Ires P.H. Ghielen Student ID: 10000806
The effectiveness of psychological interventions on stress reduction in patients
with Multiple Sclerosis, Parkinson’s disease, and Huntington’s disease:
a meta-analysis.
Master thesis Ires P.H. Ghielen
Abstract
Introduction – Psychological distress has a big impact on quality of life in patients with multiple
sclerosis (MS), Parkinson’s disease (PD), and Huntington’s disease (HD). Cognitive behavioral therapy and mindfulness based therapies have been proven to be effective in reducing psychological stress in patients with anxiety and depressive disorders, and patients with chronic somatic diseases.
Methods – A comprehensive literature search was conducted. Inclusion criteria: randomized
controlled trial (RCT), psychological intervention, psychological outcome, availability of pre- and post-measurements, patients with MS or PD or HD. Effect sizes were calculated and study quality was assessed.
Results – Through database searching and after removal of duplicates, 152 records were identified.
Eventually, 12 RCT’s were included in the analysis. A mean effect size of g = 0.350 (95% CI 0.118 – 0.583) was found with a random effects model. Overall quality of the RCT’s was good.
Conclusion –Psychological interventions have potential benefit for patients with MS and PD in reducing distress. More research with larger sample sizes needs to be conducted in especially HD patients.
Ires P.H. Ghielen Student ID: 10000806 Introduction
Progressive neurological disorders, such as Multiple Sclerosis (MS), Parkinson’s disease (PD) and Huntington’s disease (HD), are often accompanied by psychological distress [1-3]. Psychological symptoms affect the patients’ and their caregivers’ quality of life more than physical symptoms [4,5]. The resemblance between progressive neurological disorders include the progressive nature of the disease, uncertainty on disease course, and incurability (only symptom reduction is possible), which might contribute to the (amount of) psychological distress.
To address psychological distress, a lot of research has investigated potential effective treatments for psychological stress reduction and reduction of anxiety and depressive symptoms. In an extensive review and meta-analysis of Hofmann and colleagues [6], cognitive behavioral therapy (CBT) showed to be an effective treatment for especially anxiety symptoms and general stress in various disorders. In PD patients, CBT also shows positive effects in treating anxiety and depressive symptoms [7-9]. In MS, Dennison and colleagues [10] conclude that CBT is an effective treatment for both managing psychological distress and somatic symptoms associated with the disease. According to Novak and Tabrizi [11], depression and anxiety are usually treated with medication in HD patients, but CBT is also effective in well-selected patients.
Besides CBT, mindfulness-based treatments (MBTs) also have been extensively investigated. Mindfulness involves ‘paying attention in a particular way: on purpose, in the present moment, and nonjudgementally’ [12]. MBTs include mindfulness based stress reduction, mindfulness based cognitive therapy, mindfulness meditation, and acceptance and commitment therapy. MBTs have been proven to be effective in patients with anxiety and depressive disorders [13]. Also, small to moderate effect sizes have been found in populations with different chronic somatic diseases [14] and medium effect sizes were found, overall, in MBTs for MS patients [15]. However, MBTs have been less extensively investigated in PD and HD.
To reduce psychological distress in patients with progressive neurological disorders, CBTs and MBTs might be of potential benefit if it shows to be effective. A meta-analysis was performed on randomized controlled trials that investigated CBTs and MBTs on reducing psychological distress in MS, PD, and HD patients.
Methods
Selection of studies
A comprehensive literature search was conducted in PubMed, PsycInfo, the Cochrane library and EMBASE through June 2016. The following keywords were used: “Parkinson”, “Huntington”,
Ires P.H. Ghielen Student ID: 10000806 “anxiety symptoms”. Two researchers independently selected the studies for inclusion and when they disagreed a consensus was made or the supervising researcher was asked.
Inclusion criteria: MS, PD, or HD patients, availability of an English or Dutch version of the paper/study, a psychological intervention is examined, mental health outcome measures are
available, both pre- and posttreatment measures are available (not necessarily follow-up measures), available data of each study allowed for the calculation of effect sizes. Only randomized controlled trails (RCTs) will be included in this meta-analysis.
A few potential moderators were disease type, intervention type, and total hours of treatment. Depending on the amount of studies extracted, subgroup analyses were conducted.
Data extraction
Outcome measures of mental health were extracted, which include depressive and anxiety symptoms, and general mental health. All decisions on the inclusion of outcome measures were based on consensus between two researchers. When data was not available, the researchers of those studies were contacted. Pre- and post-treatment measurements were collected to examine the immediate effect of the interventions.
Calculation of effect sizes
The individual Hedges’ g effect sizes were calculated and pooled with Comprehensive Meta-analysis (CMA; version 3 for Windows). Anxiety, depressive, and general mental health outcome measures of the individual studies were combined so that one ‘psychological distress’ measure was included in the meta-analysis. As considerable heterogeneity was expected, all analyses were conducted using the random effects model. The calculation of the effect sizes was also performed independently by a second researcher.
Quality assessment
The methodological quality of the included studies was independently assessed by two researchers with five criteria of the risk of bias assessment tool, developed by the Cochrane Collaboration [16] to assess sources of bias in RCTs:
1. Adequate generation of allocation sequence 2. Concealment of allocation to conditions
3. Prevention of knowledge of the allocated intervention to assessors of outcome 4. Prevention of knowledge of the allocated intervention to participants
Ires P.H. Ghielen Student ID: 10000806 Criterion 4 is, due to the nature of psychotherapeutic studies, only partly assessed. When
participants were assessed before randomization this was considered as no risk of bias.
Results
Selected studies
After removing duplicate studies, 152 records were found. After inspection of the abstracts, 20 full-text articles were retrieved and carefully read. Figure 1 presents the flowchart of the inclusion process with reasons for exclusion, following the PRISMA statement [17]. This process resulted in 12 articles that were included in the final meta-analysis [18-29].
Figure 1. PRISMA flow chart of selection and inclusion process. RCT = randomized controlled trial.
Characteristics of included studies
Only post-test data was analyzed, one study provided only follow-up data and could therefore not be included in the analysis.
Ires P.H. Ghielen Student ID: 10000806 Table 1 shows the characteristics of the selected studies. Two independent psychologists rated the components of the interventions to determine whether these truly fit the intervention that the authors state to investigate. Ten studies were assessed to indeed investigate the type of
treatment that they stated, one study could not be assessed since the components were not known [20], and one study investigated a CBT treatment but also incorporated a mindfulness component [19]. Nine studies investigated an intervention in MS patients, of which five were CBT-based. Only three RCTs were selected in PD patients, of which two were CBT-based. No RCTs were found in HD patients. The number of intervention sessions ranged from 5 to 12, the total hours of treatment ranged from 5 ⅓ hours to 12 hours. Six studies investigated a group treatment, the other six studies investigated an individual treatment. Two studies delivered the treatment solely by telephone, two studies delivered by telephone or in person depending on the patients’ preference, and one study was internet-based.
Effects
Main effect sizes
Figure 2 displays the forest plot of the standardized effect sizes of psychological interventions on psychological distress in MS and PD patients. The mean effect size was a g of 0.350 (95% CI 0.118 – 0.583). Four studies reached a statistical significant positive effect size, the other studies probably did not have enough participants to achieve statistical high power.
As there were few studies in each outcome category, no subgroup analyses were conducted.
Ires P.H. Ghielen Student ID: 10000806 -2,0 -1,5 -1,0 -0,5 0,0 0,5 1,0 1,5 2,0 0,0 0,1 0,2 0,3 0,4 0,5 0,6 S ta n d a rd E rr o r Hedges's g
Funnel Plot of Standard Error by Hedges's g
Publication bias
There was no evidence found for publication bias. Inspection of the funnel plot did not indicate significant publication bias (figure 3). The figure does suggest, however, high heterogeneity over all included studies by showing a wide spread of studies, even outside the 95% confidence interval pyramid.
Figure 3. Funnel plot.
Quality
Overall, the quality of the included RCTs was sufficient to good. Eight out of twelve studies had a good quality, represented by meeting at least four of the five criteria considered. Two studies showed sufficient quality, meeting three of the five criteria. Two studies did not reach sufficient quality, one met fewer than three criteria and the other study could not be assessed by its quality due to unavailability of a full-text article.
Figure 4. Risk of bias graph: authors’ judgements about each risk of bias item presented as percentages across all included studies.
Ires P.H. Ghielen Student ID: 10000806 Discussion
In this study, we investigated the effectiveness of psychological interventions on stress reduction in patients with MS, PD, and HD by conducting a meta-analysis of randomized controlled trials. Twelve studies were included in the analysis and resulted in an overall effect size of g = 0.35, which is considered moderate. This outcome seems to be mostly influenced by two large studies that had individual effect sizes of g = 0.350 and g = 0.381, and had small standard error measures [24,25]. These studies investigated a CBT and a self-management treatment, both in MS patients.
The MS population is best presented in this meta-analysis, including nine RCTs. The individual effect sizes varied over the studies and there were too few studies of each treatment type to conduct subgroup analyses. The internet-based study [19] is hard to interpret, since the treatment delivery is different from the other studies and when treatment components are investigated, the intervention incorporates elements of both CBT and mindfulness. The effect size of this study (g = 0.323),
however, is close to the mean effect size. In addition, the total hours of treatment and number of treatment sessions was variable across interventions, also in PD study samples.
Although most studies adapted the intervention for the specific patient population, a large effect size was only found in the study of Okai and colleagues [27]. In this study, 28 PD patients that received CBT were compared with 17 PD patients in the wait-list condition. When the components of the treatment were critically investigated, it was notable that only this intervention included
education about executive dysfunction. This might indicate that executive dysfunction plays an important role in experiencing psychological distress, at least in PD patients. PD patients often show an impairment in executive functioning already early in the disease [30,31]. Another important factor in PD are the physical symptoms, which were addressed in combination with psychological symptoms in the study of Ghielen et al. [29]. The individual effect size g = -0.449 (not significant) is negative, which indicates that the preferred treatment in this sample was the control condition (e.g. physical therapy) in reducing psychological distress. Combining ACT with physical therapy might, in theory, benefit PD patients. However, when focusing on psychological distress, there might not have been put enough time or effort into the ACT part, which might explain the negative effect size. In addition, and maybe most importantly, the focus of this study was on improving self-efficacy and not on symptom reduction.
Overall, the investigated studies had good quality, two out of twelve studies did not reach sufficient quality. The findings can therefore be interpreted with moderate certainty.
Limitations and implications
The first limitation concerns the patient populations. The effect size is solely based on patients with MS and PD, since there were no RCTs found in HD that investigated psychological interventions in
Ires P.H. Ghielen Student ID: 10000806 reducing psychological distress. Second, no subgroup analyses could be conducted on disease type or intervention type since there were not enough studies included. This causes PD and MS patients to be one patient group, which can be considered logical since these diseases have a lot in common. However, PD and MS are separate diseases for a reason, the effects could therefore differ between the two patient groups. One difference involves the probable difference in mean age of these patient groups. More specifically, the mean age of MS patient groups might be lower compared to the PD patient groups. MS patients might therefore have to cope with different everyday problems than PD patients, such as in their work environment and family life.
Despite these limitations, we conclude that psychological interventions have a moderate effect on reducing psychological distress in patients with MS and PD and are therefore promising interventions. However, it is recommended to study psychological interventions in more detail, with a primary focus on improving psychological distress, and in larger patient samples. No subgroup analyses were possible but it would be interesting to investigate separate psychological intervention types and split the different diseases, and eventually compare them. In addition, especially HD is in need of more research, since no psychological treatment RCTs were found to include in the analysis. Lastly, it might be interesting to give attention to executive dysfunction education in interventions for PD patients.
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