Although awareness of side effects over the course of psychotherapy is growing, side effects are still not always reported. The purpose of the present study was to examine side effects in a ...randomized controlled trial comparing Metacognitive Training for Depression (D-MCT) and a cognitive remediation training in patients with depression. 84 patients were randomized to receive either D-MCT or cognitive remediation training (MyBrainTraining) for 8 weeks. Side effects were assessed after the completion of each intervention (post) using the Short Inventory of the Assessment of Negative Effects (SIAN) and again 6 months later (follow-up) using the Negative Effects Questionnaire (NEQ). D-MCT and MyBrainTraining did not differ significantly in the number of side effects. At post assessment, 50% of the D-MCT group and 59% of the MyBrainTraining group reported at least one side effect in the SIAN. The most frequently reported side effect was disappointment in subjective benefit of study treatment. At follow-up, 52% reported at least one side effect related to MyBrainTraining, while 34% reported at least one side effect related to the D-MCT in the NEQ. The most frequently reported side effects fell into the categories of "symptoms" and "quality". Our NEQ version was missing one item due to a technical error. Also, allegiance effects should be considered. The sample size resulted in low statistical power. The relatively tolerable number of side effects suggests D-MCT and MyBrainTraining are safe and well-received treatment options for people with depression. Future studies should also measure negative effects to corroborate our results.
Informing patients about potential adverse events as part of the informed consent may facilitate the development of nocebo-driven drug adverse events (nocebo side effects).
To investigate whether ...informing about the nocebo effect using a short information sheet can reduce nocebo side effects.
A total of
= 44 participants with weekly headaches for at least 6 months were recruited using the cover story of a clinical trial for a headache medicine. In reality, all participants took a placebo pill and were randomized to the nocebo information group or the standard leaflet group. Participants were instructed to read the bogus medication leaflet entailing side effects information shortly before pill intake. The nocebo group additionally received an explanation about the nocebo effect as part of the leaflet. Questionnaires were completed at baseline, 2 min, and 4 days after the pill intake. We conducted general linear models with bootstrap sampling. Baseline symptoms were included as a covariate.
Most participants (70.5%) reported nocebo side effects at 2 min. Participants who received the nocebo information (
= 24) reported less nocebo symptoms than the control group (
= 20) (estimated difference: 3.3, BCa 95% CI 1.14; 5.15,
= 0.01, Cohen's
= 0.59). Baseline symptoms, perceived sensitivity to medicine, and side effect expectations each moderated the group effect (estimated difference in slope: 0.47, BCa 95% CI 0.19; 0.73,
= 0.001,
= 0.75; 1.07 0.27; 1.61,
= 0.006,
= 0.73; 1.57 0.38; 2.76,
= 0.02,
= 0.58). No group differences were found at 4-day follow-up. After revealing the actual aim of the study, 86% of the participants evaluated the nocebo information to be helpful in general.
Results provide the first evidence that informing about the nocebo effect can reduce nocebo side effects.
This comprehensive review provides an overview about placebo and nocebo phenomena in antidepressant trials. Improvements in the placebo groups may partly be explained through methodological issues ...such as natural course of depression and regression to the mean, but also fundamentally reflect investigators' and participants' expectations. A meta-analysis by our group of 96 randomized placebo-controlled trials showed large placebo responses to antidepressant medication. Moderator analyses revealed substantially larger placebo responses in observer ratings compared with self-report. Effect sizes in observer ratings showed strong increase with publication year while this effect was not found for patients' self-ratings. This reflects the strong influence of investigators' expectations. The analysis of ‘nocebo effects’, e.g. adverse effects in placebo groups of antidepressant trials also confirms the impact of expectations: nocebo symptoms reflected the typical side-effect patterns expected in the drug group, with higher symptoms rates in the placebo groups of tricyclic antidepressant trials compared with placebo groups of trials testing selective serotonin reuptake inhibitors. While the placebo response seems to be similar for women and men, gender differences were found for nocebo rates. In the conclusion, we discuss potential implications for clinical trial designs and argue for interventions aimed at optimizing positive expectations of treatment benefit while minimizing the impact of adverse effects.
The quality of decision-making in multidisciplinary team meetings (MDTMs) depends on the quality of information presented and the quality of team processes. Few studies have examined these factors ...using a standardized approach. The aim of this study was to objectively document the processes involved in decision-making in MDTMs, document the outcomes in terms of whether a treatment recommendation was given (none vs. singular vs. multiple), and to identify factors related to type of treatment recommendation.
An adaptation of the observer rating scale Multidisciplinary Tumor Board Metric for the Observation of Decision-Making (MDT-MODe) was used to assess the quality of the presented information and team processes in MDTMs. Data was analyzed using descriptive statistics and mixed logistic regression analysis.
N = 249 cases were observed in N = 29 MDTMs. While cancer-specific medical information was judged to be of high quality, psychosocial information and information regarding patient views were considered to be of low quality. In 25% of the cases no, in 64% one, and in 10% more than one treatment recommendations were given (1% missing data). Giving no treatment recommendation was associated with duration of case discussion, duration of the MDTM session, quality of case history, quality of radiological information, and specialization of the MDTM. Higher levels of medical and treatment uncertainty during discussions were found to be associated with a higher probability for more than one treatment recommendation.
The quality of different aspects of information was observed to differ greatly. In general, we did not find MDTMs to be in line with the principles of patient-centered care. Recommendation outcome varied substantially between different specializations of MDTMs. The quality of certain information was associated with the recommendation outcome. Uncertainty during discussions was related to more than one recommendation being considered. Time constraints were found to play an important role. Some of those aspects seem modifiable, which offers possibilities for the reorganization of MDTMs.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Open-label (honestly prescribed) placebos are an ethical way to evoke placebo effects in patients. As part of a mixed-methods study, we conducted in-depth interviews with eight menopausal women who ...underwent and benefitted from open-label placebo treatment in a randomized-controlled trial of hot flushes. Data were analyzed using Interpretative Phenomenological Analysis. We found that the women had low expectations about the placebo treatment yet endorsed what they referred to as “hope” and openness to “see what happens”. Recording hot flushes via the symptom diary was viewed as a valuable opportunity for self-examination and appraising outcomes. Receiving relief from the placebo treatment empowered women and enhanced their sense of control and agency. In summary, participants’ initial openness towards placebos, their hopes to get better, monitoring symptoms closely, and taking the initiative to address symptoms were components of a positive open-label placebo experience.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary
Objective
Depression and anxiety are highly prevalent among people with epilepsy (PwE) but often remain unrecognized and treated inadequately. Effective psychosocial treatments such as ...cognitive behavioral therapy (CBT) are rarely available to most PwE, which is one reason electronically delivered CBT (eCBT) is regarded as promising. This study examined an eCBT intervention, termed Emyna, that was tailored to suit the needs of PwE. It includes CBT‐related content on depression, stress and anxiety, seizure triggers and auras, and lifestyle habits. The trial examined the efficacy of Emyna in reducing symptoms of depression (primary outcome) and anxiety as well as improving quality of life.
Methods
Participants (N = 200) with epilepsy, a diagnosis of a depressive disorder, and at least moderate depressive symptoms were randomized to Emyna or care as usual. At baseline and after 3, 6, and 9 months, participants were invited to complete online questionnaires. The primary outcome was improvement of depressive symptoms at 3 months.
Results
Relative to the control group, intervention group participants experienced significantly greater improvements in depression, anxiety, stress, social‐occupational impairment, and epilepsy‐related quality of life, in both intention‐to‐treat (ITT) and per‐protocol analyses. In ITT analyses, effects of medium magnitude were observed, as measured by the Patient Health Questionnaire–9 items (Cohen d = 0.54, 95% confidence interval CI = 0.25‐0.82, P < 0.001) and the Neurological Disorders Depression Inventory for Epilepsy (d = 0.51, 95% CI = 0.23‐0.79, P < 0.01). At 3 months, intervention group participants also reported fewer illness‐related days off work and fewer days hospitalized over the preceding months, compared to control group participants (P ≤ 0.05), whereas no such differences were present at baseline (P > 0.30).
Significance
These findings showed that Emyna, used adjunctively to usual care, could help improve mental health, social‐occupational functioning, and quality of life among PwE. The program provides an additional treatment option that could produce clinically relevant symptom reductions and reduce key cost drivers (ie, hospitalization rates and illness‐related inability to work).
Abstract Improvements in placebo groups of antidepressant trials account for a major part of the expected drug effects. We aimed to determine overall effect sizes of placebo and drug effects in ...antidepressant trials, and to analyze whether the placebo effect in antidepressant trials also occurs for patient self-perception, general psychopathology, and quality of life. Methods: Search terms covered different variants of pharmacotherapy for patients with depressive disorders from January 1980 to December 2005 in the databases Medline/Pubmed, PsychInfo and CENTRAL, a.o. We included RCTs with a placebo group and an antidepressant group in people with depression. Results: We computed within group effect sizes for several outcome variables and integrated them using random-effect models. A total of 96 studies were included. Mean effect size in the placebo group for primary outcome variables was d = 1.69 (95% CI = 1.54–1.84) compared to 2.50 in the drug group (95% CI = 2.30–2.69). There was a major difference between placebo effect sizes assessed with observer ratings ( d = 1.85, 95% CI = 1.69–2.01) versus patient self-perception ( d = 0.67; 95% CI = 0.49–0.85). The effect sizes in placebo groups in 2005 were more than twice as great as those in 1980, but only for observer ratings, not for patient self-ratings. The result was partly due to increased homogeneity of samples of recently published trials. Conclusions: The placebo effect accounted for 68% of the effect in the drug groups. Whereas clinical trials need to control the placebo effect, clinical practice should attempt to use its full power.
ObjectivePatients’ expectations—as a central mechanism of placebo and nocebo effects—are an important predictor of health outcomes. However, the lack of a way to assess expectations across different ...settings restricts progress in understanding the role of expectations and to quantify their importance in medical and psychological treatments. The aim of this study was to develop a theory-based, generic, multidimensional measure assessing patient expectations of medical and psychological treatments.DesignThe Treatment Expectation Questionnaire (TEX-Q) was developed based on the integrative model of expectations and a systematic literature review of treatment expectation scales. After creating a comprehensive item pool, the scale was further refined by use of expert ratings and patient interviews.SettingPatients were recruited in primary care at two hospitals in Hamburg, Germany.Participants13 scientific experts participated in the expert survey. 11 patients waiting for psychological or surgical treatments participated in the qualitative interviews.ResultsThe 2×2×2 multidimensional structure of the TEX-Q assesses two expectation constructs (probabilistic vs value-based) across two outcome domains with two valences (direct benefits and adverse events, broader positive and negative impact), plus process and behavioural control expectations. We examined 583 items from 38 scales identified in the systematic review and developed 78 initial items. Content validity was then rated by experts according to item fit and comprehensibility. The best 53 items were further evaluated for comprehensibility, acceptability, phrasing preference and understanding by interviewing patients prior to treatment using the ‘think aloud’ technique. This resulted in a first 35-item version of the TEX-Q.ConclusionsThe TEX-Q is a generic, multidimensional measure to assess patient expectations of medical and psychological treatments and allows comparison of the impact of multidimensional expectations across different conditions. The final TEX-Q will be available after psychometric validation.
Patients' expectations, as a central mechanism behind placebo and nocebo effects, are an important predictor of health outcomes. Yet, theoretically based generic assessment tools allowing for an ...integrated understanding of expectations across conditions and treatments are lacking. Based on the preliminary 35-item version, this study reports the development and validation of the Treatment Expectation Questionnaire (TEX-Q), a generic, multidimensional self-report scale measuring patients' expectations of medical and psychological treatments.
The TEX-Q was developed in a validation sample of n = 251 patients undergoing different treatments using exploratory factor analyses and item analyses, as well as analysis of convergent and divergent validity. Confirmatory factor analysis was conducted in an independent sample of n = 303 patients undergoing cancer treatment. Two-weeks test-retest reliability was assessed in n = 28 psychosomatic outpatients.
Factor analyses revealed six theoretically founded stable subscales. The TEX-Q assesses expectations of treatment benefit, positive impact, adverse events, negative impact, process and behavioural control with a total of 15 items. Results for the subscales and the sum score indicated good internal consistency (α = .71-.92), moderate to high test-retest reliability (r = .39-.76) as well as good convergent validity with regard to other expectation measures (r = .42-.58) and divergent validity with regard to measures of generalized expectations (r < .32) and psychopathology (r < .28).
While further validation is needed, the results suggest that the TEX-Q is a valid and reliable scale for the generic, multidimensional assessment of patients' treatment expectations. The TEX-Q overcomes constraints of ad-hoc and disease-specific scales, while allowing to compare the impact of different expectation constructs across conditions and treatments.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Children and adolescents with major depressive disorder (MDD) appear to be more responsive to placebo than adults in randomized placebo-controlled trials (RCTs) of second and newer generation ...antidepressants (SNG-AD). Previous meta-analyses obtained conflicting results regarding modifiers. We aimed to conduct a meta-analytical evaluation of placebo response rates based on both clinician-rating and self-rating scales. Based on the most recent and comprehensive study on adult data, we tested whether the placebo response rates in children and adolescents with MDD also increase with study duration and number of study sites. We searched systematically for published RCTs of SNG-AD in children and/or adolescents (last update: September 2017) in public domain electronic databases and additionally for documented studies in clinical trial databases. The log-transformed odds of placebo response were meta-analytically analyzed. The primary and secondary outcomes were placebo response rates at the end of treatment based on clinician-rating and self-rating scales, respectively. To examine the impact of study duration and number of study sites on placebo response rates, we performed simple meta-regression analyses. We selected other potential modifiers of placebo response based on significance in at least one previous pediatric meta-analysis and on theoretical considerations to perform explorative analyses. We applied sensitivity analyses with placebo response rates closest to week 8 to compare our data with those reported for adults. We identified 24 placebo-controlled trials (2229 patients in the placebo arms). The clinician-rated placebo response rates ranged from 22 to 62% with a pooled response rate of 45% (95% CI 41–50%). The number of study sites was a significant modifier in the simple meta-regression analysis odds ratio (OR) 1.01, 95% CI 1.01–1.02,
p
= 0.0003,
k
= 24) with more study sites linked to a higher placebo response. Study duration was not significantly associated with the placebo response rate. The explorative simple analyses revealed that publication year may be an additional modifier. However, in the explorative multivariable analysis including the number of study sites and the publication year only the number of study sites reached a
p
value ≤ 0.05. The self-rated placebo response rates ranged from 1 to 68% with a pooled response rate of 26% (95% CI 10–54%) (
k
= 6;
n
= 396). This meta-analysis confirms a high pooled placebo response rate in children and adolescents based on clinician ratings, which exceeds that observed in the most recent meta-analysis of placebo effects in adults (36%; 95% CI 35–37%) published in 2016. However, and similar to findings in adults, the pooled response rates based on self-ratings were substantially lower. In accordance with previous meta-analyses, we corroborated the number of study sites as significant modifier. In comparison to the recent adult meta-analysis, the substantially lower number of pediatric studies entails a reduced power to detect modifiers. Future studies should provide more precise and homogenous information to support discovery of potential modifiers and consider no-treatment—if ethically permissible—to allow differentiation between placebo and spontaneous remission rates. If these differ, practicing clinicians should facilitate placebo effects as an addition to the
verum
effect to maximize benefits. Further research is required to explain the discrepant response rates between clinician and self-ratings.
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