Objective To evaluate the long-term effects of deep brain stimulation (DBS) on quality of life (QOL) in therapy-refractory obsessive–compulsive disorder (OCD) patients.
Design 16 patients who met Diagnostic and Statistical Manual of Mental Disorders (4th ed) (DSM-IV) criteria for OCD and were considered therapy-refractory were treated with DBS. Patients were assessed 1 month before device implantation (T0), at 8 months of active stimulation (T1) and at 3–5 years of active stimulation (T2). QOL was measured with the WHO Quality of Life Scale-Brief Version (WHOQOL-BREF) that covers physical, psychological, social and environmental domains. The study was conducted between April 2005 and January 2011 at the Academic Medical Center, Amsterdam, The Netherlands.
Results At T1 and T2, we found significant improvement (p<0.05) in the general score and in the physical, psychological and environmental domains of WHOQOL-BREF. Between T1 and T2, the physical and psychological domains improved further (p<0.05). At T2, the general score improved by a total of 90%, the physical and psychological domains both improved by 39.5% and the environmental domain improved by 16%. The social domain did not change between baseline and follow-up assessments.
Conclusions In line with symptom improvement, patient's QOL improved in the general score and in three of the four WHOQOL-BREF domains. This suggests that the improvement caused by DBS is not limited to symptom reduction alone, but also has a positive influence on patients’ perception of their physical, psychological, environmental and global QOL.
- Quality Of Life
Statistics from Altmetric.com
Obsessive–compulsive disorder (OCD) is characterised by obsessions (persistent thoughts) and compulsions (repetitive ritualistic behaviour). The prevalence of OCD in the general population is estimated between 1% and 3%.1 From previous research, we know that quality of life (QOL) in OCD patients is seriously impaired compared with general population.2–4 Treatment options for OCD include cognitive behavioural therapy (CBT) and/or pharmacotherapy. Even when the best treatment options are used, approximately 10% of these patients remain severely affected and are considered therapy-refractory,5 resulting in marked suffering and impairment in self-care, work and social life.6 For these patients, deep brain stimulation (DBS), a neurosurgical treatment that involves stereotactic implantation of electrodes in specific deep-seated brain regions, has emerged as a new treatment option. Recent studies have shown promising results of DBS in OCD,7–9 indicating an overall response rate (Yale–Brown Obsessive Compulsive Scale (Y-BOCS) score decrease >35%) of ±50%, and a limited number of adverse events.10
Treatment success, however, is not restricted to symptom reduction alone. Patient's perception of treatment outcome, conceptualised as QOL, is becoming an important variable in the evaluation of treatment success.11 Especially in chronic treatments like DBS, it is important to know whether the benefits of symptom reduction outweigh the possible discomfort caused by the surgery, the device or the stimulation.7 Furthermore, information about how patients’ experience their QOL after surgery may help improve follow-up care.
To date, only two studies reported on the impact of DBS on QOL in OCD. Huff et al12 reported improvement in the general score of the Modular System for QOL in nine patients after 1 year of unilateral stimulation of the nucleus accumbens (NAc). Goodman et al13 assessed health-related QOL and found improvement in the vitality subscale of the Medical Outcomes Study Short Form Health Survey (SF-36) in six patients during a period of 12 months of bilateral stimulation of the ventral capsule/ventral striatum. In these studies, QOL is examined in a small sample population and only touched upon very briefly as a secondary measure spanning over only the first year of treatment. To date, it remains unclear how a longer period of stimulation affects patient's QOL. The present study describes the short-term and long-term QOL outcomes of 16 OCD patients who have been treated with bilateral DBS targeted at the NAc. Changes in clinical symptoms of these patients have been extensively described earlier.7 The primary objective of this study was to determine to what extent DBS affects QOL over a period of at least 3 years. We investigated also whether symptom improvement correlates with improvement in QOL.
Between April 2005 and January 2008, we included 16 patients with severe therapy-refractory OCD. For details on inclusion and exclusion criteria, surgical procedure and postoperative management, see Denys et al.7 In brief, patients had to be diagnosed as having primary OCD according to Diagnostic and Statistical Manual of Mental Disorders (4th ed) (DSM-IV) criteria and score at least 28 points in Y-BOCS. The length of illness had to be at least 5 years. Patients had to be considered refractory to at least two treatments with a selective serotonin reuptake inhibitor, plus a treatment with clomipramine hydrochloride, plus one augmentation trial with atypical antipsychotics, plus one CBT trial for a minimum of 16 sessions. Bilateral implantation of DBS electrodes targeted at the NAc was performed according to standard stereotactic procedures.7 When an initial decrease in symptoms (on an average six points in Y-BOCS) was established with DBS, usually after 8 weeks of stimulation, a standardised CBT programme of 60 min a week for 24 weeks was added. Ten patients used psychotropic medication before surgery. All of these patients were tapered off their medication prior to surgery for safety reasons. After surgery, medication was restarted. When we observed a favourable and stable response to DBS treatment, medication was tapered off. This was the case in three patients at the first follow-up measurement (8 months after surgery) and in five patients at the second follow-up measurement (3–5 years after surgery). All patients consented to participate in the study and signed an informed consent form. The study was approved by the medical ethical committee of the Academic Medical Center, Amsterdam.
Psychologists who received training on a regular basis to ensure inter-rater reliability administered all scales to patients at three time points: 1 month before electrode implantation (T0), after the end of CBT programme ca. 8 months after DBS surgery (T1) and between November 2010 and January 2011 (T2). T2 was after 3–5 years of active stimulation depending on the date of patient's electrode implantation. In the original study of Denys et al,7 patients entered after T1 double-blinded, sham-controlled phase, where stimulation was switched on–off blinded. This phase has not influenced the outcome of T2 because T2 was assessed 2 years later.
At each time, point severity of obsessive–compulsive symptoms was measured with Y-BOCS,14 ,15 a 10-item scale with scores ranging from 0 to 40. Depressive symptoms were rated with the 17-item Hamilton Depression Rating Scale (HAM-D),16 ,17 with scores ranging from 0 to 54. Anxiety was evaluated with the Hamilton Anxiety Scale (HAM-A),18 ,19 a 14-item scale with a range of 0–56. All three scales are widely used and have well-established psychometrics. On all three measures, higher scores indicate more severe symptoms.
Disability was measured with the Sheehan Disability Scale (SDS).20 ,21 SDS consists of three self-rated 10-point Likert response subscales measuring disability in work/school activities, social functioning and family relationships. Scores range from 0: no impairment to 10: severe impairment.
Quality of life
QOL was measured with the Dutch version of WHO Quality of Life Scale-Brief Version (WHOQOL-BREF).22 This translated abbreviated version of WHOQOL-100 QOL assessment is a self-administered questionnaire measuring individual's perceptions of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards and concerns. WHOQOL-BREF comprises 26 items and are all rated on a 1–5 point Likert scale. For example, how much do you enjoy your life? 1=not at all, 5=an extreme amount. The rated items are summarised into five scores: one general score and four domain scores. The general score consists of two items focusing on global level of QOL and satisfaction with health. The four domains are physical (seven items on pain, medical assistance, energy, mobility, sleep, ability to perform daily activities and work capacity), psychological (six items focusing on negative/positive feelings, body images and appearance, concentration, self-esteem and meaningfulness of life), social (three items on satisfaction with social support, sexual life and personal relationships) and environmental (eight items on financial recourses, safety, physical environment, home environment, opportunities for recreation, availability of information, access to health services and transport). The score for general QOL ranges from 2 to 10. The transformed score of the four domains ranges from 4 to 20. Higher scores indicate a higher perceived QOL. WHOQOL-BREF is validated in Dutch language and displays a good content and construct validity and test–retest reliability in a psychiatric population.23
Y-BOCS, HAM-A, HAM-D, SDS and WHOQOL-BREF scores were analysed using a repeated measures analysis of variance with the three time points as within-subject factors. Paired samples t tests were used to compare scores at different time points. Variables were tested with Shapiro–Wilk test for normality and proved to be normally distributed. Correlation between QOL outcome and clinical and demographic characteristics was performed with Spearman’s rho to increase robustness of our results, given the presence of outliers in a relatively small data set. Data are presented as mean (SD) at a two-tailed 5% level of significance. All p values are nominal (not adjusted for multiple comparisons) to preserve statistical power. All statistical analyses were conducted using commercially available statistical software (SPSS, V.18.0; SPSS Inc, Chicago, Illinois, USA).
Nine women and seven men were included, with a mean age of 42±11.56 years. Their duration of illness was 29±12.52 years with a mean age of onset of 14±7.36 years. The mean duration of post-surgery follow-up from DBS implantation to last follow-up visit was 4 years and 3 months (SD 9.3 months). For an individual overview of the clinical and demographic characteristics of our patients, we refer to our original article.7 Fifteen patients completed all the assessments at T0; one patient was excluded because of incomplete data. At T1, two patients were excluded; one patient because of incomplete data and one patient did not want to cooperate because of disappointment in the effect of treatment. This patient also did not want to cooperate at T2. In total, three patients were excluded from QOL analysis.
Clinical symptoms and disability
Repeated measures analysis revealed significant improvement over time in Y-BOCS, HAM-A, HAM-D and SDS. These scores are shown in table 1. As reported in our original article,7 we found significant improvement (p<0.05) between T0 and T1 in Y-BOCS, HAM-D, HAM-A and SDS. Between T1 and T2, no significant differences were found in the clinical symptom scales or SDS (not shown). In terms of response rate (Y-BOCS decrease >35%) at T1, 9 of 16 patients were classified as responders. At T2, 11 of 16 patients were classified as responders.
Quality of life
Baseline WHOQOL-BREF scores of OCD patients were significantly lower (p<0.01) in all WHOQOL-BREF domains compared with a Dutch normative population with comparable age and sex characteristics24 (figure 1). The greatest differences were found in the physical domain (mean difference: 5.5 points) and the psychological domain (mean difference: 5.5 points). The mean differences between baseline scores of DBS group and healthy population for the social domain and environmental domain were 3.9 and 3.2 points.
Repeated measures analysis revealed significant improvement over time in the general WHOQOL-BREF score (F 13.229 DF 2, p<0.001) and in the physical (F 9.67, DF 2, p=0.001), psychological (F 16.936, DF 2, p<0.001) and environmental (F 6.751 DF 2, p=0.005) domains. The social domain failed to show a statistically significant effect of time across the three time points (F 1.883 DF 2, p=0.173) (figure 2).
Paired samples t tests revealed the following effects (table 2). Between T0 and T1, we found significant improvement in the general score and in the physical, psychological and environmental domains of WHOQOL-BREF (p<0.05).
This resulted in improvement at T1 of 74% in the general score, 23% in the physical domain, 27% in the psychological domain and 8% in the environmental domain.
This improvement continued for the physical domain and psychological domain between T1 and T2 (p<0.05). Between T0 and T2, we found significant improvement in the general score and in all domains except the social domain (p<0.05). At T2, the general score of WHOQOL-BREF showed a total improvement of 90%. The physical and psychological domains both improved by 39.5% and the environmental domain by 16%. The social domain failed to show a statistically significant effect between T0 and follow-up assessments. Compared with a Dutch normative population, the scores at T2 are still lower (p<0.01) in all the domains (figure 1).
Comparing the mean differences in QOL scores between T0 and T1 and T0 and T2 separately for responders and non-responders, we find the following changes (table 2). The mean difference score of responders increased in all domains except in the social domain between T0 and T1. The mean difference score of non-responders increased as well in all domains except in the environmental domain between T0 and T2.
Relations between clinical changes, demographic variables and changes in QOL
Comparing change scores between T0 and T1 (n=13), a decrease in Y-BOCS correlated with improvement in the physical (rs=−0.576, p<0.05) and environmental (rs=−0.676, ρ<0.05) domains. This correlation was also found for improvements in HAM-D and the physical (rs=−0.626, ρ<0.05) and environmental (rs=−0.600, p<0.05) domains. The HAM-A decrease correlated with the physical (rs=−0.697, p<0.01) and environmental (rs=−0.592, p<0.05) domains and with the general WHOQOL-BREF score (rs = −0.643, p<0.05).
Comparing change scores between T0 and T2 (n=13), changes in Y-BOCS did not showe a significant relation with any of the changes in WHOQOL-BREF variables. Decreases in HAM-A correlated with improvement in the physical (rs=−0.591, p<0.05) and psychological (rs=−0.613, ρ<0.05) domains. These domains also correlated with improvement in HAM-D: physical (rs=−0.672, p<0.05) and psychological (rs =−0.590, p<0.05).
Correlation analyses between demographic variables (such as age, sex, age of onset and duration of illness) at T0 on the one hand and WHOQOL-BREF outcome at T2 (n=13) on the other hand showed a significant relationship between improvement in the social domain and gender (rs = −0.752, p=0.003), suggesting that women improved more than men in the social domain. Also in this domain, a significant relationship with duration of illness (rs = −0.587, p=0.035) was found, suggesting that patients who had a longer duration of illness tended to improve less in the social domain. In the psychological domain, we found a correlation with the age of onset (rs = 0.596, p=0.032), which may indicate that a later age of onset indicates a better improvement in the psychological QOL. None of the other demographic variables showed significant correlations.
This is the first study that describes long-term effects of DBS on QOL in OCD patients. The primary finding of our study is that QOL of therapy-refractory OCD patients who have been treated with bilateral DBS targeted at the NAc show a mean improvement of 90% in the general score, 39.5% in the physical and psychological domains and 16% in the environmental domain of WHOQOL-BREF after at least 3 years of active stimulation. Comparing these results with previous studies is difficult, because QOL was measured with different scales. However, the finding that all studies2 showed improvement in some aspects of QOL and none found a decrease suggests that despite the invasive character of the treatment, the benefits of the treatment cause an increase in QOL.
The finding that baseline QOL in our DBS group was lower in all QOL domains compared with a Dutch norm population stresses the interference of refractory OCD on patient's QOL. Three other studies used WHOQOL-BREF to compare OCD patients with healthy controls. Stengler-Wenzke et al4 found indications that OCD patients scored lower in all WHOQOL-BREF domains except for the environmental domain. Kivircik Akdede et al3 examined OCD patients without comorbid depression and found lower psychological and social QOL compared with a healthy control group. Hou et al2 compared OCD patients with healthy controls; they found lower QOL in the general score and in all WHOQOL-BREF domains except the environmental domain. Our finding that DBS patients scored significantly lower in all domains, including the environmental domain, might be associated with the refractory state and comorbid depression that often occurs in these patients. We assume that especially in refractory patients the severity and persistence of OCD symptoms have affected almost all aspects of patient's life, including those associated with environmental QOL like financial resources, opportunities for leisure activities, feelings of safety and security.
After 8 months of stimulation, we found marked improvement in the general score and in the physical, psychological and environmental domains. Between 8 months and 3–5 years, the physical and psychological domains improved even further. This improvement was not seen in the symptom scales or in SDS. This suggests that although psychiatric symptoms and the level of disability experienced by these patients remain stable, patient's QOL improve. One could say that it takes time before patients fully experience the benefits from this treatment, even after initial symptom decrease has taken place. We hypothesise that patients need time to adapt to and benefit of their new situation due to long duration of illness (on an average 29 years) and widespread avoidance behaviour that accompanies this.
After 3–5 years, three out of four domains of QOL increased. Compared with healthy individuals, mean scores are still lower, but tend to reach the normal range, which indicates that DBS patients might regain a normal standard of QOL. In all probability, the addition of CBT to DBS may have contributed to the benefits on QOL we found. Unfortunately, due to the nature of our design we cannot determine whether these changes were caused by DBS, CBT or the combination of both. Future research has to examine the role of addition of CBT in DBS separately and its influence on QOL. Along similar lines, medication changes during the study might have influenced QOL. However, tapering off medication only occurred in patients who experienced long-lasting and stable responses on DBS treatment. Therefore, it is unlikely that medication changes have had any effect on these results.
Because the chance of a type II error was considered more serious than the chance of a type I error,25 results were not adjusted for multiple comparisons; however, when applying Bonferroni–Holm correction for multiple comparisons, all findings remained significant except for the physical domain and the environmental domain between baseline and short term. This indicates the robustness of the improvement in QOL in the long term.
Comparing the scores over time for responders and non-responders separately, surprisingly both responders and non-responders showed improvement in QOL. This finding demonstrates that non-responders also benefit from the treatment and questions the relevance of Y-BOCS changes as primary outcome measure. It is not unlikely that DBS directly affects general measures of well-being. These results, however, were found in very small groups; further research towards QOL in non-responders has to examine this further.
The social domain was the only QOL domain that did not change over a longer period of stimulation. This finding is incongruent with other studies using WHOQOL-BREF where an improvement in social functioning was found following successful treatment.26 ,27 Interestingly, disability in social functioning, measured with SDS, improved from severe–extreme disability at baseline to moderate disability after NAc DBS treatment. These findings suggest that although patients experience less disability in social functioning following DBS, this is not translated into a higher level of satisfaction with their social relationships. On the other hand, it could be that due to our relatively small sample size, changes in social QOL could not be found. We indeed found a trend towards improvement, but it failed to reach significance. Future studies with larger samples and greater power will have to examine whether the social domain improves and whether these changes are meaningful.
Relation between symptom improvement, demographic variables and QOL improvement
Correlating clinical symptom improvement with QOL improvement after 8 months of stimulation, we found that decrease in psychiatric symptoms is associated with higher QOL in the physical and environmental domains. Improvement in the general score showed a unique relation with anxiety reduction, suggesting anxiety reduction plays an important role in patient's general QOL. Interestingly, the psychological domain, although increased, showed no relation with symptom improvement. This may indicate the influence of other variables, for example, the direct freestanding influence of stimulation on QOL. Our group has recently demonstrated that stimulation normalises NAc function and its connected frontostriatal network.28 These changes entail healthy reward processing and motivation and may thus explain improved QOL as well. Alternatively, but highly hypothetical, improved QOL, anxiety and depression scores may be explained by stimulation of the medial forebrain bundle (MFB), as the most effective stimulation area was located at the border of the NAc core and anterior limb of the internal capsule, which connects with MFB. Future research should examine the neuroanatomical underpinnings of DBS-related QOL improvement.
After 3–5 years, we found improvement in the physical and psychological domains to be related to lesser anxiety and depressive symptoms, but not to lesser OCD symptoms. These findings emphasise the importance of anxiety and depressive symptom reduction next to OCD symptom reduction. Furthermore, these relations could also indicate the antidepressant role of NAc DBS, as the NAc is also a target for therapy-resistant depressive disorders.29 The finding that the general score and the environmental domain showed no significant relation at T2 but did at T1 suggests that the relation found at T1 wears off, possibly due to the influence of other variables thus far not measured.
The findings that women and patient with shorter illness duration are more likely to improve in the social domain and that patients with an earlier age of onset are less likely to improve in psychological QOL should be further examined.
The main limitation of this study is that there was no control group. We therefore do not know whether there are fluctuations in QOL during the follow-up period that are normal in this population. Second, although our sample population is one of the biggest groups that has been described thus far, it consists of a relatively small number of patients, so generalisation to a larger population is hard to make. Third, because of the subjective nature of QOL, it could be that our results are influenced by a temporary state or subject bias, which may lead to an overestimation or underestimation of the influence of DBS on QOL. Research with more patients at more different time points has to be done to minimise the state-dependent effects. The fourth limitation of our study is that two of the three patients who were excluded from our QOL analyses because of missing data were considered as non-responders. This exclusion must have had a positive influence on the mean QOL results.
We conclude that bilateral DBS targeted at the NAc for OCD has a positive effect on patient's perceived QOL. This improvement seems to carry on between short-term and long-term stimulations. This finding is an important step in the implementation of DBS in general practice; furthermore, it stresses the importance of QOL as an outcome measure in DBS treatment studies.
Contributors PO, MM and DD designed the research. PO, MM and MF acquired the data. PO, MM, PM, RS and DD analysed and interpreted the data. All authors were involved in the writing of the paper.
Funding This study was supported by an unrestricted investigator-initiated research grant by Medtronic Inc (Denys and Schuurman), which provided the devices used herein, and by grant 916.66.095 from the Netherlands Organisation for Scientific Research ZON-MW VENI programme (Denys). The funders of this study had no role in the design or conduct of the study; in the collection, management, analysis or interpretation of the data; or in the preparation, review or approval of the manuscript.
Competing interests None.
Ethics approval Medical ethical committee of the Academic Medical Center (AMC), Amsterdam.
Provenance and peer review Not commissioned; externally peer reviewed.
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.