Department of Psychiatry, Academic Medical Centre, Amsterdam, the Netherlands.
J Psychopharmacol. 2012 Jan;26(1):189-95. doi: 10.1177/0269881111408957. Epub 2011 Jul 18.
Substance abuse and psychotic disorders have a high rate of comorbidity. Both disorders are associated with changes in the dopaminergic transmission in the mesocorticolimbic pathways of the brain. Since antipsychotic medications interact with the dopamine receptors in these pathways, these medications could affect craving for substances. In the current study, the effect of clozapine (n = 27, mean dosage 350 mg), risperidone (n = 54, mean dosage 3.46 mg) and olanzapine (n = 60, mean dosage 13.78 mg) on subjective craving for cannabis was compared in 123 patients with cannabis dependence and psychotic disorder. Patients treated with risperidone reported significantly more craving compared with patients treated with clozapine (Z = -3.19, p = .001) or olanzapine (Z = -2.24, p = .025). No significant differences in craving between clozapine and olanzapine were found. These results are in concordance with findings in the literature on this subject and could be explained by differences in three dopamine mediated mechanisms of these compounds: 1) occupancy rate of dopamine D(2) receptors, 2) dissociation rate of dopamine D(2) receptors, 3) D(1)/D(2) occupancy ratio. Risperidone and clozapine show a maximal difference in D(2) receptor occupancy rate, dissociation rate and D(1)/D(2) ratio. Olanzapine is intermediate between risperidone and clozapine in these characteristics.
物质滥用和精神病障碍的共病率很高。这两种疾病都与大脑中中皮质边缘多巴胺能传递的变化有关。由于抗精神病药物与这些途径中的多巴胺受体相互作用，这些药物可能会影响对物质的渴望。在目前的研究中，比较了氯氮平（n = 27，平均剂量 350mg）、利培酮（n = 54，平均剂量 3.46mg）和奥氮平（n = 60，平均剂量 13.78mg）对 123 例患有大麻依赖和精神病障碍的患者对大麻的主观渴望的影响。与接受氯氮平治疗的患者相比，接受利培酮治疗的患者报告的渴望明显更多（Z = -3.19，p =.001）或奥氮平（Z = -2.24，p =.025）。氯氮平和奥氮平之间的渴望差异没有统计学意义。这些结果与该主题文献中的发现一致，并且可以通过这些化合物的三种多巴胺介导机制的差异来解释：1）多巴胺 D2 受体的占有率，2）多巴胺 D2 受体的解离率，3）D1/D2 占有率比。利培酮和氯氮平在 D2 受体占有率、解离率和 D1/D2 比值方面表现出最大差异。奥氮平在这些特征上介于利培酮和氯氮平之间。
