Anticholinergic use in hospitalised schizophrenic patients in Belgium

This naturalistic study aims to evaluate the influence of antipsychotic treatment on the use of anticholinergics. The observed use of anticholinergics will give an indication of the occurrence of extrapyramidal side effects (EPS) in the different antipsychotic treatment conditions. The medication use of 1215 hospitalised patients with DSM-IV 295.xx diagnosis is recorded. Four antipsychotic treatment conditions are distinguished: 1) only first generation antipsychotics (FGA): patients receive one or a combination of first generation antipsychotics, 2) a combination of high potency FGA and second generation antipsychotics (SGA), 3) a combination of low potency FGA and SGA, and 4) only SGA: patients receive one or a combination of SGA. Antipsychotic treatment significantly influences the use of anticholinergics. Anticholinergic use is highest in patients treated with high potency FGA (whether or not in combination with SGA) as compared with patients only treated with SGA and patients combining SGA with low potency FGA. The two latter groups do not significantly differ. However, there were no significant differences in the prevalence of EPS with the exception of akathisia between FGA and SGA. Thus, through the use of anticholinergics, EPS induced by FGA can be effectively reduced.     

Evaluating the CANSAS self-report (CANSAS-P) as a screening instrument for care needs in people with psychotic and affective disorders

The metabolic profiles of Chinese patients treated with second-generation antipsychotic (SGA) medication and first-generation antipsychotic (FGA) medication were compared. The sample comprised 99 patients treated with SGA (risperidone, olanzapine and ziprasidone) and 99 with FGA (chlorpromazine, haloperidol and trifluoperazine) from the outpatient clinic of a teaching hospital in Hong Kong. The most frequent psychiatric diagnosis was schizophrenia, followed by affective disorder and other psychiatric diagnoses. Subjects were measured for body weight, body height, fasting lipid and glucose levels. SGA was associated with higher LDL-cholesterol level than FGA. Individual comparison of different antipsychotics showed that patients on olanzapine had the greatest increases in cholesterol and triglycerides among all antipsychotics. The finding suggested SGA, particularly olanzapine, were associated with more metabolic risk factors than first-generation antipsychotics.     

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.     

Time to rehospitalization in patients with schizophrenia discharged on first generation antipsychotics, non-clozapine second generation antipsychotics, or clozapine

Rehospitalization is an important outcome of drug effectiveness in schizophrenia. In this study, the hypothesis that clozapine and some second generation antipsychotics (SGA) were superior to first generation antipsychotics (FGA) in preventing rehospitalization of patients with schizophrenia discharged from a university hospital in Brazil was tested. A retrospective observational study was conducted designed to evaluate time to rehospitalization of patients with schizophrenia discharged on a regimen of oral FGA, depot FGA, risperidone, olanzapine and amisulpride, other SGA, or clozapine, during a three-year follow-up period. Risk factors associated with rehospitalization were examined. Of the 464 patients with schizophrenia discharged from hospital, 242 met criteria for study entry. Higher rehospitalization rates were observed in patients treated with depot FGA (30%), risperidone (30%) and other SGA groups (28.5%), respectively. Clozapine was significantly associated with lower rehospitalization risk compared with risperidone. The risk of rehospitalization in patients on olanzapine and amisulpride, and oral FGA, was similar to that of patients in use of clozapine. These results however, are limited by the heterogeneity of illness severity across the groups.     

Antipsychotics and seizures: Higher risk with atypicals?

PurposeAlmost all antipsychotics have been associated with a risk of epileptic seizure provocation. Among the first-generation antipsychotics (FGA) chlorpromazine appears to be associated with the greatest risk of seizures among the second-generation antipsychotics (SGA) clozapine is thought to be most likely to cause convulsions. This information is largely based on studies that are not sufficiently controlled. Besides, information about the seizure risk associated with newer antipsychotics is scarce.MethodThe Pharmacovigilance Unit of the Basque Country (network of centers of the Spanish Pharmacovigilance System, SEFV) provided reporting data for adverse reactions (AR) from the whole SEFV to estimate the reporting odds ratio (ROR) for antipsychotics and seizures (“convulsions” as Single MedDra Query). Data was obtained from SEFV database from 1984 to the June 2011.ResultsThe total number of convulsions reported for SGA was 169 (total reported AR 3.204). The number of convulsions reported for FGA was 35 (total reported AR 2.051). 94 convulsions were reported in association with clozapine (total AR 1.052). The ROR for SGA versus FGA was 3.2 (CI 95%: 2.21–4.63). The ROR for SGA excluding clozapine versus FGA was 2.08 (CI 95%: 1.39–3.12).ConclusionOur results show that SGA may pose a higher risk of seizures than FGA, mainly, but not only due to clozapine. This is line with recent studies suggesting that some SGA carried a higher average risk of electroencephalographic abnormalities than many FGA. Nonetheless, It is well known that spontaneous reports do not allow strong inferences about adverse drug effects, because differences in reporting fractions by time, drug or type of event are difficult or even impossible to distinguish from differences in the occurrence rates of adverse events. Still, we consider that the possibility of SGA carrying a higher risk of seizure induction than FGA warrants further research.     

Impact of Coordinated Behavioral Health Management on Quality Measures of Antipsychotic Use

A state Care Management Entity (CME) using the wraparound practice model provided intensive care coordination for youth with severe mental illness, those most likely to receive antipsychotics. The model has led to improved clinical/functional outcomes, but little is known about the impact on antipsychotic prescribing and safety monitoring. A pre-post study was conducted to evaluate antipsychotic dosing, concomitant antipsychotic use, and metabolic monitoring among CME-enrolled and non-CME-enrolled comparison groups. CME-enrolled youth had greater decrease in concomitant antipsychotic use than non-CME-enrolled youth, but no difference in dosing or metabolic monitoring. More education of prescribing antipsychotics and team-based engagement in care coordination are needed.     

第二代抗精神病药对慢性精神分裂症患者的治疗作用

目的：探讨第1代抗精神病药（FGA）联合与未联合第2代抗精神病药（SGA）对慢性精神分裂症患者临床疗效、认知功能及社会功能的影响。方法：74例慢性精神分裂症患者被随机分为联合组和对照组,联合组为FGA联合SGA,对照组则为持续应用FGA,治疗至少12周。采用简明精神病量表（BPRS）分别于治疗前后评估患者临床疗效,以探究性眼动检测来评估患者的认知功能,采用个人和社会功能量表（PSP）评估社会功能。结果：探究性眼动检测治疗前凝视点数联合组显著低于对照组（P〈0.05）;尽管经过联合SGA治疗后两组间凝视点数虽不存在差异（P〉0.05）,但联合组治疗前后的凝视点数增加值却显著好于对照组（P〈0.001）;反应性探索（RSS）评分在疗前、疗后两组间均差异无显著性。所有联合SGA患者在治疗后PSP评分均显著优于未联合用药组（P〈0.05或P〈0.001）;LSD分析提示：尤以联合利培酮或阿立哌唑对患者PSP评分改善最为显著（P均〈0.001）。结论：联合SGA对慢性精神分裂症患者疗效显著,尤其对患者认知和社会功能改善明显。     

Ziprasidone-related oculogyric crisis in an adult

Introduction

Drug-induced dyskinesias are common side-effects of first-generation antipsychotics (FGAs) but are not usually related to second-generation antipsychotics (SGAs). Oculogyric crisis (OGC) is a disabling acute dystonia that affects extra-ocular muscles usually resulting in an upward deviation of the eyes, which lasts from minutes to hours.

Case report

We describe an adult patient, previously exposed to an FGA, who developed OGC on 80 mg/day of ziprasidone. The movement disorder significantly improved after use of 1 mg/day of clonazepam without the need to switch to another SGA.

Discussion

The clinical features of the movement disorder of our patient meet the criteria for OGC. It is, sometimes, difficult to directly correlate a drug-induced dyskinesia to a SGA due to previous exposures to FGAs. The onset of OGC after exposure to ziprasidone without simultaneous use of other antipsychotic suggests a casual relationship between the former and the movement disorder. It is possible that previous use of an FGA was a risk factor for the development of OGC.

Conclusion

To the best of our knowledge, this is the first report of ziprasidone-related OGC in an adult patient. Physicians must be aware of its occurrence in order to improve care of patients treated with these agents.     

Attitudes towards long-acting depot antipsychotics: A survey of patients,relatives and psychiatrists

In many countries fewer than 20% of individuals with schizophrenia receive depot antipsychotic medication. Frequently stated reasons are psychiatrist's, patient's and relative's objections to depot treatment. This is the first study that directly compares the attitudes to depot antipsychotics of psychiatrists, patients and relatives. A semi-structured questionnaire about their attitudes towards depot antipsychotics was completed by 255 participants (83 patients diagnosed with schizophrenic disorder, 81 psychiatrists in private practice and 91 relatives, not directly related to the patients). Patients were more negative towards depot injections than psychiatrists and relatives. They particularly fear to be constricted in their autonomy when treated with depot antipsychotics and that injections might be painful. About 67% of all patients in our sample did not receive information about depot antipsychotics from their psychiatrist. Less than 10% of psychiatrists offer depot treatment after a first psychotic episode. Psychiatrists use depot antipsychotics in a conservative way, although they attribute positive traits to the method. Patients' negative attitudes might relate to the low level of information. To enhance the use of depot antipsychotics, information practices of psychiatrists should be improved. Patients should be informed about different forms of treatment during early stages of the illness.     

Does short-term antipsychotic discontinuation of up to 3 weeks worsen symptoms in acute schizophrenia? A pooled analysis of placebo washout data

Aim

This study aimed to examine symptom changes during short-term discontinuation of antipsychotics up to 3 weeks including the placebo washout phase in acute schizophrenia.

Methods

The data from three double-blind, randomized, controlled trials comparing lurasidone versus placebo in patients with acute exacerbation of schizophrenia were analyzed. Symptom severity was assessed using the Positive and Negative Syndrome Scale (PANSS) total and the Clinical Global Impression–Severity scale (CGI-S) scores. The scores before and after the antipsychotic discontinuation phase were compared, and factors associated with score changes were explored.

Results

Among 2154 patients participating in the trials, 600 who received antipsychotic monotherapy and completed the antipsychotic discontinuation phase were included in the analysis. No patients received clozapine. The mean duration of the discontinuation phase was 5.9 ± 2.5 days. The PANSS total and CGI-S scores significantly changed from 94.0 ± 9.5 to 95.4 ± 10.5 (P < 0.001) and from 4.9 ± 0.6 to 4.9 ± 0.7 (P = 0.041), respectively, during this phase; however, the absolute difference was minimal. The score changes were not associated with the type or dose of prior antipsychotics, or the duration or strategy (abrupt vs gradual) of antipsychotic discontinuation.

Conclusions

Symptoms may not worsen to a clinically meaningful degree after short-term discontinuation of non-clozapine antipsychotics up to 3 weeks in patients with acute exacerbation of schizophrenia, suggesting that antipsychotic efficacy persists at least several days after discontinuation. This finding supports once-daily dosing regimen of antipsychotics and abrupt antipsychotic discontinuation when switching to another antipsychotic.     

Drug treatments for schizophrenia: pragmatism in trial design shows lack of progress in drug design

Aims.The introduction of second generation antipsychotic (SGA) medication over a decade ago led to changes in prescribing practices; these drugs have eclipsed their predecessors as treatments for schizophrenia. However, the metabolic side effects of these newer antipsychotics have been marked and there are increasing concerns as to whether these novel drugs really are superior to their predecessors in terms of the balance between risks and benefits. In this article, we review the literature regarding comparisons between first generation antipsychotic (FGA) and SGA in terms of clinical effectiveness.Methods.Large (n > 150) randomized-controlled trials (RCTs) comparing the effectiveness (efficacy and side effects) of FGA and SGA medications other than clozapine were reviewed, as were meta-analyses that included smaller studies.Results.The superiority in efficacy and reduced extrapyramidal side effects (EPSE) of SGAs is modest, especially when compared with low-dose FGAs. However, the high risk of weight gain and other metabolic disturbances associated with certain SGAs such as olanzapine is markedly higher than the risk with FGAs at the doses used in the trials.Conclusions.The efficacy profiles of various FGAs and SGAs are relatively similar, but their side effects vary between and within classes. Overall, large pragmatic trials of clinical effectiveness indicate that the care used in prescribing and managing drug treatments to ensure tolerability may be more important than the class of drug used.Key words: antipsychotic drugs, clinical effectiveness, schizophrenia, randomized controlled trials     

Different serine and glycine metabolism in patients with schizophrenia receiving clozapine

Dysfunction of the N-methyl-d-aspartate receptor, which is modulated by excitatory amino acids (EAA), is involved in the pathophysiology of schizophrenia. The effects of antipsychotics on EAA metabolism are uncertain. Positive clinical effects of treatment with antipsychotics were not always associated with changes in EAA serum levels in patients with schizophrenia in clinical trials. To examine EAA serum levels in relation to the intensity of psychotic symptoms and the type of medication received we compared these variables among patients with schizophrenia (n = 49) treated with first (FGA) or second (SGA) generation antipsychotics or clozapine. Glutamate, aspartate, glycine, total serine and d-serine serum levels were measured by High Performance Liquid Chromatography. The Positive and Negative Syndrome Scale (PANSS) and the Scale for the Assessment of Negative Symptoms (SANS) were used to assess symptoms of schizophrenia. Lower average levels of glycine and total serine were found in the serum of patients receiving clozapine when compared to the groups of patients treated with FGA or SGA. There were no differences in serum glutamate, aspartate or d-serine levels or in the intensity of schizophrenic symptoms assessed by PANSS or SANS among the groups of patients treated with FGA or SGA or clozapine. Lower glycine and total serine serum levels could be caused by the particular characteristics of the population of patients receiving clozapine rather than as an effect of the clozapine. The results suggest selective deficiency of l-serine synthesis in the patients with resistance to non-clozapine treatment. It might be an unique biochemical and pathophysiological characteristic of the treatment-resistance in schizophrenia.     

Sex, ethnicity, and antipsychotic medication use in patients with psychosis

Previous studies suggested that African American patients with psychotic disorders receive higher doses of antipsychotic medication than white patients, are more likely to receive depot antipsychotics, and are less likely to be prescribed second-generation antipsychotics. African-American men in particular may be most likely to receive excessive doses of antipsychotics and depot antipsychotics, although this is less clear. Few studies have examined how sex and ethnicity interactions affect treatment of psychotic disorders. In this study, we examined whether the interaction of sex and ethnicity predicted the use of depot antipsychotics and the dosing of antipsychotics in a sample of inpatients with psychotic disorders. The inpatient records of 167 patients with psychotic disorders were evaluated for type and dose of medication at discharge. African-American men received depot antipsychotic medication more frequently than African-American women and white patients. This difference persisted after controlling for sociodemographic and clinical variables. African-American men and women with psychotic mood disorders were also more likely to be discharged on high antipsychotic doses compared with white patients. There were no ethnic or sex differences in the dosing of antipsychotics for the treatment of schizophrenia spectrum disorders. There were also no ethnic or sex differences in the use of second-generation antipsychotics.