Londborg P D, Smith W T, Glaudin V, Painter J R
Summit Research Network, 1849 NW Kearney, Suite 201, 97209, Portland, OR, USA.
J Affect Disord. 2000 Dec;61(1-2):73-9. doi: 10.1016/s0165-0327(99)00195-0.
SSRIs resolve depression slowly and may increase anxiety or insomnia. Adding clonazepam to fluoxetine sped response, raising the question of mechanism of action: reducing symptoms co-existing with depression, suppressing side-effects, and/or alleviating core depressive symptoms.
Adult outpatients randomly assigned to double-blind treatment with fluoxetine 20 mg+placebo or fluoxetine+clonazepam 0.5-1.0 mg were assessed by a HAM-D anxiety cluster, sleep disturbance cluster, and core symptoms cluster.
No serious AEs were noted; no cotherapy patients dropped for AEs. Cotherapy proved superior (HAM-D total, anxiety cluster, sleep disturbance cluster ANOVA P<0.001; core symptoms P<0.011). Treatment-emergent anxiety was reported for 25% of placebo patients and 7% of cotherapy patients (P<0.037); sleep disturbance for 10% of placebo patients and no cotherapy patients (P<0.055). Sedation and dry mouth were more common for cotherapy treatment (P>0.20).
Extended treatment and refractory depression were not addressed.
Low-dose cotherapy of fluoxetine with clonazepam was safe and accelerated response over 21 days of treatment, decreasing anxiety and sleep disturbance as symptoms and partially suppressed them as SSRI side-effects; it also modestly reduced core symptoms of low mood and loss of interest.
选择性5-羟色胺再摄取抑制剂（SSRI）缓解抑郁症起效缓慢，且可能会加重焦虑或失眠。在氟西汀中添加氯硝西泮可加快疗效，这引发了关于其作用机制的问题：减轻与抑郁症共存的症状、抑制副作用和/或缓解核心抑郁症状。
将成年门诊患者随机分配至接受20毫克氟西汀+安慰剂或氟西汀+0.5 - 1.0毫克氯硝西泮的双盲治疗，通过汉密尔顿抑郁量表（HAM-D）的焦虑症状群、睡眠障碍症状群和核心症状群进行评估。
未观察到严重不良事件；没有联合治疗的患者因不良事件退出。联合治疗被证明更具优势（HAM-D总分、焦虑症状群、睡眠障碍症状群方差分析P<0.001；核心症状P<0.011）。报告显示，25%的接受安慰剂治疗的患者出现治疗中突发的焦虑，而接受联合治疗的患者中这一比例为7%（P<0.037）；10%接受安慰剂治疗的患者出现睡眠障碍，接受联合治疗的患者中无此情况（P<0.055）。联合治疗中镇静和口干更为常见（P>0.20）。
未涉及延长治疗和难治性抑郁症。
氟西汀与氯硝西泮的低剂量联合治疗在21天的治疗期内安全且能加快疗效，减少作为症状的焦虑和睡眠障碍，并部分抑制其作为SSRI副作用的情况；它还适度减轻了情绪低落和兴趣丧失这些核心症状。
