Machielsen Marise Wj, Veltman Dick J, van den Brink Wim, de Haan Lieuwe
Department of Psychiatry, Academic Medical Centre, Amsterdam, The Netherlands
Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands.
J Psychopharmacol. 2014 Jul;28(7):633-42. doi: 10.1177/0269881114527357. Epub 2014 Mar 19.
Cannabis use disorders (CUDs) are highly comorbid in patients with schizophrenia and are associated with poor outcome. Clozapine has been put forward as the first choice antipsychotic in this comorbid group. However, little is known about the mechanisms underlying the assumed superiority of clozapine. We compared the effects of clozapine and risperidone on attentional bias, subjective craving and associated regional brain activity in patients with schizophrenia and CUD. Overall, 36 patients with schizophrenia and 19 healthy controls were included. Patients were randomised to antipsychotic treatment with clozapine or risperidone. At baseline and after 4 weeks of medication use, regional brain responses were measured during a classical Stroop and a cannabis word Stroop using functional magnetic resonance imaging. Clozapine-treated CUD patients showed a larger reduction in craving and in activation of the insula during the cannabis word Stroop, while risperidone-treated patients showed a larger decrease in activation of the right anterior cingulate cortex during the classical Stroop. A significant association was found between decreases in subjective craving and decreases in insula activation during the cannabis word Stroop. These findings strongly suggest that clozapine may be a better treatment choice in patients with schizophrenia and CUD than risperidone.
大麻使用障碍（CUDs）在精神分裂症患者中高度共病，且与不良预后相关。氯氮平已被提出作为这一共病群体的首选抗精神病药物。然而，对于氯氮平假定优势背后的机制知之甚少。我们比较了氯氮平和利培酮对精神分裂症合并CUD患者的注意偏向、主观渴望及相关脑区活动的影响。总共纳入了36例精神分裂症患者和19名健康对照者。患者被随机分配接受氯氮平或利培酮的抗精神病治疗。在基线期及用药4周后，使用功能磁共振成像在经典Stroop任务和大麻词汇Stroop任务期间测量脑区反应。氯氮平治疗的CUD患者在大麻词汇Stroop任务期间渴望及脑岛激活的减少更为明显，而利培酮治疗的患者在经典Stroop任务期间右侧前扣带回皮质的激活减少更为明显。在大麻词汇Stroop任务期间，主观渴望的降低与脑岛激活的降低之间存在显著关联。这些发现强烈表明，对于精神分裂症合并CUD的患者，氯氮平可能比利培酮是更好的治疗选择。
