Department of Psychology, University of Manchester, UK
Correspondence: Professor Richard Bentall, Department of Psychology,University of Manchester, Oxford Road, Manchester M13 9PL,UK. E-mail: bentall{at}psy.man.ac.uk
Funding detailed in Acknowledgements.
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ABSTRACT |
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Aims To determine 2-year outcomes for the same treated patients and the response to treatment of patients formerly in the control condition.
Method Patients in the treatment groups (n=114) were followed up at 2 years; 32 patients from the control group were offered the intervention after 1 year and were assessed 1 year later. Assessments were the self-rated measures used in the original trial.
Results At 2 years 63 of the treated patients (55%) no longer fulfilled trial criteria for CFS compared with 64 patients (56%) at 1 year. Fourteen of 30 crossover patients (47%) achieved a good outcome at 1 year and seven (23%) no longer fulfilled criteria for CFS.
Conclusions Benefits of the intervention were maintained at 2 years. Delaying treatment is associated with reduced efficacy and required more intensive therapy.
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INTRODUCTION |
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METHOD |
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Treatment interventions in the original study
Patients in the control group received standard medical care comprising a
medical assessment and a short information booklet that encouraged increased
activity and positive thinking without explanation of symptoms. Active
intervention groups received a medical assessment followed by evidence-based
physiological explanations of symptoms that focused on physical deconditioning
and sleep abnormalities. A home-based graded exercise programme was designed
collaboratively with each patient and individualised to suit functional
abilities. Once the patient was engaged in treatment, the role of predisposing
and perpetuating psychosocial factors was discussed. The treatment rationale
was supported by a comprehensive educational information pack which reiterated
the verbal explanations offered.
Three dosages of treatment were compared. Patients in the minimum intervention group received two individual face-to-face sessions and monitored access to a telephone helpline that was reported with the trial; the telephone intervention group received an additional seven planned follow-up telephone calls; and the maximum intervention group received the minimum intervention plus an additional seven face-to-face treatment sessions. These sessions were used to reiterate the treatment rationale, discuss problems associated with graded exercise using motivational interviewing techniques (Miller & Rollnick, 1991) and explore any relevant psychosocial factors. Self-reporting validated outcome measures were sent by post to the participants before randomisation, and 3 months, 6 months and 12 months after the start of treatment.
Further assessments and interventions in this study
For those who completed the treatment, a 2-year assessment of outcome was
conducted using the same self-rated validated questionnaires used in the
original study. Patients in the original control group were offered a similar
educational intervention at the end of the 1-year trial period. This was
delivered by the same therapist (P.P.) who had treated the patients in the
original experimental groups. The former control group patients were not given
a further medical assessment before participating in active treatment, which
was a combination of telephone and face-to-face sessions similar to those
offered to treatment patients in the original trial. The number of sessions
was determined pragmatically on the basis of patient need and was allowed to
exceed those given to the original treatment groups. Patients' 1-year control
outcome assessments were used as their pre-treatment baseline measures. These
measures were reassessed 1 year after the start of treatment.
Assessments
Primary outcomes were measured on the physical functioning sub-scale of the
SF-36 (range 10 to 30, where 10 indicates maximum physical limitation
including self-care, and 30 indicates ability to do vigorous sports) and the
fatigue scale (Chalder et al,
1993; range 0-11, scores over 3 indicate excessive fatigue). The
predetermined criterion of clinically significant improvement was a score of
25 or over or an increase of 10 or more in the baseline score on the physical
functioning sub-scale of the SF-36. This is virtually equivalent to normal
daily functioning for the UK general population
(Garratt et al, 1993).
The intention-to-treat mean score for physical functioning of the educational
intervention patients at 1 year was 24.74. The comparable mean physical
functioning score for the control group, used as a baseline measure before
crossover into active treatment, was 16.94.
Secondary outcome measures administered to both groups at the same time points included the Hospital Anxiety and Depression (HAD) scale (Zigmond & Snaith, 1983; scores above 10 indicate caseness on each of the anxiety and depression sub-scales); a four-item sleep problem questionnaire (Jenkins et al, 1988; range 0-20, where 0 indicates no sleep problems and 20 indicates maximum sleep problems); and a seven-point global impression of change score taken 1 year from trial entry and ranging from very much better to very much worse (Guy, 1976).
Statistical analysis
Analyses of the outcome data from both the 2-year assessment group and the
crossover control group were carried out separately. In each case we used an
intention-to-treat analysis and included all patients who were randomised into
the original trial. Crossover analysis included all who accepted crossover
treatment.
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RESULTS |
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The median number of telephone and face-to-face treatment sessions in the crossover intervention was 16 (minimum 1, maximum 36). The mean duration of treatment was 40.8 weeks (minimum 1 week, maximum 1 year).
Two-year outcome of original intervention patients
Table 1 and
Fig. 1 show the outcome
measures at the original trial baseline assessment and at 1-year and 2-year
follow-up. Repeated-measures analysis of variance (ANOVA) was used to compare
the three treatment groups at each point. For physical functioning scores,
there was no significant difference between the treatment groups
(F2,111=0.47, P=0.63) and the group x
treatment interaction was also non-significant
(F4,222=9.55, P=0.51). However, there was a
highly significant difference between scores at the three time points
(F2,222=248.58, P<0.001). Bonferroni tests
confirmed that there was no significant difference between scores at 1 year
and 2 years, but that scores at both time points were improved compared with
baseline (P<0.001 for each comparison).
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For fatigue scores an identical pattern was observed, with a significant effect for time points (F2,222=227.30, P<0.001) but no significant group effect (F2,111=0.45, P=0.64) or interaction (F4,222=8.34, P=0.36). Again, scores at both follow-up points were improved compared with those at baseline (P<0.001 for each comparison) but there was no significant difference between scores at the two follow-up points.
Table 2 shows the number of patients from the different educational interventions who achieved a clinically significant outcome and/or no longer fulfilled trial criteria for the condition at the 1-year and 2-year follow-up assessments. On the clinical global impression scale, 70 of 90 patients (78%) who completed the educational intervention reported being very much better or much better at 2 years compared with 80 of 95 (84%) at 1 year.
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Outcome of former control patients after 1 year of active treatment
Table 3 and
Fig. 1 show the outcome
measures at the pre-treatment assessment and 1-year follow-up for patients who
crossed over into active treatment. Repeated-measures ANOVA was used to
compare the patients at baseline during the original trial, the pre-treatment
assessment at the end of the control period, and 1 year after the end of
treatment. On the physical functioning scale, a significant effect was found
for time (F2,58=23.65, P<0.001). Bonferroni
tests revealed that this was accounted for by significant differences between
scores after treatment and at both pre-treatment assessments
(P<0.001 for each comparison) but that there was no significant
difference between scores at the original trial baseline and pre-treatment
assessments. A similar pattern was observed in the fatigue scores of these
patients, with a significant effect for time (F2,58=22.76,
P<0.001) accounted for entirely by differences between scores at
the final follow-up point and both pretreatment assessments
(P<0.001 for each comparison). At the end of treatment, almost a
half of the crossover patients (14 out of 30; 47%) achieved a clinically
significant outcome; almost a quarter no longer fulfilled the trial criteria
for chronic fatigue syndrome (7 out of 30; 23%); and more than two-thirds of
those who completed the educational intervention (17 out of 25; 68%) reported
being very much better or much better on the
global assessment of outcome.
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Comparison of outcomes between the original treatment groups and the crossover group
To assess the relative responsiveness to treatment of the control group
compared with the original treatment groups, oneway ANOVAs were calculated for
the primary assessment measures taken from each group 1 year after their
treatment had commenced (which was 1 year after inception in the case of the
originally treated groups and 2 years after inception for the control group).
In the case of physical functioning scores, no difference was observed between
the groups (F3,140=1.49, P=0.22). However, a
significant difference was observed for fatigue scores
(F3,140=3.41, P<0.02) which was accounted for
by better scores in the minimum and maximum original treatment groups
(BonferroniP<0.05 for each comparison) compared with the crossover
patients. There was a significant difference between the number of patients
who no longer met the trial criteria for chronic fatigue syndrome
(2=10.25,P<0.02), but no significant difference
was observed in the proportion of patients achieving a clinically significant
outcome (
2=5.37, P=0.15).
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DISCUSSION |
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Follow-up of control patients after 1 year of active treatment
Patients who had been in the no-treatment control group for 1 year and then
crossed over into active treatment were judged by the therapist to require
more sessions over a longer period. Although this could be seen as evidence
that treatment was harder to implement following a delay, the treatments
delivered in the original treatment arms were constrained in length, and it is
possible that the therapist would have chosen to extend these interventions if
allowed to do so. However, there was evidence that the crossover patients
showed less response on the measure of fatigue than the originally treated
patients and were also less likely to recover as defined by the trial criteria
for chronic fatigue. Although we found no relationship between duration of
illness and outcome in our previous analysis of the 1-year follow-up data
(Bentall et al, 2002),
others have found an association between these variables
(Clark et al, 1995;
Vercoulen et al,
1996). Therefore, the possible relative unresponsiveness of the
crossover patients might be due to the duration of illness, or the
psychological effects of being placed in a waiting group.
Consistency with previous findings
Our findings support the long-term efficacy of treatments for chronic
fatigue syndrome that incorporate graded exercise, including
cognitive-behavioural therapy (Bonner
et al, 1994; Deale
et al, 2001). The effectiveness of such treatments may
reflect the way in which they directly address physiological factors that can
perpetuate the condition. Although there is no evidence of consistent
pathological changes in chronic fatigue syndrome, there is evidence of a
disturbance in bodily functioning involving cardiovascular and muscular
deconditioning (Edwards et al,
1994; De Lorenzo et
al, 1998). There is also evidence of sleep abnormalities
(Morriss et al,
1997), mild cortisol deficiency
(Demitrack et al,
1991) and desynchronisation of circadian rhythms
(Williams et al,
1996) in patients with the syndrome. In the absence of an
appropriate explanation, the subsequent symptoms can be misinterpreted as
signs of an underlying pathological condition leading to reduced activity and
chaotic sleep patterns, which perpetuate the syndrome. Our finding that the
provision of physiological explanations for symptoms is associated with
improved patient outcome is consistent with previous research. Patients have a
basic physical conception of the body and its functions
(Mabeck & Olesen, 1997); consequently, physical explanations for the causal mechanism of symptoms can
lead to reattribution and are empowering in the self-management of illness
(Salmon et al, 1999).
Indeed, the vast majority of patients who completed treatment in the original
trial (Powell et al,
2001) reported that the physical explanations convinced them to
carry out graded exercise and regulate chaotic sleep patterns; furthermore,
they reported that they would recommend an educational intervention to other
people with chronic fatigue syndrome.
Limitations of this study
This study has several limitations. Patients who withdrew from treatment in
the original trial were not followed up and, although in the analysis their
last values were carried forward, it would have been better if we had been
able to obtain patients' actual outcome scores. There was no control
comparison for 2-year followup of the treated patients. However, in view of
the reduced efficacy of treatment when delivered after a 1-year wait, it would
have been neither desirable nor ethically possible to justify a 2-year control
period without treatment. Patient outcome was assessed by self-report
measures, and it would have been helpful in addition to use objective measures
of physiological exercise. Although the comparison of the crossover patient
group with the original treatment group involved confounded time points, it is
unlikely that this could explain the findings. No economic analysis was
performed.
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Clinical Implications and Limitations |
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LIMITATIONS
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ACKNOWLEDGMENTS |
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REFERENCES |
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Bonner, D., Ron, M., Chalder, T., et al (1994) Chronic fatigue syndrome: a follow up study. Journal of Neurology, Neurosurgery and Psychiatry, 57, 617 -621.[Abstract]
Chalder, T., Berelowitz, G., Pawlikowska, T., et al (1993) Development of a fatigue scale. Journal of Psychosomatic Research, 37, 147 -153.[CrossRef][Medline]
Clark, M., Katon,W., Russo, J., et al (1995) Chronic fatigue: risk factors for symptom persistence in a two and a half year follow-up study. American Journal of Medicine, 98, 187 -195.[CrossRef][Medline]
Deale, A., Chalder, T., Marks, I., et al
(2001) Longterm outcome of cognitive behavior therapy versus
relaxation therapy for chronic fatigue syndrome: a 5-year follow-up study.
American Journal of Psychiatry,
158, 2038
-2042.
De Lorenzo, F., Xiao, H., Mukherjee, M., et al (1998) Chronic fatigue syndrome: physical and cardiovascular deconditioning. Quarterly Journal of Medicine, 91, 475 -481.[Abstract]
Demitrack, M., Dale, J., Straus, S., et al (1991) Evidence for impaired activation of the hypothalamicpituitaryadrenal axis in patients with chronic fatigue syndrome. Journal of Clinical Endocrinology and Metabolism, 73, 1224 -1234.[Abstract]
Edwards, R., Clague, J., Gibson, H., et al (1994) Muscle metabolism, histopathology, and physiology in chronic fatigue syndrome. In Chronic Fatigue Syndrome (ed. S. Straus), pp. 241-261. New York: Marcel Dekker.
Garratt, A., Ruta, D., Abdalla, M., et al (1993) The SF36 health survey questionnaire: an outcome measure suitable for use within the NHS?BMJ, 306, 1440 -1444.[Medline]
Guy,W. (1976) Clinical Global Impressions. In ECDEU Assessment Manual for Psychopharmacology, pp. 218 -222. Rockville, MD: National Institute of Mental Health.
Jenkins, D., Stanton, B., Niemcryk, S., et al (1988) A scale for the estimation of sleep problems in clinical research. Journal of Clinical Epidemiology, 41, 313 -321.[Medline]
Mabeck, C. & Olesen, F. (1997) Metaphorically transmitted diseases. How do patients embody medical explanations? Family Practitioner, 14, 271 -278.[CrossRef]
Miller,W. & Rollnick, S. (1991) Motivational Interviewing. New York: Guilford Press.
Morriss, R.,Wearden, A. & Battersby, L. (1997) The relation of sleep difficulties to fatigue, mood and disability in chronic fatigue syndrome. Journal of Psychosomatic Research, 42, 597 -605.[CrossRef][Medline]
Powell, P., Bentall, R., Nye, F., et al
(2001) Randomised controlled trial of patient education to
encourage graded exercise in chronic fatigue syndrome.
BMJ, 322, 387
-390.
Salmon, P., Peters, S. & Stanley, I. (1999)
Patients' perceptions of medical explanations for somatisation disorders:
qualitative analysis. BMJ,
318, 372
-376.
Sharpe, M., Archard, L., Banarvala, J., et al (1991) A report chronic fatigue syndrome: guidelines for research. Journal of the Royal Society of Medicine, 84, 118 -121.[Medline]
Vercoulen, J., Swanink, C., Fennis, J., et al (1996) Prognosis in chronic fatigue syndrome: a prospective study on the natural course. Journal of Neurology, Neurosurgery and Psychiatry, 60, 489 -494.[Abstract]
Ware, J. & Sherbourne, C. (1992) The MOS 36-item short form health survey (SF36). Medical Care, 30, 473 -483.[Medline]
Whiting, P., Bagnall, A., Sowden, A., et al
(2001) Interventions for the treatment and management of
chronic fatigue syndrome: a systematic review. JAMA,
286, 1360
-1388.
Williams, G., Piromohamed, J., Minors, D., et al (1996) Dissociation of body-temperature and melatonin secretion circadian rhythms in patients with chronic fatigue syndrome. Clinical Physiology, 16, 327 -337.[Medline]
Zigmond, A. & Snaith, R. (1983) The Hospital Anxiety and Depression Scale. Acta Psychiatrica Scandinavica, 67, 361 -370.[Medline]
Received for publication February 27, 2003. Revision received June 25, 2003. Accepted for publication July 30, 2003.
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