Involvement of magnitude of ambient temperature change in nonspecific effect in perceived placebo effect on lower urinary tract symptoms: study on switching of naftopidil in patients with benign prostatic hyperplasia

Abstract

Purpose: To determine if switching from one brand of the α1-adrenoceptor antagonist naftopidil (Avishot™) to another brand (Flivas™) under the same conditions causes the same changes in lower urinary tract symptoms (LUTS) and quality of life (QOL) as the perceived placebo effect, and if ambient temperature as a nonspecific factor is related to those changes in benign prostatic hyperplasia (BPH) patients.

Patients and methods: A retrospective study was carried out on 217 BPH patients who had received Avishot™ for more than 6 months and then were switched to Flivas™ at the same dose and timing. The two drugs contain the same principal ingredient and display the same pharmacokinetic properties. The International Prostate Symptom Score (IPSS), QOL score, and average monthly ambient temperature at the patients' residence area from the Automated Meteorological Data Acquisition System in Japan were used for the evaluation.

Results: A significant change in urinary storage symptoms (P = 0.006), and especially in nighttime frequency (P< 0.001), was observed by switching drugs, suggesting the perceived placebo effect. There was significant improvement of daytime frequency (P< 0.05), nighttime frequency (P< 0.001), storage symptoms (P< 0.001), and total IPSS (P< 0.05) when the magnitude of ambient temperature change from before and 3 months after switching drugs was higher than 10°C, while no significant improvement was noted in any of the parameters examined when the same was lower than 10°C.

Conclusion: The present study showed the nonspecific effect of magnitude of ambient temperature change was involved in the perceived placebo effect on LUTS, especially on storage symptoms, by switching drugs. The nonspecific effect on LUTS with BPH needs to be considered when evaluating subjective treatment efficacy of drugs for LUTS with BPH in routine clinical practice. The present study supports the lifestyle advice "avoid exposing the lower body to cold temperature" or "keep warm when it is cold" for LUTS with BPH.

Keywords: ambient temperature; benign prostatic hyperplasia; lower urinary tract symptoms; naftopidil; nonspecific effect; placebo effect.

Figure 1

Average monthly ambient temperature around patients’ residential area obtained from AMeDAS. Data is for Oyama city, Tochigi, Japan (longitude 139°E, latitude 36°N, in a temperate zone). Abbreviation: AMeDAS, automated meteorological data acquisition system.

Figure 2

Changes in IPSS and QOL score by switching drugs. Notes: (n = 217). Mean values were plotted for the total International Prostate Symptom Score (IPSS), the scores of individual IPSS items, voiding symptoms (intermittency, weak stream, straining), storage symptoms (daytime frequency, nighttime frequency, urgency), post-voiding symptom (incomplete emptying), and quality of life (QOL) score before and 3 months after switching drugs. *P < 0.001, **P = 0.006 compared to the baseline by Wilcoxon signed rank test.

Figure 3

Association between number of parameters with significant change and average monthly ambient temperature at three months. Notes: The number of parameters with significant change shown in Table 2 was not associated with average monthly ambient temperature at three months (Figure 1) in each period by Spearman rank correlations (n = 217). For the statistical analysis, one significantly improved parameter was assigned as +1 while one significantly deteriorated parameter was assigned as −1.

Figure 4

Changes in IPSS and QOL score by average monthly ambient temperature at three months after switching drugs. Notes: Patients were divided into two groups according to the average monthly ambient temperature at 3 months in each period higher than 20°C (n = 98) or lower than 20°C (n = 119). Mean values were plotted for the total International Prostate Symptom Score (IPSS), the scores of individual IPSS items, voiding symptoms (intermittency, weak stream, straining), storage symptoms (daytime frequency, nighttime frequency, urgency), post-voiding symptom (incomplete emptying), and quality of life (QOL) score before and 3 months after switching drugs. *P < 0.05, **P < 0.01, ^§P < 0.001 compared to the baseline in each group by Wilcoxon signed rank test.

Figure 5

Magnitude of changes in average monthly ambient temperature from baseline to three months around patients’ residential area obtained from AMeDAS. Notes: Magnitude of change in average monthly ambient temperature from baseline to 3 months in each period equals the average monthly ambient temperature at 2 months minus that at the baseline. Abbreviation: AMeDAS, automated meteorological data acquisition system.

Figure 6

Association between number of parameters with significant change and magnitude of changes in average monthly ambient temperature. Notes: The number of parameters with significant change shown in Table 2 was significantly associated with the magnitude of changes in average monthly ambient temperature from baseline to 3 months (Figure 5) in each period by Spearman rank correlation (P = 0.0322) (n = 217). For the statistical analysis, one significantly improved parameter was assigned as +1 while one significantly deteriorated parameter was assigned as −1.

Figure 7

Changes in IPSS and QOL score by magnitude of changes in average monthly ambient temperature from baseline to three months. Notes: Patients were divided into two groups according to magnitude of change in average monthly ambient temperature from baseline to 3 months higher than 10°C (n = 128) or lower than 10°C (n = 89). Magnitude of change in average monthly ambient temperature from baseline to 3 months in each period equals the average monthly ambient temperature at three months minus that at the baseline. Mean values were plotted for the total International Prostate Symptom Score (IPSS), the scores of individual IPSS items, voiding symptoms (intermittency, weak stream, straining), storage symptoms (daytime frequency, nighttime frequency, urgency), post-voiding symptom (incomplete emptying), and quality of life (QOL) score before and three months after switching drugs. *P < 0.05, ^§P < 0.001 compared to the baseline in each group by Wilcoxon signed rank test.