Stimmel G L
University of Southern California School of Pharmacy, Los Angeles 90033, USA.
Pharmacotherapy. 1996 Nov-Dec;16(6 Pt 2):148S-151S; discussion 166S-168S.
Benzodiazepines have a checkered history in the United States; public and professional attitudes about them have ranged from their being wonder drugs in the 1970s to being virtually purged from many formularies as addictive and dangerous in the 1980s. The attitude today is that they are useful for specific indications. In the last 20 years they have been investigated as adjunctive agents to conventional antipsychotic drugs in the treatment of schizophrenia. Benzodiazepines may be effective in schizophrenia because stress is one mediator of relapse in these patients. In addition, inhibition of dopamine neurotransmission through gamma-aminobutyric acid-enhancing activity may provide a direct antipsychotic effect. As monotherapy or adjuncts to antipsychotic agents, benzodiazepines produced antipsychotic effects in schizophrenia in approximately 50% of controlled trials. Although there is no particular benzodiazepine of choice, low-potency compounds with long elimination half-lives are recommended. Adverse effects of concern include sedation and cognitive impairment, behavioral disinhibition, exacerbation of psychotic symptoms, and the potential for dependence, withdrawal, and abuse. The recent arrival of atypical antipsychotic drugs has significantly slowed research and interest in benzodiazepines in schizophrenia beyond their initial beneficial sedative effects for acute psychotic episodes.
苯二氮䓬类药物在美国的历史可谓波折不断；公众和专业人士对它们的态度从20世纪70年代视其为神奇药物，到80年代因其具有成瘾性和危险性而几乎从许多处方中被剔除。如今的态度是它们在特定适应症方面有用。在过去20年里，人们研究了它们作为传统抗精神病药物的辅助药物用于治疗精神分裂症。苯二氮䓬类药物在精神分裂症中可能有效，因为压力是这些患者病情复发的一个介导因素。此外，通过增强γ-氨基丁酸活性来抑制多巴胺神经传递可能会产生直接的抗精神病作用。作为单一疗法或抗精神病药物的辅助药物，在大约50%的对照试验中，苯二氮䓬类药物在精神分裂症中产生了抗精神病作用。虽然没有特别推荐使用的苯二氮䓬类药物，但建议使用消除半衰期长的低效化合物。值得关注的不良反应包括镇静和认知障碍、行为脱抑制、精神病症状加重以及依赖、戒断和滥用的可能性。非典型抗精神病药物的出现显著减缓了对精神分裂症中苯二氮䓬类药物的研究和兴趣，除了它们对急性精神病发作最初有益的镇静作用之外。
