比较氯氮平和利培酮对伴有大麻使用障碍的男性精神分裂症患者线索反应的影响：一项随机 fMRI 研究。
Comparing the effect of clozapine and risperidone on cue reactivity in male patients with schizophrenia and a cannabis use disorder: A randomized fMRI study.
机构信息
Department of Psychiatry, Academic Medical Centre, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Department of Psychiatry, Academic Medical Centre, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands; Department of Psychiatry, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
出版信息
Schizophr Res. 2018 Apr;194:32-38. doi: 10.1016/j.schres.2017.03.030. Epub 2017 Mar 25.
OBJECTIVE
Cannabis use disorders (CUDs) are highly comorbid in patients with schizophrenia and associated with poor outcome. Clozapine has been put forward as the first choice antipsychotic in this patient group. However, little is known about the mechanisms underlying the assumed superiority of clozapine.
METHODS
A total of 38 patients with DSM-IV schizophrenia (30 with and 8 without a DSM-IV CUD) and 20 healthy comparison subjects were included between April 2009 and June 2012. Patients were randomized to antipsychotic treatment with clozapine or risperidone. At baseline and after 4weeks of medication, brain response to cannabis-related, positive and neutral images was measured using functional MRI. Neural correlates of cue reactivity were assessed in the following regions of interest: amygdala, ventral striatum, insula, thalamus, orbitofrontal cortex and anterior cingulate cortex. Subjective craving was assessed using self-report questionnaires (OCDUS and MCQ).
RESULTS
At baseline, patients with a comorbid CUD showed higher subjective craving and greater activation in response to cannabis-related images compared to patients without a CUD and healthy controls in most regions of interest. Clozapine treated patients reported a greater reduction in craving (F(1,28)=6.0, p=0.04) and showed a larger decrease in amygdala activation during cannabis-related images compared to risperidone treated patients (T=3.94, pFWE=0.006). In addition, significant correlations were found between subjective craving and thalamus and insula activation during cannabis-related images.
CONCLUSION
These findings provide evidence that clozapine is superior to risperidone in decreasing subjective craving and cue reactivity for cannabis-related images probably due to a differential effect on dopaminergic neurotransmission.
TRIAL REGISTRATION
'Nederlands trial register' (http://www.trialregister.nl), nr NTR1761, http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1761.
目的
大麻使用障碍（CUD）在精神分裂症患者中高度共病，并与不良结局相关。氯氮平已被提出作为该患者群体的首选抗精神病药物。然而，关于氯氮平假定优势的机制知之甚少。
方法
总共纳入了 38 名符合 DSM-IV 精神分裂症标准的患者（30 名有 DSM-IV CUD，8 名没有）和 20 名健康对照者，纳入时间为 2009 年 4 月至 2012 年 6 月。患者被随机分配接受氯氮平或利培酮的抗精神病治疗。在基线和药物治疗 4 周后，使用功能磁共振成像测量对大麻相关、阳性和中性图像的大脑反应。在以下感兴趣区域评估线索反应的神经相关性：杏仁核、腹侧纹状体、岛叶、丘脑、眶额皮质和前扣带皮质。使用自我报告问卷（OCDUS 和 MCQ）评估主观渴求。
结果
在基线时，与没有 CUD 的患者和健康对照组相比，患有共病 CUD 的患者对大麻相关图像的主观渴求更高，对大麻相关图像的反应更强烈，在大多数感兴趣区域均如此。与接受利培酮治疗的患者相比，接受氯氮平治疗的患者报告的渴求减少更大（F(1,28)=6.0，p=0.04），并且在大麻相关图像中杏仁核激活减少更大（T=3.94，pFWE=0.006）。此外，在大麻相关图像中，主观渴求与丘脑和岛叶的激活之间存在显著相关性。
结论
这些发现提供了证据表明，氯氮平在减少对大麻相关图像的主观渴求和线索反应方面优于利培酮，这可能是由于对多巴胺能神经传递的不同影响。
试验注册
“荷兰试验注册处”（http://www.trialregister.nl），编号 NTR1761，http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1761。
Zotero 插件