Antipruritic Placebo Effects by Conditioning H1-antihistamine

Abstract

Objective: Allergic rhinitis symptoms can be reduced by behaviorally conditioning antihistamine. It is unclear whether these findings extend to histamine-induced itch or work when participants are informed about the conditioning procedure (open-label conditioning). The current study aims to investigate the efficacy of (open-label) antipruritic behavioral conditioning for histamine-induced itch.

Methods: Healthy participants (n = 92; 84% female) were randomized to I) an open-label conditioned, II) closed-label conditioned, III) conditioned-not-evoked control, or IV) nonconditioned control group. A two-phase conditioning paradigm was used. During acquisition, a conditioned stimulus (CS; distinctively tasting beverage) was repeatedly paired with the H1-antihistamine levocetirizine (groups I-III). During evocation, the CS was paired with placebo (I, II), or instead of the CS, water was paired with placebo (III). The nonconditioned control group (IV) received CS with placebo in both phases. Itch after histamine iontophoresis and physiological data (i.e., spirometry, heart rate, skin conductance) were assessed. Combined conditioned and combined control groups were first compared, and analyses were repeated for separate groups.

Results: Marginally lower itch was reported in the combined conditioned compared with the control groups (F(1,88) = 2.10, p = .076, ηpartial = 0.02); no differences between separate groups were found. No effects on physiological data were found, except for heart rate, which reduced significantly and consistently for control groups, and less consistently for conditioned groups (group by time interaction: F(7,80) = 2.35, p = .031, ηpartial = 0.17).

Conclusion: Limited support was found for the efficacy of antipruritic behavioral conditioning, regardless of whether participants were informed about the conditioning procedure. The application of open-label conditioning in patient populations should be further researched.

Trial registration: www.trialregister.nl; ID NTR5544.

FIGURE 1

Overview of the study protocol. A conditioned stimulus (CS; distinctively tasting drink) was combined with an unconditioned stimulus (UCS; levocetrizine) or placebo capsule (PLAC) during acquisition. During evocation, the CS was combined with PLAC, and for the conditioned-not-evoked group, PLAC was provided with water (H₂O). Histamine iontophoresis (ITCH) was conducted at baseline and in the final evocation session.

FIGURE 2

Overview of the measurement schedule. Numbers on the timeline are deducted from CS administration, with −10 representing pre-CS, and +30, +60, and +90 representing post-CS measurements. Personality questionnaires (Q); expected itch (EXP); measurement sets for well-being (A); spirometry, heart rate, and skin conductance (B); and histamine iontophoresis (e.g., itch; C) and blood samples (BL) were taken. Filler tasks consisted of neutral magazines, Sudokus, and puzzles.

FIGURE 3

Means and standard errors of expected itch, with (A) the effects of the combined conditioned groups and the combined control groups on expected itch, controlled for baseline expected itch as measured postiontophoresis during the screening, and (B) the effects of the separate groups on expected itch.

FIGURE 4

Means and standard errors of the mean for itch during iontophoresis in the final evocation session, with (A) mean itch for the combined conditioned and the combined control groups, and (B) mean itch for the separate groups.