Curran Monique P, Perry Caroline M
Adis International Limited, Auckland, New Zealand.
CNS Drugs. 2002;16(3):207-11. doi: 10.2165/00023210-200216030-00007.
Amisulpride, a substituted benzamide derivative, is a second-generation (atypical) antipsychotic. At low doses, it enhances dopaminergic neurotransmission by preferentially blocking presynaptic dopamine D(2)/D(3) autoreceptors. At higher doses, amisulpride antagonises postsynaptic D(2) and D(3) receptors, preferentially in the limbic system rather than the striatum, thereby reducing dopaminergic transmission. In patients with acute exacerbations of schizophrenia, the recommended dosage of amisulpride is 400 to 800 mg/day, although dosages < or = 1200 mg/day may be administered. In comparative trials, amisulpride administered within this range (400 to 1200 mg/day) was as effective as haloperidol 5 to 40 mg/day, flupenthixol 25 mg/day and risperidone 8 mg/day in patients with acute exacerbations of schizophrenia with predominantly positive symptoms. Amisulpride was more effective than haloperidol but equally effective as risperidone in controlling negative symptoms. Amisulpride 400 to 800 mg/day was more effective than haloperidol, risperidone and flupenthixol in controlling affective symptoms in these patients. In randomised, double-blind trials involving patients with predominantly negative symptoms of schizophrenia, amisulpride 50 to 300 mg/day was more effective than placebo. Amisulpride is effective as maintenance therapy in patients with chronic schizophrenia. Long-term treatment with amisulpride was associated with improvements in quality of life and social functioning. Amisulpride is generally well tolerated. In well-controlled trials, the neurological tolerability profile (including ratings on extrapyramidal symptom scales) of amisulpride 400 to 1200 mg/day was superior to that of the conventional antipsychotics (haloperidol or flupenthixol), but was similar to that of the atypical antipsychotic risperidone. At low dosages of amisulpride (< or = 300 mg/day), the incidence of adverse events (including extrapyramidal symptoms) reported with amisulpride was similar to that with placebo.
In comparative trials, amisulpride 400 to 1200 mg/day showed efficacy in reducing overall symptomatology and positive symptoms similar to that of conventional antipsychotics and newer atypical antipsychotics in patients with acute exacerbations of schizophrenia. Moreover, its effective alleviation of negative and affective symptoms, its lower association with extrapyramidal symptoms and loss of cognitive function than conventional antipsychotics and its long-term efficacy justifies consideration of the use of higher dosages of amisulpride in this group of patients. Consequently, the dosage of amisulpride that is recommended in patients with acute exacerbations of schizophrenia is 400 to 800 mg/day, although dosages < or = 1200 mg/day may be administered. Lower dosages of amisulpride (50 to 300 mg/day) should be considered for the management of patients with negative symptoms of schizophrenia. Amisulpride is a first-line treatment option in the management of schizophrenia in the acute phase and for the maintenance of treatment response.
氨磺必利是一种取代苯甲酰胺衍生物,属于第二代(非典型)抗精神病药物。低剂量时,它通过优先阻断突触前多巴胺D(2)/D(3)自身受体来增强多巴胺能神经传递。高剂量时,氨磺必利拮抗突触后D(2)和D(3)受体,优先作用于边缘系统而非纹状体,从而减少多巴胺能传递。在精神分裂症急性加重患者中,氨磺必利的推荐剂量为400至800毫克/天,尽管也可给予≤1200毫克/天的剂量。在比较试验中,对于以阳性症状为主的精神分裂症急性加重患者,在此剂量范围内(400至1200毫克/天)给予氨磺必利与给予5至40毫克/天的氟哌啶醇、25毫克/天的氟奋乃静和8毫克/天的利培酮效果相当。在控制阴性症状方面,氨磺必利比氟哌啶醇更有效,但与利培酮效果相当。在这些患者中,400至800毫克/天的氨磺必利在控制情感症状方面比氟哌啶醇、利培酮和氟奋乃静更有效。在主要为精神分裂症阴性症状患者参与的随机双盲试验中,50至300毫克/天的氨磺必利比安慰剂更有效。氨磺必利作为慢性精神分裂症患者的维持治疗有效。长期使用氨磺必利与生活质量和社会功能改善相关。氨磺必利一般耐受性良好。在严格控制的试验中,400至1200毫克/天氨磺必利的神经耐受性(包括锥体外系症状量表评分)优于传统抗精神病药物(氟哌啶醇或氟奋乃静),但与非典型抗精神病药物利培酮相似。在低剂量氨磺必利(≤300毫克/天)时,报告的氨磺必利不良事件(包括锥体外系症状)发生率与安慰剂相似。
在比较试验中,对于精神分裂症急性加重患者,400至1200毫克/天的氨磺必利在减轻总体症状和阳性症状方面显示出与传统抗精神病药物及新型非典型抗精神病药物相似的疗效。此外,与传统抗精神病药物相比,它能有效缓解阴性和情感症状,与锥体外系症状及认知功能丧失的关联较低,且具有长期疗效,这证明在该组患者中考虑使用更高剂量的氨磺必利是合理的。因此,对于精神分裂症急性加重患者,推荐的氨磺必利剂量为400至800毫克/天,尽管也可给予≤1200毫克/天的剂量。对于精神分裂症阴性症状患者的管理,应考虑使用较低剂量的氨磺必利(50至300毫克/天)。氨磺必利是精神分裂症急性期管理及维持治疗反应的一线治疗选择。