TABLE 2.
Study characteristics and results
| (a) Trials including patients | ||||||
|---|---|---|---|---|---|---|
| Trials | Population | Information modifying the power of the placebo effect | Treatment group | Endpoints | Interaction found? (which model?) | Risk of bias |
| Faasse et al (2016) 41 | 87 patients with chronic headaches | Oral information provided on the treatment brand administered: minimized or maximized situations | Ibuprofen | Pain | Yes (antagonistic) | Unclear |
| Bergmann et al (1994) 9 | 49 cancer patients | Oral information provided or not on the study procedure: neutral or maximized situations | Naproxen | Pain | Yes (antagonistic) | High |
| Wise et al (2009) 42 | 601 poorly controlled asthmatics | Oral information provided on the treatment administered, its brand and its colour: neutral or maximized situations | Montelukast | Peak expiratory flow, spirometry and four self‐assessment asthma scales | Yes (antagonistic) | High |
| Levine et al (1984) 45 | 96 patients having undergone dental extraction | Hidden administration of treatments, manually or by a machine: minimized, neutral or maximized situations | Naloxone | Pain | Yes (antagonistic) | High |
| Uhlenhuth et al (1959) 7 | 52 psychiatric patients suffering from anxiety | Neutral or positive attitude concerning the treatments administered: neutral or maximized situations | Meprobamate or phenobarbital | Improvement perceived by patients, assessment by a psychiatrist and a scale grouping together 45 symptoms | Yes (synergistic) | High |
| Uhlenhuth et al (1966) 46 | 138 patients referred to psychiatric clinic | Neutral or positive attitude concerning the treatments administered: neutral or maximized situations | Meprobamate in neutral or maximized situation | Modifications on different scales | Yes (antagonistic) | High |
| Kam‐Hansen et al (2014) 25 | 66 chronic migraine patients | Oral information on the treatment administered: minimized, neutral or maximized situations | Razatriptan | Pain | No (additive) | Low |
| Kemeny et al (2007) 43 | 55 poorly controlled asthmatics | Oral information provided on the treatment administered: neutral or maximized situations | Salmeterol | Concentration of methacholine needed to induce a 20% FEV1 decrease | No (no effect) | Low |
| Mathews et al (1983) 47 | 48 couples presenting with sexual disorders | Frequency of administration and number of therapists: weekly, monthly and at least one therapist | Testosterone | Improvement of symptoms evaluated by an outside investigator and the couples themselves | No (no effect) | High |
| De Craen et al (2001) 16 | 112 chronic pain patients | Written information on the treatment administered: neutral or maximized situations | Tramadol | Pain | No (no effect) | High |
| Brandwhaite et al (1981) 36 | 835 women with chronic headaches | Oral information provided on the “brand” of treatment administered: minimized or maximized situations | Aspirin | Pain | No (additive) | High |
| (b) Trials including healthy volunteers | ||||||
|---|---|---|---|---|---|---|
| Trials | Population | Information modifying the power of the placebo effect | Treatment group | Endpoints | Interaction found? (which model?) | Risk ok bias |
| Schenk et al (2013) 40 | 34 healthy volunteers | Oral information provided on the treatment administered: minimized or maximized situation | Lidocaine | Pain after painful thermal stimulus | Yes (synergistic) | Low |
| Hammami et al (2016) 27 | 480 healthy volunteers | Oral information on the treatment administered: minimized, neutral or maximized situations | Hydroxyzine | Drowsiness and dry mouth | Yes (synergistic) | Low |
| Berna et al (2017) 33 | 100 healthy volunteers | Oral information that an analgesic yielding a dry mouth would be administered (in fact, it was atropine): minimized or maximized situations | Diclofenac | Pain after painful thermal stimulus | Yes (synergistic) | Low |
| Lund et al (2014) 31 | 46 healthy volunteers | Oral information on the treatment administered: minimized or maximized situations | Lidocaine | Self‐assessed pain duration and its maximal intensity after painful stimulus by IM injection | Yes (antagonistic) | Unclear |
| Kirsch et al (1993) 38 | 100 healthy volunteers | Oral information on the treatment administered: minimized or maximized situation | Caffeine | Level of alertness and stress, systolic and diastolic tension and cardiac rhythm | Yes (synergistic) | High |
| Penick et al (1965) 39 | 14 healthy volunteers | Oral information on the treatment administered: minimized or maximized situations | Epinephrine | Level of perceived stress, glucose and free fatty acid concentration and cardiac rhythm | Yes (synergistic) | High |
| Van Der Molen et al (1988) 48 | 13 healthy volunteers | Oral information provided on the treatment administered: minimized (relaxing information) and maximized (stressful information) situations | Lactate | Anxiety, pCO2 and respiratory rate | Yes (synergistic) | High |
| Rose et al (2001) 44 | 53 healthy volunteers | Oral and written information on the treatment administered: minimized or maximized situations | Melatonin | 12‐question assessment sleeping scale | Yes (antagonistic) | High |
| Mitchell et al (1996) 30 | 40 healthy volunteers | Oral information on the treatment administered: minimized or maximized situations | d‐amphetamine | Different scales of drug response (ARCI, DEQ, POMS) | Yes (antagonistic) | High |
| Hammami et al (2010) 28 | 180 healthy volunteers | Oral information on the treatment administered: maximized or minimized situations | Caffeine | Subjective self‐assessed (energy, fatigue, nausea) and objective parameters (systolic blood pressure) | Yes (antagonistic) | High |
| Butcher et al (2012) 32 | 20 healthy volunteers | Oral information on the treatment administered: minimized or maximized situations | Ibuprofen | Pain after painful electric stimulus | No (no effect) | Low |
| Flaten et al (2004) 35 | 94 healthy volunteers | Oral information on the treatment administered: minimized, neutral or maximized situation | Carisoprodol or caffeine | Eyeblink reflex, self‐assessment of level of wakefulness and calm, skin conductance, cardiac rhythm, arterial tension | No (no effect) | Low |
| Alasken et al (2015) 10 | 142 healthy volunteers | Oral information that analgesic or hyperalgesic cream was going to be administered: minimized or maximized situations | EMLA cream | Endpoints evaluated after painful stimulus, including pain, stress and blood pressure | No (additive) | Unclear |
| Atlas et al (2012) 37 | 14 healthy volunteers | Oral information on the treatment administered: minimized or maximized situation | Remifentanil | Pain after painful thermal stimulus | No (additive) | Unclear |
| Ross et al (1962) 19 | 80 healthy volunteers | Hidden administration of treatments to minimize their effect: minimized or neutral situations | d‐amphetamine | Mood swings (Clyde mood scale) and level of performance (tapping task and H‐bar test) | No (no effect) | High |
| Walach et al (2009) | 75 healthy volunteers | Oral information on the treatment administered | Caffeine | Objective parameters (SAT, DAT, CF, reaction time) and subjective parameters | No (no effect) | High |
| Bjorkedal et al (2011) 29 | 20 healthy volunteers | Oral information that a powerful painkiller was administered (in fact, caffeine): minimized or maximized situations | Caffeine | Wakefulness, stress, pain, expectations and laser‐evoked potentials | No (no effect) | High |
| Flaten et al (1999) 34 | 66 healthy volunteers | Oral information on the treatment administered: minimized, neutral or maximized situations | Carisoprodol | Eyeblink reflex, skin conductance, self‐assessment of level of stress and drowsiness | No (no effect) | High |
| Lyerly et al (1964) 49 | 90 veterans and 90 young employees | Oral information provided on the treatment administered: minimized, neutral or maximized situations | Amphetamine and chloral hydrate | Mood swings (Clyde mood scale) and level of performance (tapping task and H‐bar test) | No (no effect) | High |
Abbreviations: ARCI, addiction research center inventory; CF, cognitive function; DAT, divided attention task; DEQ, drug effect questionnaire; EMLA, eutectic mixture of local anaesthetics; FEV1, forced expiratory volume in 1 second; IM, intramuscular; pCO2, partial pressure of carbon dioxide; POMS, profile of mood states; SAT, spontaneous awakening trials; VAS, visual analogue scale.