Assessing cognitive function in bipolar disorder: challenges and recommendations for clinical trial design.
Assessing cognitive function in bipolar disorder: challenges and recommendations for clinical trial design.
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DOI：
10.4088/jcp.14cs09399
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发表时间：
2015-03
期刊：
影响因子：
--
通讯作者：
Calabrese JR
中科院分区：
文献类型：
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作者：
Burdick KE;Ketter TA;Goldberg JF;Calabrese JR
精神分裂症的神经认知功能障碍已被确认超过一个世纪。相比之下，直到最近才认识到双相情感障碍中存在显著的神经认知缺陷。汇聚的数据表明，认知问题的重要性，在双相情感障碍的生活质量，强调需要治疗和预防工作，针对双相情感障碍患者的认知。未来针对认知缺陷的治疗试验将遇到方法学挑战，因为这种疾病固有的复杂性和异质性，包括显著的诊断合并症、疾病的发作性、频繁使用多种药物、认知异质性以及缺乏关于双相情感障碍患者认知和结局测量的共识。需要为设计未来试验提供指南。共识小组的成员（每位署名作者）是根据他们在双相情感障碍方面的专业知识选择的。Burdick博士是一位神经心理学家，他研究这种疾病的认知已有15年; Ketter博士，Calabrese博士和Goldberg博士在对照临床试验内外都带来了相当多的双相情感障碍治疗方面的专业知识。该共识声明源自科学会议（例如，美国临床精神药理学学会2014年年会上的专题讨论会等）的共同工作以及通过电话会议进行的持续讨论。除关于这一专题的公开介绍外，这些会议均不对外部与会者开放。作者进行了文献综述，以确定与双相情感障碍神经认知治疗试验的设计和实施相关的疾病特异性挑战。每个作者的专家意见指导了共识建议。本文提供了作者一致意见达成的共识建议，作为未来试验设计的初步指南。建议包括排除某些综合征水平的共病诊断和当前情感不稳定，限制药物的数量和类型，以及使用预筛选评估，以确保入组的受试者具有足够的基线认知损害客观证据。解决双相情感障碍认知缺陷的临床试验面临独特的设计挑战。随着这些试验从概念验证转向临床疗效确认，重要的是要纳入独特的设计修改，以充分应对这些挑战，并增加证明认知修复效果的可能性。该领域现在已准备好应对这些挑战，下一个至关重要的步骤是全面努力正式确定最佳做法准则。
Neurocognitive impairment in schizophrenia has been recognized for more than a century. In contrast, only recently have significant neurocognitive deficits been recognized in bipolar disorder. Converging data suggest the importance of cognitive problems in relation to quality of life in bipolar disorder, highlighting the need for treatment and prevention efforts targeting cognition in bipolar patients. Future treatment trials targeting cognitive deficits will be met with methodological challenges due to the inherent complexity and heterogeneity of the disorder, including significant diagnostic comorbidities, the episodic nature of the illness, frequent use of polypharmacy, cognitive heterogeneity, and a lack of consensus regarding measurement of cognition and outcome in bipolar patients. Guidelines for use in designing future trials are needed. The members of the consensus panel (each of the bylined authors) were selected based upon their expertise in bipolar disorder. Dr. Burdick is a neuropsychologist who has studied cognition in this illness for 15 years; Drs. Ketter, Calabrese, and Goldberg each bring considerable expertise in the treatment of bipolar disorder both within and outside of controlled clinical trials. This consensus statement was derived from work together at scientific meetings (e.g. symposium presention at the 2014 Annual meeting of the American Society of Clinical Psychopharmacology, among others) and ongoing discussions by conference call. With the exception of the public presentations on this topic, these meetings were closed to outside participants. A literature review was undertaken by the authors to identify illness-specific challenges relevant to the design and conduct of treatment trials targeting neurocognition in bipolar disorder. Expert opinion from each of the authors guided the consensus recommendations. Consensus recommendations, reached by unanimous opinion of the authors, are provided here as a preliminary guide for future trial design. Recommendations comprise exclusion of certain syndromal level comorbid diagnoses and current affective instability, restrictions on numbers and types of medications, and use of pre-screening assessment to ensure enrollment of subjects with adequate objective evidence of baseline cognitive impairment. Clinical trials to address cognitive deficits in bipolar disorder face distinctive design challenges. As such trials move from proof-of-concept to confirmation of clinical efficacy, it will be important to incorporate distinctive design modifications to adequately address these challenges and increase the likelihood of demonstrating cognitive remediation effects. The field is now primed to address these challenges and a comprehensive effort to formalize best practice guidelines will be a critically important next step.