Credible Placebo Research Articles

Brief cognitive behavior group therapy for social anxiety among medical students: A randomized placebo-controlled trial.

To compare brief cognitive behavior group therapy (bCBGT) for social anxiety disorder (SAD) to a credible placebo, psychoeducational-supportive therapy (PST), in a sample of medical students. This was a single-center, rater-blind, randomized, attention placebo-controlled, parallel-group study. Participants were 50 consenting undergraduate medical students of a state government medical college in Cuttack, India having a primary diagnosis of SAD, who recieved 6 weekly 2-h group sessions. Assessments were carried out at baseline, post intervention and at two-month follow. Independent raters assessed the participants on the Liebowitz Social Anxiety Scale and Clinical Global Impression- Improvement scale (CGI-I). Social Phobia Inventory (SPIN), a self-rated measure, was administered in the same periods. bCBGT group improved significantly across periods from pre-treatment to post-treatment and from pre-treatment to two-month follow-up. bCBGT was statistically superior to PST at the post-treatment and follow-up assessments and showed large effect sizes at both post-treatment and follow-up. A 6-session bCBGT is an efficacious treatment for SAD among medical students. A longer follow-up and replication in other groups, and clinical settings are necessary for generalization to a broader SAD population.

Placebo Devices as Effective Control Methods in Acupuncture Clinical Trials: A Systematic Review.

While the use of acupuncture has been recognised by the World Health Organisation, its efficacy for many of the common clinical conditions is still undergoing validation through randomised controlled trials (RCTs). A credible placebo control for such RCTs to enable meaningful evaluation of its efficacy is to be established. While several non-penetrating acupuncture placebo devices, namely the Streitberger, the Park and the Takakura Devices, have been developed and used in RCTs, their suitability as inert placebo controls needs to be rigorously determined. This article systematically reviews these devices as placebo interventions. Electronic searches were conducted on four English and two Chinese databases from their inceptions to July 2014; hand searches of relevant references were also conducted. RCTs, in English or Chinese language, comparing acupuncture with one of the aforementioned devices as the control intervention on human participants with any clinical condition and evaluating clinically related outcomes were included. Thirty-six studies were included for qualitative analysis while 14 were in the meta-analysis. The meta-analysis does not support the notion of either the Streitberger or the Park Device being inert control interventions while none of the studies involving the Takakura Device was included in the meta-analysis. Sixteen studies reported the occurrence of adverse events, with no significant difference between verum and placebo acupuncture. Author-reported blinding credibility showed that participant blinding was successful in most cases; however, when blinding index was calculated, only one study, which utilised the Park Device, seemed to have an ideal blinding scenario. Although the blinding index could not be calculated for the Takakura Device, it was the only device reported to enable practitioner blinding. There are limitations with each of the placebo devices and more rigorous studies are needed to further evaluate their effects and blinding credibility.

Psychological treatment of hypnotic-dependent insomnia in a primarily older adult sample

ObjectiveThis study tested cognitive behavior therapy (CBT) in hypnotic-dependent, late middle-age and older adults with insomnia. MethodSeventy volunteers age 50 and older were randomized to CBT plus drug withdrawal, placebo biofeedback (PL) plus drug withdrawal, or drug withdrawal (MED) only. The CBT and PL groups received eight, 45 min weekly treatment sessions. The drug withdrawal protocol comprised slow tapering monitored with about six biweekly, 30 min sessions. Assessment including polysomnography (PSG), sleep diaries, hypnotic consumption, daytime functioning questionnaires, and drug screens collected at baseline, posttreatment, and 1-year follow-up. ResultsOnly the CBT group showed significant sleep diary improvement, sleep onset latency significantly decreased at posttreatment. For all sleep diary measures for all groups, including MED, sleep trended to improvement from baseline to follow-up. Most PSG sleep variables did not significantly change. There were no significant between group differences in medication reduction. Compared to baseline, the three groups decreased hypnotic use at posttreatment, down 84%, and follow-up, down 66%. There was no evidence of withdrawal side-effects. Daytime functioning, including anxiety and depression, improved by posttreatment. Rigorous methodological features, including documentation of strong treatment implementation and the presence of a credible placebo, elevated the confidence due these findings. ConclusionsGradual drug withdrawal was associated with substantial hypnotic reduction at posttreatment and follow-up, and withdrawal side-effects were absent. When supplemented with CBT, participants accrued incremental self-reported, but not PSG, sleep benefits.

Modulation of laser-evoked potentials and pain perception by transcutaneous electrical nerve stimulation (TENS): A placebo-controlled study in healthy volunteers

ObjectiveTo investigate the effects of transcutaneous electrical nerve stimulation (TENS) on brain nociceptive responses (laser-evoked potentials, LEPs) and pain perception. MethodsTwenty healthy subjects were included. Nociceptive CO2-laser pulses were sequentially delivered to the dorsum of both feet. The amplitude of LEPs and nociceptive thresholds were collected in three consecutive conditions: T1: “sham” TENS (2Hz/low-intensity) positioned heterotopically, over the left thigh; T2: “active” TENS (120Hz/low-intensity) applied homotopically, over the left common peroneal nerve; and T3: “sham” TENS (replication of condition T1). ResultsCompared with “sham” TENS, “active” TENS significantly decreased the LEPs amplitude. This effect was observed exclusively when “active” TENS was applied ipsilaterally to the painful stimulus. Nociceptive thresholds increased with sessions in both limbs, but the increase observed during the “active” condition of TENS (T2) exceeded significantly that observed during the condition T3 only on the foot ipsilateral to TENS. ConclusionsCompared with a credible placebo TENS, high-frequency TENS induced a significant attenuation of both the acute pain and LEPs induced by noxious stimuli applied on the same dermatome. SignificanceThis modulation of subjective and objective concomitants of pain processing reflects a real neurophysiological TENS-related effect on nociceptive transmission.

A randomized, placebo-controlled trial of online cognitive behavioral therapy for chronic insomnia disorder delivered via an automated media-rich web application.

The internet provides a pervasive milieu for healthcare delivery. The purpose of this study was to determine the effectiveness of a novel web-based cognitive behavioral therapy (CBT) course delivered by an automated virtual therapist, when compared with a credible placebo; an approach required because web products may be intrinsically engaging, and vulnerable to placebo response. Randomized, placebo-controlled trial comprising 3 arms: CBT, imagery relief therapy (IRT: placebo), treatment as usual (TAU). Online community of participants in the UK. One hundred sixty-four adults (120 F: [mean age 49y (18-78y)] meeting proposed DSM-5 criteria for Insomnia Disorder, randomly assigned to CBT (n = 55; 40 F), IRT placebo (n = 55; 42 F) or TAU (n = 54; 38 F). CBT and IRT each comprised 6 online sessions delivered by an animated personal therapist, with automated web and email support. Participants also had access to a video library/back catalogue of session content and Wikipedia style articles. Online CBT users had access to a moderated social network/community of users. TAU comprised no restrictions on usual care and access to an online sleep diary. Major assessments at baseline, post-treatment, and at follow-up 8-weeks post-treatment; outcomes appraised by online sleep diaries and clinical status. On the primary endpoint of sleep efficiency (SE; total time asleep expressed as a percentage of the total time spent in bed), online CBT was associated with sustained improvement at post-treatment (+20%) relative to both TAU (+6%; d = 0.95) and IRT (+6%: d = 1.06), and at 8 weeks (+20%) relative to IRT (+7%: d = 1.00) and TAU (+9%: d = 0.69) These findings were mirrored across a range of sleep diary measures. Clinical benefits of CBT were evidenced by modest superiority over placebo on daytime outcomes (d = 0.23-0.37) and by substantial improved sleep-wake functioning on the Sleep Condition Indicator (range of d = 0.77-1.20). Three-quarters of CBT participants (76% [CBT] vs. 29% [IRT] and 18% [TAU]) completed treatment with SE > 80%, more than half (55% [CBT] vs. 17% [IRT] and 8% [TAU]) with SE > 85%, and over one-third (38% [CBT] vs. 6% [IRT] and 0% [TAU]) with SE > 90%; these improvements were largely maintained during follow-up. CBT delivered using a media-rich web application with automated support and a community forum is effective in improving the sleep and associated daytime functioning of adults with insomnia disorder. ISRCTN - 44615689.

Should we reconsider the routine use of placebo controls in clinical research?

BackgroundModern clinical-research practice favors placebo controls over usual-care controls whenever a credible placebo exists. An unrecognized consequence of this preference is that clinicians are more limited in their ability to provide the benefits of the non-specific healing effects of placebos in clinical practice.MethodsWe examined the issues in choosing between placebo and usual-care controls. We considered why placebo controls place constraints on clinicians and the trade-offs involved in the choice of control groups.ResultsWe find that, for certain studies, investigators should consider usual-care controls, even if an adequate placebo is available. Employing usual-care controls would be of greatest value for pragmatic trials evaluating treatments to improve clinical care and for which threats to internal validity can be adequately managed without a placebo-control condition.ConclusionsIntentionally choosing usual-care controls, even when a satisfactory placebo exists, would allow clinicians to capture the value of non-specific therapeutic benefits that are common to all interventions. The result could be more effective, patient-centered care that makes the best use of both specific and non-specific benefits of medical interventions.

Does EMDR reduce post‐traumatic stress disorder symptomatology in combat veterans?

AbstractPrior meta‐analyses have suggested that eye‐movement desensitization and reprocessing (EMDR) may be effective in alleviating the symptoms of post‐traumatic stress disorder (PTSD). EMDR is now being recommended as a treatment for military combat veterans who suffer from PTSD. We provide a review of published outcome studies that appeared in print from 1987 – April, 2008 which examined the specific effects of EMDR on PTSD among military combat veterans. Studies were identified through electronic bibliographic databases, web sites, and manual searches of article reference lists. A total of six randomized controlled trials (RCTs) and three quasi‐experimental studies met our inclusionary criteria and are reviewed. The evidence supporting the use of EMDR to treat combat veterans suffering from PTSD is sparse and equivocal, and does not rise to the threshold of labeling the therapy as an empirically supported treatment. It is premature to incorporate EMDR into routine care for veterans to alleviate combat‐related PTSD. EMDR needs a considerably stronger evidentiary foundation which includes large‐scale RCTs involving credible placebo controlled treatment conditions. Copyright © 2009 John Wiley & Sons, Ltd.

Augmenting In Vivo Exposure With Fear Antagonistic Actions: A Preliminary Test

The current study investigated the efficacy of an exposure augmentation strategy in which the phobic individual is encouraged to enact actions that are in direct opposition to the fear action tendencies associated with acrophobia. Participants ( N = 88) meeting DSM-IV criteria for specific phobia (acrophobia) were randomized to (a) exposure with oppositional actions (E + OA), (b) exposure only (EO), (c) a credible placebo consisting of pulsed audio-photic stimulation (APS), or (d) a waitlist control (WLC). Treatment consisted of six, 6-min exposure trials. Participants were assessed with questionnaire, behavioral, and physiologic measures at pre- and posttreatment, and at a 1-month follow-up session. Participants receiving E + OA showed significantly greater improvement on behavioral and questionnaire measures than those in the other 3 conditions at both posttreatment and follow-up. Further, whereas treatment improvement generalized to an untrained context for those receiving E + OA, such was not the case for EO- and APS-treated participants. Findings suggest augmenting exposure with oppositional actions may enhance treatment outcome and thus warrant additional investigation with clinical samples.

Experts Dispute Report Critical of Antidepressants

Experts Dispute Report Critical of Antidepressants

Psychological treatment of insomnia in hypnotic-dependant older adults

Background The existing literature does not address the question of whether cognitive-behavioral therapy would have an impact on insomnia in older adults who are chronic users of sleep medication and have current insomnia, but are also stable in their quantity of medication usage during treatment. The present report seeks to answer this question. Methods Hypnotic-dependant older adults, who were stable in their amount of medication usage and still met the criteria for chronic insomnia put forth by American Academy of Sleep Medicine, were treated using a cognitive-behavioral intervention for insomnia. The three-component treatment included relaxation training, stimulus control, and sleep hygiene instructions. Participants were randomly assigned to either the active treatment group or a comparably credible placebo control group, and were instructed not to alter their pattern of hypnotic consumption during treatment. Results The active treatment group had significantly better self-report measures of sleep at post-treatment. Statistically significant improvement was paralleled by clinically meaningful improvement for key sleep variables. As planned, there was no significant change in sleep medication usage from pre- to post-treatment. Conclusions The findings support the use of cognitive-behavioral therapy for insomnia in hypnotic-dependant older adults.

Sports medicine pearls and pitfalls: Pearls on the power of placebo

Placebo Wars: Sham Acupuncture Beats Sugar Pills A recent study suggests that different placebo treatments can produce different results. A total of 270 adults with persistent arm pain from repetitive use were studied. The study was a duel between two placebos: sham acupuncture versus inert pills. The main outcome measure was pain self-reported on a 10-point scale. During the first 2 weeks, little difference was seen, but over the next 4 weeks, pain scores decreased significantly more in the sham acupuncture group than in the pill group. The sham acupuncture group also improved more on the Levine symptom severity scale. Sham acupuncture also was the more credible placebo: three quarters of participants on it thought they were getting active treatment, compared with less than half of participants on the placebo pill. Another point: reported side effects were different in each group and mirrored what they were told to expect. This study, like all studies, has limitations and confounders, but it suggests that placebo effects are malleable and depend on behaviors embedded in medical rituals [1]. Sham Arthroscopy Surgery itself can be a placebo. In a controlled trial of arthroscopic surgery for the pain and stiffness of osteoarthritis of the knee, 180 men were randomized (about 60 in each group) to lavage, debridement, or sham surgery. Most men reported some improvement over the next 1 to 2 years, but at no point did either of the intervention groups report less pain or better function than the placebo group [2]. In fact, if anything, the sham surgery group did slightly better in terms of the major outcomes. This study sparked criticism and controversy, but it is not the first study to suggest that surgery can have a strong placebo effect.

How to put hypnosis into a placebo pill?

Many case studies and several controlled clinical trials have indicated the effectiveness of hypnotherapy for some medical conditions. However, because of methodological inadequacies hypnotherapy is still criticized for not having strong scientific evidence to support its claims. While randomized placebo-controlled clinical trial is generally accepted as the gold standard study design, creating a credible placebo control for hypnotherapy is a major challenge. This paper recommends "neutral hypnosis" as a credible placebo control for hypnotherapy trials.

Testing Public Anxiety Treatments Against a Credible Placebo Control

Research investigating public speaking anxiety treatments is subject to demand effects. This study tests the relative effectiveness of systematic desensitization (SD) and multiple treatment method (MT) containing visualization therapy against no-treatment and credible placebo controls. Data (n=238) were collected at six points in a public speaking class. Reported anxiety decreased over time, but neither treatment outperformed the placebo control. Short-term gains were apparent for the MT group with participants selected on the basis of extreme high scores, but these gains did not persist relative to the control conditions over time. The current data suggest no evidence of lasting improvement of SD or MT treatments over a credible placebo control and enrollment in a standard public speaking class.

The use of placebo in clinical nursing research

This paper reviews placebo and placebo effects and their measurement and application to nursing. Ethical and methodological issues are also discussed. Implications for nursing and recommendations for future study are offered. Placebos have been used for decades in clinical trials but discussion about conceptual, methodological and ethical issues has been comparatively scarce. It is concluded that true placebo effects are difficult to measure and control and the use of credible placebo is sometimes impractical in clinical nursing research. This leads to the increased use of usual care as a control by researchers. However, more information should be reported in studies that use this approach, including the specification of usual care, its monitoring and patient adherence. Where its use is considered ethical, safe and feasible, a placebo arm should be included in studies of efficacy to distinguish between active and inactive treatment.

A Placebo-Controlled Trial of Constraint-Induced Movement Therapy for Upper Extremity After Stroke

Constraint-Induced Movement therapy (CI therapy) is a neurorehabilitation technique developed to improve use of the more affected upper extremity after stroke. A number of studies have reported positive effects for this intervention, but an experiment with a credible placebo control group has not yet been published. We conducted a placebo-controlled trial of CI therapy in patients with mild to moderate chronic (mean=4.5 years after stroke) motor deficit after stroke. The CI therapy group received intensive training (shaping) of the more affected upper extremity for 6 hours per day on 10 consecutive weekdays, restraint of the less affected extremity for a target of 90% of waking hours during the 2-week treatment period, and application of a number of other techniques designed to produce transfer to the life situation. The placebo group received a program of physical fitness, cognitive, and relaxation exercises for the same length of time and with the same amount of therapist interaction as the experimental group. After CI therapy, patients showed large (Wolf Motor Function Test) to very large improvements in the functional use of their more affected arm in their daily lives (Motor Activity Log; P<0.0001). The changes persisted over the 2 years tested. Placebo subjects showed no significant changes. The results support the efficacy of CI therapy for rehabilitating upper extremity motor function in patients with chronic stroke.

The efficacy of videotape feedback for enhancing the effects of exposure-based treatment for social anxiety disorder: A controlled investigation

Correcting patients’ faulty beliefs concerning social evaluative threats is the hallmark of cognitive–behavioral treatment of social anxiety disorder. The current study examined the efficacy of two videotape feedback procedures as adjuncts to exposure-based treatment. Participants suffering from social phobia ( N = 77 ) were randomly assigned to one of four conditions: (a) credible placebo treatment (PLA); (b) exposure+no feedback (EXP); (c) exposure+videotape feedback of performance (PER); or (d) exposure+videotape feedback of audience responses (AUD). Contrary to prediction, the videotape feedback procedures did not enhance the effects of exposure-based treatment. Clinical and theoretical implications are discussed.

Hypnotic Treatment of Chronic Pain

This article reviews controlled trials of hypnotic treatment for chronic pain in terms of: (1) analyses comparing the effects of hypnotic treatment to six types of control conditions; (2) component analyses; and (3) predictor analyses. The findings indicate that hypnotic analgesia produces significantly greater decreases in pain relative to no-treatment and to some non-hypnotic interventions such as medication management, physical therapy, and education/advice. However, the effects of self-hypnosis training on chronic pain tend to be similar, on average, to progressive muscle relaxation and autogenic training, both of which often include hypnotic-like suggestions. None of the published studies have compared hypnosis to an equally credible placebo or minimally effective pain treatment, therefore conclusions cannot yet be made about whether hypnotic analgesia treatment is specifically effective over and above its effects on patient expectancy. Component analyses indicate that labeling versus not labeling hypnosis treatment as hypnosis, or including versus not including hand-warming suggestions, have relatively little short-term impact on outcome, although the hypnosis label may have a long-term benefit. Predictor analyses suggest that global hypnotic responsivity and ability to experience vivid images are associated with treatment outcome in hypnosis, progressive relaxation, and autogenic training treatments. The paper concludes with a discussion of the implications of the findings for future hypnosis research and for the clinical applications of hypnotic analgesia.

Psychological Treatments for Social Phobia

To review the empirical status of psychological treatments for social phobia (SP), commenting both on cognitive-behavioural interventions and on more recent iterations of those approaches. We also review the effective components of cognitive-behavioural therapy (CBT). We qualitatively reviewed the empirical literature on the psychological treatment of SP. We include empirical studies, metaanalyses, and recent conference presentations in this review. Cognitive and behavioural interventions for SP appear to be more effective than wait-list controls and supportive therapy. Comparisons of CBT and pharmacologic treatment have produced inconsistent results. Several new treatments for SP demonstrate promising results. Evidence suggests that various psychosocial treatments for SP are better than wait-list controls and credible placebo interventions. Ongoing projects investigate the relative efficacy of combining medication and psychosocial treatments over monotherapies; this line of research is important to continue. Further research should also focus on which components of CBT are most effective.

Bias Control in Trials of Bodywork: A Review of Methodological Issues

To review and summarize the methodological challenges in clinical trials of bodywork or handson mind-body therapies such as Feldenkrais Method, Alexander Technique, Trager Work, Eutony, Body Awareness Therapy, Breath Therapy, and Rolfing, and to discuss ways these challenges can be addressed. Review and commentary. Search of databases PubMed and EMBASE and screening of bibliographies. Published clinical studies were included if they used individual hands-on approaches and a focus on body awareness, and were not based on technical devices. Of the 53 studies identified, 20 fulfilled inclusion criteria. No studies blinded subject to the treatment being given, but 5 used an alternative treatment and blinded participants to differential investigator expectations of efficacy. No study used a credible placebo intervention. No studies reported measures of patient expectations. Patient expectations have been measured in studies of other modalities but not of hands-on mind-body therapies. Options are presented for minimizing investigator and therapist bias and bias from differential patient expectations, and for maintaining some control for nonspecific treatment effects. Practical issues with recruitment and attrition resulting from volunteer bias are addressed. Rigorous clinical trials of hands-on complementary and alternative therapy interventions are scarce, needed, and feasible. Difficulties with blinding, placebo, and recruitment can be systematically addressed by various methods that minimize the respective biases. The methods suggested here may enhance the rigor of further explanatory trials.

Control Conditions in Hypnotic-analgesia Clinical Trials: Challenges and Recommendations 1

Case studies and controlled clinical trials indicate that hypnotic analgesia can effectively reduce pain in patients with a number of different chronic pain conditions. However, because none of the studies published to date have included a credible control condition that adequately controls for expectancy effects, at this point we cannot conclude that hypnotic-analgesia treatment has a specific effect on chronic pain beyond that that might be produced by a credible placebo intervention. This paper (a) describes the types of control conditions that have been, or might be, used in clinical trials of hypnotic analgesia for chronic pain; (b) reviews their strengths and weaknesses; and (c) concludes with specific recommendations that investigators should consider when designing clinical trials of hypnotic analgesia. 1This work was supported by grants P01 HD33988 and R01 GM42725 from the National Institutes of Health and the Hughes M. and Katherine G. Blake Endowed Professorship in Health Psychology.