Chu Che-Sheng, Tzeng Nian-Sheng, Chang Hsin-An, Chang Chuan-Chia, Chen Tien-Yu
Department of Psychiatry, Puli Branch, Taichung Veterans General Hospital, Taichung, Taiwan, ROC.
Department of Psychiatry, Tri-Service General Hospital, Taipei, Taiwan, ROC; School of Medicine, National Defense Medical Center, Taipei, Taiwan, ROC; Student Counseling Center, National Defense Medical Center, Taipei, Taiwan, ROC.
Med Hypotheses. 2014 Sep;83(3):407-9. doi: 10.1016/j.mehy.2014.07.008. Epub 2014 Jul 18.
The high comorbidity between major depressive disorder (MDD) and nicotine dependence (ND) is well recognized. Patients with comorbid MDD and ND often have increased suicidal risk and poor outcomes. A dysfunctional dopaminergic brain reward system might be a neurobiological link between MDD and ND. Aripiprazole has been considered as a dopamine stabilizer and was the first atypical antipsychotic agent approved by the US Food and Drug Administration as an adjunctive to the treatment of unipolar MDD. Bupropion is well known as a dual norepinephrine and dopamine reuptake inhibitor, and has been shown to be effective in smoking cessation. One reason bupropion is useful in treating ND is that it enhances the level of dopamine in the brain. Aripiprazole might act as a dopamine agonist similar to the way that bupropion does because of its partial dopamine D2 agonist and 30% intrinsic dopaminergic activity. Several recent studies have applied the unique pharmacodynamic characteristics of aripiprazole to treat patients with ND. Based on neuroimaging findings, aripiprazole can reduce substance cravings by altering brain activity, particularly in the brain regions of the anterior cingulate cortex. Therefore, we hypothesize that adjunctive aripiprazole with antidepressant may be an effective treatment for patients with MDD and ND comorbidity. A new drug invention that combines an antidepressant with an adequate dose of aripiprazole thus should be considered. The neurobiological basis for this combination to treat patients with MDD and ND comorbidity deserves further study.
重度抑郁症（MDD）与尼古丁依赖（ND）之间的高共病率已得到充分认识。患有MDD和ND共病的患者通常自杀风险增加且预后不良。功能失调的多巴胺能脑奖赏系统可能是MDD和ND之间的神经生物学联系。阿立哌唑被认为是一种多巴胺稳定剂，是美国食品药品监督管理局批准用于辅助治疗单相MDD的首个非典型抗精神病药物。安非他酮是一种广为人知的去甲肾上腺素和多巴胺双重再摄取抑制剂，已被证明在戒烟方面有效。安非他酮对治疗ND有用的一个原因是它能提高大脑中的多巴胺水平。由于阿立哌唑具有部分多巴胺D2激动剂和30%的内在多巴胺能活性，它可能像安非他酮一样作为多巴胺激动剂发挥作用。最近的几项研究已应用阿立哌唑独特的药效学特性来治疗ND患者。基于神经影像学研究结果，阿立哌唑可通过改变大脑活动，特别是前扣带回皮质区域的大脑活动来减少对物质的渴望。因此，我们假设阿立哌唑联合抗抑郁药可能是治疗MDD和ND共病患者的有效方法。因此，应考虑一种将抗抑郁药与适当剂量阿立哌唑联合的新药发明。这种联合用药治疗MDD和ND共病患者的神经生物学基础值得进一步研究。
