Major Depressive Disorder and Patient Satisfaction in Relation to Methadone Pharmacokinetics and Pharmacodynamics in Stabilized Methadone Maintenance Patients
Major Depressive Disorder and Patient Satisfaction in Relation to Methadone Pharmacokinetics and Pharmacodynamics in Stabilized Methadone Maintenance Patients
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DOI：
10.1097/jcp.0b013e318192eb00
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发表时间：
2009-02-01
影响因子：
2.9
通讯作者：
Sproule, Beth Ann
中科院分区：
文献类型：
--
作者：
Elkader, Alexander K.;Brands, Bruna;Sproule, Beth Ann
许多参加美沙酮维持治疗的患者经历了显著的剂量间阿片类药物戒断。情绪状态与患者对治疗的满意度有关，并可能影响美沙酮患者如何经历阿片类药物戒断。本研究的目的是探讨美沙酮维持治疗患者中抑郁症对美沙酮反应的影响。17例美沙酮患者（7例抑郁和10例非抑郁）在一个24小时给药间隔内进行了药代动力学和药效学评估（阿片类药物戒断、药物作用和情绪）。受试者还根据他们对美沙酮治疗的满意度进行了划分：12名持有者和5名非持有者。根据成瘾研究中心量表的测量，抑郁受试者经历了更多的焦虑阿片类药物效应（效应与时间曲线下面积，14 32 vs-31 +/- 47 P <0. 04），并且在主观阿片类药物戒断量表上得分较高（效应与时间曲线下面积，33 97 vs-74 +/- 67。P < 0.02）。汉密尔顿抑郁评分与谷主观阿片类戒断量表评分显著相关（r = 0.7。P < 0.004）。与持有者相比，非持有者对未结合的（S）-美沙酮的暴露显著更高，具体而言：谷浓度（6.1 ± 2.7 ng/mL vs 2.7 ± 1.7 ng/mL，P < 0.01），平均稳态浓度（7.6 +/- 4.0 ng/mL vs 4.1 +/- 2.5 ng/mL，P < 0.05），最大浓度（14.6 +/- 7.1 ng/mL vs 7.5 +/- 4.2 ng/mL，P < 0.04）和曲线下面积（183 95 h*ng/mL vs 99 +/- 61 h*ng/mL，P < 0.05）。研究结果显示，（S）-美沙酮可能与病人对美沙酮治疗不满有关。抑郁的美沙酮患者可能对阿片类药物的负作用和阿片类药物戒断更敏感。
Many patients enrolled in methadone maintenance treatment experience significant interdose opioid withdrawal. Mood states have been related to patient satisfaction with treatment and may influence how methadone patients experience opioid withdrawal. The objective of this study was to investigate the influence of major depressive disorder on response to methadone in patients on methadone maintenance treatment. Seventeen methadone patients (7 depressed and 10 not depressed) had pharmacokinetic and pharmacodynamic assessments (opioid withdrawal, drug effects, and mood) over one 24-hour dosing interval. Subjects were also divided based on their satisfaction with methadone treatment: 12 holders and 5 nonholders. Depressed subjects experienced more dysphoric opioid effects as measured by the Addiction Research Centre Inventory (area tinder the effect versus time curve, 14 32 vs -31 +/- 47 P < 0.04) and had higher scores on the Subjective Opioid Withdrawal Scale (area under the effect versus time curve, 33 97 vs -74 +/- 67. P < 0.02) over the dosage interval. Hamilton Depression scores significantly correlated with trough subjective opioid withdrawal scale scores (r = 0.7. P < 0.004). Nonholders had significantly higher exposure to unbound (S)-methadone compared with holders, specifically: trough concentration (6.1 +/- 2.7 ng/mL vs 2.7 +/- 1.7 ng/mL, P < 0.01), average steady-state concentration (7.6 +/- 4.0 ng/mL vs 4.1 +/- 2.5 ng/mL, P < 0.05), maximum concentration (14.6 +/- 7.1 ng/mL vs 7.5 +/- 4.2 ng/mL, P < 0.04), and area under the curve (183 95 h*ng/mL vs 99 +/- 61 h*ng/mL, P < 0.05). Study findings Suggest that (S)-methadone may relate to patients' dissatisfaction with methadone treatment. Depressed methadone patients may be more sensitive to negative opioid effects and opioid withdrawal.