Deep Brain Stimulation for Obsessive-Compulsive Disorders
Deep Brain Stimulation for Obsessive-Compulsive Disorders
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. 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. 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, 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.
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).
Clinical Symptoms. At each time, point severity of obsessive–compulsive symptoms was measured with Y-BOCS, 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), with scores ranging from 0 to 54. Anxiety was evaluated with the Hamilton Anxiety Scale (HAM-A), 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. Disability was measured with the Sheehan Disability Scale (SDS). 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). 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.
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).
Methods
Patients
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. 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. 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.
Procedure
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, 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.
Statistical Analysis
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).
Measures
Clinical Symptoms. At each time, point severity of obsessive–compulsive symptoms was measured with Y-BOCS, 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), with scores ranging from 0 to 54. Anxiety was evaluated with the Hamilton Anxiety Scale (HAM-A), 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. Disability was measured with the Sheehan Disability Scale (SDS). 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). 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.
Statistical Analysis
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).
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