The Influence of Expectancy Level and Personal Characteristics on Placebo Effects: Psychological Underpinnings

Abstract

Placebo effects benefit a wide range of clinical practice, which can be profoundly influenced by expectancy level and personal characteristics. However, research on the issue of whether these factors independently or interdependently affect the placebo effects is still in its infancy. Here, we adopted a 3-day between-subject placebo analgesia paradigm (2-day conditioning and 1-day test) to investigate the influence of expectancy levels (i.e., No, Low, and High) and personal characteristics (i.e., gender, dispositional optimism, and anxiety state) on placebo effects in 120 healthy participants (60 females). Our results showed that the reduction of pain intensity in the test phase was influenced by the interaction between expectancy and gender, as mainly reflected by greater reductions of pain intensity in females at Low expectancy level than females at No/High expectancy levels, and greater reductions of pain intensity in males than in females at High expectancy level. Additionally, the reduction of pain unpleasantness was not only modulated by the interaction between expectancy and gender, but also by the interaction between expectancy and dispositional optimism, as well as the interaction between expectancy and anxiety state. Specifically, participants who were more optimistic in Low expectancy group, or those who were less anxious in High expectancy group showed greater reductions of pain unpleasantness. To sum up, we emphasized on regulating the expectancy level individually based on the assessment of personal characteristics to maximize placebo effects in clinical conditions.

Keywords: anxiety state; dispositional optimism; expectancy; gender; placebo analgesia.

Figure 1

Flowchart of the experimental design. (Top) For each experimental group (No, Low, and High expectancy), the experiment consisted of two phases: Conditioning phase (Day 1 and Day 2) and Test phase (Day 3), and each day consisted of three sessions: a pre-treatment session, a treatment session, and a post-treatment session. Sessions, in which the electrical stimuli elicit a low sensation at ~2 rating, moderate sensation at ~4 rating, and high sensation at ~6 rating on the 11-point Numerical Rating Scale, are marked in blue, red, and orange, respectively. Treatment sessions are marked in green. (Middle) The experimental procedure in a representative day contained a 20-trial pre-treatment session, a 15 min treatment session, and a 40-trial post-treatment session, which are marked in orange, green, and blue, respectively. (Bottom) A representative trial of the pre-treatment session or the post-treatment session was starting with a 1-s cue, followed by a 5 s waiting, a 2 s electrical stimulus, another 5 s waiting, and a 16 s rating of the perception of pain intensity, unpleasantness, anxiety level, and satisfaction of drug efficacy (post-treatment session in Low and High expectancy groups). The trial was ended with a rest of 8–12 s.

Figure 2

The influences of expectancy level and gender on placebo effects. Significant main effect of expectancy level was only observed for changes of pain intensity (Left). Significant interactions of expectancy level and gender were observed for changes of pain intensity (Left) and unpleasantness (Right). Error bars indicate standard error, and data from female and male participants are marked in blue and red, respectively.

Figure 3

The influences of expectancy level and dispositional optimism (LOT-R) on placebo effects. Significant main effect of expectancy level was only observed for changes of pain intensity (Left). Significant interaction of expectancy level and dispositional optimism (LOT-R) was observed for changes of unpleasantness (Right), but not for changes of pain intensity (Left). Error bars indicate standard error, and data from participants with low and high scores of Life Orientation Test-Revised (Low LOT-R and High LOT-R) are marked in blue and red, respectively.

Figure 4

The influences of expectancy level and anxiety state (STAI-S) on placebo effects. Significant main effect of expectancy level was only observed for changes of pain intensity (Left). Significant interaction of expectancy level and anxiety state (STAI-S) was observed for changes of unpleasantness (Right), but not for changes of pain intensity (Left). Error bars indicate standard error, and data from participants with low and high scores of State subscale of State-Trait Anxiety Inventory (Low STAI-S and High STAI-S) are marked in blue and red, respectively.