Sexual function of patients with schizophrenia receiving first-generation (FGA) or second-generation antipsychotic (SGA) treatment

Abstract

Objectives. The aim of the study was to investigate sexual function in patients with schizophrenia receiving treatment with a first-generation antipsychotic (FGA) or a second-generation antipsychotic (SGA) drug. Sexual function is an important aspect of human experience, which can be affected by antipsychotic drug treatment. Sexual dysfunction in patients with schizophrenia may be less prevalent with SGA than with FGA drug treatment. Methods. A cross-sectional prevalence study assessed sexual function in a sample of 144 patients with DSM-IV schizophrenia aged between 18 and 65, using the Derogatis Interview for Sexual Functioning (self-report version: DISF-SR). Two equal-sized groups (N = 72) received treatment with an FGA or an SGA drug for at least 12 weeks. Results. No significant differences were seen on DISF-SR total score or subscale score between the two treatment groups. Conclusions. There are no differences in measured sexual function of non-randomised patients with schizophrenia treated with an FGA compared with SGA-treated patients.     

氯氮平与氯丙嗪治疗精神分裂症的对照研究

为进一步验证氯氮平在治疗精神分裂症中的地位。方法对病程＜５年的１２２例首次住院的精神分裂症患者，采用分层随机法分为两组，分别首选氯氮平和氯丙嗪进行８周治疗。以ＢＰＲＳ、ＳＡＰＳ、ＳＡＮＳ评定疗效，以ＴＥＳＳ评定副反应。结果治疗前后比较，两组ＢＰＲＳ、ＳＡＰＳ分均显著下降（Ｐ＜０．０１），ＳＡＮＳ分氯氮平组显著降低（Ｐ＜０．０１），氯丙嗪组无明显差异（Ｐ＞０．０５）；疗后氯氮平组的ＢＰＲＳ、ＳＡＰＳ、ＳＡＮＳ总分均明显低于氯丙嗪组（Ｐ＜０．０１）；ＴＥＳＳ总分氯氮平组亦低于氯丙嗪组，且无锥体外系副反应。结论氯氮平确是一种十分有效且药物副反应并不多见的抗精神病药。在严密监测血象的情况下，氯氮平实际上可作为一个可供选择的治疗精神分裂症的第一线药使用。     

抗精神病药对精神分裂症患者认知功能的影响

目的：比较非经典抗精神病药奎硫平、奥氮平、氯氮平与经典抗精神病药氯丙嗪对精神分裂症患者认知功能的影响。方法：对160例住院精神分裂症患者随机开放分配接受奎硫平、奥氮平、氯氮平和氯丙嗪药物治疗。12周的急性期治疗后,获得临床稳定期的患者[阳性与阴性量表（PANSS）总分≤60或减分率／〉50％]进入固定剂量的24周治疗。分别在基线、治疗12周和24周进行威斯康星卡片分类测验（WCST）、言语流畅性测验、霍普金斯词语学习测验（HVLT-R）、持续操作功能测验（CPT）、韦克斯勒记忆测定（WMS）、韦克斯勒智能测定（WAIS）、连线试验测定、手指叩击试验测定。结果：奎硫平组、奥氮平组、氯氮平组治疗12周和24周后认知功能均有不同程度的改善（P均〈0．05）,明显优于氯丙嗪,而氯丙嗪组无显著改善。治疗12周后奎硫平组在改善执行功能、言语流畅性和警觉性显著优于奥氮平组和氯氮平组（P〈0．05）。奥氮平组在数字特征和连线测定上明显优于氯氮平组（P〈0．05）。3种非经典抗精神病药在认知功能总分的改善与PANSS总分、阴性症状分的改善有显著相关性（r=-0．32,P〈0．05）。结论：3种非经典抗精神病药奎硫平、奥氮平、氯氮平可不同程度改善精神分裂症患者的认知功能。     

抗精神病药对男性精神分裂症患者垂体-性腺轴的影响

目的：研究氯丙嗪、利培酮、奎硫平及奥氮平对男性精神分裂症患者垂体．性腺轴的影响。方法：88例首发男性精神分裂症患者随机分为氯丙嗪组、利培酮组、奎硫平组及奥氮平组，检测治疗前、治疗4周及8周血清促卵泡素（FSH）、黄体生成素（LH）、催乳素（PRL）、睾酮（T）的水平变化。结果：氯丙嗪组治疗8周后，血清PRL水平显著高于治疗前。利培酮组在治疗4周及8周后PRL水平均显著高于治疗前，治疗8周后T及LH水平显著低于治疗前。奎硫平组在治疗4周及8周后血清PRL、LH、T水平与治疗前比较差异均无显著性。奥氮平组治疗4周后PRL水平显著高于治疗前，治疗8周后即与治疗前差异无显著性。结论：奎硫平对垂体．性腺轴激素水平无明显影响。     

RGS4 genotype is not associated with antipsychotic medication response in schizophrenia

Summary. The aims of the present study were to compare the allele frequencies of a common single nucleotide polymorphism located upstream of the regulator of G-protein signaling 4 (RGS4) gene (T > G, Rs 951436) in 219 Finnish patients with schizophrenia and in 389 control subjects, to analyze corresponding frequencies between two different subtypes of 93 schizophrenia patients according to their medication response, and to study the effect of this SNP on age at onset in schizophrenia. The RGS4 (T > G, Rs 951436) genotype was not associated with incidence or age at onset in schizophrenia. Neither was the RGS4 genotype associated with medication response with two different subpopulations with schizophrenia.     

抗精神病药对男性精神分裂症患者垂体-性腺轴的影响

目的:研究氯丙嗪、利培酮、奎硫平及奥氮平对男性精神分裂症患者垂体性腺轴的影响。方法:88例首发男性精神分裂症患者随机分为氯丙嗪组、利培酮组、奎硫平组及奥氮平组,检测治疗前、治疗4周及8周血清促卵泡素(FSH)、黄体生成素(LH)、催乳素(PRL)、睾酮(T)的水平变化。结果:氯丙嗪组治疗8周后,血清PRL水平显著高于治疗前。利培酮组在治疗4周及8周后PRL水平均显著高于治疗前,治疗8周后T及LH水平显著低于治疗前。奎硫平组在治疗4周及8周后血清PRL、LH、T水平与治疗前比较差异均无显著性。奥氮平组治疗4周后PRL水平显著高于治疗前,治疗8周后即与治疗前差异无显著性。结论:奎硫平对垂体性腺轴激素水平无明显影响。     

抗精神病药对老年精神分裂症患者血清催乳素的影响

目的：探讨几种抗精神病药对老年精神分裂症患者血清催乳素（PRL）的影响。方法：随机选取抗精神病药治疗老年精神分裂症患者121例,分别在治疗前后测定血清PRL水平。结果：患者经舒必利、奋乃静、氟哌啶醇和利培酮治疗后血清PRL明显升高,各药物之间以及治疗前后比较差异均有显著性（F=15．95,P〈0．01）。PRL水平的升高与药物剂量呈正相关。氯氮平对PRL水平影响不明显。结论：典型和非典型抗精神病药对老年精神分裂症患者血清PRL水平的影响同样明显,强弱的顺序依次是舒必利、奋乃静、氟哌啶醇和利培酮。     

非典型抗精神病药对精神分裂症患者血清甲状腺激素水平的影响

目的探讨非典型抗精神病药利培酮、奥氮平对精神分裂症患者甲状腺功能的影响。方法将符合《中国精神障碍分类与诊断标准(第3版)》(CCMD-3)的54例精神分裂症患者,采用随机数字表法分成服用利培酮和奥氮平两组,其中利培酮组29例,给药初始剂量为4 mg/d,2周内逐渐加至6 mg/d,观察至8周末;奥氮平组25例,给药初始剂量为10 mg/d,2周内逐渐加至15mg/d,观察至8周末。分别在治疗前、治疗第8周末测血清总三碘甲状腺原氨酸(TT3)、血清总甲状腺素(TT4)、游离三碘甲状腺原氨酸(FT3)、血清游离甲状腺素(FT4)及促甲状腺激素(TSH)水平。结果利培酮组治疗前后血清TT3、TT4、FT3、FT4、TSH水平差异均无统计学意义(P0.05),奥氮平组治疗前后血清TT3、TT4、TSH水平差异无统计学意义(P0.05),治疗前后FT3、FT4差异有统计学意义[(3.01±0.28)pg/mlvs.(2.81±0.26)pg/ml,(0.91±0.2)pg/mlvs.(0.77±0.14)pg/ml,P0.05]。利培酮组治疗后血清TT3、FT3水平升高,较奥氮平组差异有统计学意义(P0.05)。结论利培酮对精神分裂症患者甲状腺功能无实质影响,奥氮平能影响精神分裂症患者血清FT3、FT4的水平,在治疗中应注意监测服用奥氮平的精神分裂症患者的甲状腺激素水平。     

精神分裂症患者用药依从性及复发情况的调查

目的 研究在自然非干预状态下影响精神分裂症患者服药依从性和复发率的因素,探讨精神分裂症患者出院后1年的服药依从性和复发情况.方法 在全国4家精神卫生中心随机抽取规定时间跨度内(2009年1-8月)任意2个月各中心出院的精神分裂患者的整体作为研究对象,采用病历调查和电话采访的方式,对精神分裂症患者出院后1年的治疗情况进行回顾性问卷调查.主要观察指标为依从率和出院后1年复发率.结果 共完成有效调查问卷537份,患者出院后1年服药依从率为57.9％,复发率为40.8％.服药依从者与不依从者复发率的差异有统计学意义,依从性与复发情况有关联(x2=34.62,P＜0.01;OR =0.31,OR值95％可信区间为0.21～0.46);经济水平与依从性有关联(x2 =12.43,P＜0.05;OR =2.59,OR值95％可信区间为1.51 ～4.42);共同居住人情况与复发率有关联(x2=12.37,P＜0.05;OR =0.31,OR值95％可信区间为0.11 ～ 0.91).结论 接受调查的精神分裂症患者出院1年后的用药依从性较高,复发率与国外研究相当;依从性、共同居住人情况可能影响复发率,经济水平可能影响依从性.     

Effects of psychotherapy in schizophrenia. A retrospective study

Effects of individual long-term psychotherapy carried out by a single therapist with 14 schizophrenic male patients were studied 6 and 8 years after the start of therapy. The outcome measures were: time spent in hospital, ability to work, social contacts and symptoms, plus a total outcome score. The psychotherapy patients were compared with a control group of schizophrenic patients treated by conventional methods. The two groups were matched with regard to prognostically important variables (age, sex, time in hospital, ability to work) in order to obtain comparable groups. At the first follow-up video-taped personal interviews focusing on the patient's status the year before the investigation were performed, followed by ratings by "blind raters". The psychotherapy patients had significantly more favourable scores on scales for hospitalization, work, symptoms and total outcome in spite of very low prescribed doses of neuroleptics in the last year. At the second follow-up these differences were maintained. In addition, a difference between the two groups in the variable 'social contacts' had emerged.     

Effects of acute paliperidone palmitate treatment in subjects with schizophrenia recently treated with oral risperidone

Objective

To examine efficacy and safety of acute treatment with paliperidone palmitate in subjects with schizophrenia whose disease remained symptomatic despite recent treatment with oral risperidone.

Methods

Post hoc analysis of a 13-week, double-blind, placebo-controlled study of subjects with symptomatic schizophrenia randomized to paliperidone palmitate 39, 156, or 234 mg (25, 100, or 150 mg equivalents of paliperidone) or placebo. Paliperidone palmitate subjects received a 234-mg day 1 dose, followed by their assigned dose on day 8 and monthly thereafter. Subjects treated with oral risperidone within 2 weeks before randomization regardless of duration were included. Assessments: PANSS, CGI-S, PSP scores; AEs. ANCOVA models with LOCF methodology evaluated treatment group differences.

Results

216 subjects received prior oral risperidone (paliperidone palmitate 39 mg, n = 53; 156 mg, n = 58; 234 mg, n = 48; placebo, n = 57). Median prior risperidone use was 22 days. Significant improvement was observed with paliperidone palmitate 156-mg or 234-mg versus placebo in least-squares mean (SE) score change at end point in PANSS total (156 mg, −15.8 [3.0], p = 0.0001; 234 mg, −17.6 [3.2], p = 0.0001), CGI-S (156 mg, −0.9 [0.2], p = 0.0068; 234 mg, −1.1 [0.2], p = 0.0003), and PSP (156 mg, 10.7 [2.3], p = 0.0061; 234 mg, 12.9 [2.4], p = 0.0009). Most common AEs (≥ 10%) in any paliperidone palmitate group were insomnia, anxiety, and headache.

Conclusions

In subjects with schizophrenia who recently received oral risperidone but who remained symptomatic, acute treatment with monthly doses of 156-mg and 234-mg paliperidone palmitate significantly improved clinical symptoms, global illness ratings, and functioning compared with placebo, with no unexpected safety findings.     

Efficacy of risperidone versus olanzapine in patients with schizophrenia previously on chronic conventional antipsychotic therapy: a switch study

The objective of the study was to examine whether patients with schizophrenia who were judged to be stable on long-term treatment with conventional antipsychotic medications would further benefit from a switch to an atypical antipsychotic drug. Thirty-six subjects with schizophrenia spectrum disorder, on conventional antipsychotic medication therapy for at least 2 years, were randomized in double-blind fashion to risperidone versus olanzapine. Patients were titrated up to 6 mg risperidone or 15 mg olanzapine as tolerated, followed by tapering and discontinuation of conventional antipsychotic medication. Atypical antipsychotic agents were then administered alone (monotherapy) for 12 weeks. Efficacy and tolerability were assessed using the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Scale, and Simpson Angus Scale. Body weight was measured at each visit. Both treatment groups exhibited marked and similar improvement in the total PANSS score from baseline to study endpoint (22 weeks) [risperidone: baseline=59.3 (SE 3.1), 22 weeks=44.3 (SE 2.3) (p<0.001); olanzapine: baseline=55.9 (SE 3.3), 22 weeks=46.9 (SE 3.2) (p<0.001). Both groups also exhibited significant reductions in PANSS factor scores for positive and negative symptoms and disorganized thoughts. Only risperidone-treated patients exhibited significant decreases in uncontrolled hostility/excitement and anxiety and depression. Of note, while positive factor scores exhibited the majority of change within the first 10 weeks, negative factor scores continued to decline significantly in both treatment groups throughout the study. Tolerability assessments did not differ between groups. The results indicate that both atypical antipsychotic medications provided significant additional improvement in symptom severity in patients with schizophrenia previously on conventional antipsychotic agents.     

Regional change in brain morphometry in schizophrenia associated with antipsychotic treatment

The purpose of this pilot study was to: (1) determine if regional brain volume change occurs in schizophrenia patients during very short periods of withdrawal from, or stable treatment with, antipsychotics, and; (2) compare results of region-of-interest (ROI) to voxel-based morphometry (VBM) methods. In two small groups of schizophrenic inpatients, magnetic resonance imaging was performed before and after antipsychotic withdrawal, and at two time points during stable chronic antipsychotic treatment. Regional brain volumes were measured using ROI methods. Grey matter volume was measured with VBM. The medication withdrawal group showed no effect of treatment state or antipsychotic type on regional brain volumes with ROI analysis, but effects of both treatment state and antipsychotic type on grey matter volume were observed with VBM in right middle frontal, right medial frontal, right and left superior frontal, right cingulate, and right superior temporal gyrii as well as in the right and left hippocampal gyrii. The chronic stable treatment group showed an effect of time on right caudate, left hippocampal, and total cerebrospinal fluid volumes with ROI analysis, while effects of both time and antipsychotic type were observed with VBM on grey matter volume in the left superior temporal lobe. No findings survived correction for multiple comparisons. A positive correlation between regional volume change and emerging psychopathology was demonstrated using ROI methods in the medication withdrawal group. Treatment state and emergent symptoms in schizophrenia patients were associated with regional volume change over very short time periods. Longitudinal regional brain volume change in schizophrenia patients is likely physiologic and therefore potentially reversible.     

Effects of alcohol consumption and antipsychotic medication on brain morphology in schizophrenia

Magnetic resonance imaging (MRI) studies have shown smaller volumes of grey matter (GM) and white matter (WM) both in schizophrenia and among patients with alcohol abuse or dependence. The effect of alcohol consumption in non-clinical alcohol consumers, i.e. subjects not recruited as having alcohol use disorders is less studied. In the present study, we investigated the effects of alcohol consumption, antipsychotic medication and a diagnosis of schizophrenia on variation in brain volumes among patients recruited for having schizophrenia and a group of age and gender matched control subjects. A total of 69 patients with schizophrenia (n = 56), schizoaffective disorder (n = 12) and schizophreniform disorder (n = 1) and 97 control subjects were included. Alcohol Use Disorder Identification Test (AUDIT) was used to estimate alcohol consumption. In the entire group of patients and controls higher AUDIT score was significantly related to smaller volumes of WM. When ten patients and six control subjects who met lifetime diagnostic criteria for alcohol use disorders were excluded only a trend level association between AUDIT score and WM volumes was found. Having a diagnosis of schizophrenia was related to smaller volumes of total, frontal and temporal WM, total and temporal GM, and larger volumes of total, frontal and temporal cerebrospinal fluid (CSF). A diagnosis of schizophrenia remained a significant factor for smaller WM volumes even when the effect of alcohol consumption was taken into account. Antipsychotic medication was related to larger volumes of temporal CSF. This study demonstrates that alcohol consumption is an important factor for variation in WM volumes, and this effect should be taken into account in all studies evaluating brain volumes from MR images.     

精神分裂症神经内分泌、免疫、自由基代谢与治疗药物的关系

目的 探讨典型,非典型抗精神病药对精神分裂症神经内分泌,免疫,自由基代谢的作用及其与疗效的关系。方法 用固定剂量（利培酮为６ｍｇ／ｄ,氟哌啶醇２０ｍｇ／ｄ,在１周内增至治疗量）利培酮,氟哌啶醇随机,双盲治疗７８例精神分裂症例患者１２周,在治疗前后分别评定阳笥和阴性症状量表（ＰＡＮＳＳ）并测定帕罗西汀激发的神经内分泌试验,白细胞介素２（ＩＬ－２）白细胞介素８（ＩＬ－８）和超氧化物歧化酶（ＳＯＤ）等,     

Lipid peroxidation products and changes in phospholipid composition induced by indobufen in diabetic platelets

Indobufen is an antiaggregatory drug which first of all inhibits platelet aggregation by interfering with cyclooxygenase enzymes in platelets. We have investigated the influence of indobufen (200 mg twice daily for 10 days) on platelet lipid peroxidation and phospholipid metabolism in diabetic patients. The production of lipid peroxidation products was significantly lower after drug treatment. Indobufen administration, however, had no influence on the fatty acid composition of platelet phospholipids.     

3H-spiperone binding in platelet membranes: a possible biological marker for schizophrenia

High-affinity-specific 3H-spiperone binding to platelet membranes was carried out in 30 schizophrenic patients, without prior antipsychotic medication, fulfilling the Research Diagnostic Criteria, and in 30 matched control subjects. The psychosis was rated on the Modified Brief Psychiatric Rating Scale. Compared with healthy subjects, schizophrenic patients had significantly higher 3H-spiperone binding due to a lower dissociation constant (38%), i.e. increased affinity. No significant difference was observed in the maximum number of binding sites (Bmax) between the two groups. It is our contention that 3H-spiperone binding to platelets may be a biological marker for schizophrenia.     

Effects of antipsychotic drugs on memory functions of schizophrenic patients.

In this research we investigated the effects of 4 antipsychotic drugs with different anticholinergic components on different memory functions of schizophrenic patients. Drugs were administered in cumulative doses and memory was tested 90 min after each drug was administered. The results show that chlorpromazine and thioridazine impaired short-term verbal memory after 6 h of sequential administration. Trifluoperazine and haloperidol improved short-term verbal memory from the third to the fifth administration. Immediate memory, long-term memory and visual short-term memory were not impaired by any drug.