ABORDAJE ESCLEROSIS

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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)

Copyright 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
http://www.thecochranelibrary.com/http://www.thecochranelibrary.com/


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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. [email protected].

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.


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).

1Psychological interventions for multiple sclerosis (Review)

mailto:[email protected]:[email protected]


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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




10/58

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




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).




Psychological functioning:Immediately post-treatment:-No data


Medium term follow-up:-No dataLong term follow-up:-No data

Measures of disability:Immediately post treatment:-No data




Cognitive outcomes:Immediately post-treatment:-No data




Secondary outcomes:

Immediately post-treatment:-No dataShort 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:





General quality of life:Immediately post-treatment:-No data





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).



Psychological functioning:Immediately post-treatment:- 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.


Long term follow-up:-No dataSecondary outcomes:





(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).






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).



Psychological functioning:Immediately post-treatment:- No data






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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).



Secondary outcomes:


Short term follow-up:-No dataMedium 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:









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).




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




14/58

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










Secondary outcomes:





(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:









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).




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).




Measures of disability:

Immediately post treatment:-No data







Secondary outcomes:





(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:









Psychiatric symptoms:Immediately post-treatment:- 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,




15/58

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.



Long term follow-up:-No dataMeasures of disability:Immediately post treatment:-No data








Secondary outcomes:




(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:












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).





Immediately post-treatment:- No data





Immediately post treatment:-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.




Secondary outcomes:





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:











16/58


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).





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)





Immediately post treatment:-No dataShort term follow-up:-No data







Secondary outcomes:




(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:




Long term follow-up:-No dataGeneral quality of life:Immediately post-treatment:-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




17/58

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 dataSecondary outcomes:





(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)




18/58

behaviours, to care as usual).

Primary outcomes:










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

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