据9月28日出版的《美国医学会杂志》(JAMA)上发表的一项Meta分析，非典型抗精神病药物目前广泛存在超适应证使用，但其中仅少数有效。
非典型抗精神病药物获准用于精神分裂症和双相型障碍，部分药物可选择性用于抑郁症。但近年来该类药物的使用范围迅速扩大，据估计在1995~2008年间超适应证使用翻番。为评估非典型抗精神病药物超适应证使用的疗效，南加州循证实践中心、兰德健康中心的Alicia Ruelaz Maher博士及其同事查阅了2011年5月以前发表的有关阿立哌唑、阿塞纳平、伊潘立酮、帕潘立酮、喹硫平、利培酮以及齐拉西酮超适应证使用的2,066篇文章，对162项疗效试验和231项针对不良事件的试验或大规模观察性研究进行了Meta分析。
结果显示，阿立哌唑、奥氮平和利培酮与痴呆症行为症状治疗获益呈微弱但具有统计学意义的相关性。这些药物可改善精神状态、激动、幻觉、多疑、烦躁、焦虑、攻击行为、脱抑制和冷漠等症状，但作用有限，仅能达到临床上可观察到的最小改变。在最近3项大规模试验中，喹硫平可使广泛性焦虑障碍患者显著受益。但鉴于结果并不一致且所有试验均由药品生产商资助，所以证据强度属于中等。利培酮可显著改善强迫性神经官能症(OCD)，但由于发表偏倚影响合并结果，其可信性大打折扣。喹硫平用于OCD患者的证据强度已由既往分析的中度降至低度。没有充分证据支持非典型抗精神病药物用于物质滥用、饮食障碍或失眠症，用于创伤后应激障碍(PTSD)和人格障碍的证据则存在争议，利培酮与改善PTSD相关性较弱。
研究者强调，大多数研究是由药品制造商资助，包括38项痴呆试验中的27项，14项焦虑试验中的12项。3种最新的非典型抗精神病药物阿塞那平、伊潘立酮和帕潘立酮均未见超适应证使用的相关研究报道。此外，本次分析没有纳入2011年6月1日以后发表的研究结果，包括一项利培酮用于PTSD军人患者和选择性5-HT再摄取抑制剂(SSRI) 抵抗症状的大规模随机对照试验。尽管如此，研究者认为，Meta分析将会对临床医生超适应证使用非典型抗精神病药物提供指导。
该研究由美国保健研究与质量管理局资助，并得到美国退伍军人事务部的部分资助。Maher博士的一位同事报告与礼来公司存在利益关系。
相关英文论文摘要：
Efficacy and Comparative Effectiveness of Atypical Antipsychotic Medications for Off-Label Uses in Adults
Context Atypical antipsychotic medications are commonly used for off-label conditions such as agitation in dementia, anxiety, and obsessive-compulsive disorder.
Objective To perform a systematic review on the efficacy and safety of atypical antipsychotic medications for use in conditions lacking approval for labeling and marketing by the US Food and Drug Administration.
Data Sources and Study Selection Relevant studies published in the English language were identified by searches of 6 databases (PubMed, EMBASE, CINAHL, PsycInfo, Cochrane DARE, and CENTRAL) from inception through May 2011. Controlled trials comparing an atypical antipsychotic medication (risperidone, olanzapine, quetiapine, aripiprazole, ziprasidone, asenapine, iloperidone, or paliperidone) with placebo, another atypical antipsychotic medication, or other pharmacotherapy for adult off-label conditions were included. Observational studies with sample sizes of greater than 1000 patients were included to assess adverse events.
Data Extraction Independent article review and study quality assessment by 2 investigators.
Data Synthesis Of 12 228 citations identified, 162 contributed data to the efficacy review. Among 14 placebo-controlled trials of elderly patients with dementia reporting a total global outcome score that includes symptoms such as psychosis, mood alterations, and aggression, small but statistically significant effects sizes ranging from 0.12 and 0.20 were observed for aripiprazole, olanzapine, and risperidone. For generalized anxiety disorder, a pooled analysis of 3 trials showed that quetiapine was associated with a 26% greater likelihood of a favorable response (defined as at least 50% improvement on the Hamilton Anxiety Scale) compared with placebo. For obsessive-compulsive disorder, risperidone was associated with a 3.9-fold greater likelihood of a favorable response (defined as a 25% improvement on the Yale-Brown Obsessive Compulsive Scale) compared with placebo. In elderly patients, adverse events included an increased risk of death (number needed to harm [NNH] = 87), stroke (NNH = 53 for risperidone), extrapyramidal symptoms (NNH = 10 for olanzapine; NNH = 20 for risperidone), and urinary tract symptoms (NNH range = 16-36). In nonelderly adults, adverse events included weight gain (particularly with olanzapine), fatigue, sedation, akathisia (for aripiprazole), and extrapyramidal symptoms.
Conclusions Benefits and harms vary among atypical antipsychotic medications for off-label use. For global behavioral symptom scores associated with dementia in elderly patients, small but statistically significant benefits were observed for aripiprazole, olanzapine, and risperidone. Quetiapine was associated with benefits in the treatment of generalized anxiety disorder, and risperidone was associated with benefits in the treatment of obsessive-compulsive disorder; however, adverse events were common.
