How effective is it to sequentially switch among Olanzapine, Quetiapine and Risperidone?—A randomized, open-label study of algorithm-based antipsychotic treatment to patients with symptomatic schizophrenia in the real-world clinical setting

Rationale Evidence on sequential trial with atypical antipsychotics has been scarce. Objectives We conducted an algorithm-based antipsychotic pharmacotherapy. Materials and methods In this open-label study, patients with schizophrenia (DSM-IV) were treated with antipsychotic monotherapy, step-by-step, with each trial lasting up to 8 weeks. At baseline, they were highly symptomatic to score more than 54 in the total Brief Psychiatric Rating Scale (BPRS_1–7) score. When the posttreatment BPRS score was above 70% of the baseline, they were subsequently treated with another and up to three atypicals. Basically, anticholinergics were prohibited, and only adjunctive allowed was lorazepam. The secondary endpoint was a clinical status good enough to be discharged for 66 inpatients and a successful continuation therapy with the same antipsychotic agent for more than 6 months for 12 outpatients. Results Three groups of 26 patients each were randomized to Olanzapine, Quetiapine, or Risperidone. Thirty-nine (50%) responded to the first agent (Olanzapine16, Quetiapine9, Risperidone14), and 14 responded to the second. Only two showed response to the third, and 16 failed to respond to all three antipsychotics, with only 7 dropouts. Overall, there were 22 Olanzapine, 14 Quetiapine, and 19 Risperidone responders. Based on the secondary outcome, 20 Olanzapine-treated (average maximum dose, 15.4 mg), 10 Quetiapine-treated (418 mg), and 20 Risperidone-treated (4.10 mg) patients responded. The difference in response as the first choice was significant (p < 0.05). Relative doses of those failing to respond were comparable (Olanzapine 18.3 mg, Quetiapine 564 mg, Risperidone5.47 mg). Extrapyramidal symptoms did not change significantly. Conclusions When the first atypical antipsychotic is inadequate, switching to the second is worth trying, although some remain treatment-refractory. Quetiapine may be inferior to Olanzapine and Risperidone in symptomatic patients.     

Interaction of the novel antipsychotic aripiprazole with 5-HT1A and 5-HT2A receptors: functional receptor-binding and in vivo electrophysiological studies

Background Aripiprazole (7-{4-[4-(2,3-dichlorophenyl)-1-piperazinyl]butoxy}-3,4-dihydro-2(1H)-quinolinone) is a novel antipsychotic with a mechanism of action that differs from current typical and atypical antipsychotics. Aripiprazole interacts with a range of receptors, including serotonin [5-hydroxytryptamine (5-HT)] and dopamine receptors. Materials and methods This study examined aripiprazole’s interactions with 5-HT systems in vitro and in vivo to further clarify its pharmacologic properties. Results Aripiprazole produced increases in [³⁵S]GTPγS binding to rat hippocampal membranes. Its potency (pEC₅₀ = 7.2) was similar to that of ziprasidone (7.1) and greater than that of 5-HT (6.7) and buspirone (6.4), a 5-HT_1A-receptor partial agonist, whereas its intrinsic activity was similar to that of ziprasidone and buspirone. The stimulatory effect of aripiprazole was blocked by WAY-100635, a 5-HT_1A-receptor antagonist. In in vivo electrophysiology studies, aripiprazole produced a dose-related reduction in the firing rate of 5-HT-containing dorsal raphe neurons in rats, which was both prevented and reversed by WAY-100635 administration. Aripiprazole showed a high affinity for human 5-HT_1A receptors (K _i = 4.2 nM) using parietal cortex membrane preparations. In membranes from cells expressing human recombinant receptors, aripiprazole bound with high affinity to 5-HT_2A receptors (K _i = 3.4 nM), moderate affinity to 5-HT_2C (K _i = 15 nM) and 5-HT₇ (K _i = 39 nM) receptors, and low affinity to 5-HT₆ receptors (K _i = 214 nM) and 5-HT transporter (K _i = 98 nM). In addition, aripiprazole potently blocked 5-HT_2A-receptor-mediated increases in intracellular Ca²⁺ levels in a rat pituitary cell line (IC₅₀ = 11 nM). Discussion These results support a partial agonist activity for aripiprazole at 5-HT_1A receptors in vitro and in vivo, and suggest important interactions with other 5-HT-receptor subtypes. This receptor activity profile may contribute to the antipsychotic activity of aripiprazole in humans.     

舒肝解郁胶囊联合氨磺必利治疗肝脾不和型精神分裂症的临床疗效观察

目的　探讨舒肝解郁胶囊联合氨磺必利治疗肝脾不和型精神分裂症的临床疗效。方法　选取2019年3月至2021年3月在三门峡市康复医院确诊的85例肝脾不和型精神分裂症患者,简单随机将其分为观察组和对照组。将采用氨磺必利治疗的42例患者纳入对照组,将采用舒肝解郁胶囊联合氨磺必利治疗的43例患者纳入观察组,均持续治疗6周。观察组男23例,女20例,年龄（40.35±6.17）岁;对照组男18例,女24例,年龄（41.27±6.24）岁。评估观察组和对照组患者治疗后的临床疗效,比较两组患者治疗前后的中医症候积分及治疗期间的不良反应发生率。计量资料组间比较采用独立样本t检验,组内治疗前后比较采用配对t检验,计数资料采用χ²检验。结果　观察组治疗有效率为95.35%（41/43）,高于对照组80.95%（34/42）（P<0.05）。治疗6周后,观察组胁腹胀痛、食少纳呆及神疲懒言症候积分分别为（2.08±0.28）分、（1.96±0.37）分及（2.17±0.21）分,低于对照组的（2.23±0.22）分、（2.17±0.24）分及（2.32±0.27）分（均P<0.05）。观察组患者治疗期间不良反应发生率为13.95%（6/43）与对照组的9.52%（4/42）比较差异无统计学意义（P>0.05）。结论　舒肝解郁胶囊联合氨磺必利治疗可以明显提高肝脾不和型精神分裂症患者的临床疗效。     

基于logistic回归分析的康复方案对住院精神分裂症患者攻击行为的预防作用

目的　分析住院精神分裂症患者攻击行为的影响因素,探究针对性康复干预对患者攻击行为的预防效果。方法　选择2019年1月至2020年8月山东省精神卫生中心接收248例住院精神分裂症患者,其中男135例,女113例,年龄23～67（38.03±0.41）岁。根据修改版外显攻击行为量表（MOAS）总加权分划分为攻击组（MOAS≥4分）、非攻击组（MOAS<4分）。比较两组患者的一般临床资料、阴性及阳性症状量表的兴奋因子（PANSS-EC）与中文版模棱两可、目的和敌意问卷（AIHQ-C）、社会支持评定量表（SSRS）、疾病不确定感（MUIS-A）情况。多因素logistic分析患者攻击行为的独立影响因素,并制定针对性康复方案。采用随机数字表法将山东省精神卫生中心2020年9月至2021年9月接收的100例精神分裂症患者［男57例,女43例,年龄20～69（38.38±2.51）岁］划分为两组。对照组实施常规干预,研究组在对照组基础上联合实施针对性康复方案。入院两个月,比较两组干预前后的攻击行为情况以及PANSS-EC、AIHQ-C、SSRS、MUIS-A评分。研究数据应用SPSS 26.0软件处理,计量资料给予t检验,计数资料给予χ²检验,等级资料给予秩和检验。结果　多因素logistic分析显示,男性、入院前1个月有攻击行为史、非自愿住院、首次住院、PANSS-EC评分、AIHQ-C敌意偏向总分、AIHQ-C责备偏向总分、AIHQ-C攻击偏向总分、SSRS客观支持得分、SSRS主观支持得分、MUIS-A不明确性得分、MUIS-A复杂性得分是住院精神分裂症患者攻击行为的独立影响因素（均P<0.05）;患者入院两个月,实施针对性康复方案后,研究组攻击行为发生率（16.00%,8/50）低于对照组（36.00%,18/50）,MOAS评分为（2.01±0.32）分,低于对照组的（3.56±0.24）分,两组比较,差异均有统计学意义（χ²=5.198,t=27.400,均P<0.05）;干预后,研究组PANSS-EC评分为（9.20±0.32）分、AIHQ-C评分为（13.48±1.11）分、SSRS评分为（33.21±2.47）分、MUIS-A评分为（70.31±3.56）分,均优于对照组［（11.21±0.28）分、（17.46±1.29）分、（30.29±3.03）分、（85.35±3.20）分］,两组比较,差异均有统计学意义（t=33.426、16.537、5.282、22.217,均P<0.05）。结论　精神分裂症患者攻击行为受多方面因素共同影响,针对性康复方案干预可有效改善患者攻击行为诱因,降低攻击行为发生率。     

抗精神病药对血清酶水平的影响

目的：比较氯丙嗪、氯氮平及利培酮对精神分裂症患者血清胆碱酯酶(CHE)、丙氨酸氨基转移酶(ALT)、门冬氨酸氨基转移酶(AST)、γ-谷氨酰转肽酶(GGT)、碱性磷酸酶(ALP)、乳酸脱氢酶(LDH)、肌酸激酶(CK)及γ-羟丁酸脱氢酶(HBDH)活性的影响。方法：对单用氯丙嗪(30例)、氯氮平(29例)或利培酮(32例)治疗的精神分裂症患者于治疗前、治疗4、8和12周末分别进行血清酶测定及对比分析。采用阳性和阴性症状量表(PANSS)评定疗效。结果：氯丙嗪、氯氮平及利培酮均可引起精神分裂症患者AST、CK及HBDH活性明显下降，氯丙嗪组和氯氮平组下降更明显。氯丙嗪、氯氮平均可引起精神分裂症患者LDH活性明显下降。结论：氯丙嗪、氯氮平及利培酮均可影响精神分裂症患者部分血清酶活性，但这些酶活性的改变不能说明精神分裂症发病和严重程度，也不能作为抗精神病药疗效指标。     

“一站式”社区系统家庭治疗模式对精神分裂症康复效果分析

目的探讨"一站式"社区系统家庭治疗模式对精神分裂症患者家庭环境和自测健康状况的影响。方法将病情处于缓解期的精神分裂症患者120例分为研究组和对照组各60例,两组病例均维持抗精神病药物治疗和一般性健康教育,研究组在"社区工疗站"定期接受系统家庭治疗,对照组不参与"社区工疗站"活动。采用阳性和阴性症状量表(PANSS)、自测健康评定量表(SRHMS)、家庭环境量表中文版(FES-CV)在治疗前及治疗两年后对两组患者进行评定。结果治疗后研究组和对照组PANSS评分、SRHMS总评分差异均有统计学意义[(50.01±13.93)分vs.(78.59±14.88)分,(339.97±41.86)分vs.(290.46±41.84)分,P均0.01]。结论 "一站式"社区系统家庭治疗可能有助于稳定精神分裂症患者的病情,减少复发,提高患者的健康自测水平。     

Frontal-striatal-thalamic mediodorsal nucleus dysfunction in schizophrenia-spectrum patients during sensorimotor gating

Prepulse inhibition (PPI) refers to a reduction in the amplitude of the startle eyeblink reflex to a strong sensory stimulus, the pulse, when it is preceded shortly by a weak stimulus, the prepulse. PPI is a measure of sensorimotor gating which serves to prevent the interruption of early attentional processing and it is impaired in schizophrenia-spectrum patients. In healthy individuals, PPI is more robust when attending to than ignoring a prepulse. Animal and human work demonstrates that frontal–striatal–thalamic (FST) circuitry modulates PPI. This study used functional magnetic resonance imaging (fMRI) to investigate FST circuitry during an attention-to-prepulse paradigm in 26 unmedicated schizophrenia-spectrum patients (13 schizotypal personality disorder (SPD), 13 schizophrenia) and 13 healthy controls. During 3T-fMRI acquisition and separately measured psychophysiological assessment of PPI, participants heard an intermixed series of high- and low-pitched tones serving as prepulses to an acoustic-startle stimulus. Event-related BOLD response amplitude curves in FST regions traced on co-registered anatomical MRI were examined. Controls showed greater activation during attended than ignored PPI conditions in all FST regions—dorsolateral prefrontal cortex (Brodmann areas 46, 9), striatum (caudate, putamen), and the thalamic mediodorsal nucleus. In contrast, schizophrenia patients failed to show differential BOLD responses in FST circuitry during attended and ignored prepulses, whereas SPD patients showed greater-than-normal activation during ignored prepulses. Among the three diagnostic groups, lower left caudate BOLD activation during the attended PPI condition was associated with more deficient sensorimotor gating as measured by PPI. Schizophrenia-spectrum patients exhibit inefficient utilization of FST circuitry during attentional modulation of PPI. Schizophrenia patients have reduced recruitment of FST circuitry during task-relevant stimuli, whereas SPD patients allocate excessive resources during task-irrelevant stimuli. Dysfunctional FST activation, particularly in the caudate may underlie PPI abnormalities in schizophrenia-spectrum patients.     

A projection pursuit algorithm to classify individuals using fMRI data: Application to schizophrenia

Schizophrenia is diagnosed based largely upon behavioral symptoms. Currently, no quantitative, biologically based diagnostic technique has yet been developed to identify patients with schizophrenia. Classification of individuals into patient with schizophrenia and healthy control groups based on quantitative biologically based data is of great interest to support and refine psychiatric diagnoses. We applied a novel projection pursuit technique on various components obtained with independent component analysis (ICA) of 70 subjects' fMRI activation maps obtained during an auditory oddball task. The validity of the technique was tested with a leave-one-out method and the detection performance varied between 80% and 90%. The findings suggest that the proposed data reduction algorithm is effective in classifying individuals into schizophrenia and healthy control groups and may eventually prove useful as a diagnostic tool.     

Failure to confirm an association between <Emphasis Type="Italic">Epsin 4</Emphasis> and schizophrenia in a Japanese population

Previous studies suggested that genetic variations in the 5' region of Epsin 4, a gene encoding enthoprotin on chromosome 5q33, are associated with schizophrenia. However, conflicting results have also been reported. We examined the possible association in a Japanese sample of 354 patients and 365 controls. Seventeen polymorphisms of Epsin 4 [3 microsatellites and 14 single nucleotide polymorphisms (SNPs)] were selected. A microsatellite marker (D5S1403) demonstrated a significant difference in the allele frequency between patients and controls (uncorrected P = 0.04). However, there was no significant difference in the genotype or allele frequency between the two groups for the other microsatellites or SNPs. Haplotype-based analysis provided no evidence for an association. The positive result at D5S1403 no longer reached statistical significance when multiple testing was taken into consideration. Our results suggest that the examined region of Epsin 4 does not have a major influence on susceptibility to schizophrenia in Japanese.