Lisa Conboy

Components of placebo effect: randomised controlled trial in patients with irritable bowel syndrome

Objective To investigate whether placebo effects can experimentally be separated into the response to three components—assessment and observation, a therapeutic ritual (placebo treatment), and a supportive patient-practitioner relationship—and then progressively combined to produce incremental clinical improvement in patients with irritable bowel syndrome. To assess the relative magnitude of these components. Design A six week single blind three arm randomised controlled trial. Setting Academic medical centre. Participants 262 adults (76% women), mean (SD) age 39 (14), diagnosed by Rome II criteria for and with a score of ≥150 on the symptom severity scale. Interventions For three weeks either waiting list (observation), placebo acupuncture alone (“limited”), or placebo acupuncture with a patient-practitioner relationship augmented by warmth, attention, and confidence (“augmented”). At three weeks, half of the patients were randomly assigned to continue in their originally assigned group for an additional three weeks. Main outcome measures Global improvement scale (range 1-7), adequate relief of symptoms, symptom severity score, and quality of life. Results At three weeks, scores on the global improvement scale were 3.8 (SD 1.0) v 4.3 (SD 1.4) v 5.0 (SD 1.3) for waiting list versus “limited” versus “augmented,” respectively (P<0.001 for trend). The proportion of patients reporting adequate relief showed a similar pattern: 28% on waiting list, 44% in limited group, and 62% in augmented group (P<0.001 for trend). The same trend in response existed in symptom severity score (30 (63) v 42 (67) v 82 (89), P<0.001) and quality of life (3.6 (8.1) v 4.1 (9.4) v 9.3 (14.0), P<0.001). All pairwise comparisons between augmented and limited patient-practitioner relationship were significant: global improvement scale (P<0.001), adequate relief of symptoms (P<0.001), symptom severity score (P=0.007), quality of life (P=0.01).Results were similar at six week follow-up. Conclusion Factors contributing to the placebo effect can be progressively combined in a manner resembling a graded dose escalation of component parts. Non-specific effects can produce statistically and clinically significant outcomes and the patient-practitioner relationship is the most robust component. Trial registration Clinical Trials NCT00065403.

The placebo effect in irritable bowel syndrome trials: a meta-analysis1

Abstract  Background:  Despite the apparent high placebo response rate in randomized placebo‐controlled trials (RCT) of patients with irritable bowel syndrome (IBS), little is known about the variability and predictors of this response.

Patient and Practitioner Influences on the Placebo Effect in Irritable Bowel Syndrome

Objective: To determine whether placebo responses can be explained by characteristics of the patient, the practitioner, or their interpersonal interaction. Methods: We performed an analysis of videotape and psychometric data from a clinical trial of patients with irritable bowel syndrome who were treated with placebo acupuncture in either a warm empathic interaction (Augmented, n = 96), a neutral interaction (Limited, n = 97), or a waitlist control (Waitlist, n = 96). We examined the relationships between the placebo response and a) patient personality and demographics; b) treating practitioner; and c) the patient-practitioner interaction as captured on videotape and rated by the Psychotherapy Process Q-Set. Results: Patient extraversion, agreeableness, openness to experience, and female gender were associated with placebo response, but these effects held only in the augmented group. Regression analyses controlling for all other independent variables suggest that only extraversion is an independent predictor of placebo response. There were significant differences between practitioners in outcomes; this effect was twice as large as the effect attributable to treatment group assignment. Videotape analysis indicated that the augmented group fostered a treatment relationship similar to a prototype of an ideal healthcare interaction. Conclusions: Personality and gender influenced the placebo response, but only in the warm, empathic, augmented group. This suggests that, to the degree a placebo effect is evoked by the patient-practitioner relationship, personality characteristics of the patient will be associated with the placebo response. In addition, practitioners differed markedly in effectiveness, despite standardized interactions. We propose that the quality of the patient-practitioner interaction accounts for the significant difference between the groups in placebo response. IBS = irritable bowel syndrome; FFI = Five Factor Inventory; PQS = Psychotherapy Process Q-Set; M-PQS = Modified Psychotherapy Process Q-Set.

Catechol-O-Methyltransferase val158met Polymorphism Predicts Placebo Effect in Irritable Bowel Syndrome

Identifying patients who are potential placebo responders has major implications for clinical practice and trial design. Catechol-O-methyltransferase (COMT), an important enzyme in dopamine catabolism plays a key role in processes associated with the placebo effect such as reward, pain, memory and learning. We hypothesized that the COMT functional val158met polymorphism, was a predictor of placebo effects and tested our hypothesis in a subset of 104 patients from a previously reported randomized controlled trial in irritable bowel syndrome (IBS). The three treatment arms from this study were: no-treatment (“waitlist”), placebo treatment alone (“limited”) and, placebo treatment “augmented” with a supportive patient-health care provider interaction. The primary outcome measure was change from baseline in IBS-Symptom Severity Scale (IBS-SSS) after three weeks of treatment. In a regression model, the number of methionine alleles in COMT val158met was linearly related to placebo response as measured by changes in IBS-SSS (p = .035). The strongest placebo response occurred in met/met homozygotes treated in the augmented placebo arm. A smaller met/met associated effect was observed with limited placebo treatment and there was no effect in the waitlist control. These data support our hypothesis that the COMT val158met polymorphism is a potential biomarker of placebo response.

A meta-analysis of the placebo response in complementary and alternative medicine trials of irritable bowel syndrome

Abstract  Among patients with irritable bowel syndrome (IBS) enrolled in clinical trials of conventional medical therapy, the placebo response rate is high. IBS patients also frequently use complementary and alternative medicine (CAM), which may act through an ‘enhanced placebo effect’. The purpose of this study was to estimate the magnitude of the placebo response rate in CAM trials for IBS and to identify factors that influence this response. We performed a systematic review and meta‐analysis of randomized, placebo‐controlled clinical trials of CAM therapies for IBS identified from MEDLINE/EMBASE/PsychLIT databases from 1970 to 2006. Placebo and active treatment response rates for global symptom improvement were assessed. Nineteen studies met the inclusion criteria. The pooled estimate of the placebo response rate was 42.6% (95% confidence interval, 38.0–46.5%). Significant heterogeneity existed across trials (range 15.0–72.2%, P < 0.00001). Higher placebo response rates correlated with a longer duration of treatment (r = 0.455, P = 0.05) and a greater number of office visits (r = 0.633, P = 0.03). Among IBS patients in CAM trials, the placebo response rate is high. That this rate is similar in magnitude to that seen in conventional medicine trials suggests that the placebo response is independent of the type of therapy used and that it is not particularly ‘enhanced’ in CAM trials.

A treatment trial of acupuncture in IBS patients.

OBJECTIVES:This study aimed to compare the effects of true and sham acupuncture in relieving symptoms of irritable bowel syndrome (IBS).METHODS:A total of 230 adult IBS patients (75% females, average age: 38.4 years) were randomly assigned to 3 weeks of true or sham acupuncture (6 treatments) after a 3-week “run-in” with sham acupuncture in an “augmented” or “limited” patient–practitioner interaction. A third arm of the study included a waitlist control group. The primary outcome was the IBS Global Improvement Scale (IBS-GIS) (range: 1–7); secondary outcomes included the IBS Symptom Severity Scale (IBS-SSS), the IBS Adequate Relief (IBS-AR), and the IBS Quality of Life (IBS-QOL).RESULTS:Although there was no statistically significant difference between acupuncture and sham acupuncture on the IBS-GIS (41 vs. 32%, P=0.25), both groups improved significantly compared with the waitlist control group (37 vs. 4%, P=0.001). Similarly, small differences that were not statistically significant favored acupuncture over the other three outcomes: IBS-AR (59 vs. 57%, P=0.83), IBS-SSS (31 vs. 21%, P=0.18), and IBS-QOL (17 vs. 13%, P=0.56). Eliminating responders during the run-in period did not substantively change the results. Side effects were generally mild and only slightly greater in the acupuncture group.CONCLUSIONS:This study did not find evidence to support the superiority of acupuncture compared with sham acupuncture in the treatment of IBS.

Japanese-Style Acupuncture for Endometriosis-Related Pelvic Pain in Adolescents and Young Women: Results of a Randomized Sham-Controlled Trial

STUDY OBJECTIVE To assess feasibility, and collect preliminary data for a subsequent randomized, sham-controlled trial to evaluate Japanese-style acupuncture for reducing chronic pelvic pain and improving health-related quality of life (HRQOL) in adolescents with endometriosis. DESIGN Randomized, sham-controlled trial. SETTINGS Tertiary-referral hospital. PARTICIPANTS Eighteen young women (13-22y) with laparoscopically-diagnosed endometriosis-related chronic pelvic pain. INTERVENTIONS A Japanese style of acupuncture and a sham acupuncture control. Sixteen treatments were administered over 8 weeks. MAIN OUTCOME MEASURES Protocol feasibility, recruitment numbers, pain not associated with menses or intercourse, and multiple HRQOL instruments including Endometriosis Health Profile, Pediatric Quality of Life, Perceived Stress, and Activity Limitation. RESULTS Fourteen participants (out of 18 randomized) completed the study per protocol. Participants in the active acupuncture group (n = 9) experienced an average 4.8 (SD = 2.4) point reduction on a 11 point scale (62%) in pain after 4 weeks, which differed significantly from the control groups (n = 5) average reduction of 1.4 (SD = 2.1) points (P = 0.004). Reduction in pain in the active group persisted through a 6-month assessment; however, after 4 weeks, differences between the active and control group decreased and were not statistically significant. All HRQOL measures indicated greater improvements in the active acupuncture group compared to the control; however, the majority of these trends were not statistically significant. No serious adverse events were reported. CONCLUSION Preliminary estimates indicate that Japanese-style acupuncture may be an effective, safe, and well-tolerated adjunct therapy for endometriosis-related pelvic pain in adolescents. A more definitive trial evaluating Japanese-style acupuncture in this population is both feasible and warranted.

Effects of a yoga-based intervention for young adults on quality of life and perceived stress: The potential mediating roles of mindfulness and self-compassion

The purpose of this pilot study was to investigate the effects of a yoga-based program on quality of life, perceived stress, mindfulness, and self-compassion in young adults. These variables were measured in 33 self-selected participants of a four-month residential yoga intervention before and after the program. Forty-three demographically matched controls completed the same questionnaires at two time points with a four-month interval inbetween. Participation in the program predicted increases in quality of life and decreases in perceived stress, mediated by mindfulness and self-compassion. Multiple mediator models revealed that the effect of group on quality of life was simultaneously mediated by mindfulness and self-compassion, while the effect of group on perceived stress was only mediated by self-compassion. These positive effects on perceived stress and quality of life suggest that yoga-based interventions may be of value in cultivating subjective well-being in young adults. Furthermore, yoga-based and mindfulness-based interventions may share underlying mechanisms.

Women at mid-life: symptoms, attitudes, and choices, an internet based survey

OBJECTIVES This Internet-based survey questioned middle-aged women (age 35-69) regarding their current attitudes, beliefs, symptoms, and treatment choices surrounding the climacteric. METHODS 448 respondents completed the 189 item, WEB-based survey that included measures of quality of life, lifestyle habits, anxiety symptoms, and questions regarding attitude toward and sources of information about menopause. RESULTS Three relationships were hypothesized and supported: frequency of self-reported menopause symptoms would be: (1) negatively associated with healthy behaviors; (2) positively associated with anxiety; (3) positively associated with stress. All measures were self-report. Fatigue, muscle and joint aches, and impatience were the most commonly reported symptoms. No particular symptom was strongly correlated (r > 0.4) to lifestyle behaviors. Questions regarding information exchange reveal that many women are not consulting with their healthcare providers about HRT or frequently discussing alternatives. Many receive health information from lay sources. CONCLUSIONS There is a need for improved information exchange on this subject. Our results are similar to those found using large randomized telephone survey methods, which supports the use of the Internet as a reliable and convenient venue for gathering data regarding health issues. It is important to consider healthy lifestyle behaviors toward the regulation of the climacteric syndrome.

Qualitative Evaluation of a High School Yoga Program: Feasibility and Perceived Benefits

This is the first published qualitative assessment of a yoga program applied in a high school setting. This qualitative interview study was nested in a randomized, controlled trial studying the effects of a yoga program offered in place of a semester of physical education classes at a rural public high school. Student interviews were conducted after taking part in a semester of the yoga program. A formal passive consent with information about the qualitative study was sent home to parents/guardians of all students in the parent study before the interviews. Most students enjoyed the yoga classes and felt benefits. Negative reports of yoga practice were associated with gender as most males sensed peer pressure against practicing yoga. Despite this finding, most students wanted to continue yoga and would continue if it were offered in school. Positive reports include a greater kinesthetic awareness, which some students associated with a greater respect for the body and improved self-image. Among students reporting psychological benefits, many cited stress reduction; many used yoga to manage negative emotions; and some propagated more optimism. Most thought yoga could reduce interest in the use of drugs and alcohol and increase social cohesion with family and peers. We found that a yoga program is feasible in this sample of 9th and 10th graders, especially after benefits are perceived. We also found evidence that yoga may lead to emergent positive benefits in health behaviors not directly prescribed by the program. These results suggest that school-based yoga programs may be appropriate for promoting healthy behaviors at a societal level by focusing on the prevention of negative patterns during the adolescent transition.