Trial reportTrials2010
Interaction between drug and placebo effects: a cross-over balanced placebo design trial.
Trial report in Trials, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 11 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Measuring Placebo Effect by Elimination and Investigating Its Mechanism of Action
Drug Effects on Mood and Behavior - Expectancy
Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it.
- How do they add up? The interaction between the placebo and treatment effect: A systematic review.British journal of clinical pharmacology · 2022Pooled it
- Does the placebo effect modulate drug bioavailability? Randomized cross-over studies of three drugs.Journal of negative results in biomedicine · 2017Trial
- Drug*placebo interaction effect may bias clinical trials interpretation: hybrid balanced placebo and randomized placebo-controlled design.BMC medical research methodology · 2016Trial
- Randomised controlled trials may underestimate drug effects: balanced placebo trial design.PloS one · 2014Trial
- A novel provocation protocol to identify nocebo effects in clinical practice-a proof-of-concept n-of-1 study.Frontiers in pharmacology · 2026Article
- Harnessing placebo: Lessons from psychedelic science.Journal of psychopharmacology (Oxford, England) · 2023Review
- Adenosine, caffeine, and sleep-wake regulation: state of the science and perspectives.Journal of sleep research · 2022Review
- The Placebo Effect in Pain Therapies.Annual review of pharmacology and toxicology · 2019Review
- Lay People's Ethical Attitudes To Placebo Treatment: A Q-Methodology Study.Patient preference and adherence · 2019Article
- Does the model of additive effect in placebo research still hold true? A narrative review.JRSM open · 2017Article
- Cumulative neurobehavioral and physiological effects of chronic caffeine intake: individual differences and implications for the use of caffeinated energy products.Nutrition reviews · 2014Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe total effect of a medication is the sum of its drug effect, placebo effect (meaning response), and their possible interaction. Current interpretation of clinical trials' results assumes no interaction. Demonstrating such an interaction has been difficult due to lack of an appropriate study design.
methods180 adults were randomized to caffeine (300 mg) or placebo groups. Each group received the assigned intervention described by the investigators as caffeine or placebo, in a randomized crossover design. 4-hour-area-under-the-curve of energy, sleepiness, nausea (on 100 mm visual analog scales), and systolic blood pressure levels as well as caffeine pharmacokinetics (in 22 volunteers nested in the caffeine group) were determined. Caffeine drug, placebo, placebo-plus-interaction, and total effects were estimated by comparing outcomes after, receiving caffeine described as placebo to receiving placebo described as placebo, receiving placebo described as caffeine or placebo, receiving caffeine described as caffeine or placebo, and receiving caffeine described as caffeine to receiving placebo described as placebo, respectively.
resultsThe placebo effect on area-under-the-curve of energy (mean difference) and sleepiness (geometric mean ratio) was larger than placebo-plus-interaction effect (16.6 [95% CI, 4.1 to 29.0] vs. 8.4 [-4.2 to 21.0] mm*hr and 0.58 [0.39 to 0.86] vs. 0.69 [0.49 to 0.97], respectively), similar in size to drug effect (20.8 [3.8 to 37.8] mm*hr and 0.49 [0.30 to 0.91], respectively), and its combination with the later was larger than total caffeine effect (29.5 [11.9 to 47.1] mm*hr and 0.37 [0.22 to 0.64]). Placebo-plus-interaction effect increased caffeine terminal half-life by 0.40 [0.12 to 0.68] hr (P=0.007).
conclusionsDrug and placebo effects of a medication may be less than additive, which influences the interpretation of clinical trials. The placebo effect may increase active drug terminal half-life, a novel mechanism of placebo action.
trial registrationClinicalTrials.gov identification number - NCT00426010.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.