Is treatment-resistant schizophrenia categorically distinct from treatment-responsive schizophrenia? a systematic review.
Is treatment-resistant schizophrenia categorically distinct from treatment-responsive schizophrenia? a systematic review.
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DOI：
10.1186/s12888-016-1177-y
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发表时间：
2017-01-13
期刊：
影响因子：
4.4
通讯作者：
MacCabe JH
中科院分区：
文献类型：
--
作者：
Gillespie AL;Samanaite R;Mill J;Egerton A;MacCabe JH
精神分裂症是一种高度异质性的疾病，大约三分之一的患者对治疗有抵抗力。对这些患者的唯一循证治疗是氯氮平，一种多巴胺拮抗作用相对较弱的非典型抗精神病药。对抗精神病药物不同程度的反应反映了不同的疾病亚型，这对研究和临床实践具有重要意义。如果这些亚型可以在疾病发作时区分开来，这可能代表精神病学迈向个性化医疗的第一步。本系统性综述调查了目前的证据是否支持将治疗抵抗性和治疗反应性精神分裂症概念化为分类不同的亚型。使用PubMed、EMBASE、PsycInfo、CINAHL和OpenGrey数据库进行了一次系统性文献检索，以确定所有比较难治性精神分裂症（定义为对两项抗精神病药物试验或氯氮平处方缺乏应答）与治疗应答性精神分裂症（定义为已知对非氯氮平抗精神病药物有应答）的研究。19项中等质量的研究符合纳入标准。最强有力的发现表明，与治疗反应性患者相比，治疗抵抗性患者表现出多巴胺能异常，缺乏多巴胺能异常，灰质显著减少。据报道，耐药患者也有较高的家族负荷;然而，没有个别基因相关研究报告他们的发现生存校正多重比较。初步证据支持将难治性精神分裂症概念化为与治疗反应性精神分裂症完全不同的疾病亚型。然而，研究是有限的，确认将需要复制和严格控制的研究，大样本量和前瞻性研究设计。本文的在线版本（doi：10.1186/s12888-016-1177-y）包含补充材料，可供授权用户使用。
Schizophrenia is a highly heterogeneous disorder, and around a third of patients are treatment-resistant. The only evidence-based treatment for these patients is clozapine, an atypical antipsychotic with relatively weak dopamine antagonism. It is plausible that varying degrees of response to antipsychotics reflect categorically distinct illness subtypes, which would have significant implications for research and clinical practice. If these subtypes could be distinguished at illness onset, this could represent a first step towards personalised medicine in psychiatry. This systematic review investigates whether current evidence supports conceptualising treatment-resistant and treatment-responsive schizophrenoa as categorically distinct subtypes. A systematic literature search was conducted, using PubMed, EMBASE, PsycInfo, CINAHL and OpenGrey databases, to identify all studies which compared treatment-resistant schizophrenia (defined as either a lack of response to two antipsychotic trials or clozapine prescription) to treatment-responsive schizophrenia (defined as known response to non-clozapine antipsychotics). Nineteen studies of moderate quality met inclusion criteria. The most robust findings indicate that treatment-resistant patients show glutamatergic abnormalities, a lack of dopaminergic abnormalities, and significant decreases in grey matter compared to treatment-responsive patients. Treatment-resistant patients were also reported to have higher familial loading; however, no individual gene-association study reported their findings surviving correction for multiple comparisons. Tentative evidence supports conceptualising treatment-resistant schizophrenia as a categorically different illness subtype to treatment-responsive schizophrenia. However, research is limited and confirmation will require replication and rigorously controlled studies with large sample sizes and prospective study designs. The online version of this article (doi:10.1186/s12888-016-1177-y) contains supplementary material, which is available to authorized users.