Singh Jaskaran, Chen Guang, Canuso Carla M
Janssen Pharmaceutical Research and Development, L.L.C., Titusville, NJ 08560, USA.
Handb Exp Pharmacol. 2012(212):187-212. doi: 10.1007/978-3-642-25761-2_8.
Atypical antipsychotics have an important role in the acute and maintenance treatment of bipolar disorder. While robust evidence supports the efficacy of these agents in the treatment of mania and in the prevention of manic relapse, few atypical antipsychotics have shown efficacy in the treatment or prevention of depressive episodes. These agents pose a lower risk of extrapyramidal side effects compared to typical neuroleptics, but carry a significant liability for weight gain and other metabolic side effects such as hyperglycemia and hyperlipidemia. More comparative effectiveness studies are needed to assess the optimal treatment regimens, including the relative benefits and risks of antipsychotics versus mood stabilizers. The exploration of the molecular mechanisms of antipsychotics has helped to shed further light on the underlying neurobiology of bipolar disorder, since these compounds target systems thought to be key to the pathophysiology of bipolar disorder. In addition to modulating monoaminergic neurotransmission, atypical antipsychotics appear to share properties with mood-stabilizing agents known to alter intracellular signal transduction leading to changes in neuronal activity and gene expression. Atypical antipsychotic drugs have been shown to exhibit neuroprotective properties that are mediated by upregulation of trophic and cellular resilience factors. Building on our understanding of existing therapeutics, especially as it relates to underlying disease pathology, newer "plasticity enhancing" strategies hold promise for future treatments of bipolar disorder.
非典型抗精神病药物在双相情感障碍的急性和维持治疗中发挥着重要作用。虽然有力的证据支持这些药物在治疗躁狂症和预防躁狂复发方面的疗效，但很少有非典型抗精神病药物在治疗或预防抑郁发作方面显示出疗效。与典型抗精神病药物相比，这些药物引起锥体外系副作用的风险较低，但会带来显著的体重增加和其他代谢副作用，如高血糖和高脂血症。需要更多的比较有效性研究来评估最佳治疗方案，包括抗精神病药物与心境稳定剂的相对益处和风险。对抗精神病药物分子机制的探索有助于进一步阐明双相情感障碍的潜在神经生物学，因为这些化合物作用于被认为是双相情感障碍病理生理学关键的系统。除了调节单胺能神经传递外，非典型抗精神病药物似乎还具有与已知可改变细胞内信号转导从而导致神经元活动和基因表达变化的心境稳定剂相同的特性。非典型抗精神病药物已被证明具有通过上调营养和细胞复原因子介导的神经保护特性。基于我们对现有治疗方法的理解，特别是与潜在疾病病理相关的理解，更新的“增强可塑性”策略有望用于双相情感障碍的未来治疗。
