University of Genova, Department of Psychiatry, Genoa, Italy.
Ann Gen Psychiatry. 2011 Feb 28;10(1):5. doi: 10.1186/1744-859X-10-5.
Serotonin reuptake inhibitors (SRIs) currently represent the cornerstone of obsessive-compulsive disorder (OCD) pharmacotherapy. However, OCD is characterized by high rates of partial and/or absent response to standard, recommended treatments, often prompting pharmacological and non-pharmacological augmentation or switching of strategies. Agomelatine, a novel melatonin agonist and selective serotonin antagonist (MASSA) antidepressant approved for major depressive disorder (MDD) has recently been additionally proposed as a treatment for anxiety disorders such as social anxiety disorder (SAD) and panic disorder (PD), but not yet OCD. Nonetheless, agomelatine may have a role in the management of OCD, essentially due to its anxiolytic 5-hydroxytryptamine (HT)2C blockade action, while melatonin (MT)1 and MT2 modulation might contribute to circadian rhythm restoration if impaired.
This case series reports the outcome of six patients with or without comorbid mood and/or other anxiety disorders who were treated with SRIs at adequate doses for at least 8 weeks, showing partial or no response. Patients were then switched to agomelatine 50 mg/day, and followed up for 12 weeks.
Three out of six patients, in particular those with relevant circadian rhythm subjective impairment, showed a Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score reduction of ≥35%. No relevant side effects were observed, but initial, transient, self-remitting dizziness in one patient and weight gain in another were seen.
Although clinical confounding factors (subthreshold bipolarity and eventually the presence of impaired circadian rhythms) and methodological boundaries (lack of control and neurophysiological recording, tiny sample size and short follow-up) limit the validity of this preliminary observation, it does indicate agomelatine may have a role in some SRI-refractory OCD cases, thus prompting the validity of investigation by further controlled studies, even for drug-naïve OCD patients.
目前，选择性 5-羟色胺再摄取抑制剂（SSRIs）是治疗强迫症（OCD）的基石。然而，OCD 的特征是对标准推荐治疗的部分和/或完全无反应率较高，这常常促使采用药理学和非药理学的增强或策略转换。阿戈美拉汀，一种新型褪黑素激动剂和选择性 5-羟色胺 2C 拮抗剂（MASSA）抗抑郁药，已被批准用于治疗重度抑郁症（MDD），最近还被提议用于治疗焦虑症，如社交焦虑症（SAD）和惊恐障碍（PD），但尚未用于 OCD。尽管如此，阿戈美拉汀可能在 OCD 的治疗中发挥作用，主要是由于其抗焦虑 5-羟色胺（HT）2C 阻断作用，而褪黑素（MT）1 和 MT2 的调节可能有助于恢复昼夜节律，如果受损的话。
本病例系列报告了 6 名患者的结果，这些患者或伴有或不伴有共病情绪和/或其他焦虑障碍，在接受足够剂量的 SSRIs 治疗至少 8 周后，显示出部分或无反应。然后，患者被转换为阿戈美拉汀 50mg/天，并随访 12 周。
6 名患者中有 3 名，特别是那些有相关昼夜节律主观损害的患者，耶鲁-布朗强迫症量表（Y-BOCS）评分降低≥35%。未观察到相关的不良反应，但有 1 名患者出现初始、短暂、自限性头晕，另 1 名患者出现体重增加。
尽管临床混杂因素（亚阈值双相性和最终存在昼夜节律受损）和方法学界限（缺乏对照和神经生理记录、样本量小和随访时间短）限制了这一初步观察的有效性，但它确实表明阿戈美拉汀可能在一些 SRI 难治性 OCD 病例中发挥作用，从而促使通过进一步的对照研究来验证其有效性，甚至对药物初治的 OCD 患者也是如此。
