Abstract Major depression is a serious psychiatric disorder and remains a leading cause of disability worldwide. Con- ventional antidepressants take at least several weeks to achieve a therapeutic response and this la...Abstract Major depression is a serious psychiatric disorder and remains a leading cause of disability worldwide. Con- ventional antidepressants take at least several weeks to achieve a therapeutic response and this lag period has hin- dered their ability to attain beneficial effects in depressed individuals at high risk of suicide. The non-competitive N- methyl-D-aspartate glutamate receptor antagonist ketamine has been shown to have rapid antidepressant effects in both rodents and humans. The emergence of ketamine as a fast- acting antidepressant provides promising new insights into the development of a rapid treatment response in patients with clinical depression. However, its safety and toxicity remain a concem. In this review, we focus on the limitations of ketamine, including neurotoicity, cognitive dysfunction, adverse events associated with mental status, psy- chotomimetic effects, cardiovascular events, and uropathic effects. Studies have shown that its safety and tolerability profiles are generally good at low doses and with short-term treatment in depressed patients. The adverse events associ- ated with ketamine usually occur with very high doses that are administered for prolonged periods of time and can be relieved by cessation. The antidepressant actions of its two enantiomers, S-ketamine （esketamine） and R-ketamine, are also discussed. R-ketamine has greater antidepressantactions than S-ketamine, without ketamine-related side- effects. Future treatment strategies should consider using R- ketamine for the treatment of depressed patients to decrease the risk of adverse events associated with long-term keta- mine use.展开更多
基金supported by the National Natural Science Foundation of China(81371489)the Strategic Research Program for Brain Sciences from the Japan Agency for Medical Research and Development.AMED
文摘Abstract Major depression is a serious psychiatric disorder and remains a leading cause of disability worldwide. Con- ventional antidepressants take at least several weeks to achieve a therapeutic response and this lag period has hin- dered their ability to attain beneficial effects in depressed individuals at high risk of suicide. The non-competitive N- methyl-D-aspartate glutamate receptor antagonist ketamine has been shown to have rapid antidepressant effects in both rodents and humans. The emergence of ketamine as a fast- acting antidepressant provides promising new insights into the development of a rapid treatment response in patients with clinical depression. However, its safety and toxicity remain a concem. In this review, we focus on the limitations of ketamine, including neurotoicity, cognitive dysfunction, adverse events associated with mental status, psy- chotomimetic effects, cardiovascular events, and uropathic effects. Studies have shown that its safety and tolerability profiles are generally good at low doses and with short-term treatment in depressed patients. The adverse events associ- ated with ketamine usually occur with very high doses that are administered for prolonged periods of time and can be relieved by cessation. The antidepressant actions of its two enantiomers, S-ketamine （esketamine） and R-ketamine, are also discussed. R-ketamine has greater antidepressantactions than S-ketamine, without ketamine-related side- effects. Future treatment strategies should consider using R- ketamine for the treatment of depressed patients to decrease the risk of adverse events associated with long-term keta- mine use.
