Włodarczyk Adam, Szarmach Joanna, Cubała Wiesław Jerzy, Wiglusz Mariusz Stanisław
Department of Psychiatry, Medical University of Gdańsk, Dębinki St. 7 build. 25, 80-952 Gdańsk, Poland.
Psychiatr Danub. 2017 Sep;29(Suppl 3):345-348.
Antipsychotics are a key intervention strategy in pharmacotherapy of schizophrenia. However, benzodiazepines are often prescribed to control sleep disturbances, anxiety or behavioural disinhibition. There is clinical evidence for the beneficial effect of the combined treatment of antipsychotics and benzodiazepines resulting in more favorable treatment outcome in schizophrenia with regard to positive and negative symptoms. This clinical phenomenon seems to be associated with the GABA-ergic activit ythat is believed to be disrupted in the schizophrenia and direct benzodiazepines effect on GABA-A receptors. In the brain there are both excitatory and inhibitory neurotransmitters which cooperate between themselves maintaining the proper functioning of the brain. GABA neurons carry inhibitory signals that help keep brain activity at optimal levels of operation, Glutamate, on the other hand, carry excitatory signals. As the interplay between these two exists they keep the dopamine levels in the average levels. The disruption of GABA-ergic transmission in schizophrenia may induce alternations in dopaminergic neurotransmission providing no inhibitory effect to the central glutamate activity, resulting in the rise of the dopamine levels being associated with psychosis precipitation. Benzodiazepines are believed to reduce presynaptic dopamine release at the mesolimbic level and delay postsynaptic adaptation of dopaminergic neurons to antipsychotics potentiating the action of antipsychotics in resistant schizophrenia. Benzodiazepines also act on mesocortical regions where antipsychotics are less effective and where there is a particular sensitivity to stress. This association is particularly useful in resistant patients or in patients with severe anxiety with or without intolerance to antipsychotics. Improvement concerns anxious symptoms but also positive symptoms (hallucinations, delirium and dissociative syndrome) and negative (social withdrawal, affect flattening). As the available studies are limited there is some clinical evidence that the use of antipsychotic drugs with addition of benzodiazepines can provide better general outcome in ill patients than antipsychotics administration alone.
抗精神病药物是精神分裂症药物治疗的关键干预策略。然而，苯二氮䓬类药物常被用于控制睡眠障碍、焦虑或行为抑制。有临床证据表明，抗精神病药物与苯二氮䓬类药物联合治疗具有有益效果，在精神分裂症的阳性和阴性症状方面能带来更有利的治疗结果。这种临床现象似乎与γ-氨基丁酸（GABA）能活性有关，据信精神分裂症中该活性被破坏，且苯二氮䓬类药物对GABA-A受体有直接作用。在大脑中，存在兴奋性和抑制性神经递质，它们相互协作以维持大脑的正常功能。GABA神经元传递抑制性信号，有助于将大脑活动保持在最佳运作水平，而谷氨酸则传递兴奋性信号。由于这两者之间存在相互作用，它们使多巴胺水平保持在平均水平。精神分裂症中GABA能传递的破坏可能会导致多巴胺能神经传递的改变，无法对中枢谷氨酸活性产生抑制作用，从而导致与精神病发作相关的多巴胺水平升高。据信苯二氮䓬类药物可减少中脑边缘系统水平的突触前多巴胺释放，并延迟多巴胺能神经元对抗精神病药物的突触后适应，从而增强抗精神病药物在难治性精神分裂症中的作用。苯二氮䓬类药物还作用于中脑皮质区域，而抗精神病药物在该区域效果较差，且该区域对压力特别敏感。这种联合在难治性患者或伴有或不伴有对抗精神病药物不耐受的严重焦虑患者中特别有用。改善的不仅是焦虑症状，还有阳性症状（幻觉、谵妄和分离综合征）和阴性症状（社交退缩、情感平淡）。由于现有研究有限，有一些临床证据表明，与单独使用抗精神病药物相比，联合使用抗精神病药物和苯二氮䓬类药物可为患病患者带来更好的总体疗效。
