Harvey Rebecca C, James Anthony C, Shields Gemma E
BresMed Health Solutions, North Church Business House, 84 Queen Street, Sheffield, S1 2DW, UK.
Highfield Unit Oxford, Warneford Hospital, Oxford, UK.
CNS Drugs. 2016 Jan;30(1):27-39. doi: 10.1007/s40263-015-0308-1.
Early-onset schizophrenia (EOS) is a serious debilitating disorder with considerable morbidity and a reduced life expectancy; therefore, early diagnosis and effective treatments are particularly important. Negative symptoms are more prominent in adolescents and children (compared with adults), and are key predictors of worse functional and clinical outcomes in EOS. Therefore, this study aimed to explore the relative efficacy of antipsychotics used in the treatment of EOS, with a focus on studies reporting effectiveness using the Positive and Negative Syndrome scale (PANSS), a scale that includes an overall symptom measure, in addition to separate subscales for positive and, importantly, negative symptoms.
A systematic literature review was conducted using the MEDLINE and Cochrane Central Register of Controlled Trials databases to identify trials conducted in children and adolescents with schizophrenia, and symptom control was reported using the PANSS. A Bayesian random-effects network meta-analysis was performed, synthesising data for a number of outcomes, including mean change from baseline in PANSS scores, treatment discontinuation and weight gain.
Eleven studies were included in the evidence synthesis, comprising 1714 patients across eight active interventions (aripiprazole, haloperidol, molindone, olanzapine, paliperidone, quetiapine, risperidone and ziprasidone) and placebo. All treatments showed a greater reduction in total PANSS scores vs placebo; however, only three interventions (molindone, olanzapine and risperidone) were associated with a statistically significant reduction in total PANSS scores at 6 weeks vs placebo. Haloperidol had the greatest reduction vs placebo; however, this result was not statistically significant [mean difference, -15.6, 95% credible interval (-35.4, 4.1)]. Haloperidol, olanzapine and risperidone showed a statistically significant reduction in positive PANSS scores vs placebo; however, whilst all interventions showed a trend of reduction in negative PANSS scores vs placebo, no comparisons were statistically significant.
Many of the treatments are efficacious in controlling symptoms, and all showed a trend of superiority vs placebo for total, positive and negative PANSS scores, although only olanzapine and risperidone yielded statistically significant results vs placebo for both total and positive PANSS scores. Varying results for discontinuation and weight gain demonstrate a need to balance efficacy with side-effect profiles.
早发性精神分裂症（EOS）是一种严重的致残性疾病，发病率高且预期寿命缩短；因此，早期诊断和有效治疗尤为重要。阴性症状在青少年和儿童中（与成人相比）更为突出，并且是EOS中功能和临床结局较差的关键预测因素。因此，本研究旨在探讨用于治疗EOS的抗精神病药物的相对疗效，重点关注使用阳性和阴性症状量表（PANSS）报告有效性的研究，该量表除了有阳性症状和重要的阴性症状的单独子量表外，还包括一个总体症状测量。
使用MEDLINE和Cochrane对照试验中央注册库数据库进行系统的文献综述，以识别在患有精神分裂症的儿童和青少年中进行的试验，并使用PANSS报告症状控制情况。进行了贝叶斯随机效应网络荟萃分析，综合了多个结局的数据，包括PANSS评分相对于基线的平均变化、治疗中断和体重增加。
证据综合纳入了11项研究，包括1714名患者，涉及8种活性干预措施（阿立哌唑、氟哌啶醇、吗茚酮、奥氮平、帕利哌酮、喹硫平、利培酮和齐拉西酮）和安慰剂。与安慰剂相比，所有治疗的PANSS总分均有更大程度的降低；然而，只有三种干预措施（吗茚酮、奥氮平和利培酮）在6周时与安慰剂相比，PANSS总分有统计学意义的降低。与安慰剂相比，氟哌啶醇的降低幅度最大；然而，这一结果无统计学意义[平均差，-15.6，95%可信区间（-35.4，4.1）]。与安慰剂相比，氟哌啶醇、奥氮平和利培酮的PANSS阳性评分有统计学意义的降低；然而，虽然所有干预措施与安慰剂相比阴性PANSS评分均有降低趋势，但无比较具有统计学意义。
许多治疗方法在控制症状方面有效，并且在PANSS总分、阳性和阴性评分方面，所有治疗与安慰剂相比均显示出优势趋势，尽管只有奥氮平和利培酮在PANSS总分和阳性评分方面与安慰剂相比产生了统计学意义的结果。治疗中断和体重增加的结果各异，表明需要在疗效和副作用之间进行平衡。
