Antipsychotic effects on auditory sensory gating in schizophrenia patients

P50 sensory gating deficit has repeatedly been demonstrated in schizophrenia. Studies have produced inconsistent findings with respect to normalization of P50 gating in patients with schizophrenia receiving treatment with different antipsychotics. The current study was designed to determine whether there is a difference in P50 gating in schizophrenia patients treated with first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs), including clozapine. P50 evoked potential recordings were obtained from 160 patients with schizophrenia and 77 healthy comparison subjects. Forty-three patients were being treated with clozapine, sixty-eight were taking SGAs (33 risperidone, 21 olanzapine, 11 aripiprazole, and 3 combinations of SGAs) and 49 were being treated with FGAs. Schizophrenia patients exhibited significantly higher P50 ratios than healthy subjects. When patients treated with different antipsychotics were compared, there were no differences in any of the neurophysiological findings. Second-generation antipsychotics were not related to more normal sensory gating in this population of patients with chronic schizophrenia.     

Antipsychotic drugs in schizophrenia: current issues

In the 1950s antipsychotic antidopaminergic drugs were introduced as the pharmacological treatment of schizophrenia. In the last 35 years a large fund of knowledge has been acquired about these drugs. Still, a number of issues regarding them require further addressing. We have reviewed the literature on some of these issues, focusing on those factors that the previous studies have resolved inadequately. The issue of optimal dosages of antipsychotics in schizophrenia has been analyzed from the perspective of the dose requirements during "rapid tranquilization", "in acute psychotic phases of schizophrenia", "in chronically hospitalized psychotic schizophrenic patients" and during "maintenance phases of schizophrenia". We have briefly discussed the different methodologies available for measuring neuroleptic levels in plasma, their methodological weaknesses and strengths and some of the larger studies done with chlorpromazine, haloperidol and fluphenazine to establish correlations between levels, treatment response, oral dosages and side-effects. The theoretically fascinating concept of supersensitivity psychosis has been reviewed and the theoretical and practical weaknesses that exist in most of the papers that have claimed validity for this concept are presented. The article also reviews the preclinical, postmortem and clinical research that demonstrates the presence of site selectivity for dopamine receptors in the newer atypical neuroleptics. Finally, the article briefly reviews the current status of some unorthodox clinical strategies, that may be potentially applicable in managing schizophrenic disorders.     

The effect of neuroleptics and other psychotropic drugs on negative symptoms in schizophrenia

It has been hypothesized that the negative symptoms of schizophrenia are related to structural brain abnormalities and respond poorly to treatment with neuroleptics and other drugs since they are persistent, if not irreversible. Because this issue has important clinical and theoretical implications, the authors reviewed the relevant literature on the effect of neuroleptics, L-dopa, and other psychotropic agents on these symptoms. Contrary to the above conclusions, several large scale, controlled studies of the therapeutic effects of conventional neuroleptics have reported clinically relevant improvement in negative symptoms in a significant proportion of schizophrenics. The improvement tended to occur early in the course of treatment and was most notable in those patients with relatively shorter durations of illness. A specific class of neuroleptic drugs not studied in these earlier large scale trials, the diphenylbutylpiperidines, has been suggested to be particularly likely to ameliorate negative symptoms, possibly because of their significant calcium channel blocking action. A review of the clinical studies comparing this group of neuroleptics with those from different classes supports the suggestion that they can produce greater improvement in anergia and emotional withdrawal. Six open and four controlled trials of L-dopa treatment of negative symptoms with L-dopa alone or in combination with neuroleptics. As with neuroleptics alone, improvement tended to be greater in those with a shorter duration of illness. The available evidence suggests that negative symptoms, at least in less chronic schizophrenic patients, may be partially responsive to currently available pharmacological intervention in a significant proportion of schizophrenics.     

Antipsychotic drugs for elderly patients with schizophrenia: A systematic review and meta-analysis

Elderly patients with schizophrenia are a particularly vulnerable group often excluded from clinical trials. Currently there is no evidence-synthesis about the efficacy and safety of antipsychotics in this subgroup.We reviewed all randomized-controlled-trials, about antipsychotics in elderly schizophrenics (last search Dec 12, 2017). Pairwise meta-analyses were conducted. The primary outcome was overall symptoms. Secondary outcomes included positive symptoms, negative symptoms, response, dropouts, quality of life, social functioning and side-effects.We included 29 references from 18 unique randomized-controlled-trials with 1225 participants published from 1958 to 2009. The definition of “elderly” was very heterogeneous across the studies (minimum age 46–65, mean age 57–73). There were evidence gaps for most drugs in many outcomes. In terms of efficacy paliperidone was associated with fewer dropouts due to inefficacy than placebo in the only placebo-controlled-trial. Olanzapine was superior to haloperidol in overall symptoms, negative symptoms and response, and it was associated with fewer dropouts than risperidone. Risperidone and haloperidol produced more prolactin increase than olanzapine, and olanzapine was associated with less use of antiparkinson medication than haloperidol.Although we found no marked differences of the effects of these drugs in the elderly, the evidence presented was based on very few usually small studies. To examine specifically whether there are differences in efficacy and side-effects in elderly, which differs in meaningful ways from the general population, studies in patients who are defined by critiera as truly geriatric, which incorporates older age together with multimorbidity and fraility dimensions, may be more informative.     

精神分裂症患者院内获得性肺炎与精神药物治疗相关性分析

目的探讨精神分裂症患者医院获得性肺炎与精神药物治疗的相关性。方法对温州康宁医院5年间顺序出院的普通精神科精神分裂症患者2037人进行回顾性调查分析。结果医院获得性肺炎85例(4.17%),经Logistic回归分析发现医院获得性肺炎与抗精神病药物剂量、加药速度、使用氯氮平、利培酮、氟哌啶醇注射剂、氯硝西泮注射剂、氯硝西泮片等7个因素相关。结论精神分裂症医院获得性肺炎与抗精神药物治疗种类、方式、剂量、途径以及联合使用苯二氮(艹卓)类药物等医源性因素有关。     

Correlation between hospital-acquired pneumonia and psychotropic treatments in patients with schizophrenia

目的 探讨精神分裂症患者医院获得性肺炎与精神药物治疗的相关性.方法 对温州康宁医院5年间顺序出院的普通精神科精神分裂症患者2037人进行回顾性调查分析.结果 医院获得性肺炎85例(4.17％),经Logistic回归分析发现医院获得性肺炎与抗精神病药物剂量、加药速度、使用氯氮平、利培酮、氟哌啶醇注射剂、氯硝西泮注射剂、氯硝西泮片等7个因素相关.结论 精神分裂症医院获得性肺炎与抗精神药物治疗种类、方式、剂量、途径以及联合使用苯二氮(革)类药物等医源性因素有关.     

认知行为干预对精神分裂症患者服药依从性及重新入院率的影响

目的探讨认知行为干预对精神分裂症患者服药依从性和重新入院率的影响。方法选取2018年1～12月随机抽查94例精神分裂症患者,按照随机数字表法分为对照组和观察组,各47例。两组均接受常规抗精神病药物治疗、日常性健康教育及娱疗活动,观察组在此基础上予认知行为干预。比较两组患者干预前、干预2、4、5周后服药依从性。采用简明精神病评定量表(BPRS)评价患者干预前及干预6周后康复效果,并比较两组患者重新入院率。结果干预前、干预2周后两组患者服药依从性差异无统计学意义(P 0.05),干预4、5周后观察组服用依从性高于对照组,差异有统计学意义(P 0.05);干预前两组患者BPRS评分差异无统计学意义(P 0.05),干预后观察组患者BPRS评分明显低于对照组,差异有统计学意义(P 0.05);观察组患者重新入院率(17.02%)显著低于对照组(36.17%),差异有统计学意义(P 0.05)。结论为精神分裂症患者开展认知行为干预可有效提升患者服用依从性,对改善患者病情及降低其重新入院率具有积极影响,因此该种干预模式在临床中大力推广。     

时间护理在精神分裂症患者健康教育中的作用分析

目的对时间护理在精神分裂症患者健康教育中的临床作用进行分析。方法选取2015年6月~2016年6月间我院收治的精神分裂症患者100例作为本次观察对象,将其按照随机原则分为对照组和观察组两组,均采取基础护理以及健康教育干预,而观察组病患则与此同时采取时间护理干预,后对比两组患者的入院时至康复期至出院前的简明精神病量表评分情况,分析两组患者的疾病健康知识掌握情况、护理满意情况以及社会支持评定量表与医学应对问卷评定情况。结果观察组患者入院初期与康复期至出院前N-BPRS评分均明显较入院时优异,且均明显低于对照组(P<0.05);观察组患者的疾病健康知识掌握评分及护理满意度评分均显著高于对照组(P<0.05);护理前两组患者的客观支持、主观支持、支持利用度、面对、屈服及回避评分均比较差异无统计学意义(P>0.05),护理后,观察组患者的上述评分均明显优于对照组(P<0.05)。结论针对精神分裂症病患,采取基础护理措施及健康教育基础上,采用时间护理干预对于改善健康教育效果有较好的临床价值。     

Donepezil augmentation of clozapine monotherapy in schizophrenia patients: a double blind cross-over study

Increasing evidence suggests that the cholinergic system is involved in the pathogenesis of schizophrenia. Donepezil, a central cholinesterase inhibitor, improves psychotic symptomatology in demented patients, however, evidence for its role in the management of active psychosis in schizophrenia remains limited. An 18-week double blind cross-over study was conducted in which eight patients were randomly assigned to either donepezil (5 mg/day for the first 4 weeks and 10 mg/day for the following 4 weeks) or placebo as augmentation treatment to clozapine. After this initial phase, there was a 2-week washout period of the study medication after which the same regimen was crossed over at the same dose and for the same period (8 weeks). No significant difference was noted in the total positive and negative symptom scale scores when donepezil was compared with placebo (16.7%+12.97% vs 3.20%+13.94% respectively, p = 0.18). However, three patients improved (>15%) in the total PANSS scores (37.03%, 16.6% and 25.33%) during the donepezil treatment phase, while only one patient improved (20.87%) during the placebo phase. No differences were noted in the Calgary depression scale (p = 0.305), Simpson Angus scale (p = 0.374), clinical global impression-improvement scale (p = 0.23) and clinical global impression-severity of illness scores (p = 0.116). Although this preliminary study failed to demonstrate a clear effect of donepezil augmentation in clozapine treated chronic schizophrenia patients, it seems that the subtle positive effect of donepezil observed in some of our patients should encourage further investigation in a larger sample of this patient subpopulation.     

Antipsychotic response in first-episode schizophrenia: efficacy of high doses and switching

Clinicians treating schizophrenia routinely employ high doses and/or antipsychotic switching to achieve response. However, little is actually known regarding the value of these interventions in early schizophrenia. Data were gathered from a treatment algorithm implemented in patients with first-episode schizophrenia that employs two antipsychotic trials at increasing doses before clozapine. Patients were initially treated with either olanzapine or risperidone across three dose ranges, (low, full, high), and in the case of suboptimal response were switched to the alternate antipsychotic. We were interested in the value of (a) high dose treatment and (b) antipsychotic switching. A total of 244 patients were evaluated, with 74.5% (184/244) responsive to Trial 1, and only 16.7% (10/60) responsive to Trial 2. Percentage of response for subjects switched from olanzapine to risperidone was 4.0% (1/25) vs. 25.7% (9/35) for those switched from risperidone to olanzapine. High doses yielded a 15.5% response (14.6% for risperidone vs. 16.7% for olanzapine).The present findings concur with other research indicating that response rate to the initial antipsychotic trial in first-episode schizophrenia is robust; thereafter it declines notably. In general, the proportion of responders to antipsychotic switching and high dose interventions was low. For both strategies olanzapine proved superior to risperidone, particularly in the case of antipsychotic switching (i.e. risperidone to olanzapine vs. vice versa). It remains to be established whether further antipsychotic trials are associated with even greater decrements in rate of response. Findings underscore the importance of moving to clozapine when treatment resistance has been established.     

Antipsychotic properties of neuroleptic-like neuropeptides in schizophrenia: A clinical review

Recently much interest has been shown in the antipsychotic efficacy of neuroleptic-like neuropeptides in schizophenia. In this article the clinical effects of the non-opioid fragments of γ-endorphin, the so-called γ-type endorphins DTγE and DEγE, are reviewed. In addition, preliminary clinical studies of peptides related to cholecystokinin are considered. It is concluded that γ-type endorphins possess antipsychotic properties in a subgroup of patients who may belong to Type I schizophrenia. With cholecystokinin-related peptides, in particular ceruletide, antipsychotic effects have been reported which seem to be more or less comparable to those observed with γ-type endorphins.     

Antipsychotic switching: results from a one-year prospective,observational study of patients with schizophrenia

ABSTRACT

Objective: The Health Outcomes of a Canadian Community Cohort (HOCCC) study is a 1-year prospective observational study of outpatients with schizophrenia or related psychotic disorders. The purpose of the study was to compare effectiveness of antipsychotic treatment as measured by 1-year treatment completion rates.

Design and methods: Patients (N?=?929) were enrolled if in the course of usual clinical practice they switched to a second-generation antipsychotic (SGA). Observational data were collected for up to 1 year. The primary analysis compared 1-year treatment-completion rates for the olanzapine cohort with the other SGA cohort (quetiapine, risperidone, clozapine), using a chi-squared test.

Results: Of 929 patients enrolled, 64.8% (516/796) of evaluable patients completed 1 year of treatment. There was no statistically significant difference in the proportion of treatment completers between the olanzapine cohort (67.4%, 256/380) and the other SGA cohort (62.5%, 260/416). Treatment-completion rates were risperidone 62.0% (127/205), quetiapine 63.7% (123/193) and clozapine 55.6% (10/18). Antipsychotic polypharmacy was common. Patients treated with olanzapine or risperidone had significantly higher increases in BMI than quetiapine-treated patients. There were no major differences between olanzapine monotherapy and pooled other SGA monotherapy groups in status of extrapyramidal symptoms from baseline to endpoint.

Conclusions: Olanzapine and other SGAs exhibited similar rates of 1-year treatment completion. Further study of medication combinations is needed, given their perceived clinical value, and the high frequency of antipsychotic polypharmacy in clinical practice.

Limitations: As most patients received several psychotropics and power was reduced in monotherapy analyses, comparisons between cohorts must be interpreted cautiously. Comparisons between individual antipsychotics were post hoc and not powered a priori. Accuracy and completeness of adverse event information for drugs other than olanzapine is limited.     

Antipsychotic medication,functional outcome and quality of life in schizophrenia: focus on amisulpride

Abstract

Background:

Restoration of quality of life is considered as the ultimate treatment goal in the management of schizophrenia and is important for destigmatising the disease. However, few studies, including the most recent, have collected quality of life data prospectively or evaluated the relationship of treatment with quality of life.     

Metabonomic studies of schizophrenia and psychotropic medications: focus on alterations in CNS energy homeostasis

Schizophrenia is a severe neuropsychiatric disorder with a poorly understood etiology and progression. We and other research groups have found that energy metabolic pathways in the CNS are perturbed in many subjects with this disorder. Antipsychotic drugs that generally target neurotransmission are currently used for clinical management of the disorder, although these can also have marked effects on energy metabolism in the CNS and periphery. Recent proteomic and metabonomic studies have shown that molecular pathways associated with brain energy metabolism are altered in both the disorder and by antipsychotic treatments. This review focuses on discussion of these molecular alterations. Increased knowledge in this area could facilitate biomarker identification and drug discovery based on improving brain energy metabolism in this debilitating disorder.     

The efficacy of topical tazarotene monotherapy and combination therapies in psoriasis

Tazarotene (Tazorac, Allergan, Inc.) is the first topical retinoid approved for the treatment of plaque psoriasis. It has a similar onset of action compared to potent topical steroids and has the advantage of a longer remission. The common side effects associated with the drug include skin irritation (including pruritus), erythema and a burning sensation. To overcome some of these shortcomings, it has been used in combination with steroids, calcipotriene and phototherapy. Combination therapy not only results in a decrease in adverse side effects, but also enhanced efficacy. Clinical study data have shown that combination therapy is just as important as tazarotene monotherapy, if not more.     

The efficacy of topical tazarotene monotherapy and combination therapies in psoriasis

Tazarotene (Tazorac^®, Allergan, Inc.) is the first topical retinoid approved for the treatment of plaque psoriasis. It has a similar onset of action compared to potent topical steroids and has the advantage of a longer remission. The common side effects associated with the drug include skin irritation (including pruritus), erythema and a burning sensation. To overcome some of these shortcomings, it has been used in combination with steroids, calcipotriene and phototherapy. Combination therapy not only results in a decrease in adverse side effects, but also enhanced efficacy. Clinical study data have shown that combination therapy is just as important as tazarotene monotherapy, if not more.     

Therapeutic tolerance and rebound psychosis during quetiapine maintenance monotherapy in patients with schizophrenia and schizoaffective disorder

A 3-year open-label study was conducted to determine the long-term safety and efficacy of quetiapine monotherapy in schizophrenia and schizoaffective disorder.Twenty-three male outpatients previously stable but with inter-episode residual symptoms on classical antipsychotics and/or risperidone and who had complained of side effects were selected. To initiate quetiapine, patients were hospitalized for 13 days and then treated as outpatients. Quetiapine dosage was adjusted according to therapeutic effects.Only five patients (21.7%) completed 77 to 96 weeks of the study. Initial dose was 261 +/- 65.6 mg/day (mean +/- S.D.) administered in divided doses, with an ending dose of 487 +/- 209.6 mg/day, corresponding with an 86.6% dose increase over the course of the study. For those completing 12 weeks or less (n = 11), mean ending dose was 362 +/- 184.8 mg/day a 38.7% dose increase over baseline. For those completing 25 weeks or more (n = 12), mean ending dose was 592 +/- 178.2 mg/day, a 126.8% dose increase over baseline. Six of the seven patients who relapsed after being stabilized on quetiapine for at least three months met criteria for supersensitivity psychosis (SSP).Therapeutic tolerance and rebound psychosis were found to develop with quetiapine in male patients with a history of chronic treatment with classical antipsychotics. Seeman and Tallerico3 have proposed pharmacologic explanations for quetiapine and clozapine drug-induced rebound phenomena.