Health Psychology - Placebo
Meta Analysis of Sham-Controlled Surgeries (4)
**Overall 65% of these surgeries were "sham effect"* Surgeries included: ▪ *Pain - 78% sham* ▪ Obesity - 71% sham ▪ GERD - 57% sham ▪ Other conditions - 57% sham ▪ Classic surgery - 21% sham ▪ Endoscopic Procedures - 73% sham ▪ Percutaneous procedures - 64% sham ▪ This is the first systematic review using a meta-analysis approach to estimate both specific and non-specific components in sham-controlled surgical trials, and to what extent those effects differ among conditions and procedures. ▪ All sensitivity analyses showed similar results as the main analysis, except one, namely the sensitivity analysis for large studies (≥100 patients), which showed a smaller non-significant effect size. ▪ Our results have implications for clinical research and practice by *arguing against the continued use of ineffective invasive treatments, especially in the field of chronic pain*. ▪ One limitation might be that the conclusions from our meta-analysis are restricted to available published data on surgical interventions that have been tested in sham-controlled clinical trials. --------------------------------------------------------------------- **Jones et al Kaptchuk et al 2015 To what extent are surgery and invasive procedures effective beyond a placebo response A systematic review with meta-analysis of randomised, sham controlled trials- BMJ Objectives: To assess the quantity and quality of randomised, sham-controlled studies of surgery and invasive procedures and estimate the treatment-specific and non-specific effects of those procedures. Design: Systematic review and meta-analysis. Data sources: We searched PubMed, EMBASE, CINAHL, CENTRAL (Cochrane Library), PILOTS, PsycInfo, DoD Biomedical Research, clinicaltrials.gov, NLM catalog and NIH Grantee Publications Database from their inception through January 2015. Study selection: We included randomised controlled trials of surgery and invasive procedures that penetrated the skin or an orifice and had a parallel sham procedure for comparison. Data extraction and analysis: Three authors independently extracted data and assessed risk of bias. Studies reporting continuous outcomes were pooled and the standardised mean difference (SMD) with 95% CIs was calculated using a random effects model for difference between true and sham groups. Results: 55 studies (3574 patients) were identified meeting inclusion criteria; 39 provided sufficient data for inclusion in the main analysis (2902 patients). The overall SMD of the continuous primary outcome between treatment/sham-control groups was 0.34 (95% CI 0.20 to 0.49; p<0.00001; I2=67%). The SMD for surgery versus sham surgery was non-significant for pain-related conditions (n=15, SMD=0.13, p=0.08), marginally significant for studies on weight loss (n=10, SMD=0.52, p=0.05) and significant for gastroesophageal reflux disorder (GERD) studies (n=5, SMD=0.65, p<0.001) and for other conditions (n=8, SMD=0.44, p=0.004). Mean improvement in sham groups relative to active treatment was larger in pain related conditions (78%) and obesity (71%) than in GERD (57%) and other conditions (57%), and was smaller in classical-surgery trials (21%) than in endoscopic trials (73%) and those using percutaneous procedures (64%). Conclusions: The non-specific effects of surgery and other invasive procedures are generally large. Particularly in the field of pain-related conditions
Placebo and Weight Loss: mean weight & waist/hip ratio
*In the group that was told they exercised more , their weight & waist/hip ratio actually decreased from time 1 to time 2
Provider Effects on Treatment Response graph - *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.
Provider Effects on Treatment Response graph - *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.
Placebo & Nocebo Responses
*The Nocebo response was even stronger than the placebo response
Placebo Effect: Anxiety Conclusions.
*This study indicates that high and moderate levels of psychopathology are associated with heightened placebo analgesia in chronic low back pain patients.* Expectations were only an influence in the high psychopathology group, and neuropathic pain affects placebo responses. These findings have implications for future research characterizing placebo responders.
Placebo as therapeutic tool? (2)
- 50% of doctors prescribe drugs at doses they think will have no effect or drugs that aren't specific for the disorder to take advantage of the placebo effect -->Cheaper, safer, equally effective, but ethical?
Testing for Placebo Effects: Migraine Example (Maxalt Study)
- 66 patients suffering from migraines - Given envelopes containing different information on the outside as well as different pills on the inside - When feel headache, record pain score then open envelope and take pill in envelope -->2.5 hours later record pain score -->No treatment control condition as well (e.g. don't take pill) *Study Design allows you to test the effects of expectations, labeling, and drug Treatment order was randomized. Maxalt was superior to placebo for pain relief. *When participants were given placebo labeled as (i) placebo, (ii) Maxalt or placebo, and (iii) Maxalt, the placebo effect increased progressively. Maxalt had a similar progressive boost when labeled with these three labels*. The efficacies of Maxalt labeled as placebo and placebo labeled as Maxalt were similar. *The efficacy of open-label placebo was superior to that of no treatment*. Relative to no treatment, the placebo, under each information condition, accounted for more than 50% of the drug effect. Increasing "positive" information incrementally boosted the efficacy of both placebo and medication during migraine attacks. *The benefits of placebo persisted even if placebo was honestly described*. Whether treatment involves medication or placebo, the information provided to patients and the ritual of pill taking are important components of care.
Psychological Explanations for the Placebo Effect (4)
- Emotion (Anxiety - patient characteristics) - Cognitive (expectations) - Social Norms - Situational Effects
What causes a sick person to get better? (4)
- The ailment runs its course (called *"natural history effects"*) - Specific active components of a treatment help the person. >>Non-specific effects of a treatment (e.g. *placebo effects*), particularly the psychosocial context, help the person. - Can lead to *attributions* of efficacy and induce future *expectancy effects*
Placebo: Outline
1. Demonstration of Placebo Effects 2. Studying the Placebo Effect (Experimental Methods Issues) 3. Provider Effects 4. Psychological Explanations for the Placebo Effect - Emotion (Anxiety - Patient characteristics) - Cognitive (Expectations) - Social Norms - Situational effects
Placebo: Outline (Extended)
1. Demonstration of Placebo Effects 2. Studying the Placebo Effect (Experimental Methods Issues) 3. Provider Effects 4. Psychological Explanations for the Placebo Effect - Emotion (Anxiety - Patient characteristics) - Cognitive (Expectations) - Social Norms - Situational effects 5. Biological Mechanisms (see upcoming lecture)
Plaebo Effect: Expectancy Open - Hidden Design (3)
>>A study typically done in post operative surgical pain recovery >>Open: treatment given by clinician and patient informed of it >>Hidden: same dose and duration of drug, but delivered by computer controlled drug infusion pump without patients awareness From Price, DD.; Finniss, DG.; Benedetti, F. "A comprehensive review of the placebo effect- recent advances and current thought." Annual Review of Psychology, v. 59, 2008, p. 565-90.
Expectations and Physiological Effects (2)
>>If in group where psychological benefits emphasized, self-esteem improves >>Physiological benefits (maximum oxygen uptake capacity) increased similarly in the two groups --Desharnais, R., et al. "Aerobic exercise and the placebo effect- a controlled study." Psychosomatic Medicine, v. 55 issue 2, 1993, p. 149-54
Brand Name vs. Generic
>>Study of 87 students with regular headaches --Given 4 doses of medication to take on 4 different days when had headaches --Doses were labelled either Brand Name or Generic and were active or placebo (4 conditions) --Complete survey on Pain Relief and Side Effects Faase et al 2015 Impact of brand or generic labeling on medication effectiveness and side effects - Health Psych *Objective*: Branding medication with a known pharmaceutical company name or product name bestows on the drug an *added assurance of authenticity and effectiveness compared to a generic preparation*. This study examined the impact of brand name and generic labeling on medication effectiveness and side effects. *Method*: 87 undergraduate students with frequent headaches took part in the study. Using a within-subjects counterbalanced design, each participant took tablets labeled either as brand name "Nurofen" or "Generic Ibuprofen" to treat each of 4 headaches. In reality, half of the tablets were placebos, and half were active ibuprofen (400 mg). Participants recorded their headache pain on a verbal descriptor and visual analogue scale prior to taking the tablets, and again 1 hour afterward. Medication side effects were also reported. *Results*: Pain reduction following the use of brand name labeled tablets was similar in active ibuprofen or a placebo. However, if the tablets had a generic label, placebo tablets were significantly less effective compared to active ibuprofen. Fewer side effects were attributed to placebo tablets with brand name labeling compared to the same placebo tablets with a generic label. *Conclusions*: *Branding of a tablet appears to have conferred a treatment benefit in the absence of an active ingredient, while generic labeled tablets were substantially less effective if they contained no active ingredient*. Branding is also associated with reduced attribution of side effects to placebo tablets. Future interventions to improve perceptions of generics may have utility in improving treatment outcomes from generic drugs
Placebo and Weight Loss (8)
>>Study of hotel maids. Participants informed that goal of the study was to improve health and happiness in the workplace • "Treatment" Group (maids at 4 hotels): - participants told their job meets Surgeon Generals recommendations for daily exercise informed of calorie consumption of their daily tasks (e.g. changing linens for 15 min burns 40 calories etc) - Results in Health benefit • Control Group (maids at 3 hotels): not given this information - This is not a drug study, but a placebo effect *They were asked to report the amount of exercise they do -manipulation increased perceived exercise (see image) --------------------------------------------- Crum & Langer 2007 Mind-Set Matters- Exercise and the Placebo Effect In a study testing whether the relationship between exercise and health is moderated by one's mindset, 84 female room attendants working in seven different hotels were measured on physiological health variables affected by exercise. Those in the informed condition were told that the work they do (cleaning hotel rooms) is good exercise and satisfies the Surgeon General's recommendations for an active lifestyle. Examples of how their work was exercise were provided. Subjects in the control group were not given this information. Although actual behavior did not change, 4 weeks after the intervention, the informed group perceived themselves to be getting significantly more exercise than before. As a result, compared with the control group, they showed a decrease in weight, blood pressure, body fat, waist-to-hip ratio, and body mass index. These results support the hypothesis that exercise affects health in part or in whole via the placebo Logic The Surgeon General has stated that all adults should accumulate at least 30 min of physical exercise per day for a healthy lifestyle (Centers for Disease Control and Prevention, CDC, 1996). Everyday moderate physical activity can be achieved by taking a brisk walk, climbing the stairs, or performing active housework (CDC, 1996). Although many people today have sedentary jobs, there are some jobs that are intrinsically physical. Hotel room attendants, for example, clean on average 15 rooms a day (each room taking between 20 and 30 min to complete), and engage in exerting activities that require walking, bending, pushing, lifting, and carrying, clearly meeting and exceeding the Surgeon General's requirements. Room attendants may not perceive their work as exercise. If they do not, and if the relationship between exercise and health is moderated by mind-set as we hypothesize, then these workers may not be receiving the full health benefits of their exercise. Similarly, if their mind-sets are shifted so that they become aware of the exercise they are getting, then health improvements would be expected to follow. Design Each of seven hotels was randomly assigned to one of two conditions: informed or control. Subjects in the informed condition received a write-up discussing the benefits of exercise and were informed that their daily housekeeping work satisfied the CDC's recommendations for an active lifestyle. Specifically, they were told that exercise does not need to be hard or painful to be good for one's health, but that it is simply a matter of moving one's muscles and burning calories (accumulating approximately 200 calories per day to meet the recommendations). They were given specific details of the average calorie expenditure for various activities (changing linens for 15 min burns 40 calories, vacuuming for 15 min burns 50 calories, and cleaning bathrooms for 15 min burns 60 calories), and they were told that although these figures were based on results for a 140-pound woman and each of them would burn calories at a different rate, it was clear that they were easily meeting and even exceeding the Surgeon General's recommendations. 2 This sheet, written in both English and Spanish, was read and explained to the subjects and then posted on the bulletin board in their lounge.3
Placebo Effect: Expectancy Effect of Verbal Instructions
>>Verbal instructions affect the amount of painkiller requested --Pollo A, Amanzio M, Arslanian A, Casadio C, Maggi G, et al. 2001. Response expectancies in placebo analgesia and their clinical relevance. Pain 93:77-84 Response expectancies have been proposed as the major determinant of placebo effects. Here we report that different expectations produce different analgesic effects which in turn can be harnessed in clinical practice. Thoracotomized patients were treated with buprenorphine on request for 3 consecutive days, together with a basal intravenous infusion of saline solution. However, the symbolic meaning of this basal infusion was changed in three different groups of patients. The ®rst group was told nothing about any analgesic effect (natural history). The second group was told that the basal infusion was either a powerful painkiller or a placebo (classic double-blind administration). The third group was told that the basal infusion was a potent painkiller (deceptive administration). Therefore, whereas the analgesic treatment was exactly the same in the three groups, the verbal instructions about the basal infusion differed. The placebo effect of the saline basal infusion was measured by recording the doses of buprenorphine requested over the three-days treatment. We found that the double-blind group showed a reduction of buprenorphine requests compared to the natural history group. However, this reduction was even larger in the deceptive administration group. Overall, after 3 days of placebo infusion, the ®rst group received 11.55 mg of buprenorphine, the second group 9.15 mg, and the third group 7.65 mg. Despite these dose differences, analgesia was the same in the three groups. These results indicate that different verbal instructions about certain and uncertain expectations of analgesia produce different placebo analgesic effects, which in turn trigger a dramatic change of behaviour leading to a signi®cant reduction of opioid intake
Placebo (2)
>>any medical procedure that produces an effect in a patient because of its therapeutic *intent* and not bc of its specific nature --one of the best examples of the biopsychosocial model
Placebo Effect: Anxiety Background
Chronic low back pain patients have a high rate of psychopathology, comprised mainly of depression, anxiety, and high levels of neuroticism. We previously found that psychopathology is associated with increased placebo analgesia in this patient group.
Provider Effects on Treatment Response graph
Kelley, JM., et al. "Patient and practitioner influences on the placebo effect in irritable bowel syndrome." Psychosomatic Medicine, v. 71 issue 7, 2009, p. 789-97. *Key words*: placebo effect, irritable bowel syndrome, acupuncture, personality, patient-practitioner relationship
Nocebo
Nocebo = "I will hurt" , opposite of placebo effect
Brand Name vs. Generic - Results
Results: >>No difference between active generic and name brand on headaches >>Placebo labelled with name brand, more effective than placebo labelled with generic >>Side effects for the generic placebo were higher (not shown)
Testing for Placebo Effects: Migraine Example
Summary: 1. Getting the placebo and even being told you were getting the placebo still had better effects than getting no treatment at all 2. 3.
Placebo Effect: Anxiety Objective
To better understand this finding in the context of other known predictors of placebo response (such as expectations for relief), we performed a detailed analysis of expectations and other possible covariates.
Provider Effects on Treatment Response graph - Objective
To determine whether placebo responses can be explained by characteristics of the patient, the practitioner, or their interpersonal interaction.
Placebo Response Changing over Time
Tuttle et al Mogil 2015 *Increasing placebo responses over time in U.S. clinical trials of neuropathic pain* - Pain Recent failures of clinical trials of novel analgesics designed to treat neuropathic pain have led to much speculation about the underlying reasons. One often discussed possibility is that the placebo response in these trials has increased in recent years, leading to lower separation between the drug and placebo arms. Whether this has indeed occurred has not yet been adequately addressed. Here, we extracted data from published randomized controlled trials (RCTs) of drugs for the treatment of chronic neuropathic pain over the years 1990 to 2013.We find that placebo responses have increased considerably over this period, but drug responses have remained stable, leading to diminished treatment advantage. This trend has been driven by studies conducted in the United States. Consideration of participant and study characteristics revealed that in the United States but not elsewhere, RCTs have increased in study size and length. These changes are associated with larger placebo response. Analysis of individual RCT time courses showed different kinetics for the treatment vs placebo responses, with the former evolving more quickly than the latter and plateauing, such that maximum treatment advantage was achieved within 4 weeks
Placebo Effect: Anxiety
Wasan, AD.; Kaptchuk, TJ.; Davar, G.; Jamison, RN. "The association between psychopathology and placebo analgesia in patients with discogenic low back pain." Pain Medicine, v. 7 issue 3, 2006, p. 217-28
Placebo Effect: Anxiety Design
We conducted a double-blind, placebo-controlled, randomized, crossover-designed trial of intravenous morphine vs. placebo in 60 subjects with chronic low back pain and discogenic abnormalities. Patients were stratified into three groups of psychiatric symptom severity (Low, Moderate, and High), based on composite scores on depression, anxiety for pain, and neuroticism scales. Subjects were given intravenous morphine and placebo in random order on separate visits, and completed serial pain ratings over 3 h at each session.
Provider Effects on Treatment Response graph - *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.
Placebo Response Changing over Time - A Placebo Response by Region
Why are placebos getting more effective? - BBC N *the placebo response has been steadily strengthening.* Tests reveal that some well-known drugs for depression and anxiety would struggle to pass their clinical trials if they were re-tested in 2015. This trend has become a huge concern for the pharmaceutical industry. A slew of drugs have flopped at these final clinical trials, by which time drugs companies have typically spent more than $1bn in research and development. Why? *Americans more responsive because of drug advertising* Research staff don't want to miss subjects so much more patient contact (and support) Maybe doctors are giving inappropriately optimistic body language
Placebo Effect: Anxiety Results.
With 20 subjects per group, there were small, but significant differences between groups in baseline pain ratings. No differences were found between groups in age, gender, and radicular pain. Patients with low psychological symptomatology reported 7.7% total pain relief with placebo compared with 23.4% in the Moderate group and 23.5% in the High group (P < 0.05). Expectations were not significantly different between groups, but in the High group expectation levels predicted placebo analgesia (P < 0.001). Neuropathic pain quality was also a predictor (P < 0.05).
Complementary and Alternative Medicine (11 total) -examples from the book (8)
p. 182-187 of Shelley Taylors 9th edition. -
Testing for Placebo Effects: (6) Experimental Design Issues
• Double-blind studies do not inform on the magnitude of the placebo response • At least, three groups are needed - experimental group (e.g. active drug) - placebo group - no treatment group (no placebo AND no active drug) • Objective measures are better
Expectations and Psychological Effects (6)
• Exercise is thought to have effects on psychological well-being, including self-esteem • By what mechanism? Could expectation explain some of the effect? Study: • 10 week supervised exercise program, with three 90 minute sessions each week • Condition 1: Trainer emphasizes biological benefits during introduction and subsequent meetings • Condition 2: Trainer emphasizes biological *AND* psychological benefits during introduction and subsequent meetings >>Measure self-esteem at multiple time points --Desharnais, R., et al. "Aerobic exercise and the placebo effect- a controlled study." Psychosomatic Medicine, v. 55 issue 2, 1993, p. 149-54.
Placebo in Antidepressant Trials (2)
• In general, ~30 to 45% of patients receiving placebo, depression successfully treated • In general ~50 to 70% of patients receiving antidepressants successfully treated
Placebo Effect: Anxiety (a.k.a. Patient Characteristic in textbook) (5)
• Negative affect can make the pain response worse • Does reduction of anxiety contribute to placebo response? Study of patients with low back pain: • patients complete self-report inventories of depression, neuroticism, and anxiety. Then divided into 3 groups (low, medium, high) • All patients received placebo ------------------------------------------------------------------------------------------------ Wasan, AD.; Kaptchuk, TJ.; Davar, G.; Jamison, RN. "The association between psychopathology and placebo analgesia in patients with discogenic low back pain." Pain Medicine, v. 7 issue 3, 2006, p. 217-28 Background. Chronic low back pain patients have a high rate of psychopathology, comprised mainly of depression, anxiety, and high levels of neuroticism. We previously found that psychopathology is associated with increased placebo analgesia in this patient group. Objective. To better understand this finding in the context of other known predictors of placebo response (such as expectations for relief), we performed a detailed analysis of expectations and other possible covariates. Design. We conducted a double-blind, placebo-controlled, randomized, crossover-designed trial of intravenous morphine vs. placebo in 60 subjects with chronic low back pain and discogenic abnormalities. Patients were stratified into three groups of psychiatric symptom severity (Low, Moderate, and High), based on composite scores on depression, anxiety for pain, and neuroticism scales. Subjects were given intravenous morphine and placebo in random order on separate visits, and completed serial pain ratings over 3 h at each session. Results. With 20 subjects per group, there were small, but significant differences between groups in baseline pain ratings. No differences were found between groups in age, gender, and radicular pain. Patients with low psychological symptomatology reported 7.7% total pain relief with placebo compared with 23.4% in the Moderate group and 23.5% in the High group (P < 0.05). Expectations were not significantly different between groups, but in the High group expectation levels predicted placebo analgesia (P < 0.001). Neuropathic pain quality was also a predictor (P < 0.05). Conclusions. This study indicates that high and moderate levels of psychopathology are associated with heightened placebo analgesia in chronic low back pain patients. Expectations were only an influence in the high psychopathology group, and neuropathic pain affects placebo responses. These findings have implications for future research characterizing placebo responders
Placebo Response in Surgery (10)
• Osteoarthritis elicits joint pain of unknown origin • Surgical treatment effective in ~50% of the cases *Study Design • 180 patients with osteoarthritis of the knee, 3 groups: 1. Debridement (removal of the dead/damaged tissue) 2. Lavage (wash/irrigation of the joint) 3. Placebo - anesthesia and incision, no insertion of scope • Followed for two years - Pain assessments - motor function assessments ********** Moseley et al 2002 A CONTROLLED TRIAL OF ARTHROSCOPIC SURGERY - NEJM Background Many patients report symptomatic relief after undergoing arthroscopy of the knee for osteoarthritis, but it is unclear how the procedure achieves this result. We conducted a randomized, placebo-controlled trial to evaluate the efficacy of arthroscopy for osteoarthritis of the knee. Methods A total of 180 patients with osteoarthritis of the knee were randomly assigned to receive arthroscopic débridement, arthroscopic lavage, or placebo surgery. Patients in the placebo group received skin incisions and underwent a simulated débridement without insertion of the arthroscope. Patients and assessors of outcome were blinded to the treatmentgroup assignment. Outcomes were assessed at multiple points over a 24-month period with the use of five self-reported scores — three on scales for pain and two on scales for function — and one objective test of walking and stair climbing. A total of 165 patients completed the trial. Results At no point did either of the intervention groups report less pain or better function than the placebo group. For example, mean (±SD) scores on the Knee-Specific Pain Scale (range, 0 to 100, with higher scores indicating more severe pain) were similar in the placebo, lavage, and débridement groups: 48.9±21.9, 54.8±19.8, and 51.7±22.4, respectively, at one year (P=0.14 for the comparison between placebo and lavage; P=0.51 for the comparison between placebo and débridement) and 51.6±23.7, 53.7±23.7, and 51.4± 23.2, respectively, at two years (P=0.64 and P=0.96, respectively). Furthermore, the 95 percent confidence intervals for the differences between the placebo group and the intervention groups exclude any clinically meaningful difference. Conclusions In this controlled trial involving patients with osteoarthritis of the knee, the outcomes after arthroscopic lavage or arthroscopic débridement were no better than those after a placebo procedure
Placebo Effect: Price Effects (7)
• Participants informed that experimenters are testing a new FDA approved analgesic • Group 1: Told pill is worth $2.50 and experimenters paid full price • Group 2: Told pill is worth $2.50, but was discounted to $ 0.1 • To inflict pain, participants were give multiple shocks at different intensities first at baseline and then 30 minutes after taking the pill. >>Mean *difference* in pain ratings, after vs. before placebo, by voltage intensity >>Higher value indicates greater pain reduction -->if you get the more expensive drug you're getting more pain relief
Provider Effects on Treatment Response (5)
• Study of irritable bowel syndrome patients • All participants receive placebo acupuncture Group 1: Clinician is warm and empathetic, optimistic about the treatment and practices good listening skills Group 2: Clinician is neutral and businesslike Group 3: Wait-list control
The "Double-Blind" Study (6)
• To obtain FDA approval all drugs are tested against placebo • Typical design (participants randomized to groups) Group 1: drug Group 2: placebo (sugar pill) • Blind 1: Patients don't know what they got • Blind 2: Experimenter doesn't know what patient got (In addition to the patients not knowing)
Maxalt Study: Testing for Placebo (2)
•The placebo effect is the difference between the blue group and the natural history effects •Getting a placebo (and knowing it's a placebo) actually has better results than doing nothing at all.
Can expectancies reverse the effect of a drug? (5)
▪ Emla is a clinically approved topical analgesic (lidocaine/prilocaine made by AstraZeneca) ▪ 6 conditions: Emla, Emla reduced info, Placebo, Nocebo, Emla Nocebo, & Natural History. ▪ Emla group and the Placebo group were told: "The cream that will be applied to your arm reduces pain. The substance in the cream is used as a local anesthetic in many pain-reducing remedies, and is effective against heat pain." ▪ Emla Nocebo and the Nocebo group were told: "The cream that will be applied to your arm increases the effect of the heat pain and you will feel more pain. The substance in this cream is used in many medical remedies. Even though the pain feels more intense, the cream will not inflict any burn wounds." ▪ The Emla reduced information group was told: "You will now receive treatment with a medical cream. Because of the fact that we are interested in the pharmacological effect of this cream, we cannot provide information about which kind of medical properties it contains." ------------------------- Aslaksen et al. (2015) -Reversal of topical analgesia by nocebo information Several studies have shown that psychological factors such as learning, expectation, and emotions can affect pharmacological treatment and shape both favorable and adverse effects of drugs. This study investigated whether nocebo information provided during administration of an analgesic cream could reverse topical analgesia to hyperalgesia. Furthermore, we tested whether nocebo effects were mediated by negative emotional activation. A total of 142 healthy volunteers (73 women) were randomized into 6 groups. A topical analgesic cream (Emla) was administered together with suggestions of analgesia in 1 group, whereas another group received Emla with suggestions of hyperalgesia. Two other groups received a placebo cream together with the same information as the groups receiving Emla. A fifth group received Emla with no specific information about the effect, and the sixth group received no treatment but the same pain induction as the other groups. Heat pain stimulation (48°C) was administered during a pretest and 2 posttests. Pain was continuously recorded during stimulation, and measures of subjective stress and blood pressure were obtained before the pretest, after the application of cream, and after the posttests. The results revealed that pain was significantly lower in the group receiving Emla with positive information and highest in the groups receiving suggestions of hyperalgesia, regardless of whether Emla or the placebo was administered. Mediation analyses showed that stress and blood pressure mediated hyperalgesia after nocebo suggestions. These results suggest that nocebo information can reverse topical analgesia and that emotional factors can explain a significant proportion of variance in nocebo hyperalgesia