigued MS patients; MSnf) scored below the 25th percentile. The patients underwent clinical evaluation (Expanded Disability Status Scale (EDSS)), further assessment of fatigue (Fatigue Impact Scale), scales evaluating depression (Hamilton Depression Rating Scale (HDRS) and Beck's Depression Inventory (BDI)) and neuropsychological tests. All patients were evaluated for muscle fatigability and central activation by means of a biomechanical test of sustained contraction; they also underwent somatosensory evoked potentials (SSEPs) and transcranial magnetic stimulation (TMS). The patients of the MSf subgroup were then randomized to one of the following two treatments: 4-aminopyridine (4-AP) 24 mg/day and fluoxetine (FLX) 20 mg/day. After a one-week titration this treatment proceeded for 8 weeks. At the end of the treatment, EDSS, fatigue and depression scores were further evaluated. At baseline, fatigue test scores consistently correlated with depression and cognitive test scores, but not with the fatigability test. Fatigue scores decreased in both treatment groups in a similar way. Due to the design of the study, this cannot be disjoined from a placebo effect. The changes of fatigue scores could not be predicted in the FLX group, whereas in the 4-AP group higher basal fatigability test scores were associated with greater reduction in fatigue scores.