Does Inclusion of a Placebo Arm Influence Response to Active Antidepressant Treatment in Randomized Controlled Trials? Results From Pooled and Meta-Analyses

ArticleinThe Journal of Clinical Psychiatry 71(3):270-9 · March 2010with42 Reads
DOI: 10.4088/JCP.08r04516blu · Source: PubMed
Abstract
To determine if the inclusion of a placebo arm and/or the number of active comparators in antidepressant trials influences the response rates of the active medication and/or placebo. Searches of MEDLINE, PsycINFO, and pharmaceutical Web sites for published trials or trials conducted but unpublished between January 1996 and October 2007. 2,275 citations were reviewed, 285 studies were retrieved, and 90 were included in the analysis. Trials reporting response and/or remission rates in adult subjects treated with an antidepressant monotherapy for unipolar major depression were included. The primary investigator recorded the number of responders and/or remitters in the intent-to-treat population of each study arm or computed these numbers using the quoted rates. Poisson regression analyses demonstrated that mean response rate for the active medication was higher in studies comparing 2 or more active medications without a placebo arm than in studies comparing 2 or more active medications with a placebo arm (65.4% vs 57.7%, P < .0001) or in studies comparing only 1 active medication with placebo (65.4% vs 51.7%, P = .0005). Mean response rate for placebo was significantly lower in studies comparing 1 rather than 2 or more active medications (34.3% vs 44.6%, P = .003). Mean remission rates followed a similar pattern. Meta-analysis confirmed results from the pooled analysis. These data suggest that antidepressant response rates in randomized control trials may be influenced by the presence of a placebo arm and by the number of treatment arms and that placebo response rates may be influenced by the number of active treatment arms in a study.
    • "Such studies have been performed either with a placebo or with an active drug, in healthy volunteers or in the context of various pathological conditions including Parkinson's disease. They have consistently shown that clinical outcomes are positively related to the expected probability of receiving a supposedly active treatment [4,[9][10][11]. Other studies have successfully disentangled the interpersonal relationship component from the effects of conditioning by the medical ritual [8] . According to a recent meta-analysis, the patient-clinician relationship has a small but statistically significant effect on health outcomes [12]. "
    [Show abstract] [Hide abstract] ABSTRACT: Context Previous studies suggested that many patients, who have given their informed consent to participate in randomized controlled trials (RCT), have somewhat limited understanding of what a placebo treatment is. We hypothesized that the relationship between patients and their health professionals plays a central role in this understanding. Methods We interviewed 12 patients included in RCTs (nine suffering from Parkinson’s disease and three from Huntington’s disease) and 18 health professionals involved with RCTs (eight principal investigators, four associated physicians and six clinical research associates). Semi-structured interviews were conducted after the RCTs had ended but before the treatment allocation was revealed. Results Only two patients clearly understood the aim of placebo-controlled RCTs. Only one principal investigator said she asks all her patients whether they agree to participate in RCTs. The seven others said they only ask patients who seem more likely to be compliant. Their selection criteria included docility and personality traits associated in other studies with enhanced placebo responses. According to 13 of the 18 health professionals, their relationship with patients may influence the amplitude of the placebo response. All but one clinical research associates added that the placebo response could result from a “maternal” type of care. All principal investigators said they have a strong influence on their patient's decision to participate. Finally, when interviewees were asked to narrate a memory of a medically unexplained healing, in eight of 11 physicians' narratives the beneficiary was a child while in 10 of 12 patients' narratives it was an adult. Conclusion Our observations suggest that the interrelationship between health professionals and patients involved in RCTs could be compared to that between parents and children. Therefore, adherence to formal rules regarding informed consent does not ensure a balanced relationship between patients and health professionals.
    Full-text · Article · May 2016
    • "@BULLET If possible, try to apply a standardized protocol that ensures a) comparability of physical activity, social influences, and other stimulating environmental influences, and that ensures b) effects steering pharmacological reactions to positive outcome. @BULLET Try to include at least one study arm that attempts to optimize the interaction of pharmacological and context factors, to receive an estimate about the full potential of the treatment plan, but note that assay sensitivity is higher if patients believe that the chance to be in a placebo group is 50% (Sinyor et al., 2010). For further recommendations to improve assay sensitivity see Enck et al. (2013). "
    Dataset · Jan 2016 · PLoS ONE
    • "Previous studies have described that fatigue in FM has several dimensions. The peripheral or physical fatigue is dependent on muscle contractions, and this is in agreement with the results from the present study that showed an increase in fatigue during dynamic contractions [79, 80], while central or mental fatigue mainly is associated with cognitive impairment [79]. Previous studies have also reported a positive correlation between pain and fatigue [81] , and that increased ratings of fatigue are highly correlated to increased ratings of pain intensity at exhaustion, indicating that patients with FM have a more pronounced response to the input from the muscle nociceptors than healthy CTR [78]. "
    [Show abstract] [Hide abstract] ABSTRACT: Objective: Fibromyalgia is associated with central hyperexcitability, but it is suggested that peripheral input is important to maintain central hyperexcitability. The primary aim was to investigate the levels of pro-inflammatory cytokines released in the vastus lateralis muscle during repetitive dynamic contractions of the quadriceps muscle in patients with fibromyalgia and healthy controls. Secondarily, to investigate if the levels of pro-inflammatory cytokines were correlated with pain or fatigue during these repetitive dynamic contractions. Material and methods: 32 women with fibromyalgia and 32 healthy women (controls) participated in a 4 hour microdialysis session, to sample IL-1β, IL-6, IL-8, and TNF from the most painful point of the vastus lateralis muscle before, during and after 20 minutes of repeated dynamic contractions. Pain (visual analogue scale; 0-100) and fatigue Borg's Rating of Perceived Exertion Scale; 6-20) were assessed before and during the entire microdialysis session. Results: The repetitive dynamic contractions increased pain in the patients with fibromyalgia (P < .001) and induced fatigue in both groups (P < .001). Perceived fatigue was significantly higher among patients with fibromyalgia than controls (P < .001). The levels of IL-1β did not change during contractions in either group. The levels of TNF did not change during contractions in patients with fibromyalgia, but increased in controls (P < .001) and were significantly higher compared to patients with fibromyalgia (P = .033). The levels of IL-6 and IL-8 increased in both groups alike during and after contractions (P's < .001). There were no correlations between pain or fatigue and cytokine levels after contractions. Conclusion: There were no differences between patients with fibromyalgia and controls in release of pro-inflammatory cytokines, and no correlations between levels of pro-inflammatory cytokines and pain or fatigue. Thus, this study indicates that IL-1β, IL-6, IL-8, and TNF do not seem to play an important role in maintenance of muscle pain in fibromyalgia.
    Full-text · Article · Dec 2015
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