- 學位論文
就診前使用經皮吸收曲唑酮藥膏減少貓的緊迫和焦慮
Use of transdermal trazodone prior to veterinary visits for reducing stress and anxiety in cats
摘要
曲唑酮氫氯化合物是一種普遍用於人類及犬病患的選擇型血清素拮抗劑和重吸收抑制劑，也是一種四環類三唑吡啶抗憂鬱劑。此藥在貓病患越來越常被用作於看診前優先經口投予的抗焦慮劑和鎮靜劑。經口投藥對貓飼主來說經常是困難的挑戰，可能因此限制曲唑酮在貓的實用度。為了發展更便利的投藥方式，本次以單中心、隨機的前瞻性研究，評估一款新型的經皮吸收曲唑酮藥膏使用於貓的藥效和安全性。參與的貓隻被隨機分配至每隻貓使用100毫克(低劑量)或每隻貓使用150毫克(高劑量)經皮吸收曲唑酮藥膏的組別，每隻貓會有用藥前和用藥後共兩次就診，這兩次就診分別就是每隻貓自己的控制組和實驗組，過程中會觀察並記錄貓在來回交通上和檢查操作時的行為。我們根據動物行為學和相關的過去文獻設計出一系列評分系統來評估貓的緊迫程度和易處理性，包含貓緊迫評分(cat stress score, CSS)、整體鎮靜評分(global sedation score, GSS)、行為反應評分(behavioral response score, BRS)和飼主的總體經驗評分(overall experience score, OES)。最後將每隻貓用藥前後的就診數據相互比較，包含上述各項評分以及生理數值(呼吸速率、心跳速率、血壓收縮壓、脈搏速率和耳溫)，也會另外評估血液檢驗變化、副作用和藥效反應時間。總共有20隻室內飼養貓參與本研究，其中7隻被分配至低劑量組，另外13隻被分配至高劑量組。在低劑量組，經皮吸收曲唑酮藥膏顯著降低了貓來醫院路上的CSS (P = 0.042)，但回家路上的CSS沒有顯著差異(P = 0.104)。在高劑量組，經皮吸收曲唑酮藥膏顯著降低了貓來醫院(P = 0.005)和回家(P = 0.005)路上的CSS。兩個組別在門診檢查時的CSS和GSS於用藥後都沒有顯著的改變。門診檢查時的BRS在低劑量組(P = 0.034)和高劑量組(P = 0.018)用藥後皆有顯著下降的情形，意即貓在檢查操作時的易處理性增加，但其顯著性依照不同的檢查操作步驟或行為層面來看有不一致的結果。根據OES問卷調查結果，高劑量組的飼主認為貓在使用此藥膏後於來醫院路上(P = 0.002)、回家路上(P = 0.005)和門診檢查(P = 0.003)的緊迫程度都有顯著地減輕，而低劑量組的飼主認為使用此藥膏後貓的緊迫程度只有在來醫院路上獲得顯著改善(P = 0.020)。本研究顯示此藥膏對生理數值以及血檢數值皆無顯著影響，產生的副作用也只佔少數且程度輕微，可見該族群貓對單次100毫克或150毫克經皮吸收曲唑酮藥膏的耐受度佳。透過本篇研究可知，就診前優先使用足夠劑量的經皮吸收曲唑酮藥膏可以減輕貓的緊迫和焦慮，並改善貓與飼主的就醫經驗。對於經皮吸收曲唑酮藥膏降低貓就診時的恐懼與抗拒，未來仍需要進一步的研究以探討更多資訊。
並列摘要
Trazodone hydrochloride is a serotonin antagonist and reuptake inhibitor (SARI) and a tetracyclic triazolopyridine antidepressant commonly used in human and canine patients, and has been gaining its popularity as a pre-appointment anxiolytic and sedative in feline patients. However, the oral administration in cats often challenges the owners and limits the practicality. To find a more convenient route of administration, this study evaluated the efficacy and safety of a novel formulation of transdermal trazodone cream in cats. This was a single-center and randomized prospective study. Enrolled cats were randomly assigned to receive 100 mg/cat (low-dose group) or 150 mg/cat (high-dose group) of transdermal trazodone. Each cat served as its own controlled individual between two different visits (pre- and post-administration), and the behavior during transportation and examination was observed. According to feline behaviorology and previous studies, several assessment scoring systems were designed to help estimate the degree of stress and tractability, including the cat stress score (CSS), global sedation score (GSS), behavioral response score (BRS), and owner-assessed overall experience score (OES). Theses scores along with the respiratory rate (RR), heart rate (HR), systolic blood pressure (SBP), pulse rate (PR) and aural temperature were compared between two visits respectively. Laboratory blood test, adverse effects and response time were also evaluated. Twenty indoor owned cats were enrolled in the study, seven of which were assigned to low-dose group and the other thirteen cats were assigned to high-dose group. In low-dose group, transdermal trazodone lowered CSS of outward trip significantly (P = 0.042), but lower CSS of return trip with no significant difference (P = 0.104). In high-dose group, transdermal trazodone lowered CSS of outward trip (P = 0.005) as well as return trip (P = 0.005) significantly. CSS and GSS of examination didn’t change remarkably in both groups after administration. BRS of examination in low-dose (P = 0.034) and high-dose (P = 0.018) group was lowered significantly by the cream, but the significance was variable in different examination procedures and behavioral aspects. As reported by OES questionnaire, significant reduction of stress was seen during outward trip (P = 0.002), return trip (P = 0.005) and examination (P = 0.003) in high-dose group, but was only seen during outward trip (P = 0.020) in low-dose group. Physiologic parameters (e.g., RR, HR, SBP, PR and aural temperature) and laboratory values were not affected significantly, and adverse effects appeared to be few and mild in the study. Transdermal trazodone was well tolerated in this population of cats at a single dose of 100 mg/cat and 150 mg/cat. Using transdermal trazodone at sufficient dose prior to veterinary visits can reduce stress and anxiety in cats, which is helpful for better patient and owner experience. Further studies are recommended to investigate the use of transdermal trazodone in cats with the aim of decreasing fear and resistance associated with transportation and examination.