Poyares Dalva, Guilleminault Christian, Ohayon Maurice M, Tufik Sergio
Disciplina de Medicina e Biologia do Sono, Departamento de Psicobiologia da Universidade Federal de São Paulo, Brazil.
J Psychiatr Res. 2004 May-Jun;38(3):327-34. doi: 10.1016/j.jpsychires.2003.10.003.
We studied the sleep of patients with insomnia during continuous and very long-term use of benzodiazepines (BZDs), and after withdrawal. A group of 25 patients (mean age 44.3+/-11.8 years) with persistent insomnia, who had been taking BZDs nightly for 6.8+/-5.4 years was selected. The control group was comprised of 18 age-matched healthy individuals. Sleep stage parameters were analyzed during Night 1 (while taking BZDs), Night 2 (first night after completing BZD withdrawal), and Night 3 (15 days after gradual BZD withdrawal). Sleep data for control subjects was monitored in parallel. Sleep EEGs of the patients were analyzed using Period Amplitude Analysis (PAA), during Nights 1 and 3 only. During BZD use, a significant reduction of Total Sleep Time (TST) and increased sleep latency were found in the insomniac group when compared to controls. We found an increase in stage 2 non-REM (NREM) sleep, and a reduction in Slow Wave Sleep (SWS) when comparing to night 3 (after withdrawal). Sleep EEGs analysis showed an increase in sigma band and decrease in delta count in stages 2, 3, 4 NREM and REM sleep in the BZD group when comparing to night 3 (after withdrawal). During the BZD withdrawal period, six out of nine subjects taking lorazepam failed withdrawal. In the remaining 19 subjects, gradual withdrawal of BZDs was associated with immediate worsening of nocturnal sleep, as indicated by sleep parameters. However, 15 days after withdrawal (Night 3), some of the sleep structure parameters of patients were not significantly different from baseline (while taking BZDs), except for a significant increase in SWS and in delta count throughout most sleep stages, and a decrease in stage 2 NREM sleep. These values were not different from those shown by control subjects. REM sleep parameters showed no significant variation across the experimental conditions. Subjective sleep quality was significantly improved on Night 3 compared with Night 1.
Chronic intake of BZDs may be associated with poor sleep in this population. A progressive 15-day withdrawal did not avoid an immediate worsening of sleep parameters. But at the end of the protocol, SWS, delta count, and sleep quality were improved compared to those recorded during the chronic BZD intake, despite the lack of change in sleep efficiency.
我们研究了长期持续使用苯二氮䓬类药物(BZDs)及停药后失眠患者的睡眠情况。选取了25例持续性失眠患者(平均年龄44.3±11.8岁),他们每晚服用BZDs已达6.8±5.4年。对照组由18名年龄匹配的健康个体组成。在第1晚(服用BZDs期间)、第2晚(完成BZD停药后的第1晚)和第3晚(逐渐停用BZD 15天后)分析睡眠阶段参数。同时对对照组受试者的睡眠数据进行监测。仅在第1晚和第3晚使用周期振幅分析(PAA)对患者的睡眠脑电图进行分析。在使用BZD期间,与对照组相比,失眠组总睡眠时间(TST)显著减少,睡眠潜伏期增加。与第3晚(停药后)相比,我们发现2期非快速眼动(NREM)睡眠增加,慢波睡眠(SWS)减少。睡眠脑电图分析显示,与第3晚(停药后)相比,BZD组在2期、3期、4期NREM睡眠和快速眼动睡眠中的σ频段增加,δ波数量减少。在BZD停药期间,服用劳拉西泮的9名受试者中有6名停药失败。在其余19名受试者中,如睡眠参数所示,逐渐停用BZDs与夜间睡眠立即恶化有关。然而,停药15天后(第3晚),患者的一些睡眠结构参数与基线(服用BZDs期间)无显著差异,只是在大多数睡眠阶段SWS和δ波数量显著增加,2期NREM睡眠减少。这些数值与对照组受试者所示数值无差异。快速眼动睡眠参数在各实验条件下无显著变化。与第1晚相比,第3晚主观睡眠质量显著改善。
长期服用BZDs可能与该人群睡眠质量差有关。为期15天的逐渐停药并不能避免睡眠参数立即恶化。但在实验结束时,与长期服用BZD期间记录的数据相比,SWS、δ波数量和睡眠质量均有所改善,尽管睡眠效率没有变化。