Behavioral Interventions in Multiple Sclerosis

A Biopsychosocial Perspective

C Heesen; S Köpke; J Kasper; J Poettgen; A Tallner; DC Mohr; SM Gold

Expert Rev Neurother. 2012;12(9):1089-1100.

Abstract and Introduction

Abstract

Managing uncertainty is a major challenge associated with the diagnosis of multiple sclerosis (MS). In addition to physical symptoms, neuropsychiatric symptoms are highly prevalent in this disease. Depression in particular is more common in MS than in other chronic diseases. While substantial achievements have been made in the therapy of MS and an increasing number of immunomodulatory treatments are now available, the long-term benefits of these are still a matter of debate. Importantly, while the approved therapies show good efficacy on inflammatory lesions and relapse rate, and may slow certain aspects of disease progression, improvements in function have rarely been reported. On the other hand, behavioral interventions have recently been shown to significantly improve fatigue and depression as well as motor function. In addition, recent evidence suggests that group education or face-to-face behavioral interventions may decrease inflammatory disease activity (such as relapse rate or lesion formation measured by MRI). Therefore, behavioral interventions not only ameliorate symptoms but may have the potential to modify the disease process itself.

Introduction

Multiple sclerosis (MS) is the most common disabling disease in young adults. Uncertainty is a predominant feature of MS, which prompted J Kesselring, one of the fathers of MS rehabilitation, to argue that the disease should be named 'malignant uncertainty' (MU) instead of MS.^[1] Uncertainty in MS begins with disease onset and encompasses the uncertainty of diagnosis^[2] as well as the largely unpredictable course and progression of disease. Being diagnosed with MS for some patients could mean living in a nursing home 5 years after diagnosis, while other patients experience a benign disease course that enables them to continue a highly active life 30 years later.

During the last 15 years, uncertainty regarding the effectiveness of medical treatments has been added to the mix as well as very recently the uncertainty of possibly severe, even lethal, side effects of treatments.^[3,4] Coping with uncertainty is one of the major challenges in adapting to a disease,^[5] which highlights the importance of psychological factors in MS. In addition, neuropsychiatric symptoms such as depression, anxiety, fatigue and cognitive impairments show a high prevalence in MS and can have a major influence on activities and participation in daily life. Importantly, there is increasing evidence that some of these symptoms may not simply be a psychological reaction to a disabling disease, but could be biologically mediated.^[6]

The present review will provide an update on psychological risk factors linked to the pathogenesis or progression of MS and summarize recent developments regarding the potential of behavioral interventions (BI) in this patient population. We define BI as any educative or interactive approach that aims to alter health behaviors. These may range from interaction in decision-making processes to engaging in exercise programs as well as other interventional approaches such as stress management or meditation. Therefore, we will cover evidence-based patient information programs, psychological interventions as well as exercise. We will highlight studies in each section based on their methodological rigor or novelty of approach. By summarizing the evidence for these interventions in each domain, we will comment not only on symptom outcomes but also on the potential impact of such interventions on disease processes and brain function. Finally, we will outline the goals and objectives for future research in this area.

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Table 1. Highlight studies on exercise in multiple sclerosis.
Study(year)	Patients (n)	EDSS (IG/C)	Design	Intervention	Control	Primary outcome	Main result	Comment	Ref.
Petajan et al. (1996)	46	3.8 (2.9)	RCT	Aerobic stretch	No training	VO₂ max	Fitness increased	First rigorous RCT	[99]
Oken et al. (2004)	57	2.9/3.2 (3.1)	RCT	Aerobic or yoga	Wait list	Cognitive battery	No change in cognition	First study on cognition	[45]
Romberg et al. (2004)	91	2.0 (2.5)	RCT	Aerobic resistance	Wait list	25-ft walk, 500 m walking time	Walking speed improved	Largest study with longest training duration	[100]
Dalgas et al. (2009)	38	3.7 (3.9)	RCT	Resistance training	Wait list	Isometric strength	Strength improved	First rigorous resistance training study	[36]

C: Control; EDSS: Expanded-disability status scale; IG: Intervention group; RCT: Randomized controlled trial; VO₂ max: Maximal oxygen consumption.

Table 2. Highlight studies on patient information.
Study (year)	Petients (n)	Disability	Design	Intervention	Control	Primary outcome	Result	Comment	Ref.
O'Hara et al. (2002)	183	Not reported, 49% with chronic progressive MS	RCT	Self-care program	Usual care	ADL (Barthel), mobility self-care, quality of life (SF-36)	No relevant differences (e.g., Barthel)	Largest self-care trial	[60]
Köpke et al. (2009)	150	Low disability levels (UNDS)	RCT	Relapse education and information	Standard information	Relapse treatments	Altered relapse treatments (see Figure 1)	Strong behavioral effects	[59]
Solari et al. (2010)	120	EDSS 2.0	RCT	Information aid and 1-h physician counselling	Usual care	Risk knowledge, satisfaction with care	Risk knowledge and satisfaction with care improved	RCT addressing earliest time point after diagnosis	[61]

ADL: Activity of daily living; EDSS: Expanded disability status scale; MS: Multiple sclerosis; RCT: Randomized controlled trial; UNDS: United Kingdom neurological disability scale.

Table 3. Highlight studies on cognitive-behavioral and acceptance-oriented therapies.
Study (year)	Petients (n)	Disability	Design	Intervention	Control	Primary outcome	Result	Comment	Ref.
Schwartz (1999)	132	EDSS 4.7	RCT	Group coping training	Telephone support by peers	Quality of life	Improvements, no effect on depression	First larger coping intervention	[101]
Lincoln et al. (2002)	240	UNDS 16	RCT	Compensation training for cognitive deficits	Two groups: care as usual and cognitive assessment and feedback	Quality of life, mood	No effect	Largest study, focusing on cognitive compensation	[102]
Stuifbergen et al. (2003)	142	Moderate	RCT	Group coping training	Telephone support	Quality of life	Complex analysis: improvement	No clear positive finding	[103]
Rigby (2003)	147	EDSS 5–6	RCT	Group coping training	Discussion group	Anxiety, depression	No effect	Only published as a thesis	[104]
Mathiowetz et al. (2005)	169	One out of three retired	RCT	Energy conservation group	Wait list	Fatigue severity	Ameliorated	First nonpharmacological RCT on fatigue	[105]
Mohr et al. (2005)	127	Functional impairment low	RCT	Telephone depression management	T-SEFT	Depression	Reduced depression, telephone-CBT>T-SEFT	First telephone CBT RCT	[71]
Mohr et al. (2012)	121	3.4/2.8	RCT	Stress management	Wait list	GD-enhancing lesions	Fewer GD enhancements	Effects rapidly lost	[67]
Grossmann et al. (2010)	150	3.0/3.0	RCT	Mindfulness training	Usual care	Quality of life, depression, fatigue	Substantially improved	First mindfulness/acceptance RCT	[66]
Van Kessel et al. (2008)	72	EDSS 3.0/3.8	RCT	Fatigue management	Relaxation	Fatigue scale	Fatigue improved	Most rigorous fatigue RCT	[68]

CBT: Cognitive-behavioral treatment; EDSS: Expanded disability status scale; GD: Gadolinium; RCT: Randomized controlled trial; T-SEFT: Supportive emotion-focused therapy; UNDS: United Kingdom neurological disability scale.