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Psychological interventions for multiple sclerosis (Review)
Thomas PW, Thomas S, Hillier C, Galvin K, Baker R
This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library
2009, Issue 1http://www.thecochranelibrary.com
Psychological interventions for multiple sclerosis (Review)
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T A B L E O F C O N T E N T S
1HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
8RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
24DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
26AUTHORS CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
28ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
28REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
33CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
52DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 1.1. Comparison 1 Cognitive behavioural therapy versus care as usual for people with MS with depression,
Outcome 1 Self-reported measure of depression. . . . . . . . . . . . . . . . . . . . . . . 52
52APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
55WHATS NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
55HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
55CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
55DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
55SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
56DIFFERENCES BETWEEN PROTOCOL AND REVIEW . . . . . . . . . . . . . . . . . . . . .
56INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
iPsychological interventions for multiple sclerosis (Review)
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[Intervention Review]
Psychological interventions for multiple sclerosis
Peter W Thomas1, Sarah Thomas1, Charles Hillier2, Kate Galvin3, Roger Baker1
1Dorset Research and Development Support Unit, Poole Hospital NHS Trust, Poole, UK. 2Department of Neurology, Poole Hospital
NHS Trust, Poole, UK. 3School of Health and Social Care, Bournemouth University, Bournemouth, UK
Contact address: Peter W Thomas, Dorset Research and Development Support Unit, Poole Hospital NHS Trust, Cornelia House,
Longfleet Road, Poole, Dorset, BH15 2JB, UK. Peter.Thomas@poole.nhs.uk.
Editorial group: Cochrane Multiple Sclerosis Group.Publication status and date: Edited (no change to conclusions), published in Issue 1, 2009.
Review content assessed as up-to-date: 29 May 2005.
Citation: Thomas PW, Thomas S, Hillier C, Galvin K, Baker R. Psychological interventions for multiple sclerosis. Cochrane Databaseof Systematic Reviews2006, Issue 1. Art. No.: CD004431. DOI: 10.1002/14651858.CD004431.pub2.
Copyright 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
A B S T R A C T
Background
The unpredictable, variable nature of Multiple Sclerosis (MS), and the possibility of increasing disability, means that a diagnosis can
have substantial psychological consequences.
Objectives
To assess the effectiveness of psychological interventions for people with MS.
Search methods
We searched the Cochrane MS Group Specialised Register (December 2004), Cochrane Central Register of Controlled Trials (The
Cochrane Library Issue 4, 2004 ), MEDLINE (January 1966 to December 2004), PsychINFO (January 1887 to December 2004),
CINAHL (January 1982 to December 2004) and 14 others. We searched reference lists of articles, wrote to corresponding authors of
the 13 papers identified by June 2004, and searched for trials in progress using 3 research registers.
Selection criteria
Randomised controlled trials of interventions described as wholly or mostly based on psychological theory and practice, in people
with MS. Primary outcome measures were disease specific and general quality of life, psychiatric symptoms, psychological functioning,
disability, and cognitive outcomes. Secondary outcome measures were number of relapses, pain, fatigue, health care utilisation, changes
in medication, and adherence to other therapies.
Data collection and analysis
Pertinent studies were identified from abstracts by one author. Full papers were independently compared to selection criteria by four
authors. Key details were extracted from relevant papers using a standard format, and studies scored on three dimensions of quality. The
review is organised into four mini-reviews (MR) dependent on the interventions target population; people with cognitive impairments
(MR1), people with moderate to severe disability (MR2), people with MS (no other criteria) (MR3), and people with depression
(MR4).
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Main results
Overall 16 studies were identified and included. MR1: three trials (n=145). Some evidence of effectiveness of cognitive rehabilitation
on cognitive outcomes, although this was difficult to interpret because of the large number of outcome measures used. MR2: three
trials (n=80). One small trial suggesting psychotherapy may help with depression. MR3: seven studies (n=688). Some evidence that
cognitive behavioural therapy may help people adjust to, and cope with, having MS (three trials). The other trials were diverse in
nature and some difficult to interpret because of multiple outcome measures. MR4: three trials (n=93). Two small studies of cognitive
behavioural therapy showed significant improvements in depression.
Authors conclusions
The diversity of psychological interventions identified indicates the many ways in which they can potentially help people with MS.
No definite conclusions can be made from this review. However there is reasonable evidence that cognitive behavioural approaches are
beneficial in the treatment of depression, and in helping people adjust to, and cope with, having MS.
P L A I N L A N G U A G E S U M M A R Y
Psychological treatments to help improve the quality of life of people with multiple sclerosis
In many countries MS is the most common neurological disorder among young adults. Its impact can be overwhelming with the person
facing the likelihood of reduced physical function and of disability, with consequent disruptions in education, employment, sexual
and family functioning, friendships and activities of daily living. MS can have a considerable impact on the individuals sense of self,
especially if they can no longer perform previously valued activities. Unpleasant side effects from medication may also occur. Mood
disorders such as depression and anxiety are common in people with MS, and are often a result of finding it difficult to adjust to, and
cope with, having the disorder. Cognitive functioning (the mental processes of memory, concentration, reasoning and judgement) can
also be affected. Therefore a diagnosis of MS can have substantial psychological consequences.
The authors of this review wanted to assess the effectiveness of psychological interventions (such as those addressing cognitive function-ing, thoughts, mood and behaviour) for people with MS. This was done by considering their effect on quality of life, mood, cognitive
functioning and disability in particular, but also on pain, fatigue, and use of other health related services and treatments.
Sixteen relevant studies were identified and included in this review. They have researched a variety of different interventions, having
different purposes, and so a single overall definite conclusion cannot be made. However the authors cautiously conclude that Cognitive
Behavioural Therapy, a therapy that addresses thoughts and behaviours, can help people with MS adjust to, and cope with, having MS,
and can help them if they get depressed.
Psychological interventions can potentially help people with MS in many ways, including the management of symptoms such as pain
and fatigue. Additional studies are needed, particularly those that include larger numbers of people.
B A C K G R O U N D
Multiple sclerosis (MS) is the most common neurological disorder
among young adults and affects approximately 85 000 people in
the UK (Graham 2002). It is a chronic and often disabling disease
that typically commencesbetween the ages of 20 and 40 years. Itis
more common in females than males by a ratio of approximately3:
2. The cause and early development of the disease are not fully un-
derstood but the current belief is that it is an autoimmune disorder
affecting genetically susceptible individuals, possibly triggered by
environmental or other factors. MS is characterised by inflamma-
tion and demyelination of the central nervous system. Virtually
all functions innervated by the CNS can be affected. Common
symptoms include, but are not limited to, loss of function or feel-
ing in limbs, loss of bowel or bladder control, sexual dysfunction,
debilitatingfatigue, blindness due to optic neuritis, loss of balance,
pain, cognitive dysfunction and mood disorders (Mohr 2001a).
There is currently no cure and only minimal symptomatic relief
available.
MS is a disease with an unpredictable course and prognosis is
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difficult to predict. Three basic types of clinical course of MS can
be distinguished:
1. Relapse-remitting MS is characterised by stable phases alter-
nated with relapses. Relapses tend to be unpredictable and their
causes are unclear. They can last for hours, days, weeks or months
and vary from mild to severe. During a relapse new symptoms
may occur or previous symptoms may return. Remissions can last
as long as several years. Approximately 25% of people with MS
have this form of the disease.
2. Secondary progressive MS commences with an initial relapse
remitting course but is then followed by a progressive phase which
is characterised by a steadily worsening condition. Approximately
40%of peoplewith MS developthe secondaryform,usually about
15 to 20 years after the initial onset of MS.
3. In the case of primary progressive MS there is no distinct pattern
of relapses and remissions. The disease commences with steadily
worsening symptoms and progressive disability which may level
off or continue to deteriorate. Approximately 15% of people with
MS have this form of the disease.
In addition to the course of MS these types of MS differ on a
number of characteristics such as age at onset, degree of disability,
disease duration and progression rate. As MS advances, the nature
and severity of an individuals symptoms become increasingly het-
erogeneous. Some may experience few exacerbations of the illness
whereas others may experience a rapid decline of function and
eventually become wheelchair dependent. Similarly, while someindividuals may experience minimal cognitive impairment, in oth-
ers there may be severe decline.
PSYCHOLOGICAL AND SOCIAL FACTORS
A diagnosis of MS has profound social and psychological conse-
quences. Because MS usually strikes individuals in their most pro-
ductive years its impact can be overwhelming (Scheinberg 1984).
The unpredictable and variable nature of MS may make it par-
ticularly difficult to come to terms with. The individual is firstly
faced with the impact of receiving a diagnosis of a disease which is
chronic, has an unpredictable course and affects many spheres of
functioning. They face the likelihood of reduced physical function
and disability in the future. Disruptions in education, employ-
ment, sexual and family functioning, friendships and activities of
daily living are likely to occur. The unpredictability of day-to-day
health in relapse remitting MS may greatly impinge upon quality
of life (Mullins 2001). Individuals may, in addition, experience
unpleasant side effects from medication.
MS can have a considerable impact on the individuals sense of
self (LaRocca 1993). Physical changes and functional limitations
may lead to a sense of loss of identity or role strain especially when
the individual can no longer perform previously valued activities
(Mullins 2001). It may be necessary to redefine ones self-image
in order to incorporate the limitations imposed by MS. Each time
the individual experiences a new loss of function this sense of loss
may be renewed (LaRocca 1993). Because of increasing disability,individuals with MS may have problems with isolation ( OBrien
1993,Walsh 1989), perceivedsocial support (Miles1979, OBrien
1993), and social contacts (Gilchrist 1994, McIvor 1984). Loss
of social support and/or social role has also been shown to be
associated with depression (Mohr 2004).
The individuals perceptions of the uncertainty and variability of
the disease and the perceivedintrusiveness on daily activities are all
related to depression and adjustment to the illness (Mullins 2001).
Although illness related factors (such as neurological deterioration
and functional disability) may partially contribute to how well the
person with MS adjusts, the psychological response to the highly
stressful nature of this disease is also likely to be important.Individuals with MS exhibit a higher prevalence of mood disorders
relative to individuals with comparable degrees of physical dis-
ability (Rao 1992, Minden 1991, Pollock 1990, Schiaffino 1996;
Schubert 1993). Mood disorders refer to a sustained and per-
vasive emotion that influences perception of self, others and the
world such as depression or anxiety (Minden 2000). Research has
tended to focus on depression; however people with MS have also
been found to have high levels of anxiety (Maurelli 1992).
Depression is one of the more common and debilitating psycho-
logical symptoms in MS (Thompson 1996). Lifetime prevalence
of major depressive disorder (MDD) is approximately 50% (Joffe
1987; Minden 1987; Sadovnick 1991). Point prevalence estimatesare less clear, ranging from 14% to 57% depending on the as-
sessment instrument, criteria, and patient samples used (Schiffer
1983; Schubert 1993; Surridge 1969; Whitlock 1980). Rates of
depression are higher than in other chronic illness (Minden 1987;
Surridge 1969) or neurological disorders (Rabins 1986; Whitlock
1980). The high prevalence of depression in MS may have multi-
ple aetiologies (Mohr 2001a) including psychosocial factors such
as loss of social support or social role ( Barnwell 1997; Gilchrist
1994; Gulick 1997) and inadequate coping (Aikens 1997; Mohr
1997a; Pakenham 1997; Pakenham 1999). It may also be a con-
comitant of immune dysregulation associated with MS exacerba-
tions(Dalos1983; Fassbender 1998)andthedevelopmentofbrain
lesions (Franklin 1988; Pujol 1997). Thus depression can be botha complication associated with MS as well as a symptom of MS.
The psychoneuroimmunology literature suggests that depression
may induce abnormalities of immune functions that are relevant
to MS (Mohr 2001b). There is also evidence (albeit equivocal) for
depression being an iatrogenic side effect of MS disease-modify-
ing drugs (Mohr 1996; Mohr 1998; Mohr 1999a). Another com-
plicating factor is that many of the symptoms of depression are
confounded with MS (e.g. fatigue, psychomotor agitation or re-
tardation, changes in sleep patterns and diminished ability to con-
centrate). Thus the relationship of mood disorders to MS is multi-
factorial and complex, and the extent to which theyare direct con-
sequences of the disease process itself or psychological reactions
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to it remains unclear. Such issues have important implications for
the therapeutic approach that is adopted.
The relationship between medical and psychological variables is
likely to be complex: The psychological state of an individual may
affect their adherence to medical regimens (Mohr 1996), thereby
exerting an indirect effect on disease processes. Psychological states
may also directly affect MS. Stress arising from interpersonal con-
flict and disruption in routine can increase the likelihood of devel-
oping new brain lesions (Mohr 2002) and depression mayincrease
MS related auto-immune activity (Mohr 1999b, Mohr 2001b).
Literature on other emotional problems in people with MS is
scarce. Although it is recognised that in addition to depression,
emotional responses such as anxiety and anger can occur, much
less research has been undertaken in these aspects of psychological
functioning. Existing research suggests that the point prevalence
of problems with anxiety ranges from19% to 34% (Minden 1991;
Pepper 1993; Stenager 1994). A study by Feinstein (Feinstein
1999) found anxiety to be more common than depression. Co-
morbid anxiety and depression was associated with elevated rates
of suicidal ideation compared to depressed patients with little or
no anxiety (Feinstein 1999).
COGNITIVE FACTORS
Cognitive factors are those relating to the mental processes of
memory, concentration, reasoning and judgement. Cognitive
problems are common in individuals with MS and point preva-lence estimates range from 43%-72% (Prosiegal 1993). Ithas been
acknowledged that the types of patients studied, duration of ill-
ness and disease courses probably account for the wide range of
estimates (Nelson 1988; Rao 1991). Community based popula-
tions and those with relapse-remitting MS have lower rates (Rao
1991; Heaton 1985), whilst those attending hospital, the highest.
Research has shown that memory, learning, conceptual reasoning,
speed of information processing andreactiontime, attention, con-
centration and executive function are affected whereas recognition
memory, implicit learning and speech comprehension remain in-
tact (see Brassington 1998). The degree of cognitive impairment
evident in individuals with MS appears to be unrelated to their
neurological disability status or disease duration (Maurelli 1992;Penman 1991; Rao 1991). Cognitive impairment has been found
to be related to poorer social and employment outcomes (Rao
1991), low mood (Gilchrist 1994), sexual dysfunction, greater
functional impairment (Amato 1995) andpsychopathology. These
findings suggest that cognitive dysfunction is a major factor in de-
termining the quality of life of people with MS. Severe cognitive
impairment presents a major barrier to rehabilitation programmes
because individuals may be unable to retain advice or have diffi-
culty in acquiring new skills. Cognitive impairment in MS often
goes undetected or is misattributed to other problems (Lincoln
2002). Rao et al. (Rao 1991) reported that families and carers of-
ten attribute cognitive impairments to depression or other forms
of psychological dysfunction.
PSYCHOLOGICAL INTERVENTIONS
The purpose of this research is to undertake a systematic review
of randomised controlled trials of psychological interventions for
adults with MS. Psychological interventions are broadly defined
and include those that address mood and those that address cog-
nition.
The literature suggests that people with MS are not adequately
treated for their mood disorders (Minden 1987). Effective treat-
ment of mood disorders might improve functional status, self-
esteem, quality of life and compliance with medical treatment
(Spitzer 1995; Mohr 1997b). Psychological interventions may im-
prove the psychological and physical well being of individuals withMS by treating mood disorders such as anxiety and depression
(with possible benefits to immune function (Mohr 2001b)), by
improving self managementand adherence, enhancingself efficacy
and esteem, reducing stress, improving coping skills and general
quality of life. Psychological therapy on an individual basis may
help individuals develop skills to cope with emotions, thoughts
and adjustment to MS diagnosis and symptoms (Minden 1992).
Group therapy is often used to decrease feelings of alienation, fa-
cilitate expression of emotions related to the disease, and provide
peer support.
Undertaking cognitive assessments may help individuals restruc-
ture aspects of their lives to maximise their cognitive strengths.
This could lead to a decrease in the functional impact of the dis-ease (Langdon 1996), help in the planning of other rehabilitation
services, and decrease dependency. Evaluations of specific inter-
ventions for cognitive problems have demonstrated beneficial ef-
fects in other patient groups such as stroke and traumatic brain
injury (Wilson 1999). However, to date, little research has been
undertaken to assess the benefits of cognitive rehabilitation in in-
dividuals with MS.
There have been a number of intervention studies to examine
the effectiveness of psychological interventions in individuals with
MS (Mohr 1999c). A variety of psychological interventions have
been used including group therapy (Barnes 1954; Bolding 1960;
Day 1953; Hartings 1976), individual cognitive behaviouralbasedtherapies (Crawford 1987; Foley 1987; Larcombe 1984), cogni-
tive behavioural therapy delivered via the telephone (Mohr 2000),
insight-oriented group psychotherapy (Crawford 1985), coping
skills training compared with peer telephone support (Schwartz
1999), relaxation and imagery (Maguire 1996), and cognitive re-
habilitation (Lincoln 2002). A recent study by Mohr et al. com-
pared individual cognitive-behaviour therapy, with supportive ex-
pressive group therapy and the anti-depressant sertraline (Mohr
2001c). Some psychological interventions have focussed on in-
dividuals with MS and depression (e.g. Larcombe 1984), some
on individuals with cognitive deficits (Benedict 2000), some have
been administered on a one-to-one basis (Foley 1987), some in
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group settings (e.g. Crawford 1985), and some over the telephone
(Mohr 2000).
Before we started this review a number of methodological chal-
lenges were evident. Firstly, in the context of all randomised con-
trolled trials in MS, the measurement of disease and function can
be problematic, particularly when the condition has a relapse-re-
mitting course and follow-up periods are short. Secondly psycho-
logical interventions may be given at different times, for different
purposes, to different subgroups of people, at different stages of
their disease. The type of intervention, content, theoretical basis,
intensity, duration, length of each session, whether one-to-one or
in groups can vary, as can the profession and experience of the
person delivering the intervention, and the location. This hetero-
geneity could make it difficult to combine the results from differ-ent studies. Thirdly, both in clinical practice and in randomised
trials, psychological interventions often incorporate a mix of dif-
ferent components, for example blending cognitive rehabilitation
components, say, with psychotherapy components. This overlap
makes it difficult to do a series of separate Cochrane reviews that
adequately covers and summarises the randomised trial evidence
base.Fourthly, in trials, psychological interventions might be com-
pared to other psychological interventions, pharmaceutical treat-
ment, a placebo, or usual care. Each addresses different research
questions and so implies a different interpretation of the results.
Our solution to the latter three problems has been to conduct a
review that is broad in scope, but that contains within it a series of
mini-reviews that focus on the different interventions, comparisontreatments and population target groups. Meta-analysis, if carried
out, has been confined to within each mini-review. This provides
a flexible framework that easily accommodates new evidence as it
arises.
Particular attention has been paid to giving the review a clear,
logical structure and layout. This should enable the reader of the
review, despite the complexity outlined above, to find their way to
the evidence that most interests them (e.g. long-term benefits of
cognitive behavioural therapy in the management of depression).
It also helps to highlight where there are gaps in the evidence base.
For the authors, the structure will facilitate standardised updating
of the review in future years, particularly if the rate of publicationof relevant studies continues to increase.
O B J E C T I V E S
To assess the effect of psychological interventions on mental and
physical wellbeing in people with multiple sclerosis
M E T H O D S
Criteria for considering studies for this review
Types of studies
Randomised controlled trials and the pre- cross over component
of randomised cross-over trials. Studies were not excluded on the
basis of type of control group (i.e. care as usual or standard care,
placebo, waiting list controls, other psychological intervention,
other intervention).
Types of participants
People with a diagnosis of multiple sclerosis (e.g. using recognised
criteria such as Poser 1983, Schumacher 1965). Studies were in-cluded in the review regardless of clinical course or the length of
time since diagnosis of MS. Studies based on subgroups of peo-
ple with MS such as those with depression, those with cognitive
impairment, those with severe physical disability, were included,
and were considered in separate mini-reviews. If we had found
studies that included people with MS together with people with
other medical conditions, and the number of people in the study
with MS had made it worthwhile to do so (i.e. exceeded 20), the
authors would have been contacted to try and get the results for
the MS subgroup.
Types of interventions
Interventions described as wholly or mostly based on psycholog-
ical theory and practice. Interventions could have been delivered
by psychologists, counsellors, medical staff, nurses, occupational
therapists or other health professionals, and were included regard-
less of the number of therapy sessions or whether sessions were
one-to-one or group.The following gives an idea of thetypes of in-
terventions that either were included or could have been included:
Psychoanalytic therapy - looking back at past events in order to
gain insight
Behavioural therapy - a variety of techniques that attempt to mod-
ify behaviour, including stress management and relaxation.
Cognitive therapy - a variety of techniques that attempt to changeattitudes, perceptions and ways of thinking.
Educational - teaching of psychological theory in relation to the
disease
Counselling - Non-directive approach involving talking through
problems
Cognitive rehabilitation - a variety of techniques that attempt to
reduce the impact of cognitive impairments
Other - e.g. family therapy etc.
Sometimes the interventions evaluated consisted of a combination
of these techniques. Interventions that were substantively different
have been considered under separate sub-headings within each
mini-review.
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Types of outcome measures
Primary:1. Disease specific quality of life - perspective of person affected by
MS (e.g. MS Impact Scale (MSIS-29) (Hobart 2001), MSQOL-
54 (Vickrey 1995), MS Quality of Life Inventory (MSQLI ) (
LaRocca 1996), Health Related Quality of Life Questionnaire for
Multiple Sclerosis (HRQOL-MS) (Pfennings 1999)).
2.Generalqualityoflife-perspectiveofpersonaffectedbyMS(e.g.
Medical Outcomes Study 36-item Short-Form Health Survey (SF-
36) (Ware 1993), Euro-Qol (EQ5D) (EuroQoL Group 1990)).
3. Psychiatric symptoms including anxiety and depression (e.g.
anxiety and depression subscales of the Delusion-States-Symp-
toms-Inventory (Bedford 1978)) - rated by person with MS or by
clinician.
4. Psychological functioning including emotions (e.g. Profile ofMood States McNair 1981), self-efficacy (e.g. Schwarzer 1995),
self-esteem (e.g. Rosenberg 1965),etc.) - rated byperson with MS.
5. Measures of disability (e.g. Kurtzke Expanded Disability Status
Scale (EDSS) (Kurtzke 1983), Guys Neurological Disability Scale
(GNDS) (Sharrack 1999) - clinician rated.
6. Cognitive outcomes including memory, language, concentra-
tion, higher executive function etc. - rated by clinician or by per-
son with MS.
Given the broad range of interventions encompassed within this
review it was important to include a broad range of primary out-
come measures. Clearly though, not all primary outcome measures
have the same relevance for all interventions.
Secondary:
Relapses/exacerbations (e.g. number of relapses, time to first re-
lapse)
Pain
Fatigue
Health care utilisation, and economic assessment
Change in need for medication
Adherence to other therapies (e.g. drug therapies)
Outcomes were classifiedaccording to whetherthey hadbeen mea-
sured (i) within a month post-treatment (immediately post-treat-
ment), (ii) between one and six months post-treatment (short-
term follow-up), (iii) between seven and 12 months post-treat-
ment (medium-term follow-up), and (iv) over 12 months post-
treatment (long-term follow-up).
Search methods for identification of studies
To identify appropriate studies that included people with multiple
sclerosis the search strategy developedby the Cochrane MS Group
was used.
In the next update of the review we intend to add in additional
search terms relevant to identifying studies of cognitive rehabili-
tation.
For research not published in English, we either sought help with
translation or contacted the respective author.
Electronic searches
1. the Cochrane Multiple Sclerosis Group Specialised Register(December 2004)
2. the Cochrane Central Register of Controlled Trials (The
Cochrane Library issue 4, 2004)(Appendix 1)
3. MEDLINE (January 1966 to December 2004)(Appendix 2)
4. EMBASE (January 1974 to December 2004)(Appendix 3)
5. PsychINFO (January 1887 to December 2004)
6. CINAHL (January 1982 to December 2004)
7. BNID (January 1994 to December 2004)
8. AMED (January 1985 to December 2004)
9. CareData (January 1920 to December 2004)
10. ASSIA (January 1987 to December 2004)
11. IBSS (January 1951 to December 2004)
12. Web of Science (January 1981 to December 2004)
13. CAB (January 1973 to December 2004)
14. PapersFirst (OCLC) (January 1993 to December 2004)
15. ProceedingsFirst (OCLC) (January 1993 to December 2004)
16. ASLIP (January 1970 to December 2004)
17. Zetoc (January 1993 to December 2004)
18. EBSCO HOST Academic Search Elite (January 1985 to De-
cember 2004)
19. LISA (January 1969 to December 2004)
Searching other resources
Thereference lists ofidentified papersweresearchedfor furtherrel-
evant trials. InJune 2004 we wrote tothosewho hadalready under-taken trials in this area to identify other published or unpublished
trials. We searched registers of trials in progress (National Research
Register, www.controlled-trials.com and www.clinicaltrials.gov)
and contacted the primary investigator.
Data collection and analysis
The review was carried out by four authors (one with methodolog-
ical expertise, one with psychological expertise, one with clinical
expertise in multiple sclerosis, and one with expertise in nursing
research). To help get a broader view of the context, design, con-
duct and interpretation of the review, the authors were aided byan advisory group. The advisory group included the authors and
a clinical psychologist/ researcher, a clinical neurophysiologist/ re-
searcher, a senior librarian, and 2 consumers.
Abstracts of identified studies were sifted by one author to iden-
tify those that seemed pertinent: at this stage we excluded studies
that were obviously not controlled trials or randomised controlled
trials, those that had not included people with MS, or assessed
interventions of a psychological nature. The full papers of these
(including those where there was any uncertainty) were then com-
pared to the above criteria by the four authors. Where there was
disagreement between the authors or uncertainty, this was resolved
by discussion followed by either consensus or a majority vote. If
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disagreement or uncertainty remained then the authors consulted
other members of the advisory group. Authors would have beencontacted if clarification or further information had been needed
in order to reach a decision.
Each study was allocated to a mini-review based on the target
population. Different types of intervention were then addressed
in sub-sections within each mini-review. This structure was cho-
sen instead of one basing each mini-review on a type of interven-
tion, because of difficulties in classifying some interventions, the
eclectic nature of some interventions, and the overall diversity of
interventions. Currently the mini-reviews are:
Mini-review 1: People with MS with cognitive impairment
Mini-review 2: People with MS with moderate to severe disability
Mini-review 3: People with MS
Mini-review 4: People with MS with depressionThestructure of thereview permits other mini-reviewsto be added
as new research evidence becomes available. Other possibilities for
target populations include, people with MS with fatigue, people
with MS with pain, people with MS with anxiety, and so on.
Study quality
The main measure of trial quality was whether random alloca-
tion had been adequately concealed. Estimates of treatment effect
have been shown to be inflated when studies with poor allocation
concealment are included in meta-analysis (Moher 1998). Allo-
cation concealment was rated as described in the Cochrane Re-
viewers Handbook (Clarke 2000); A (adequate: e.g. central or in-
dependent randomisation, opaque sealed envelopes), B (unclear:
method not described or described but not clear), C (inadequate:open random number lists, alternation, date of birth or any other
procedure that is transparent before allocation), or D (not done).
Other components of study quality were also assessed and
recorded:
The method of randomisation generation; A (adequate,
such as random number table, computer generated random
numbers), B (partial, such as sealed envelopes but no further
details given), C (inadequate, such as birth date, alternation) or
D (unknown, with just the term randomised used).
The number of participants withdrawing or dropping out of
each arm of the study, together with a quality score; A (adequate
with number randomised and withdrawn from each group stated
along with reasons), B (partial, numbers given but not reasons,or vice versa), C (inadequate, with numbers randomised not
stated or not specified in each group), or D (no details given)
The nature of the interventions being considered made it unlikely
that the researcher or clinician who had given the intervention
could be masked. Masking of the researcher who made the assess-
ments or, of the person with MS, was possible although difficult.
Many of the primary outcome measures had been completed by
the person with MS recording their own perspectives and so as-
sessor masking could not have been achieved unless the person
with MS had been masked. It may have been possible to mask the
people undertaking the data analysis and interpretation of results.
Data extraction
Data for the review were extracted independently by the four au-
thors with disagreement and uncertainty dealt with as before. The
following information was extracted using a pre-agreed data ex-
traction tool:
Date, country and clinical setting of trial.
Description of target population
Recruitment procedures, inclusion and exclusion criteria
Flow chart showing flow of participants through all stages of the
study
Participant characteristics (age, gender, years since diagnosis, type
of MS, degree of disability, and psychiatric diagnoses).
Description of intervention, duration, frequency, how delivered,
who delivered, format of delivery, training of person delivering,whether adapted for MS, and whether concomitant interventions
were given.
Type of control group (s) and, if appropriate, description of the
duration, frequency, how delivered, who delivered, format of de-
livery, training of person delivering, whether adapted for MS, and
whether concomitant interventions were given.
Comparability of baseline characteristics between treatment and
control groups.
Description of follow-up
Outcomes measured, whether primary or secondary, and when
they were recorded
Number enrolled in trial and in each group
Presence of sample size calculationNumber included at each follow-up in each group
Attempts at masking
Description of randomisation and randomisation concealment
Number and reasons for drop-out and withdrawal in each group
Whether intention-to-treat analysis undertaken
For nominal outcomes (denominator and numerator in each cat-
egory for each group)
For interval and ordinal data (N, mean, SD for each group) or (N,
median, IQR or range) as appropriate.
If both intention-to-treat and per protocol analyses had been
conducted only the former data were extracted.
Statistical analysis
Meta-analysis was only conducted within mini-reviews and onlywhen it seemed logical to do so; that is, when groups, interven-
tions, control groups, outcomes and length of follow-up were suf-
ficiently similar. When meta-analysis was appropriate, a test of het-
erogeneity was used to assess whetherthe results from the different
studies were (statistically) sufficiently similar to combine them.
For outcomes measured on a dichotomous scale, results are pre-
sented as odds ratios and as risk differences, homogeneity was as-
sessed using a chi-squared test, and odds ratios/ risk differences
combined using the Mantel-Haenszel procedure.
For outcomes measured on an interval or ordinal scale, results are
presented as means and standard deviations, a chi-squared test
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was used to assess homogeneity and results from different stud-
ies combined using weighted mean differences. Standardised ef-fect sizes using Hedges adjusted have been used to summarise
mean differences between groups. This enables comparison of ef-
fect sizes between different outcome measures. Unless otherwise
indicated, positive standardised effect sizes indicate that the inter-
vention is producing more benefit to participants than the com-
parison group.
If two or more studies measured outcome in the same dimension
but using a different tool then we considered standardising the
scores (using the pooled within group standard deviation) and
then combining the studies as above.
By default, a fixed-effects model was used for combining studies. If
tests for heterogeneity were statistically significant and inspection
of the individual results suggested that it still seemed logical tocombine results, then a random effects model was used. Statistical
precision was summarised using 95% confidence intervals.
Within a mini-review no subgroup analyses were done.
Had the results from three or more studies within a mini-review
been combined, then a sensitivity analysis would have been con-
sidered. This would have taken two forms (a) Sequential elimina-
tion of trials from the analysis according to their level of alloca-
tion concealment (i.e. type D studies eliminated first, then type C
studies, then type B) to see how the results were affected; (b) data
reanalysed using worst case, best case, and random case scenarios
for participants without outcome data to assess the robustness of
the results.
The review was conducted using RevMan 4.2 software
R E S U L T S
Description of studies
See: Characteristicsof included studies; Characteristics of excluded
studies; Characteristics of ongoing studies.
The search strategy identified 26 relevant trials, of which six were
excluded after reading the full papers (see table of Characteristicsof excluded studies), two, identified between January and May
2005, are awaiting assessment (see reference list of studies waiting
assessment) and two are ongoing (see table of Characteristics of
ongoing studies). The remaining 16 trials, reported in 17 papers
(one trial wasreportedovertwo papers(Mohr 2001, Mohr 2003)),
are all randomised controlled trials, are included in the review,
and are described in detail in the table of Characteristics of in-
cluded studies. A further paper (Mohr 2004), listed in the table
of Characteristics of excluded studies, contained additional data
for a study that was included in the review (Mohr 2001), but none
of the outcomes reported satisfied the reviews inclusion criteria.
One of the six excluded studies appeared not to come within our
definition of a psychological intervention, one was excluded be-
cause it did not include appropriate outcome measures, and fourwere excluded because they did not appear to be randomised. The
16 included studies have been grouped together in four Mini-re-
views. Only two of the studies in one of the mini-reviews were suf-
ficiently similar in terms of type of participant, type of interven-
tion, type of comparison group, and outcome measure for a meta-
analysis to be conducted. The number of participants per study
ranged from 15 to 240, median 37, witha total of 1006 over all 16
studies. Twelve studies had a two group design, and four studies
a three group design (Crawford 1985, Lincoln 2002, Mohr 2001
(although one group was excluded because it wasnt randomised),
Rigby 2003). Length of follow-up from start of treatment ranged
from five weeks to four years.
One study used a measure of MS specific quality of life, two mea-sured general quality of life, 12 measured psychiatric symptoms,
10 measured psychological function, two measured disability, five
measured cognitive outcomes, three studies measured fatigue, one
study measured pain, one measured an aspect of health care util-
isation (none undertook an economic assessment), one measured
changes in medication usage, and onemeasuredadherence to med-
ication. None measured MS relapses. Fifteen studies measured
outcome immediately post-treatment, nine measured short-term
outcome, three measured medium term outcome and one mea-
sured long-term outcome.
Risk of bias in included studies
Study quality is given in the Methods column in the table of
Characteristics of included studies in the order (i) method of
randomisation generation, (ii) method of randomisation conceal-
ment, and (iii) description of withdrawals.
Method of randomisation generation wasnot reported for11 stud-
ies, adequate in three studies and partially adequate in two studies.
Allocation concealment was adequate in three studies, unclear in
12 studies and inadequate in one study.
Reporting of withdrawals was adequate in five studies, partial in
seven, inadequate in three and not reported in one study.
Effects of interventions
MINI-REVIEW1: Peoplewith MS with cognitive impairment
(a) Neuropsychological counseling
(i) Neuropsychological counseling versus Psychotherapy
One study Benedict 2000; a two group study of 15 people with
marked cognitive impairment and behaviour disorder (and their
caregivers), comparing individualised neurological compensatory
training(enhancing understandingof cognitive impairment, social
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skills training, and cognitive behavioural therapy to help regulate
social behaviour) to non-specific supportive psychotherapy.Primary outcomes:
Disease specific quality of life:Immediately post-treatment:-No data
Short term follow-up:-No data
Medium term follow-up:-No data
Long term follow-up:-No data
General quality of life:
Immediately post-treatment:-No data
Short term follow-up:-No data
Medium term follow-up:-No data
Long term follow-up:-No data
Psychiatric symptoms:
Immediately post-treatment:- In the Benedict study (Benedict
2000) the mean change in self-reported depression between pre-
treatment and immediately post-treatment did not differ between
treatment arms (p>0.05, no post-treatment means reported).
However overall sample size was small (n=15).
Short term follow-up:-No data
Medium term follow-up:-No data
Long term follow-up:-No data
Psychological functioning:Immediately post-treatment:-No data
Short term follow-up:-No data
Medium term follow-up:-No dataLong term follow-up:-No data
Measures of disability:Immediately post treatment:-No data
Short term follow-up:-No data
Medium term follow-up:-No data
Long term follow-up:-No data
Cognitive outcomes:Immediately post-treatment:-No data
Short term follow-up:-No data
Medium term follow-up:-No data
Long term follow-up:-No data
Secondary outcomes:
Immediately post-treatment:-No dataShort term follow-up:-No data
Medium term follow-up:-No data
Long term follow-up:-No data
(b) Cognitive rehabilitation+neuropsychotherapy
(i) Cognitive rehabilitation+neuropsychotherapy versus
placebo
One study (Jonsson 1993); a two group study of 48 people com-
paring individual cognitive rehabilitation (compensation, substi-
tution and training) and goal directed neuropsychotherapy (based
on personal problems and test profile) to a placebo individual in-
tervention.
Primary outcomes:
Disease specific quality of life:
Immediately post-treatment:-No data
Short term follow-up:-No data
Medium term follow-up:-No data
Long term follow-up:-No data
General quality of life:Immediately post-treatment:-No data
Short term follow-up:-No data
Medium term follow-up:-No data
Long term follow-up:-No data
Psychiatric symptoms:
Immediately post-treatment:-In the studyof Jonsson et al (Jonsson1993) the improvement in depression between pre-treatment and
immediately post-treatment was significantly higher in the group
receiving cognitive rehabilitation and neuropsychology (mean im-
provement 2.4 versus 0.0, p=0.04, no further details given). There
were no statistically significant differences between the interven-
tion and placebo groups in current anxiety (mean improvement
between pre-treatment to immediately post-treatment 5.6 v 2.7
respectively, p=0.17, no other details given) or general anxiety
(mean improvement 3.8 v 3.5 respectively, p=0.92, no other de-
tails given).
Short term follow-up:- In the study of Jonsson et al (Jonsson 1993)
the improvement in depression between pre-treatment and short
term follow-up was significantly higher in the group receivingcognitive rehabilitationand neuropsychology(mean improvement
1.1 versus -2.7, p=0.03, no further details given). There were no
statistically significant differences between the intervention and
placebo groups in current anxiety (mean improvement between
pre-treatment and short-term follow-up 1.1 v -1.6 respectively, p=
0.42, no other details given) or general anxiety (mean improve-
ment 1.5 v 0.6 respectively, p=0.75, no other details given).
Medium term follow-up:-No data
Long term follow-up:-No data
Psychological functioning:Immediately post-treatment:- No data
Short term follow-up:-No data
Medium term follow-up:-No dataLong term follow-up:-No data
Measures of disability:Immediately post treatment:-No data
Short term follow-up:-No data
Medium term follow-up:-No data
Long term follow-up:-No data
Cognitive outcomes:
Immediately post-treatment:-The study of Jonsson et al (Jonsson
1993) used 20 measures of cognition combined into 11 factors for
the purpose of analysis (see Table of included studies). All factors
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have been converted into age, sex and education status adjusted t-
scores based on data from a sample of healthy people without MSwhere mean t-score = 50 and SD = 10. One of these 11 factors is
a composite of four factors (memory span, verbal learning, visuo-
spatial memory and visuo-motor speed). This composite factor
showed no difference in improvement between pre-treatment and
immediately post-treatment in the intervention group compared
to the control group (mean improvement 1.8 v 1.1 respectively, p=
0.53, no other details given). There were no significant differences
in the four factors that made up this composite factor. There was a
larger improvement in visual perception in the intervention group
compared to the control group (mean improvement 2.0 v 0.6
respectively, p=0.04, no other details given), but not in verbal
intelligence (mean improvement 1.0 v 0.7 respectively, p=0.91, no
other details given), or WAIS performance (mean improvement5.2 v 7.3 respectively, p=0.42). No results reported for recognition
memory, concentration or verbal fluency.
Short term follow-up:-The study of Jonsson et al (Jonsson 1993)
used 20 measures of cognition combined into 11 factors (see Table
of included studies). All factors have been converted into age, sex
andeducation status adjusted t-scores based on data from a sample
of healthy people without MS where mean t-score = 50 and SD
= 10. One of these 11 factors is a composite of four other fac-
tors (memory span, verbal learning, visuo-spatial memory and vi-
suo-motor speed). This composite factor showed no difference in
improvement between pre-treatment and immediately post-treat-
ment in the intervention group compared to the control group
(mean improvement 1.6 v -0.5 respectively, p=0.09, no other de-tails given). Comparing thefour factors which make up this overall
measure, one was of borderline statistical significance (mean im-
provement in visuo-spatial memory from pre-treatment to short-
term follow-up 2.7 v 0.2, p=0.05, no further details given). There
was no difference between the intervention and control groups in
visual perception (mean improvement 2.2 v 1.0 respectively, p=
0.09, no other details given), verbal intelligence (mean improve-
ment 1.5 v 2.1 respectively, p=0.81, no other details given), or
WAIS performance (mean improvement 3.7 v 4.2 respectively, p=
0.87). No results reported for recognition memory, concentration
or verbal fluency.
Medium term follow-up:-No data
Long term follow-up:-No dataSecondary outcomes:
Immediately post-treatment:-No data
Short term follow-up:-No data
Medium term follow-up:-No data
Long term follow-up:-No data
(c) Cognitive rehabilitation
(i) Cognitive rehabilitation versus placebo
One study (Solari 2004); a two group study of 82 people compar-
ing computer aided retraining of memory and attention to sham
retraining.
Primary outcomes:
Disease specific quality of life:Immediately post-treatment:- In the study of Solari et al (Solari
2004) data on mentalhealthand cognitive subscalesof MS specific
quality of life were reported and analysed as percentage changes
from baseline, and statistical analyses adjusted for baseline mea-
sures, age, education, and study centre. The percentage improve-
ment in the mental health subscale was significantly better in the
cognitive rehabilitation group than the placebo group (mean (SD)
= 27% (73%) v 9% (41%) respectively, p=0.04), but there was
no significant difference for the cognitive subscale (36% (86%) v
43% (123%) respectively, p=0.51).
Short term follow-up:-In the study of Solariet al (Solari 2004) data
on mental health and cognitive subscales of MS specific quality
of life were reported and analysed as percentage changes frombaseline, and statistical analyses adjusted for baseline measures,
age, education, and study centre. The percentage improvement in
the mental health subscale was not significantly different in the
cognitive rehabilitation group than the placebo group (mean (SD)
= 16% (47%) v 23% (69%) respectively, p=0.84), and neither
was there a significant difference for the cognitive subscale (43%
(126%) v 56% (140%) respectively, p=0.59).
Medium term follow-up:-No data
Long term follow-up:-No data
General quality of life:Immediately post-treatment:-No data
Short term follow-up:-No data
Medium term follow-up:-No dataLong term follow-up:-No data
Psychiatric symptoms:Immediately post-treatment:-In the study of Solari et al (Solari
2004) data on the mood subscale of the mood depression inven-
tory were reported and analysed as percentage changes from base-
line, and statistical analyses adjusted for baseline measures, age,
education, and study centre. The percentage improvement in this
scale did not differ significantly between the cognitive rehabilita-
tion and placebo groups (mean (SD) = 2% (19%) v 0% (20%)
respectively, p=0.67).
Short term follow-up:-In the study of Solari et al ( Solari 2004)
data on the mood subscale of the mood depression inventory were
reported and analysed as percentage changes from baseline, andstatistical analyses adjusted for baseline measures, age, education,
and study centre. The percentage improvement in this scale did
not differ significantly between the cognitive rehabilitation and
placebo groups (mean (SD) = 6% (19%) v 5% (21%) respectively,
p=0.87).
Medium term follow-up:-No data
Long term follow-up:-No data
Psychological functioning:Immediately post-treatment:- No data
Short term follow-up:-No data
Medium term follow-up:-No data
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Long term follow-up:-No data
Measures of disability:Immediately post treatment:-No data
Short term follow-up:-No data
Medium term follow-up:-No data
Long term follow-up:-No data
Cognitive outcomes:Immediately post-treatment:-In the study of Solari et al (Solari
2004) data on the seven subscales of the Brief Repeatable Battery
of Neuropsychological Tests were presented and analysed as per-
centage changes from baseline, and statistical analyses adjusted for
baseline measures, age, education, and study centre. No signifi-
cant differences were found between cognitive rehabilitation and
placebo groups for Buschke Selective Reminding (verbal learn-
ing and recall) - consistent long term recall (mean (SD) = 138%(310%) v 92% (218%) respectively, p=0.54), Buschke Selective
Reminding - delayed recall (mean (SD) = 160% (317%) v 25%
(68%) respectively, p=0.78), Symbol Digit Modalities Test (sus-
tained attention and information processing speed) (mean (SD)
= 13% (25%) v 9% (29%) respectively, p=0.37), Paced Auditory
Serial Addition Test (complex attention and concentration) (mean
(SD) = 24% (56%) v 33% (85%) respectively, p=0.97), 10/36
Spatial Recall Test (visuospatial learning) - immediate recall (24%
(47%) v 28% (69%), respectively, p=0.69), and 10/36 spatial re-
call - delayed recall (20% (48%) v 81% (146%) respectively, p=
0.33). A significant difference was found for the Word List Gen-
eration Test (verbal fluency and sustained attention) with greater
improvement in the cognitive rehabilitation group compared tothe placebo group (mean (SD) = 6% (45%) v -17% (27%) respec-
tively, p=0.02. Giventhe large number of cognitive tests presented,
the possibility that this is a type 1 error cannot be discounted. The
proportion of patients in the cognitive rehabilitation group and
the placebo group who showed at least a 20% improvement in
two or more of these measures was 45% and 43% respectively (p=
0.88).
Short term follow-up:-In the study of Solari et al ( Solari 2004)
data on the seven subscales of the Brief Repeatable Battery of Neu-
ropsychological Tests were presented and analysed as percentage
changes from baseline, and statistical analyses adjusted for base-
line measures, age, education, and study centre. No significant dif-
ferences were found between cognitive rehabilitation and placebogroups for Buschke Selective Reminding - consistent long term re-
call (mean (SD) = 160% (317%) v 143% (288%) respectively, p=
0.67), Buschke Selective Reminding (verbal learning and recall) -
delayed recall(mean(SD) = 10%(40%) v 44%(99%) respectively,
p=0.06), Symbol Digit Modalities Test (sustained attention and
information processing speed) (mean (SD) = 15% (27%) v 17%
(37%) respectively, p=0.57), Paced Auditory Serial Addition Test
(complex attention and concentration) (mean (SD) = 16% (50%)
v 39% (103%) respectively, p=0.19), 10/36 spatial recall (visu-
ospatial learning) - immediate recall (17% (54%) v 27% (68%),
respectively, p=0.68), and 10/36spatial recall - delayed recall (12%
(64%) v 77% (152%) respectively, p=0.30). A significant differ-
ence was found for the Word List Generation Test (verbal fluencyand sustained attention), with greater improvement in the cogni-
tive rehabilitation group compared to the placebo group (mean
(SD) = 32% (47%) v 0% (30%) respectively, p=0.03. Given the
large number of cognitive tests presented, the possibility that this
is a type 1 error cannot be discounted. The proportion of patients
in the cognitive rehabilitation group and the placebo group who
showed at least a 20% improvement in two or more of these mea-
sures was 48% and 54% respectively (p=0.57).
Medium term follow-up:-No data
Long term follow-up:-No data
Secondary outcomes:
Immediately post-treatment:-No data
Short term follow-up:-No dataMedium term follow-up:-No data
Long term follow-up:-No data
MINI-REVIEW 2: People with MS with moderate to severe
disability
(a) Psychotherapy
(i) Psychotherapy versus placebo
One studyCrawford 1985; a three group study of 32 people com-
paring group-based insight-oriented psychotherapy to a dummy
group-based therapy and a care as usual group.
Primary outcomes:
Disease specific quality of life:Immediately post-treatment:-No data
Short term follow-up:-No data
Medium term follow-up:-No data
Long term follow-up:-No data
General quality of life:Immediately post-treatment:-No data
Short term follow-up:-No data
Medium term follow-up:-No data
Long term follow-up:-No data
Psychiatric symptoms:Immediately post-treatment:- In the Crawford study (Crawford
1985) the groupreceiving psychotherapy scored significantly lower
on the depression score than the placebo group (mean post-treat-ment score 19.3 v 23.5 respectively, p0.05, no further details given).
Short term follow-up:-No data
Medium term follow-up:-No data
Long term follow-up:-No data
Psychological functioning:Immediately post-treatment:- In the Crawford study (Crawford
1985) there were no statistically significant differences in locus
of control (mean post-treatment score 28.3 in the psychotherapy
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group, 30.7 in the placebo group, p>0.05, no other details re-
ported), or self-esteem (p>0.05, no other details reported).Short term follow-up:-No data
Medium term follow-up:-No data
Long term follow-up:-No data
Measures of disability:Immediately post treatment:-No data
Short term follow-up:-No data
Medium term follow-up:-No data
Long term follow-up:-No data
Cognitive outcomes:Immediately post-treatment:-No data
Short term follow-up:-No data
Medium term follow-up:-No dataLong term follow-up:-No data
Secondary outcomes:
Immediately post-treatment:-No data
Short term follow-up:-No data
Medium term follow-up:-No data
Long term follow-up:-No data
(ii) Psychotherapy versus care as usual
One studyCrawford 1985; a three group study of 32 people com-
paring group based insight oriented psychotherapy to a dummy
group based therapy and a care as usual group.
Primary outcomes:
Disease specific quality of life:Immediately post-treatment:-No data
Short term follow-up:-No data
Medium term follow-up:-No data
Long term follow-up:-No data
General quality of life:Immediately post-treatment:-No data
Short term follow-up:-No data
Medium term follow-up:-No data
Long term follow-up:-No data
Psychiatric symptoms:Immediately post-treatment:- In the Crawford study (Crawford
1985) the groupreceiving psychotherapy scored significantly lower
on the depression score than the care as usual group (mean score19.3 v 23.5 respectively, p0.05, no further details given).
Short term follow-up:-No data
Medium term follow-up:-No data
Long term follow-up:-No data
Psychological functioning:
Immediately post-treatment:- In the Crawford study (Crawford
1985) the group receiving psychotherapy were more internally
orientedpost-treatmentthanthe care as usual group(meanlocusof
control 28.3 v 37.0 respectively, p0.05, no other details reported).
Short term follow-up:-No data
Medium term follow-up:-No data
Long term follow-up:-No data
Measures of disability:
Immediately post treatment:-No data
Short term follow-up:-No data
Medium term follow-up:-No data
Long term follow-up:-No data
Cognitive outcomes:Immediately post-treatment:-No data
Short term follow-up:-No dataMedium term follow-up:-No data
Long term follow-up:-No data
Secondary outcomes:
Immediately post-treatment:-No data
Short term follow-up:-No data
Medium term follow-up:-No data
Long term follow-up:-No data
(b) Social skills training
(i) Social skills training versus care as usual
One study (Gordon 1997); a two group study with 26 people
comparing social skills training aimed at easing interaction strain
between people with and without disability, to care as usual.Primary outcomes:
Disease specific quality of life:Immediately post-treatment:-No data
Short term follow-up:-No data
Medium term follow-up:-No data
Long term follow-up:-No data
General quality of life:Immediately post-treatment:-No data
Short term follow-up:-No data
Medium term follow-up:-No data
Long term follow-up:-No data
Psychiatric symptoms:Immediately post-treatment:- No data
Short term follow-up:-No data
Medium term follow-up:-No data
Long term follow-up:-No data
Psychological functioning:Immediately post-treatment:- In the Gordon et al. study (Gordon
1997) there were no statistically significant differences between
intervention and control groups in mean (SD) self efficacy (79.4
(15.0) v 72.1 (28.8) respectively, standardised mean difference =
0.31 (95% CI; -0.54, 1.15)), self esteem (352 (16) v 337 (36)
respectively, standardised mean difference = 0.52 (95% CI; -0.33,
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1.37)), social distress (24.6 (8.3) v 26.5 (9.3) respectively, stan-
dardised mean difference = 0.21 (95% CI; -0.63, 1.05)), socialavoidance (24.0 (8.4) v 24.3 (8.6) respectively, standardised mean
difference = 0.03 (95% CI; -0.80, 0.87)), social anxiety using pos-
itive thoughts (57.8 (11.3) v 45.5 (17.7) respectively, standardised
mean difference = 0.80 (95% CI; -0.08, 1.67)) or social anxiety
using negative thoughts (25.8 (6.2) v 28.9 (7.9) respectively, stan-
dardised mean difference = 0.42 (95% CI; -0.43, 1.27)). It should
be noted that in this study the authors found that baseline levels
of social distress and self-esteem were reasonably normal, and that
this may be one explanation for the apparent lack of treatment
effect.
Short term follow-up:-No data
Medium term follow-up:-No data
Long term follow-up:-No dataMeasures of disability:Immediately post treatment:-No data
Short term follow-up:-No data
Medium term follow-up:-No data
Long term follow-up:-No data
Cognitive outcomes:Immediately post-treatment:-No data
Short term follow-up:-No data
Medium term follow-up:-No data
Long term follow-up:-No data
Secondary outcomes:
Immediately post-treatment:-No data
Short term follow-up:-No dataMedium term follow-up:-No data
Long term follow-up:-No data
(c) Cognitive assessment and rehabilitation
(i) Cognitiveassessment and rehabilitation versus care as usual
One study (Mendoza 2001); 20 people in a long-term nursing
facility, comparinga cognitive remediation strategy involving daily
interviews with nursing staff and a memory notebook, to care as
usual. .
Primary outcomes:
Disease specific quality of life:
Immediately post-treatment:-No data
Short term follow-up:-No data
Medium term follow-up:-No data
Long term follow-up:-No data
General quality of life:
Immediately post-treatment:-No data
Short term follow-up:-No data
Medium term follow-up:-No data
Long term follow-up:-No data
Psychiatric symptoms:
Immediately post-treatment:- Mendoza et al. (Mendoza 2001)found mean depression to be 5.5 in the intervention group and
8.6 in the control group (no further information reported).
Short term follow-up:-No data
Medium term follow-up:-No data
Long term follow-up:-No data
Psychological functioning:
Immediately post-treatment:- No data
Short term follow-up:-No data
Medium term follow-up:-No data
Long term follow-up:-No data
Measures of disability:
Immediately post treatment:-No data
Short term follow-up:-No data
Medium term follow-up:-No data
Long term follow-up:-No data
Cognitive outcomes:
Immediately post-treatment:-Mendoza et al. (Mendoza 2001)
measured a number of cognitive outcomes (mental status, adult
reading, and verbal learning).Unfortunatelyno dataare presented.
Short term follow-up:-No data
Medium term follow-up:-No data
Long term follow-up:-No data
Secondary outcomes:
Immediately post-treatment:-No data
Short term follow-up:-No data
Medium term follow-up:-No data
Long term follow-up:-No data
MINI-REVIEW 3: People with MS
(a) Cognitive behavioural therapy
(i) Cognitive behavioural therapy versus minimal psychother-
apy
One study (Foley 1987) of 41 people comparing individual stress
inoculation training (cognitive behavioural therapy and relax-
ation) with care as usual that incorporated two hours of supportivepsychotherapy.
Primary outcomes:
Disease specific quality of life:
Immediately post-treatment:-No data
Short term follow-up:-No data
Medium term follow-up:-No data
Long term follow-up:-No data
General quality of life:Immediately post-treatment:-No data
Short term follow-up:-No data
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Medium term follow-up:-No data
Long term follow-up:-No dataPsychiatric symptoms:Immediately post-treatment:- In the study of Foley et al. (Foley
1987) mean depression was significantly lower in the intervention
group than the control group (post-treatment mean 13.2 (10.5) v
21.6 (14.2) respectively, standardised mean difference unadjusted
for baseline depression = 0.66 (95% CI; -0.02, 1.33), p-value after
taking into account baseline depression < 0.001), as was general
(trait) anxiety (post-treatment means 37.2 (13.8) v 50.5 (13.0)
respectively, standardised mean difference unadjusted for baseline
anxiety = 0.97 (95% CI; 0.27, 1.67), p-value after taking into ac-
count baseline anxiety = 0.015), and perceived distress (post-treat-
ment means 57.5 (37.6) v 89.2 (67.1) respectively, standardised
mean difference not taking into account baseline distress = 0.57(-0.10, 1.24), p-value after taking into account baseline distress =
0.02) . The differencebetween the groupsin current (state) anxiety
was not statistically significant (mean post-treatment scores 46.2
(13.1) in intervention group, 51.9 (13.4) in control group, mean
standardised difference not taking into account baseline anxiety
= 0.42 (95% CI; -0.24, 1.08), p-value after taking into account
baseline anxiety = 0.08).
Short term follow-up:-No data
Medium term follow-up:-No data
Long term follow-up:-No data
Psychological functioning:
Immediately post-treatment:- In the study of Foley et al. (Foley1987) individuals in the intervention group tended to score more
highly on the problem-focussed coping score (mean post-treat-
ment score 16.2 (4.8) than in the intervention group, 11.8 (4.6)
in the control group, mean standardised difference without taking
into account pre-treatment coping score = 0.92 (95% CI; 0.22,
1.61), p-value after taking into account baseline coping = 0.01).
There were no differences in average locus of control (p>0.05, no
other details reported)
Short term follow-up:-No data
Medium term follow-up:-No data
Long term follow-up:-No data
Measures of disability:
Immediately post treatment:-No dataShort term follow-up:-No data
Medium term follow-up:-No data
Long term follow-up:-No data
Cognitive outcomes:Immediately post-treatment:-No data
Short term follow-up:-No data
Medium term follow-up:-No data
Long term follow-up:-No data
Secondary outcomes:
Immediately post-treatment:-No data
Short term follow-up:-No data
Medium term follow-up:-No dataLong term follow-up:-No data
(ii) Cognitive behavioural therapy versus placebo control
One study, Rigby2003; a three group study of 147people compar-
ing group-based coping-focussed cognitive therapy, to a dummy
social discussion group, and a care as usual group (all groups also
received an information booklet).
Primary outcomes:
Disease specific quality of life:Immediately post-treatment:-No data
Short term follow-up:-No data
Medium term follow-up:-No data
Long term follow-up:-No dataGeneral quality of life:Immediately post-treatment:-No data
Short term follow-up:-No data
Medium term follow-up:-No data
Long term follow-up:-No data
Psychiatric symptoms:Immediately post-treatment:- The study by Rigby 2003 found
no statistically significant differences in median anxiety (IQR)
between those receiving CBT and those receiving placebo (5.5
(5.3) v 6.0 (4.0) respectively, p>0.05), andno difference in median
(IQR) depression ( 5.0 (5.3) v 5.0 (5.0) respectively, p>0.05).
A complex statistical analysis summarising all baseline and post-
treatment measurements up to 12 months using area under thecurve suggested that over the complete period of follow-up there
was no significant difference between the two groups in either
anxiety or depression.
Short term follow-up:-The study by Rigby 2003 found no sta-
tistically significant differences in median anxiety (IQR) between
those receiving CBT and those receiving placebo (7.0 (7.0) v 6.0
(5.0) respectively at one month post-treatment, p>0.05; 9.0 (6.5)
v 5.0 (6.0) respectively at three months, p>0.05; 7.0 (7.0) v 6.5
(6.0) respectively at six months, p>0.05), and no difference in me-
dian (IQR) depression (5.0 (6.0) v 4.0 (5.0) respectively at one
month post-treatment, p>0.05; 6.0 (5.5) v 5.0 (5.0) respectively
at three months, p>0.05; 5.0 (5.0) v 5.0 (7.3) respectively at six
months, p>0.05). A complex statistical analysis summarising allbaseline and post-treatment measurements up to 12 months using
area under the curve suggested that over the complete period
of follow-up there was no significant difference between the two
groups in either anxiety or depression.
Medium term follow-up:-The study byRigby 2003 found no sta-
tistically significant differences in median anxiety (IQR) between
those receiving CBT and those receiving placebo (6.0 (7.0) v 5.0
(5.0) respectively, p>0.05), and no difference in median (IQR) de-
pression(6.5 (6.3) v 4.0 (4.5) respectively, p>0.05). A complex sta-
tistical analysis summarising all baseline and post-treatment mea-
surements up to 12 months using area under the curvesuggested
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that over the complete period of follow-upthere was no significant
difference between the two groups in either anxiety or depression.Long term follow-up:-No data
Psychological functioning:Immediately post-treatment:- The study by Rigby 2003 found
no significant differences in self-efficacy between those receiving
CBT and those receiving placebo (median (IQR) for MSSS = 50.0
(14.0) v 50.0 (15.0) respectively, p>0.05; median (IQR) for MSSE
(control subscale) = 530 (253) v 590 (280), p>0.05). A complex
statistical analysis summarising all baseline and post-treatment
measurements up to 12 months using area under the curve sug-
gested that over the complete period of follow-up there was no
significant difference between the two groups in either self-effi-
cacy measure (MSSS and MSSE). She found no difference in to-
tal dispositional resiliency between the CBT and placebo groups,nor in two (Commitment and Control) of the three subscales of
dispositional resiliency (median (IQR) total score = 86.0 (21.3)
v 88.0 (16.3), p>0.05; median (IQR) Commitment score = 31.5
(10.0) v 34.0 (7.0), p>0.05; median (IQR) Control score = 31.0
(9.0) v 32.0 (5.0), p>0.05). The Challenge subscale was signifi-
cantly higher in the group given CBT (median (IQR) = 27.0 (8.0)
v 22.0 (7.3), p0.05;
median (IQR) for MSSE = 590 (240) v 590 (320) respectively at
one month, 510 (223) v 580 (230) at three months, 540 (205) v
580 (228) at six months, all p>0.05). A complex statistical analy-
sis summarising all baseline and post-treatment measurements up
to 12 months using area under the curve suggested that over
the complete period of follow-up there was no significant differ-
ence between the two groups in either self-efficacy measure. Shefound no difference in total dispositional resiliency between the
CBT and placebo groups, nor in the three subscales of disposi-
tional resiliency (median (IQR) total score = 89.0 (19.0) v 88.0
(18.0) respectively at one month,86.0 (20.0) v 91.0 (15.0) at three
months, 89.0 (22.5) v 90.0 (18.0) at six months, all p>0.05; me-
dian (IQR) Commitment score = 32.0 (10.0) v 32.0 (9.0) at one
month, 32.0 (8.0) v 34.0 (9.0) at three months, 32.0 (10.5) v 32.0
(8.0) at sixmonths, allp>0.05; median (IQR) Control score = 32.0
(8.0) v 32.0 (7.0) at one month, 31.0 (7.0) v 33.0 (6.0) at three
months, 31.0 (8.3) v 33.0 (5.0) at six months, all p>0.05; median
(IQR) Challenge score = 26.0 (6.0) v 24.0 (7.0) respectively at
one month, 26.0 (5.0) v 25.0 (7.0) at three months, 26.0 (6.5) v
24.0 (7.0) at six months, all p>0.05). A complex statistical analysissummarising all baseline and post-treatment measurements up to
12 months using area under the curve suggested that over the
complete period of follow-up there was no significant difference
between the two groups in total dispositional resiliency, nor in the
Commitment and Control subscales, but the group given CBT
tended to have better scores on the Challenge subscale.
Medium term follow-up:-The study byRigby 2003 found no sig-
nificant differences in self-efficacy between those receiving CBT
and those receivingplacebo(median(IQR)for MSSS= 47.0 (14.3)
v 56.0 (11.0) respectively, p>0.05; median (IQR) for MSSE = 510
(200) v 640 (255), p>0.05). A complex statistical analysis sum-
marising all baseline and post-treatment measurements up to 12
months using area under the curve suggested that over the com-plete period of follow-up there was no significant difference be-
tween the two groups in either self-efficacy measure. She found no
difference in total dispositional resiliency between the CBT and
placebo groups, nor in any of the three subscales of dispositional
resiliency (median (IQR) total score = 89.0 (20.5) v 90.0 (15.0),
p>0.05; median (IQR) Commitment score = 33.0 (10.0) v 33.0
(8.0), p>0.05; median (IQR) Control score = 32.0 (6.5) v 34.0
(5.0), p>0.05; median (IQR) Challenge subscale = 26.0 (7.5) v
24.0 (5.0), p>0.05). A complex statistical analysis summarising all
baseline and post-treatment measurements up to 12 months using
area under the curve suggested that over the complete period
of follow-up there was no significant difference between the two
groups in total dispositional resiliency, nor in the Commitmentand Control subscales, but the group given CBT tended to have
better scores on the Challenge subscale.
Long term follow-up:-No data
Measures of disability:Immediately post treatment:-No data
Short term follow-up:-No data
Medium term follow-up:-No data
Long term follow-up:-No data
Cognitive outcomes:Immediately post-treatment:-No data
Short term follow-up:-No data
Medium term follow-up:-No data
Long term follow-up:-No dataSecondary outcomes:
Immediately post-treatment:-No data
Short term follow-up:-No data
Medium term follow-up:-No data
Long term follow-up:-No data
(iii) Cognitive behavioural therapy versus no treatment
Two studies; Rigby 2003 (a three group study of 147 people
comparing group-based coping-focussed cognitive therapy, to a
dummy social discussion group, and a care as usual group) and
Wassem 2003 (a two group study of 27 people comparing a pro-
gramme aimed at increasing self-efficacy for adjustment (to MS)
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behaviours, to care as usual).
Primary outcomes:
Disease specific quality of life:
Immediately post-treatment:-No data
Short term follow-up:-No data
Medium term follow-up:-No data
Long term follow-up:-No data
General quality of life:
Immediately post-treatment:-No data
Short term follow-up:-No data
Medium term follow-up:-No data
Long term follow-up:-No dataPsychiatric symptoms:Immediately post-treatment:- The study by Rigby 2003 found
no statistically significant differences in median anxiety (IQR)
between those receivingCBT and those receivinginformation (5.5
(5.3) v 6.0 (5.0) respectively, p>0.05), andno difference in median
(IQR) depression ( 5.0 (5.3) v 3.5 (5.0) respectively, p>0.05).
A complex statistical analysis summarising all baseline and post-
treatment measurements up to 12 months using area under the
curve suggested that over the complete period of follow-up there
were significantly lower levels of anxiety (p0.05; 9.0
(6.5) v 6.0 (4.0) respectively at three months, p>0.05; 7.0 (7.0) v
6.0 (6.3) respectively at six months, p>0.05), and no difference in
median (IQR) depression (5.0 (6.0) v 4.5 (3.5) respectively at one
month post-treatment, p>0.05; 6.0 (5.5) v 6.0 (4.0) respectively
at three months, p>0.05; 5.0 (5.0) v 5.0 (5.3) respectively at six
months, p>0.05). A complex statistical analysis summarising all
baseline and post-treatment measurements up to 12 months using
area under the curve suggested that over the complete period of
follow-up there were significantly lower levels of anxiety (p0.05), and no difference in median (IQR)
depression ( 6.5 (6.3) v 5.0 (4.0) respectively, p>0.05). A com-
plex statistical analysis summarising all baseline and post-treat-
ment measurements up to 12 months using area under the curve
suggested that over the complete period of follow-up there were
significantly lower levels of anxiety (p0.05; median (IQR)
for MSSE = 530 (253) v 520 (260), p>0.05). A complex statisti-
cal analysis summarising all baseline and post-treatment measure-
ments up to 12 months using area under the curve suggested
that over the complete period of follow-up there was a significant
difference in MSSE such that the intervention group had higher
self-efficacy (p0.05). She
found no difference in total dispositional resiliency between the
CBT and information groups, nor in the three subscales of dispo-
sitional resiliency (median (IQR) total score = 86.0 (21.3) v 89.0
(13.5), p>0.05; median (IQR) Commitment score = 31.5 (10.0)
v 33.5 (6.0), p>0.05; median (IQR) Control score = 31.0 (9.0) v30.0 (6.0), p>0.05; median (IQR) Challenge score = 27.0 (8.0)
v 25.0 (7.0), p>0.05). A complex statistical analysis summarising
all baseline and post-treatment measurements up to 12 months
using area under the curve suggested that over the complete pe-
r