Department of Mental Health, ASL Salerno, Mental Health Center no. 63, Cava de' Tirreni, Italy; Department of Neurosciences, Medical School "Federico II", University of Naples, Italy.
Pharmacotherapy. 2013 Oct;33(10):1087-106. doi: 10.1002/phar.1313. Epub 2013 Jun 17.
As second-generation antipsychotic long-acting injections (SGA-LAIs) are rapidly replacing depot first-generation antipsychotics as first-line agents in treating schizophrenia spectrum disorders, a systematic assessment of their adverse effects is timely. English-language, peer-reviewed articles reporting original data on the safety and tolerability of SGA-LAIs were identified electronically by searching the MEDLINE, EMBASE, PsycINFO, and DARE databases and the Cochrane Library (January 2001-April 2013). In addition to second-generation (atypical) antipsychotics and long-acting injection (depot) antipsychotics, a separate search was performed for each available drug: aripiprazole LAI, olanzapine pamoate, paliperidone palmitate, and risperidone LAI. Articles were excluded if they were review articles, post hoc analyses, analyses of subsets of patients enrolled in previous trials, single case reports, case series studies, small naturalistic studies (involving less than 50 patients), studies providing no safety data, and studies lasting less than 8 weeks. Of 181 articles identified from the search, 140 were excluded; thus, 41 articles met the inclusion criteria. Predictably, the reviewed information revealed that SGA-LAIs have safety profiles consistent with their oral parent formulations. However, they seem to also show unforeseen and worrisome safety signals. Indeed, the routine use of olanzapine-LAI in clinical practice could be limited not only by the well-known risk of postinjection syndrome, whose clinical management remains a matter of concern, but also by the risk of worsening of psychosis. The reviewed information seems to suggest that worsening of psychotic symptoms and depression could also be associated with both risperidone-LAI and paliperidone palmitate. The leading cause of death among patients enrolled in risperidone-LAI studies was suicide. Given the exponential growth in the clinical use of SGA-LAIs, further studies must be urgently performed in order to confirm or exclude the potential safety signals associated with such drugs.
随着第二代抗精神病长效注射剂（SGA-LAIs）迅速取代第一代长效抗精神病药物，成为治疗精神分裂症谱系障碍的一线药物，对其不良反应进行系统评估是及时的。通过电子搜索 MEDLINE、EMBASE、PsycINFO 和 DARE 数据库以及 Cochrane 图书馆（2001 年 1 月至 2013 年 4 月），我们确定了以英文发表的关于 SGA-LAIs 安全性和耐受性的原始数据的同行评议文章。除了第二代（非典型）抗精神病药物和长效注射（长效）抗精神病药物外，我们还对每种可用药物进行了单独搜索：阿立哌唑 LAI、奥氮平癸酸酯、棕榈酸帕利哌酮和利培酮 LAI。如果文章是综述文章、事后分析、以前试验入组患者亚组分析、个案报告、病例系列研究、小自然主义研究（涉及少于 50 例患者）、未提供安全性数据的研究或持续时间少于 8 周的研究，则将其排除在外。从搜索中确定了 181 篇文章，其中 140 篇被排除在外；因此，有 41 篇文章符合纳入标准。可以预见的是，审查的信息表明，SGA-LAIs 的安全性与它们的口服母体制剂一致。然而，它们似乎也显示出意想不到的、令人担忧的安全信号。事实上，奥氮平 LAI 的常规临床应用不仅可能受到众所周知的注射后综合征风险的限制，而且这种综合征的临床管理仍然令人担忧，还可能受到精神病恶化的风险的限制。审查的信息似乎表明，利培酮 LAI 和棕榈酸帕利哌酮也可能与精神病症状和抑郁恶化有关。在 risperidone-LAI 研究中入组的患者的主要死因是自杀。鉴于 SGA-LAIs 的临床应用呈指数级增长，必须紧急进行进一步研究，以确认或排除与这些药物相关的潜在安全信号。
