Theory in antipsychotic drug therapy for schizophrenia]

In Japan, antipsychotic polypharmacy with high doses for schizophrenia has been traditionally used. However, antipsychotic polyphamacy with high doses provide disadvantages for patient. Recent PET studies show that dopamine D2 occupancy with antipsychotics is important for the treatment of schizophrenia. First, antipsychotics become effective only at which their D2 occupancy exceeds 65%. Second, antipsychotics with D2 occupancy below 90% rarely causes occupancy exceeds 65%. Second, antipsychotics with D2 occupancy below 90% rarely causes extrapyramidal side effect. These results suggest that monopharmacy which uses a single antipsychotic agent with appropriate dose is recommended for schizophrenia treatment.     

2006年我国十省市抗精神病药处方方式的现况调查

目的 调查2006年我国10省市抗精神病药处方方式;分析4年间我国抗精神病药处方方式的变化趋势.方法 按照作者2002年的调查方法,选择10省市41所精神疾病专科医院或综合医院精神科的5898例精神分裂症门诊和住院患者,于2006年5月22-28日使用自制修订的调查问卷进行精神分裂症处方方式的现况调查.结果 (1)5898例患者中,门诊患者为2716例(46.0%);住院患者为3182例(54.0%);男3041例(51.6%),女2803例(47.5%),缺失54例数据.(2)99.1%的患者接受了抗精神病药治疗,使用频率在前7位的药物依次为:氯氮平(31.7%),利培酮(30.5%),舒必利(14.5%),氯丙嗪(10.8%),奋乃静(9.2%)、喹硫平(7.2%),氟哌啶醇(5.8%).换算为氯丙嗪等效剂量后,住院患者平均药物剂量显著高于门诊患者.(3)72.7%的患者使用第2代抗精神病药治疗;第1代抗精神病药的使用频率为38.3%;6.19%的患者接受了长效药物治疗.(4)75.6%的患者接受了单一非长效抗精神病药治疗;24.4%的患者联合使用2种或2种以上抗精神病药.(5)54.1%的患者联合了抗胆碱能药、苯二氮革类、β-受体阻断剂、抗抑郁药和心境稳定剂,主要用于控制不良反应或增效治疗.结论 第2代抗精神病药已经成为我国治疗精神分裂症的主流药物,反映出精神分裂症治疗理念和治疗技术的进展.     

Medical decision making in antipsychotic drug choice for schizophrenia

OBJECTIVE: The influence of patient and physician variables on antipsychotic drug choice for patients with schizophrenia was assessed. METHOD: Interviews with 100 psychiatrists on drug choice for 200 patients suffering from schizophrenia were conducted. Data were analyzed by using multiple logistic regression. RESULTS: Older physicians were up to five times more likely to prescribe first-generation antipsychotics. Patient variables did not influence treatment decisions significantly. CONCLUSIONS: There is an urgent need for more research on clinical decision making and quality management.     

Bone density in chronic schizophrenia with long-term antipsychotic treatment: preliminary study

Objective

Decreased bone mineral density has been found in the chronic schizophrenic patients who have been given a long-term administration of antipsychotics. Hyperprolactinemia from the antipsychotics and the negative symptom of schizophrenia were considered as the causes for this finding. In this study, the effect of hyperprolactinemia and the negative symptom of schizophrenia on bone mineral density was investigated on male schizophrenic patients.

Methods

The cross-sectional study was carried out with the subjects of 45 male schizophrenic patients who have undertaken the monotherapy with risperidone, olanzapine and clozapine for at least one year. The demographic factors, clinical symtoms, bone mineral density and hematological test were examined for all the subjects.

Results

No significant relationship was found between hyperprolactinemia and the decreased bone mineral density in the subjects. The negative schizophrenia symptom of the subjects showed a significant effect on the decreased bone mineral density.

Conclusion

The decreased bone mineral density finding in the male schizophrenic patients may be caused by the negative schizophrenia symptom rather than the hyperprolactinemia due to the antipsychotics. Additional studies are further required regarding other factors that may affect the decreased bone mineral density such as activity, calcium intake and exposure to sunlight.     

Self-reported motivation to smoke in schizophrenia is related to antipsychotic drug treatment

PURPOSE: The prevalence of smoking in schizophrenia has reliably been reported as being higher than for any other psychiatric disorder. While a number of theories have been proposed to account for such high rates of smoking, little is known about the subjective motivation for why schizophrenia patients smoke in comparison with those without the disease. OBJECTIVES: The aim of the present study was to evaluate and compare smoking motivation in control subjects and schizophrenia patients, and determine if factors such as type of medication or access to cigarettes could contribute to self-reported motivation for smoking. METHODS: We assessed motivation to smoke in 61 schizophrenia inpatients and 33 non-psychiatric health worker controls at a tertiary care psychiatric facility in a cross-sectional study. Nicotine dependency and smoking behavior were evaluated using the Fagerstrom Test for Nicotine Dependence and a validated questionnaire that assesses motivation for smoking along seven different dimensions. RESULTS: Schizophrenia patients reported a stronger motivation to smoke than controls for reasons related to pleasure from the act of smoking, as well as a need for psychomotor stimulation. Scores on both these factors were significantly associated with daily antipsychotic drug dose. The sedative and anxiolytic effects of smoking were related to anticholinergic load of psychiatric medications. CONCLUSION: The findings highlight important differences in self-reported motivation to smoke between schizophrenia patients and normals. Antipsychotic drugs may also influence aspects of motivation to smoke.     

Metabolic disturbances associated with antipsychotic drug treatment in patients with schizophrenia: State-of-the-art and future perspectives

Metabolic disturbances and obesity are major cardiovascular risk factors in patients with schizophrenia, resulting in a higher mortality rate and shorter life expectancy compared with those in the general population. Although schizophrenia and metabolic disturbances may share certain genetic or pathobiological risks, antipsychotics, particularly those of second generation, may further increase the risk of weight gain and metabolic disturbances in patients with schizophrenia. This review included articles on weight gain and metabolic disturbances related to antipsychotics and their mechanisms, monitoring guidelines, and interventions. Nearly all antipsychotics are associated with weight gain, but the degree of the weight gain varies considerably. Although certain neurotransmitter receptor-binding affinities and hormones are correlated with weight gain and specific metabolic abnormalities, the precise mechanisms underlying antipsychotic-induced weight gain and metabolic disturbances remain unclear. Emerging evidence indicates the role of genetic polymorphisms associated with antipsychotic-induced weight gain and antipsychotic-induced metabolic disturbances. Although many guidelines for screening and monitoring antipsychotic-induced metabolic disturbances have been developed, they are not routinely implemented in clinical care. Numerous studies have also investigated strategies for managing antipsychotic-induced metabolic disturbances. Thus, patients and their caregivers must be educated and motivated to pursue a healthier life through smoking cessation and dietary and physical activity programs. If lifestyle intervention fails, switching to another antipsychotic drug with a lower metabolic risk or adding adjunctive medication to mitigate weight gain should be considered. Antipsychotic medications are essential for schizophrenia treatment, hence clinicians should monitor and manage the resulting weight gain and metabolic disturbances.     

Cortical serotonin7, 1D and 1F receptors: effects of schizophrenia, suicide and antipsychotic drug treatment

Abnormalities in serotonergic function are thought to be important in the pathology of schizophrenia. Postmortem CNS studies suggest that levels of serotonin receptors may be altered in the cortex of subjects with schizophrenia. Seeking to expand this hypothesis we have examined the effect of schizophrenia and antipsychotic drug treatments on the levels of cortical serotonin7, 1D and 1F receptors. There was a significant decrease in the binding of [3H]SB 269970 to the serotonin7 receptor in Brodmann's area 9 from subjects with schizophrenia compared to controls (Mean+/-S.E.M.: 8.3+/-0.76 vs. 11.0+/-0.64 fmol/mg ETE; p<0.05) and an increase in the binding of that radioligand in the cortex of rats treated with haloperidol (p=0.03). There were no significant differences in [3H]sumatriptan binding to the serotonin1D or serotonin1F receptor in Brodmann's area 9 from subjects with schizophrenia. There was a significant increase in [3H]sumatriptan binding to the serotonin1D in binding Layer 2 from subjects who had potentially died by suicide that was not present in other binding layers or for the serotonin1F or serotonin7 receptors. There was decrease in [3H]sumatriptan binding to the serotonin1D, but not serotonin1F, receptors across all cortical binding layers in rats treated with haloperidol. These data would be consistent with the hypothesis that decreased levels of serotonin7 receptors in Brodmann's area 9 may be involved in the pathological processes of schizophrenia and that levels of cortical serotonin7 and 1D receptors can be affected by antipsychotic drug treatment.     

Regional cerebral blood flow in first-episode schizophrenia patients before and after antipsychotic drug treatment

A total of 38 patients in a first presentation of schizophrenia prior to drug treatment underwent a single photon emission computerized tomography (SPECT) scanning programme whilst undertaking a verbal fluency task. Their scans were compared with those of 38 normal volunteer controls matched for age, sex and father's social class. Schizophrenic patients displayed a trend towards a reduced blood flow in comparison with controls. Comparing right with left hemispheres, asymmetrical blood flow patterns were more likely to be found in patients in frontal regions than elsewhere. When 27 of the 38 patients underwent a repeat SPECT scanning programme after receiving 6 months of antipsychotic drug treatment, the hypofrontal blood flow pattern persisted. Increased blood flow was observed bilaterally in the putamen. The more symmetrical blood flow pattern of the patients compared to the control subjects did not alter substantially.     

Cortical serotonin7, 1D and 1F receptors: Effects of schizophrenia,suicide and antipsychotic drug treatment

Abnormalities in serotonergic function are thought to be important in the pathology of schizophrenia. Postmortem CNS studies suggest that levels of serotonin receptors may be altered in the cortex of subjects with schizophrenia. Seeking to expand this hypothesis we have examined the effect of schizophrenia and antipsychotic drug treatments on the levels of cortical serotonin₇, _1D and _1F receptors. There was a significant decrease in the binding of [³H]SB 269970 to the serotonin₇ receptor in Brodmann's area 9 from subjects with schizophrenia compared to controls (Mean ± S.E.M.: 8.3 ± 0.76 vs. 11.0 ± 0.64 fmol/mg ETE; p < 0.05) and an increase in the binding of that radioligand in the cortex of rats treated with haloperidol (p = 0.03). There were no significant differences in [³H]sumatriptan binding to the serotonin_1D or serotonin_1F receptor in Brodmann's area 9 from subjects with schizophrenia. There was a significant increase in [³H]sumatriptan binding to the serotonin_1D in binding Layer 2 from subjects who had potentially died by suicide that was not present in other binding layers or for the serotonin_1F or serotonin₇ receptors. There was decrease in [³H]sumatriptan binding to the serotonin_1D, but not serotonin_1F, receptors across all cortical binding layers in rats treated with haloperidol. These data would be consistent with the hypothesis that decreased levels of serotonin₇ receptors in Brodmann's area 9 may be involved in the pathological processes of schizophrenia and that levels of cortical serotonin₇ and _1D receptors can be affected by antipsychotic drug treatment.     

抗精神病药对精神分裂症患者认知功能的影响

目的：比较利培酮和氯氮平对精神分裂症患者认知功能的影响。方法：对58例精神分裂症患者随机分成两组,分别给予利培酮、氯氮平治疗8周。治疗前和治疗8周末分别进行简明精神病评定量表(BPRS)、韦氏成人记忆量表修订本(WMS-RC)、威斯康星卡片分类测验(WCST)和数字划销测验(CT)评定,比较利培酮和氯氮平对精神分裂症患者认知功能的影响。结果：两组8周后,各项检查项目均有显著好转。结论：利培酮和氯氮平均能改善精神分裂症患者的认知功能。     

Individualizing antipsychotic drug therapy in schizophrenia: The promise of pharmacogenetics

The first- and second-generation antipsychotic drugs have become mainstay drug treatment for schizophrenia. However, patients who receive antipsychotic drugs differ with respect to treatment response and drug-induced adverse events. The biological predictors of treatment response are being researched worldwide, with emphasis on molecular genetic predictors of treatment response. Because of the rapid and exciting developments in the field, we reviewed the recent studies of the molecular genetic basis of treatment response in schizophrenia. The accumulating data suggest that DNA information in the pathways for drug metabolism and drug target sites may be an important predictor of treatment response in schizophrenia. The data suggest that clinicians may soon be using a patient’s genotype to decide initial choice of antipsychotic drug treatment in schizophrenia. The pharmacogenetics of schizophrenia can improve the prospects of individualized treatment and drug discovery. Pharmacogenetic investigations of schizophrenia susceptibility loci, and genes controlling drug target site receptors, drug-metabolizing enzymes, the blood-brain barrier systems, and epigenetic mechanisms could lead to a molecular classification of treatment response and adverse events of psychotropic drugs.     

Oculomotor and neuropsychological effects of antipsychotic treatment for schizophrenia

Cognitive enhancement has become an important target for drug therapies in schizophrenia. Treatment development in this area requires assessment approaches that are sensitive to procognitive effects of antipsychotic and adjunctive treatments. Ideally, new treatments will have translational characteristics for parallel human and animal research. Previous studies of antipsychotic effects on cognition have relied primarily on paper-and-pencil neuropsychological testing. No study has directly compared neurophysiological biomarkers and neuropsychological testing as strategies for assessing cognitive effects of antipsychotic treatment early in the course of schizophrenia. Antipsychotic-naive patients with schizophrenia were tested before treatment with risperidone and again 6 weeks later. Matched healthy participants were tested over a similar time period. Test-retest reliability, effect sizes of within-subject change, and multivariate/univariate analysis of variance were used to compare 3 neurophysiological tests (visually guided saccade, memory-guided saccade, and antisaccade) with neuropsychological tests covering 4 cognitive domains (executive function, attention, memory, and manual motor function). While both measurement approaches showed robust neurocognitive impairments in patients prior to risperidone treatment, oculomotor biomarkers were more sensitive to treatment-related effects on neurocognitive function than traditional neuropsychological measures. Further, unlike the pattern of modest generalized cognitive improvement suggested by neuropsychological measures, the oculomotor findings revealed a mixed pattern of beneficial and adverse treatment-related effects. These findings warrant further investigation regarding the utility of neurophysiological biomarkers for assessing cognitive outcomes of antipsychotic treatment in clinical trials and in early-phase drug development.