Figure 1.
On experimental days 1 (6 pm), 2 (8 am and 6 pm) and 3 (8 am) during medication intake, all subjects in each of the 3 treatment groups received four oral doses of 2.5 mg/kg body weight of the immunosuppressive drug CsA (Sandimmun optoral, Novartis) in capsule form.
In addition, subjects in groups 1 (n = 24) and 2 (n = 26) received the CS (drink) with each capsule (CsA) intake whereas subjects in group 3 (n = 12) were not exposed to the CS (A). After five days wash out time, subjects received either identical looking capsules containing a placebo (lactose powder) or a subtherapeutic dose of CsA (0.25 mg/kg) fourteen times, twice a day (8 am and 6 pm respectively) with (groups 1 and 2) or without (group 3) the CS (B). In order to analyze possible general treatment side effects (nocebo effects), participants were asked before the start of the study (Pre I), after Medication intake (Post I) as well as before (Pre II) and after “Placebo” (Post II) intake to fill out the GASE. Blood was drawn on the first day for baseline measurement (Pre I), on day 3 (Post I) to analyze the pharmacological effect of CsA as well as on day 8 (Pre II) and 15 (Post II) to determine possible residual effects of the drug as well as effects on physiological parameters after treatment with “Placebo” (sub-therapeutical doses of CsA).
Table 1.
Sociodemographic and psychological characteristics of the three experimental groups.
Table 2.
CsA serum levels and IL-2 protein concentrations of the three treatment groups during Medication and “Placebo” intake.
Table 3.
CsA-specific and general side effects during the Medication and “Placebo” condition.
Figure 2.
General psychological and medical indispositions were analyzed with the GASE before study entry (Baseline) (A), after Medication intake (B) and “Placebo” intake (C), respectively.
Homozygous Val158 carriers experienced significantly more general psychological and medical indispositions before study entry and after four medication intakes (B). The Val/Val group also showed the strongest nocebo response, reflected by most reported side effects after the “Placebo” intake (C). Bars represent mean ±SEM; data were analyzed with univariate ANOVAs. In case of significant F tests, these were followed by Bonferroni post hoc tests; *p<0.05, **p<0.001.
Figure 3.
Reported CsA-specific side effects after Medication (A) and “Placebo” intake, respectively (B).
Significantly higher CsA-specific side effects, after four medication intakes, were reported by homozygous Val158/Val158 carriers (A). This difference was even more pronounced after fourteen “Placebo” intakes (B). Bars represent mean ±SEM. In case of significant F tests, these were followed by Bonferroni post hoc tests; *p<0.05, **p<0.001.
Table 4.
Differences in the somatosensory amplification scale (SSAS) and four subscales of the Beliefs about Medicines Questionnaire (BMQ) depending on the respective genotype group.