Rapeli Pekka, Fabritius Carola, Alho Hannu, Salaspuro Mikko, Wahlbeck Kristian, Kalska Hely
Unit for Drug Dependence, Department of Psychiatry, Helsinki University Central Hospital, Helsinki, Finland.
BMC Clin Pharmacol. 2007 Jun 12;7:5. doi: 10.1186/1472-6904-7-5.
Both methadone- and buprenorphine-treated opioid-dependent patients frequently show cognitive deficits in attention, working memory, and verbal memory. However, no study has compared these patient groups with each other during early opioid substitution treatment (OST). Therefore, we investigated attention, working memory, and verbal memory of opioid-dependent patients within six weeks after the introduction of OST in a naturalistic setting and compared to those of healthy controls.
The sample included 16 methadone-, 17 buprenorphine/naloxone-treated patients, and 17 healthy controls matched for sex and age. In both groups buprenorphine was the main opioid of abuse during the recent month. Benzodiazepine codependence, recent use, and comedication were also common in both patient groups. Analysis of variance was used to study the overall group effect in each cognitive test. Pair-wise group comparisons were made, when appropriate
Methadone-treated patients, as a group, had significantly slower simple reaction time (RT) compared to buprenorphine/naloxone-treated patients. In Go/NoGo RT methadone patients were significantly slower than controls. Both patient groups were significantly debilitated compared to controls in working memory and verbal list learning. Only methadone patients were inferior to controls in story recall. In simple RT and delayed story recall buprenorphine/naloxone patients with current benzodiazepine medication (n = 13) were superior to methadone patients with current benzodiazepine medication (n = 13). When methadone patients were divided into two groups according to their mean dose, the patient group with a low dose (mean 40 mg, n = 8) showed significantly faster simple RT than the high dose group (mean 67 mg, n = 8).
Deficits in attention may only be present in methadone-treated early phase OST patients and may be dose-dependent. Working memory deficit is common in both patient groups. Verbal memory deficit may be more pronounced in methadone-treated patients than in buprenorphine/naloxone-treated patients. In sum, to preserve cognitive function in early OST, the use of buprenorphine/naloxone may be more preferable to methadone use of, at least if buprenorphine has been recently abused and when benzodiazepine comedication is used. Longitudinal studies are needed to investigate if the better performance of buprenorphine/naloxone-treated patients is a relatively permanent effect or reflects "only" transient opioid switching effect.
接受美沙酮和丁丙诺啡治疗的阿片类药物依赖患者经常表现出注意力、工作记忆和言语记忆方面的认知缺陷。然而,尚无研究在阿片类药物替代治疗(OST)早期对这些患者群体进行相互比较。因此,我们在自然环境中对接受OST治疗六周内的阿片类药物依赖患者的注意力、工作记忆和言语记忆进行了调查,并与健康对照组进行了比较。
样本包括16名接受美沙酮治疗、17名接受丁丙诺啡/纳洛酮治疗的患者以及17名年龄和性别匹配的健康对照者。在两组中,丁丙诺啡是近一个月内主要滥用的阿片类药物。苯二氮䓬类药物共病、近期使用情况及合并用药在两组患者中也较为常见。采用方差分析研究各认知测试中的总体组效应。在适当情况下进行组间两两比较。
作为一个群体,接受美沙酮治疗的患者与接受丁丙诺啡/纳洛酮治疗的患者相比,简单反应时间(RT)明显更慢。在Go/NoGo反应时间测试中,美沙酮治疗的患者明显比对照组慢。与对照组相比,两组患者在工作记忆和言语列表学习方面均明显受损。只有美沙酮治疗的患者在故事回忆方面不如对照组。在简单反应时间和延迟故事回忆方面,目前正在服用苯二氮䓬类药物的丁丙诺啡/纳洛酮治疗患者(n = 13)优于目前正在服用苯二氮䓬类药物的美沙酮治疗患者(n = 13)。当根据平均剂量将美沙酮治疗的患者分为两组时,低剂量组(平均40 mg,n = 8)的简单反应时间明显快于高剂量组(平均67 mg,n = 8)。
注意力缺陷可能仅存在于接受美沙酮治疗的OST早期患者中,且可能与剂量有关。工作记忆缺陷在两组患者中都很常见。言语记忆缺陷在接受美沙酮治疗的患者中可能比接受丁丙诺啡/纳洛酮治疗的患者更明显。总之,为了在OST早期保留认知功能,使用丁丙诺啡/纳洛酮可能比使用美沙酮更可取,至少在丁丙诺啡近期被滥用且使用苯二氮䓬类药物合并用药的情况下如此。需要进行纵向研究来调查接受丁丙诺啡/纳洛酮治疗的患者表现更好是相对持久的效应还是仅反映“短暂的阿片类药物转换效应”。