Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada.
British Columbia Mental Health and Substance Use Services, Vancouver, British Columbia, Canada.
Psychother Psychosom. 2020;89(3):151-160. doi: 10.1159/000505876. Epub 2020 Feb 11.
It is not uncommon to find obsessive-compulsive symptoms (OCS) in patients treated with clozapine. These symptoms are attributed to anti-serotonergic effects of clozapine. The objective of this study was to conduct a systematic review of reported cases of clozapine-associated OCS to better understand the nature and management of these symptoms.
MEDLINE, Embase, and PsycINFO databases were searched with no publication year or language restrictions. Studies reporting cases of clozapine-associated OCS, either de novo or exacerbation of preexisting OCS, were included. The final search date was July 11, 2019.
Fifty-seven studies, involving 107 cases (75 de novo, 32 exacerbated OCS), were included. Clozapine triggered moderate-severe OCS at varying doses (100-900 mg/day) and treatment durations (median 6 months, interquartile range 2-24 months). Higher severity was significantly associated with preexisting OCS, poorer insight into OCS, and active psychosis at the time of OCS. Common strategies to treat clozapine-associated OCS included adding selective serotonin reuptake inhibitors, clomipramine, or aripiprazole, often accompanied by clozapine dose reduction. The rate of response to antidepressants was 49% (29/59), where younger age, shorter duration of underlying illness, shorter cloza-pine treatment duration, better insight into OCS, and presence of taboo thoughts were significantly associated with antidepressant response. Subsequent clozapine dose reduction was effective in many non-responders, where aripiprazole was simultaneously added in 50% (8/16).
Clozapine can trigger severe OCS. Adding aripiprazole with/without clozapine dose reduction may be a good alternative to antidepressants for managing clozapine-associated OCS. Clinicians should be more vigilant about these adverse effects and administer appropriate treatments.
氯氮平治疗的患者中常出现强迫症状（OCS）。这些症状归因于氯氮平的抗血清素能作用。本研究的目的是对氯氮平相关 OCS 的报告病例进行系统回顾，以更好地了解这些症状的性质和管理。
无发表年限或语言限制地检索了 MEDLINE、Embase 和 PsycINFO 数据库。纳入报告氯氮平相关 OCS 的病例研究，包括新出现的 OCS 或原有 OCS 的恶化。最终检索日期为 2019 年 7 月 11 日。
共纳入 57 项研究，涉及 107 例（75 例新出现的 OCS，32 例恶化的 OCS）。氯氮平以不同剂量（100-900mg/天）和治疗时间（中位数 6 个月，四分位距 2-24 个月）引发中重度 OCS。较高的严重程度与原有 OCS、对 OCS 的洞察力较差以及 OCS 时的活跃精神病显著相关。治疗氯氮平相关 OCS 的常见策略包括加用选择性 5-羟色胺再摄取抑制剂、氯米帕明或阿立哌唑，通常同时减少氯氮平剂量。抗抑郁药的反应率为 49%（29/59），年龄较小、潜在疾病持续时间较短、氯氮平治疗时间较短、对 OCS 的洞察力较好以及存在禁忌思维与抗抑郁药反应显著相关。随后的氯氮平剂量减少对许多无反应者有效，其中 50%（8/16）同时加用阿立哌唑。
氯氮平可引发严重 OCS。加用阿立哌唑和/或减少氯氮平剂量可能是治疗氯氮平相关 OCS 的抗抑郁药的替代方案。临床医生应更加警惕这些不良反应，并给予适当的治疗。
