涤痰汤联合哌罗匹隆治疗首发精神分裂症30例

目的:观察涤痰汤联合哌罗匹隆治疗首发精神分裂症的临床疗效。方法:将60例患者随机分为观察组、对照组各30例。2组均给予哌罗匹隆治疗,观察组同时服用涤痰汤,水煎分服,1剂/d。2组均连续治疗8周后统计疗效。结果:总有效率观察组为93.33%,对照组为73.33%,2组比较差异有统计学意义(P0.05)。阳性与阴性症状量表(PANSS)评分2组均于治疗1周开始降低,治疗前后2组组内比较,差异均有统计学意义(P0.05);至治疗第4周时2组组间比较,差异也有统计学意义(P0.05)。结论:涤痰汤联合哌罗匹隆治疗首发精神分裂症临床疗效显著。     

Contribution of perospirone and risperidone to reduce delirium in senile patients

Background: Serotonin–dopamine antagonists (SDAs) inhibit dopaminergic transmission in the mesolimbic system less than in the nigrostriatal dopaminergic pathway, which relates to the extrapyramidal side‐effects of these drugs. The SDAs seem to have an adequate receptor binding profile for the management of the behavioral and psychiatric symptoms of dementia. However, clinicians are discouraged from prescribing SDAs for elderly patients because of an advisory statement from the US Food and Drug Administration that warns about an increased mortality rate among elderly patients treated with atypical antipsychotics. Methods: We conducted a retrospective study involving 16 elderly patients (mean age 84.9 years; range 67–94 years) with delirium who were treated with one of two SDAs, namely perospirone (4–12 mg/day) or risperidone (1–2 mg/day). The time‐course of their psychiatric symptoms was assessed using subcategories of the Delirium Rating Scale (DRS) before treatment and on Days 10 and 24 of treatment. Results: Total DRS scores were significantly decreased from baseline in both treatment groups. Both agents led to significant improvements from baseline in psychomotor behavior and lability of mood. Of interest, perospirone decreased hallucinations and delusions and improved sleep–awake cycle disturbances compared with baseline. No serious side‐effects were seen with either drug. Conclusions: Both perospirone and risperidone are effective in the management of delirium in elderly patients. The improvement in the sleep–awake cycle with perospirone may be derived from its short pharmacological half‐life.     

新型抗精神病药：哌罗匹隆

哌罗匹隆是一种新型非典型抗精神病药,主要药理机制是5-羟色胺(5-HT)和多巴胺D_2受体拮抗作用。与传统抗精神病药相比,哌罗匹隆对阳性症状、阴性症状和情感症状均有较好疗效,锥体外系不良反应和致催乳素升高作用轻微。哌罗匹隆是一种安全有效的非典型抗精神病药。     

Beneficial effects of perospirone on aggressive behavior associated with dementia

The aim of this study was to assess the efficacy of the serotonin-dopamine antagonist perospirone in treating aggressive and agitated behavior in patients with dementia. Six patients were referred to the outpatient clinic of Ishizaki Hospital and were followed for 6 weeks. Their psychiatric diagnoses were made using the DSM-IV. Their behavioral symptoms and degrees of cognitive impairment were measured using the Behavioral Pathology in Alzheimer's Disease (BEHAVE-AD) and the Mini-Mental Examination State. The changes in BEHAVE-AD scores were investigated. Maximum benefit was achieved at a mean perospirone dose of 9.0 mg/day. No patient experienced severe adverse effects. Post-hoc analysis showed significant improvement in the total BEHAVE-AD and aggressiveness subscale scores within 2 weeks. This study suggests that perospirone is effective in improving aggressive and agitated behavioral symptoms in demented patients and is safe to use in elderly patients.     

Characterization of human cytochrome P450 enzymes involved in the in vitro metabolism of perospirone

In vitro studies were carried out to identify the major contribution of CYP2C8, CYP2D6 and CYP3A4 to the metabolism of perospirone (cis-N-[4-[4-(1,2-benzisothiazol-3-yl)-1-piperazinyl]butyl]cyclohexane-1,2-dicarboximide monohydrochloride dehydrate), a novel antipsychotic agent, using human liver microsomes and expressed P450 isoforms. Quinidine (a specific inhibitor of CYP2D6) did not markedly affect the metabolism of perospirone, whereas quercetin (an inhibitor of CYP2C8) and ketoconazole (an inhibitor of CYP3A4) caused a decrease in the metabolism with human liver microsomes in a concentration dependent fashion. With 10 microM quercetin, the metabolism of perospirone was inhibited by 60.0% and with 1 microM ketoconazole almost complete inhibition was apparent. Anti-CYP2C8 and anti-CYP2D6 antisera did not exert marked effects, whereas anti-CYP3A4 antiserum caused almost complete inhibition. With expressed P450s, K(m) and V(max) values were 1.09 microM and 1.93 pmol/min/pmol P450 for CYP2C8, 1.38 microM and 5.73 pmol/min/pmol P450 for CYP2D6, and 0.245 microM and 61.3 pmol/min/pmol P450 for CYP3A4, respectively. These results indicated that the metabolism of perospirone in human liver was mainly catalysed by CYP3A4, and to a lesser extent CYP2C8 and CYP2D6 were responsible because kinetic data (K(m) and V(max)) of CYP2C8 and CYP2D6 suggested catalytic potential.     

A benzisothiazole derivative and antipsychotic agent,perospirone, for augmentation of selective serotonin reuptake inhibitors (SSRIs) in refractory obsessive-compulsive disorder (OCD): two patient case series

Even though selective serotonin reuptake inhibitors (SSRIs) are the mainstay of pharamacological treatment for obsessive-compulsive disorder (OCD), as many as 40% of patients do not have an adequate response to these medications. For such SSRI-refractory patients, the augmentation of SSRIs with new-generation antipsychotics that modulate both 5-HT and DA systems has recently been proven effective in controlled augmentation studies. The benzisothiazole derivative perospirone is a new serotonin 5-HT2 and dopamine D2 antagonist available in Japan for the treatment of schizophrenia. As its unique property, perospirone also exhibits 5-HT1A agonistic action. We present two SSRI-refractory OCD patients who showed little improvement with adequate trials of SSRI monotherapy, but exhibited significant improvement in their OCD symptoms after the addition of perospirone to ongoing SSRI treatment. The cases suggest that perospirone augmentation may be an effective and well-tolerated strategy for SSRI-refractory OCD patients. Controlled studies are required to further confirm the efficacy and tolerability of perospirone augmentation for treatment-resistant OCD.     

哌罗匹隆与氟哌啶醇治疗精神分裂症对照研究

目的：探讨哌罗匹隆与氟哌啶醇治疗精神分裂症的疗效和安全性。方法将93例精神分裂症患者随机分为两组,研究组48例,口服哌罗匹隆治疗,对照组45例,口服氟哌啶醇治疗,观察8周。于治疗前后采用阳性与阴性症状量表评定临床疗效,副反应量表评定不良反应。结果治疗各时点研究组阳性与阴性症状量表总分及各因子分均较治疗前有显著下降（P＜0.01）,对照组总分及阳性症状、精神病理因子分较治疗前有显著下降（P＜0.01）,阴性症状因子分与治疗前比较差异无显著性（P＞0.05）,研究组治疗各时点阴性症状因子分显著低于对照组（P＜0.01）。治疗8周末两组显效率、总有效率比较差异无显著性（P＞0.05）。研究组不良反应发生率较低,其中锥体外系反应、静坐不能、嗜睡不良反应发生率显著低于对照组（ P＜0.01）。结论哌罗匹隆与氟哌啶醇治疗精神分裂症患者总体疗效相当,但哌罗匹隆改善阴性症状效果显著优于氟哌啶醇,且安全性高,依从性好,有利于改善患者的认知功能。     

哌罗匹隆与利培酮治疗首发精神分裂症对照研究

目的：探讨哌罗匹隆与利培酮治疗首发精神分裂症患者的临床疗效和安全性。方法将120例首发精神分裂症患者随机分为两组,研究组口服哌罗匹隆治疗,对照组口服利培酮治疗,观察8周。采用阳性与阴性症状量表评定临床疗效,副反应量表评定不良反应。结果治疗后两组阳性与阴性症状量表总分及各因子分均较治疗前显著下降（ P＜0．05或0．01）,治疗8周末研究组总有效率为83．3％,对照组为81．7％,两组比较差异无显著性（χ2＝0．06,P＞0．05）。研究组不良反应发生率为56．7％,对照组为53．3％,两组比较差异无显著性（χ2＝0．13,P＞0．05）,但研究组体质量增加、月经改变及泌乳、性欲改变等不良反应发生率低于对照组。结论哌罗匹隆与利培酮治疗首发精神分裂症疗效显著,安全性高,依从性好,但哌罗匹隆较少引起内分泌改变和体质量增加,更适用于女性首发精神分裂症患者。     

哌罗匹隆治疗精神分裂症患者的疗效以及对内分泌的影响

目的:探讨哌罗匹隆治疗精神分裂症的疗效及对内分泌的影响. 方法:64例精神分裂症患者分为哌罗匹隆组和利培酮组各32例,分别予哌罗匹隆和利培酮治疗6周.采用阳性和阴性症状量表(PANSS)及治疗中出现的症状量表(TESS)在治疗前后评定疗效及不良反应,同时测定血清催乳素(PRL)及促甲状腺激素(TSH)、三碘甲状腺原氨酸(T3)、游离三碘甲状腺原氨酸(FT3)、甲状腺素(T4)、游离甲状腺素(FT4)水平. 结果:哌罗匹隆组总有效率78.13％,利培酮组81.25％(x2=0.097,P＞0.05).两组治疗后PANSS评分均较治疗前显著下降(P＜0.05或P＜0.01)；两组TESS评分治疗1周和6周差异均无统计学意义(t=-1.84,-1.35;P均＞0.05).哌罗匹隆组PRL(t=-1.26)及各项甲状腺激素(t=0.97～1.88)水平治疗前后差异无统计学意义(P均＞0.05). 结论:哌罗匹隆治疗精神分裂症疗效与利培酮相当,但对PRL和甲状腺激素的影响较小.     

阿立哌唑与奥氮平、利培酮治疗精神分裂症的对照疗效

目的：比较阿立哌唑（奥派）、奥氮平（欧兰宁）、利培酮（西安杨森公司）治疗精神分裂症的临床疗效,为临床选择合理的用药给药方案提供参考.方法：回顾性统计分析采用在我院住院的精神分裂症患者,用不良反应量表（TESS）及阴性与阳性量表（PANSS）评定疗效及不良反应.结果：阿立哌唑与奥氮平、利培酮治疗精神分裂症均有明显疗效,统计学上无显著性差异（P〉0.05）.三者中阿立哌唑组未发现对血脂、血糖有显著性影响,而奥氮平对血脂、血糖的影响较大,利培酮也对血脂有影响.结论：阿立哌唑治疗精神分裂症是安全、有效的药物,在血脂血糖代谢方面的影响小于奥氮平和利培酮.