美沙冬維持治療個案合併睡眠障礙之預測因子及預後探討

Investigation of Predictors and Prognosis for Sleep Problems in Patients Receiving Methadone Maintenance Treatment

李典政(Dian-Jeng Li)

指導教授 ： 顏正芳

高雄醫學大學/醫學院/醫學研究所碩士班/碩士(2018年)

摘要

目的
本研究旨在探討美沙酮替代療法的病人中，若出現顯著需臨床介入的睡眠障礙(clinically predominant sleep disturbance；CPSD)時，是否有早期預測因子，並探討美沙酮劑量與CPSD或其他相關因子的顯著性及關聯性。
方法
本研究為6年期病歷回溯性研究，將使用本院美沙酮替代療法(MMT)之電子及紙本病歷資料庫，截取期間為2011年1月至2017年8月，進行兩階段分析。第一階段為分析6年中，接受MMT的海洛因成癮患者其美沙酮劑量是否能被包括CPSD等因子所顯著預測，並將使用廣義估計方程式來計算；第二部分為2015年1月至2017年8月之區間回溯，將分析是否存在基礎點的因子能有效預測海洛因成癮者在接受MMT過程中新發生的CPSD，並使用Forward conditional模型之多變量Cox比例風險模式來分析前述有顯著相關的預測因子。
結果
在第一階段分析中，總共有1290位病人符合納入條款而被納入。經與其他因子校正後，病人合併有CPSD時美沙酮日劑量相較於沒有合併CPSD高7.03mg，且達統計顯著意義(Estimate: 7.03, 95% of CI: 4.17-9.90, P < 0.001)。就病人的年齡而言，每增加一歲將顯著減少1.22mg的美沙酮日劑量(Estimate: -1.22, 95% of CI: -1.27 to -1.17, P < 0.001)；而對於初始加入MMT的年齡而言，每增加一歲將顯著增加0.44mg的美沙酮日劑量(Estimate: 0.44, 95% of CI: 0.27 to 0.61, P < 0.001)。另外，較低的教育程度 (Estimate: -0.90, 95% of CI: -0.15 to -0.30, P = 0.003)以及較低的出席率(Estimate: -0.14, 95% of CI: -0.27 to -0.01, P = 0.033)顯著與較高的美沙酮日劑量有相關。而性別、就業狀態，以及婚姻狀態並不顯著影響美沙酮日劑量。
第二階段共有152位病人符合納入條款被收入分析。經多變量校正後，越早的初始使用海洛因年齡（Odds= 0.95; P=0.044）、較低的出席率（Odds= 0.04; P=0.03）、較高的最大美沙酮劑量（Odds= 1.01; P=0.022）、和較短的初診至調至最大美沙酮劑量中間的時間（Odds= 0.98; P=0.007），依然與新發生的CPSD顯著相關
結論
本研究的第一階段分析闡明了CPSD與較高的美沙酮日劑量有顯著高相關性，另外，較低的年齡、較高的初始加入MMT年齡、較低的教育程度，以及較低的出席率，亦顯著與較高的美沙酮日劑量有相關。第二階段分析發現：越早的初始使用海洛因年齡、較低的出席率、較高的最大美沙酮劑量、較短的初診至調至最大美沙酮劑量中間之時間，可作為新形成CPSD之預測因子。

關鍵字

美沙酮 ； 睡眠障礙 ； 預測因子 ； 鴉片類藥物

並列摘要

Objective: This study aimed to investigate the predictive effect of clinically predominant sleep disturbance (CPSD) on the dose of methadone among opiate users receiving MMT during a follow-up period of 6 years in Taiwan. Moreover, it also aimed to investigate the predictors for new-onset CPSD
Methods: This retrospective study included two parts of analysis. Initially, a 6-years (2011/Jan - 2017/Aug) retrospective cohort was analyzed. Generalized estimating equations were used to analyze the effect of CPSD on the daily dose of methadone by controlling for the effects of demographic and MMT characteristics. Furthermore, we used a 2-years cohort (2015/Jan - 2017/Aug) to analyze. A univariate Cox proportional hazards regression model (Cox model) was used to estimate the potential factors of subsequent CPSD, followed by a multivariate Cox model to identify significant predictors of CPSD after adjusting for other covariates.
Results: A total of 1290 individuals were included in the first part of analysis. After controlling for the effects of demographic and MMT characteristics, the participants comorbid with CPSD had a higher dose of daily methadone than those without CPSD (estimate: 7.03, P<0.001). Furthermore, younger age (estimate: -1.22, P<0.001), older age at initial MMT (estimate: 0.44, P<0.001), lower educational level (estimate: -0.90, P=0.003) and lower attendance rates (estimate: -0.14, P=0.033) are significantly related to higher doses of daily methadone. Furthermore, a total of 152 subjects were included for advanced analysis. After forward selection in the Cox model, earlier age at onset of opioid exposure (odds ratio [OR]=0.95; P=0.044), lower attendance rate (OR=0.04; P=0.03), greater maximum dose of methadone (OR=1.01; P=0.022), and shorter time to maximum methadone dose (OR=0.98; P=0.007) were significantly associated with new-onset CPSD.
Conclusions: We reported that a higher daily dose of methadone was significantly associated with CPSD after controlling for the effects of other factors. CPSD should be routinely surveyed among heroin users receiving MMT. Furthermore, we identified predictors that were significantly associated with new-onset CPSD, and clinicians should be aware of sleep disturbance in heroin users receiving MMT with these risk factors. Future studies are necessary to verify our findings and extend the applicability.

並列關鍵字

Methadone ； sleep disturbance ； predictors ； opioid

參考文獻

Ancoli-Israel, S., Roth, T., 1999. Characteristics of insomnia in the United States: results of the 1991 National Sleep Foundation Survey. I. Sleep 22 Suppl 2, S347-353.

Anderson, I.B., Kearney, T.E., 2000. Use of methadone. West J Med 172, 43-46.

Angarita, G.A., Emadi, N., Hodges, S., Morgan, P.T., 2016. Sleep abnormalities associated with alcohol, cannabis, cocaine, and opiate use: a comprehensive review. Addict Sci Clin Pract 11, 9.

Athanasos, P., Smith, C.S., White, J.M., Somogyi, A.A., Bochner, F., Ling, W., 2006. Methadone maintenance patients are cross-tolerant to the antinociceptive effects of very high plasma morphine concentrations. Pain 120, 267-275.

Baglioni, C., Battagliese, G., Feige, B., Spiegelhalder, K., Nissen, C., Voderholzer, U., Lombardo, C., Riemann, D., 2011. Insomnia as a predictor of depression: a meta-analytic evaluation of longitudinal epidemiological studies. J Affect Disord 135, 10-19.