Yvonne Nestoriuc

Meta-analysis of the placebo response in antidepressant trials

UNLABELLED 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.

Efficacy of biofeedback for migraine: A meta-analysis

Abstract In this article, we meta‐analytically examined the efficacy of biofeedback (BFB) in treating migraine. A computerized literature search of the databases Medline, PsycInfo, Psyndex and the Cochrane library, enhanced by a hand search, identified 86 outcome studies. A total of 55 studies, including randomized controlled trials as well as pre–post trials, met our inclusion criteria and were integrated. A medium effect size (Symbol, 95% CI = 0.52, 0.64) resulted for all BFB interventions and proved stable over an average follow‐up phase of 17 months. Also, BFB was more effective than control conditions. Frequency of migraine attacks and perceived self‐efficacy demonstrated the strongest improvements. Blood‐volume‐pulse feedback yielded higher effect sizes than peripheral skin temperature feedback and electromyography feedback. Moderator analyses revealed BFB in combination with home training to be more effective than therapies without home training. The influence of the meta‐analytical methods on the effect sizes was systematically explored and the results proved to be robust across different methods of effect size calculation. Furthermore, there was no substantial relation between the validity of the integrated studies and the direct treatment effects. Finally, an intention‐to‐treat analysis showed that the treatment effects remained stable, even when drop‐outs were considered as nonresponders. Symbol. No caption available.

Meta-analysis of biofeedback for tension-type headache: efficacy, specificity, and treatment moderators.

The aims of the present meta-analysis were to investigate the short- and long-term efficacy, multidimensional outcome, and treatment moderators of biofeedback as a behavioral treatment option for tension-type headache. A literature search identified 74 outcome studies, of which 53 were selected according to predefined inclusion criteria. Meta-analytic integration resulted in a significant medium-to-large effect size (d = 0.73; 95% confidence interval = 0.61, 0.84) that proved stable over an average follow-up phase of 15 months. Biofeedback was more effective than headache monitoring, placebo, and relaxation therapies. The strongest improvements resulted for frequency of headache episodes. Further significant effects were observed for muscle tension, self-efficacy, symptoms of anxiety, depression, and analgesic medication. Moderator analyses revealed biofeedback in combination with relaxation to be the most effective treatment modality; effects were particularly large in children and adolescents. In intention-to-treat and publication-bias analyses, the consistency of these findings was demonstrated. It is concluded that biofeedback constitutes an evidence-based treatment option for tension-type headache.

Differences in Adverse Effect Reporting in Placebo Groups in SSRI and Tricyclic Antidepressant Trials

Background: Biases in adverse effect reporting in randomized controlled trials (RCTs) [e.g. due to investigator expectations or assessment quality] can be quantified by studying the rates of adverse events reported in the placebo arms of such trials.Objective: We compared the rates of adverse effects reported in the placebo arms of tricyclic antidepressant (TCA) trials and placebo arms of selective serotonin reuptake inhibitor (SSRI) trials.Methods: We conducted a literature search for RCTs across PUBMED, Scopus and the Cochrane Central Register of Controlled Trials (CENTRAL). Only studies allowing adverse effect analysis were included. Publication year ranged from 1981 to 2007.Results: Our systematic review and meta-analysis included 143 placebo-controlled RCTs and data from 12 742 patients. Only 21% of studies used structured and systematic adverse effect ascertainment strategies. The way in which trials recorded adverse events influenced the rate of adverse effects substantially. Systematic assessment led to higher rates than less systematic assessment. Far more adverse effects were reported in TCA-placebo groups compared with SSRI-placebo groups, e.g. dry mouth (odds ratio [OR] = 3.5; 95% CI 2.9, 4.2); drowsiness (OR = 2.7; 95% CI 2.2, 3.4); constipation (OR = 2.7; 95% CI 2.1,3.6); sexual problems (OR =2.3; 95% CI 1.5,3.5). Regression analyses controlling for various influencing factors confirmed the results.Conclusion: Adverse effect profiles reported in clinical trials are strongly influenced by expectations from investigators and patients. This difference cannot be attributed to ascertainment methods. Adverse effect patterns of the drug group are closely related to adverse effects of the placebo group. These results question the validity of the assumption that adverse effects in placebo groups reflect the ‘drug-unspecific effects’.

Assessing general side effects in clinical trials: reference data from the general population

Side effects in clinical trials are frequently assessed in an unstructured fashion, using ascertainment strategies with unclear quality criteria. To improve the assessment and interpretation of general side effects, a structured approach is presented and validated (General Assessment of Side Effects, GASE). Base rates and reference data of the general population as well as quality criteria of this new side effect ascertainment method are provided.

Welche Risiken und Nebenwirkungen hat Psychotherapie? - Entwicklung des Inventars zur Erfassung Negativer Effekte von Psychotherapie (INEP)

Hintergrund: Negative Effekte von Psychotherapie sind bis heute wenig systematisch untersucht. Diese Studie stellt die Konstruktion eines Selbstbeurteilungsverfahrens zur Erfassung negativer Effekte von Psychotherapie vor. Patienten und Methoden: Ein Itempool zur breiten Erfassung möglicher erlebter negativer Veränderungen durch Psychotherapie in den Bereichen intrapersonelle Veränderungen, Partnerschaft, Freunde und Familie, Arbeitsplatz, therapeutisches Fehlverhalten und Stigmatisierung wurde über Literaturrecherchen und Expertenbefragungen generiert. Items wurden bipolar formuliert, um ein negatives Priming zu verhindern. Zusätzlich wurde die jeweilige Attribution der Veränderung auf die Psychotherapie oder andere externe Ursachen erfragt. Im Zeitraum von November 2010 bis Februar 2011 nahmen 195 ehemalige Psychotherapiepatienten (74,9% weiblich; Alter M = 38,4 Jahre; SD = 11,8) an einer Onlineuntersuchung teil, bei der auch die Rahmenbedingungen der Psychotherapie erfragt wurden. Ergebnisse: Von 195 Befragten gaben 93,8% (n = 183) an, negative Effekte durch ihre Psychotherapie erlebt zu haben. Die höchsten Raten erlebter negativer Effekte ergaben sich in den Bereichen intrapersonelle Veränderungen (15,8%), Stigmatisierung (14,9%) und Partnerschaft (12,0%). Schwerwiegendes therapeutisches Fehlverhalten wie sexuelle Belästigung (2,6%) oder körperliche Gewalt (1%) durch den Therapeuten hatten eine geringe Prävalenz. Anhand von Itemanalysen sowie inhaltlichen Kriterien wurde das Inventar zur Erfassung negativer Effekte von Psychotherapie (INEP) mit 21 Items erstellt (α = 0,86). Diskussion: Ein Großteil der negativen Veränderungen trat innerhalb des therapeutischen Settings auf (z.B. verletzende Aussagen des Therapeuten, Phasen der Niedergeschlagenheit). Zudem wurden mehr negative Effekte genannt, wenn die therapeutische Beziehung als negativ beschrieben wurde. Schlussfolgerung: Negative Effekte von Psychotherapien sind feststellbar und können mittels Patientenbefragungen und einer systematischen Analyse, via INEP erfasst werden. Die Analyse des Instruments in weiteren klinischen Subpopulationen ist notwendig.

Optimizing expectations to prevent side effects and enhance quality of life in breast cancer patients undergoing endocrine therapy: study protocol of a randomized controlled trial

BackgroundAdjuvant endocrine therapy can improve disease-free survival and time before recurrence in breast cancer patients. However, it is associated with considerable side effects that negatively affect patients’ quality of life and cause non-adherence. The recently demonstrated effect of individual expectations on side-effect development (nocebo effect) suggests that psychological factors play a role in the prevention of side effects. The aim of this study is to evaluate cognitive-behavioral side-effect prevention training (SEPT) for breast cancer patients. This article describes the study protocol and applied research methods.Methods/DesignIn a randomized controlled trial, 184 female breast cancer patients are assigned to receive either SEPT, standard medical care or a manualized supportive therapy at the start of adjuvant endocrine treatment. SEPT consists of three sessions of cognitive-behavioral training including psychoeducation to provide a realistic view of endocrine therapy, imagination-training to integrate positive aspects of medication into daily life, and side-effect management to enhance expectations about coping ability. Side effects three months after the start of endocrine therapy serve as primary outcomes. Secondary outcomes include quality of life, coping ability and patients’ medication adherence. Patients’ expectations (i.e., expectations about side effects, coping ability, treatment and illness) are analyzed as mediators.DiscussionThe optimization of expectations might be a potential pathway in health care to improve patients’ quality of life during long-term medication intake. The results will provide implications for a possible integration of evidence-based prevention training into clinical practice.Trial registrationClinicalTrials.gov, (NCT01741883).

Medication adherence in the general population.

Background Adherence to medication is low in specific populations who need chronic medication. However, adherence to medication is also of interest in a more general fashion, independent of specific populations or side effects of particular drugs. If clinicians and researchers expect patients to show close to full adherence, it is relevant to know how likely the achievement of this goal is. Population based rates can provide an estimate of efforts needed to achieve near complete adherence in patient populations. The objective of the study was to collect normative data for medication nonadherence in the general population. Methods and Findings We assessed 2,512 persons (a representative sample of German population). Adherence was measured by Rief Adherence Index. We also assessed current medication intake and side effects. We found that at least 33% of Germans repeatedly fail to follow their doctors recommendations regarding pharmacological treatments and only 25% of Germans describe themselves as fully adherent. Nonadherence to medication occurs more often in younger patients with higher socioeconomic status taking short-term medications than in older patients with chronic conditions. Experience with medication side effects was the most prominent predictor of nonadherence. Conclusions The major strengths of our study are a representative sample and a novel approach to assess adherence. Nonadherece seems to be commonplace in the general population. Therefore adherence cannot be expected per se but needs special efforts on behalf of prescribers and public health initiatives. Nonadherence to medication should not only be considered as a drug-specific behaviour problem, but as a behaviour pattern that is independent of the prescribed medication.

A RANDOMIZED TRIAL OF THREE PSYCHOSOCIAL TREATMENTS FOR THE SYMPTOMS OF RHEUMATOID ARTHRITIS

OBJECTIVE To assess and compare the benefits of 3 psychosocial treatments for rheumatoid arthritis (RA). METHODS RA patients were randomized to cognitive-behavior therapy (CBT), relaxation response training (RR), or arthritis education (AE). All treatment was conducted in groups. Follow-up occurred immediately after treatment and 6 and 12 months later. Pain, other RA symptoms, role impairment, and psychological distress were assessed with standardized self-report questionnaires. Arthritis severity and activity were assessed with a joint examination, erythrocyte sedimentation rate, grip strength, and walking time. An intent-to-treat analytic strategy was employed. Linear regression was used to establish treatment effect on pain and other RA symptoms, while adjusting for sociodemographic and clinical variables. RESULTS One hundred sixty-eight patients were randomized. Pain improved significantly at 12 months in the RR and AE groups and showed a nonsignificant positive trend with CBT. Other RA symptoms improved significantly with CBT and AE and showed a nonsignificant trend with RR. There were no significant differences in the outcomes across the 3 treatment groups. When the results for all 3 groups were aggregated, significant benefits were found for pain, other RA symptoms, self-care activities, and social activities. Effect sizes ranged between 0.26 and 0.35. CONCLUSIONS These 3 psychosocial treatments were beneficial, with treatment effect sizes in the small to moderate range. The effects appeared immediately after treatment and were generally sustained at long-term follow-up. These benefits were achieved over and above those resulting from medical management. These treatments constitute an effective augmentation to standard medical therapy for RA patients.

Very low birth-weight as a risk factor for postpartum depression four to six weeks postbirth in mothers and fathers: Cross-sectional results from a controlled multicentre cohort study

BACKGROUND Preterm birth and survival rates of very low birth-weight (VLBW: <1.500g) infants have increased. Although new parents are frequently affected by depressive symptoms, little is known about prevalence, risk, and predictors of parental postpartum depression (PPD) following VLBW birth. Furthermore, most studies assessing PPD in parents of preterm children relied on self-report only. METHODS As part of the HaFEn cohort-study, data from the index groups of parents with VLBW infants and the control group of parents with term infants were cross-sectionally analysed. Families were recruited at the three largest centres of perinatal medical care in Hamburg, Germany. PPD was evaluated one month postpartum using standardized questionnaires and clinical interviews. Socioeconomic status, social support, risks during pregnancy, and psychiatric lifetime diagnoses were also assessed. A multiple random coefficient model was used to examine predictors of PPD in both parents simultaneously. RESULTS 230 mothers and 173 fathers were included. Depending on the measure, the risk of being postnatally depressed was 4 to 18 times higher in mothers and 3 to 9 times higher in fathers from the index group. The most relevant risk factor for PPD was the birth of a VLBW infant, followed by female sex, lifetime psychiatric disorder, and low social support. LIMITATIONS Results presented here, are based on cross sectional data. Therefore no temporal relationships can be established. CONCLUSIONS Our findings highlight the importance of early screening for PPD in both parents of VLBW infants. Factors contributing to developing depression should also be considered in neonatal care.