从58例住院精神病人意外死亡看安全用药

目的调查住院精神病人意外死亡情况,以指导临床治疗。方法回顾性调查我院精神科36年间出院病案,对符合意外死亡的病案进行详细统计分析。结果我院36年(1966～2001)来住院精神病人意外死亡58例,占出院病人总数的1.75‰。意外死亡主要为药物治疗中原因不明的猝死17例(29.31%)、自杀12例(20.69%)、意外窒息9例(15.52%)、过度镇静7例(12.07%)、恶性综合征(NMS)6例(10.35%)。意外死亡主要由抗精神病药毒副作用所致,与联合用药、高剂量有关,而氯氮平单一较低剂量治疗中也发生较多猝死。结论单一用药,中小剂量,慎用氯氮平,选用新型抗精神病药,做好心血管监护,加强责任心,提高应急处理能力是避免意外死亡发生的良策。     

Intramuscular (IM) ziprasidone 20 mg is effective in reducing acute agitation associated with psychosis: a double-blind, randomized trial

RATIONALE: Intramuscular (IM) conventional antipsychotics and/or benzodiazepines are effective in the short-term treatment of acutely agitated psychotic patients but may be associated with adverse effects. A short-acting IM formulation of the novel antipsychotic, ziprasidone, which may offer advantages over conventional agents, has been developed. OBJECTIVE: To compare ziprasidone IM 2 mg (n=38) and 20 mg (n=41) in the acute control and short-term management of agitated psychotic patients. METHODS: A prospective, randomized, double-blind, 24-h study assessed efficacy using the Behavioral Activity Rating Scale (BARS) and the PANSS. The BARS is a validated rating scale for the assessment of treatment response in acute agitation associated with psychosis. Following the initial dose, three more doses could be given 4 h apart if needed during the 24-h period. RESULTS: The mean BARS score had decreased 15 min after the first 20 mg IM dose and was statistically significantly lower than the 2 mg group at 30 min post-dose. The improvement with the 20 mg dose increased until 2 h, and was maintained until at least 4 h post-dose (P<0.001). Two hours after the first injection, almost all of the patients receiving ziprasidone 20 mg were BARS responders compared with just one-third of those receiving 2 mg ziprasidone (P<0.001). The calming effect of ziprasidone was also evident by the significant reduction in PANSS agitation items (P<0.05) and CGI-severity at 4 h (P=0.008). Both ziprasidone doses were very well tolerated. Ziprasidone IM 20 mg was not associated with EPS, dystonia, akathisia, respiratory depression or with excessive sedation. CONCLUSIONS: Ziprasidone IM 20 mg substantially and significantly reduced the symptoms of acute agitation in patients with psychotic disorders. Ziprasidone 20 mg IM was very well tolerated and produced no dystonia or akathisia.     

An update expert opinion on management and research strategies in Parkinson's disease psychosis

Introduction: Psychosis, a frequent complication in Parkinson's disease (PD), contributes significantly to morbidity, mortality, nursing-home placement and quality of life. Medication side effects, issues of trial design and negative outcomes have limited clinical advances of new treatments for PD psychosis. Evidence-based medicine maintains clozapine as the most effective antipsychotic in PD without motor worsening, despite risk of agranulocytosis. Safe, effective treatments that improve psychosis without exacerbating parkinsonism are urgently needed.

Areas covered: This article reviews the: i) phenomenology of PD psychosis, ii) pharmacological rationale for antipsychotics in PD; iii) clinical trials of antipsychotics in PD; iv) novel research strategies such as neuroimaging, genetics and animal models; and v) associated challenges in studying and treating PD psychosis. Preparation of this review included an extensive literature search using PubMed.

Expert opinion: Management of PD psychosis is complex. Challenges pertaining to study design, rating scales, subject recruitment and completion have limited PD psychosis treatment trials. Novel research strategies focus on nondopaminergic systems and incorporate neuroimaging, genetic associations and animal models. These strategies also have challenges but have the potential to enhance our understanding of PD psychosis and advance the development of agents that can ultimately be tested in well-designed, randomized, controlled trials.     

Iloperidone reduces sensorimotor gating deficits in pharmacological models, but not a developmental model, of disrupted prepulse inhibition in rats

Iloperidone is a novel atypical antipsychotic which acts as a broad spectrum dopamine/serotonin/norepinephrine receptor antagonist. To compare iloperidone behaviorally to other known antipsychotics, we evaluated the drug in three pharmacological models and one developmental model of disrupted prepulse inhibition (PPI) in rats. Firstly, 0.5 mg/kg apomorphine induced PPI deficits that were prevented by pretreatment with iloperidone (1 and 3 mg/kg). Secondly, treatment with the N-methyl-D-aspartate (NMDA)-receptor antagonist phencyclidine (PCP) produced robust deficits in PPI. Both doses of iloperidone (1 and 3 mg/kg) prevented the PPI-disruptive effects of treatment with 1 mg/kg PCP. Thirdly, treatment with the alpha1-adrenoceptor agonist cirazoline (0.6 mg/kg) disrupted PPI, and produced a concurrent large increase in startle magnitude. A relatively low dose of iloperidone (0.3 mg/kg) prevented cirazoline-induced PPI deficits, independent of its effects on startle magnitude. Finally, iloperidone (1 mg/kg) did not reverse PPI deficits in the isolation-rearing model of schizophrenia. These results indicate that iloperidone exerts behavioral effects in pharmacological models of disrupted sensorimotor gating consistent with "atypical" antipsychotics, mediated by antagonism of dopaminergic and noradrenergic receptors. The absence of effect in isolation-reared rats may be due to the relatively small effect size of isolation rearing on PPI or dose of iloperidone.     

非典型抗精神病药物与代谢综合征相关性分析

目的探讨应用非典型精神病药物治疗时与代谢综合征发生率影响的情况。方法选择我院精神科住院患者160例,分组应用不同药物治疗后对其餐后血糖、腹围、血压、血脂等指标进行检测。结果治疗8周末对4组患者代谢综合征的患病情况进行比较,差异无统计学意义(P>0.05);但齐拉西酮与利培酮患病率比较有明显差异(P<0.05),有统计学意义。其他组比较无明显差异(P<0.05)。第4、第8周4组患病率比较差异无统计学意义(P>0.05),组内比较,喹硫平组、利培酮组、阿立哌唑组治疗第4、第8周比较有统计学差异(P<0.05)。结论不同的非典型抗精神病药物对代谢综合征的影响也不相同,应对患者加强健康指导,适度运动、合理饮食,对体质量进行控制,提高其治疗的依从性。     

Recent developments in the management of haemophagocytic lymphohistiocytosis

Over the past two decades, the underlying pathophysiology of haemophagocytic lymphohistiocytosis (HLH) (synonyms: haemophagocytic syndrome, macrophage activation syndrome) has been well recognised. Cytokine storm plays a major role, which derives from an inappropriate immune reaction caused by proliferating and activated T-cell or natural killer (NK) cells associated with macrophage activation and inadequate apoptosis of immunogenic cells. Many biological parameters reflecting activity of disease or response to treatment have been identified, in particular, serum ferritin has been confirmed to be one of the markers for HLH. The common types of HLH consist of non-hereditary (acquired) infection-associated disease such as Epstein-Barr virus (EBV)-haemophagocytic lymphohistiocytosis (HLH) and hereditary (familial) disease such as FHL, in which, at the molecular level, dysfunctional perforin was clarified. Regarding the therapeutic strategies, prompt differential diagnosis of underlying disease is essential and choice of treatment should be based on the risk (low or high) of prognosis, where either cyclosporin A, steroids or iv. immunoglobulin (IVIG) may be indicated as initial treatment for low-risk patients, with etoposide-containing regimens for high-risk patients. Significant improvement of prognosis has been obtained by incorporating intensive supportive care at the disease onset and prompt introduction of immunosuppressants to control cytokine storm. Subsequent immunochemotherapy and haemopoietic stem cell transplantation have contributed significantly to further improve survival of hereditary and refractory HLH patients.     

Recent developments in the management of membranous nephropathy

Idiopathic membranous nephropathy is one of the most commonly encountered forms of nephrotic syndrome in adults. The natural history of the disease, observed in a small sample of untreated patients, reveals that a large proportion of patients experience spontaneous remission, whereas approximately one third of them progress towards renal insufficiency, and thus require dialysis. Hence, several attempts to treat this condition have been investigated and several protocols, based on different combinations of corticosteroids and/or immunosuppressive agents, have been proposed. However, none of these protocols has been uniformly adopted by renal physicians, either because of no or limited efficacy of most of them, or due to the potential of short- and long-term untoward effects. In this review, we examine the available data on the natural course of the disease and the possibility of identifying clinical and laboratory characteristics that could help to predict the course of membranous nephropathy. We also summarise the results of the most relevant clinical trials, and offer an updated meta-analysis of treatment studies, including the latest data on cyclosporin.     

Recent developments in the management of haemophagocytic lymphohistiocytosis

Over the past two decades, the underlying pathophysiology of haemophagocytic lymphohistiocytosis (HLH) (synonyms: haemophagocytic syndrome, macrophage activation syndrome) has been well recognised. Cytokine storm plays a major role, which derives from an inappropriate immune reaction caused by proliferating and activated T-cell or natural killer (NK) cells associated with macrophage activation and inadequate apoptosis of immunogenic cells. Many biological parameters reflecting activity of disease or response to treatment have been identified, in particular, serum ferritin has been confirmed to be one of the markers for HLH. The common types of HLH consist of non-hereditary (acquired) infection-associated disease such as Epstein-Barr virus (EBV)-haemophagocytic lymphohistiocytosis (HLH) and hereditary (familial) disease such as FHL, in which, at the molecular level, dysfunctional perforin was clarified. Regarding the therapeutic strategies, prompt differential diagnosis of underlying disease is essential and choice of treatment should be based on the risk (low or high) of prognosis, where either cyclosporin A, steroids or iv. immunoglobulin (IVIG) may be indicated as initial treatment for low-risk patients, with etoposide-containing regimens for high-risk patients. Significant improvement of prognosis has been obtained by incorporating intensive supportive care at the disease onset and prompt introduction of immunosuppressants to control cytokine storm. Subsequent immunochemotherapy and haemopoietic stem cell transplantation have contributed significantly to further improve survival of hereditary and refractory HLH patients.     

帕罗西汀联合小剂量非典型抗精神病药物在老年抑郁症患者中应用效果研究

目的探讨帕罗西汀联合小剂量抗精神病药物在老年抑郁症中的临床疗效和安全性。方法选择2011年2月～2012年2月在笔者所在医院住院治疗的86例老年抑郁症患者为研究对象,运用随机数字表法将入选患者分为对照组和观察组,对照组患者仅给予帕罗西汀进行治疗,而观察组患者则在上述治疗的基础上加用小剂量非典型抗精神病药物进行治疗,分别于入组时及治疗后8周进行自编问卷、焦虑自评量表及抑郁自评量表测评。结果经过为期8周的治疗,观察组焦虑标准分(47.86±6.65)分和抑郁标准分(48.65±4.57)分均明显低于对照组的焦虑标准分(50.63±5.83)分和抑郁标准分(51.91±4.86)分,两组患者组间焦虑标准分和抑郁标准分比较,差异均有统计学意义(P<0.05),且对照组和观察组患者药物不良反应发生率差异无统计学意义(x2=0.717,P>0.05)。结论帕罗西汀联合小剂量非典型抗精神病药物治疗老年抑郁症临床疗效确切,安全可靠,不良反应少。     

Relationship between clinical improvement and functional gains with clozapine in schizophrenia

Impairment in psychosocial functioning is a key feature in schizophrenia, but few studies have examined the relationship between improvements in symptoms and functioning. We examined the relationship between change in symptoms and change in functioning in a group of patients with treatment-resistant schizophrenia after 6 and 12 weeks of clozapine treatment. Participants were assessed prior to clozapine and again at 6 and 12-week on the 18-item Brief Psychiatric Rating Scale (BPRS) and the Social and Occupational Functioning Scale (SOFAS). Change scores in BPRS and SOFAS at 6 and 12-week post-clozapine were calculated and the direct relationship was assessed via regression models. Forty-three participants were included in this study; age of sample was 42.1±12.7 years, with 31 (72.1%) male participants. At baseline, the mean BPRS total and SOFAS scores were 46.98±12.86 and 33.07±10.79, respectively. There were significant improvements in BPRS total and SOFAS scores at 6 weeks, but no significant differences between 6 and 12-week assessments. There was no significant change in negative symptoms at both follow-up assessments. At 6-week, change in symptoms was not correlated with change in functioning and while the relationship between change in symptoms and functioning was stronger at 12 weeks, none of the BPRS factors emerged as a significant predictor. The present study found that lower baseline SOFAS score was the most robust predictor for improvements in SOFAS at 6 and 12-weeks. There appears to be a “ceiling” for functional improvements on clozapine, but follow-up studies are needed to examine functional gains beyond 12 weeks.     

Recent developments in the management of paracetamol (acetaminophen) poisoning.

Paracetamol (acetaminophen) poisoning accounts for almost a third of admissions to our district poisons unit, and is the commonest cause of death in such patients. Antidotal treatment may be effective up to 10h after overdose with oral methionine or up to 24h with acetylcysteine (not 15h as previously suggested for the latter). Patients taking paracetamol overdose while also receiving drugs which induce hepatic enzymes are more susceptible to liver damage, and antidotal treatment may be necessary at lower plasma paracetamol concentrations (50% of the normal treatment line). As survival following liver transplantation is now increasing, it is important to identify early prognostic indicators in fulminant hepatic failure, so that those patients with a high chance of fatal outcome can be considered for transplantation. Useful indicators are the presence of acidosis, marked prolongation of prothrombin time or a continued rise in prothrombin time on day 4 after the overdose. There is no evidence that paracetamol or acetylcysteine are teratogenic in pregnancy. Delays in administering acetylcysteine after paracetamol poisoning in pregnancy have been shown to increase the risk of spontaneous abortion and fetal death. Thus, acetylcysteine should be started as early as possible where treatment is indicated.     

Recent developments in analytical determination of furosemide

Furosemide (FUR), a drug that promotes urine excretion, is used in the pharmacotherapy of various diseases and is considered as a doping agent in sports. FUR is a powerful diuretic (water pill). This medicine is used to treat excessive fluid accumulation and swelling (edema) of the body caused by heart failure, cirrhosis, chronic kidney failure, and nephrotic syndrome. Owing to its extensive use as a powerful diuretic, FUR has long attracted the attention of many analysts. A variety of analytical methods have been proposed for the determination of FUR in biological fluids and pharmaceutical samples. The revision includes the most relevant analytical methodologies used in its determination from the nineties decade at present.     

Recent developments in the management of acute respiratory distress syndrome in adults.

PURPOSE: Recent developments in the management of acute respiratory distress syndrome (ARDS) in adults are reviewed. SUMMARY: Corticosteroids have been extensively studied in ARDS; however, they have not demonstrated clear benefit in patients with ARDS. Some trials have found increased complications and mortality related to corticosteroid use. The use of conservative fluid management has been associated with significant reductions in morbidity, highlighting the need to avoid fluid over-administration in patients with ARDS. A number of ventilatory strategies have also been studied. Studies have found that higher positive end-expiratory pressure settings do not appear to be harmful in patients with ARDS. In an effort to prevent alveolar overdistention, low tidal volume and plateau pressure ventilation is increasingly being used in patients with acute lung injury (ALI). Given the increasing evidence supporting the use of lower tidal volume ventilation, this strategy has become the new standard of care in patients with suspected ALI and ARDS. No clear benefit has been shown in the treatment of ARDS with nitric oxide and surfactant. Prostaglandins and acetylcysteine are not considered useful in the treatment of ARDS, while no conclusions can be drawn regarding the benefits of albuterol on mortality in patients with ARDS. The use of prone positioning should be discouraged in the treatment of ARDS based on its associated risks. CONCLUSION: Early administration of moderate-dosage corticosteroids likely helps decrease the time of ventilator dependence and duration of intensive care unit stay. Conservative fluid management and low tidal volume ventilation are becoming increasingly widespread in the management of patients with ARDS. Nitric oxide, surfactant, prostaglandins, albuterol, acetylcysteine, and prone positioning have not been shown to be beneficial in the treatment of ARDS.     

Intramuscular aripiprazole or haloperidol and transition to oral therapy in patients with agitation associated with schizophrenia: sub-analysis of a double-blind study

ABSTRACT

Objective: A sub-population analysis of 325 patients with agitation (Positive and Negative Syndrome Scale Excited Component [PEC] score ≥ 15 and ≤ 32; score of ≥ 4 on ≥ 2 items) associated with schizophrenia in a randomized, double-blind study investigating the efficacy and tolerability of intramuscular (IM) aripiprazole 9.75?mg, IM haloperidol 6.5?mg, or IM placebo and the transition to oral therapy.

Research design and methods: Over 24?h, patients could receive up to three IM injections; the second and third administered ≥ 2 and ≥ 4?h, respectively, after the first, if deemed clinically necessary. Following IM treatment, oral aripiprazole or haloperidol was administered for 4 days. The primary efficacy measure was the mean change in PEC score from baseline at 2?h.

Results: At 2?h, mean improvements in PEC scores with IM aripiprazole (–8.0) were significantly greater versus IM placebo (–5.7; p ≤ 0.01), and similar versus IM haloperidol (–8.3). Secondary efficacy measures also significantly improved with active IM treatment versus IM placebo. Continuation with oral treatment provided continued efficacy with both active treatments. The safety profiles of IM and oral aripiprazole were similar. The incidence of extrapyramidal symptom-related adverse events was 0% with IM aripiprazole, 1.6% with IM placebo and 16.5% with IM haloperidol.

Conclusion: Intramuscular aripiprazole is effective in patients with acute agitation associated with schizophrenia, comparable to IM haloperidol, and enables convenient transfer to oral aripiprazole therapy.     

A comparison of the symptoms and short-term clinical course in inpatients with substance-induced psychosis and primary psychosis

Relatively little is known about the clinical course of symptoms in patients with a substance-induced psychosis (SIP) compared with those with a primary psychotic disorder (PPD). In this study, symptoms associated with psychosis were monitored across admission in two groups of patients: those with SIP (amphetamines or cannabis; n = 47) and those with PPD (n = 51). Sixty-two percent of patients were first admissions, 23% had one previous admission, and a further 14% had had two previous admissions. Symptoms were monitored using the Brief Psychiatric Rating Scale. Scores on the positive symptoms scale, negative symptoms scale, manic excitement, and negative mood were reported as was the extent of observed disturbed behavior at admission and then at Days 4/5, 8/9, 15/16, 22/23, 29/30, 36/37, 43/44, and 50/51. Patients with a SIP experienced more severe mania and disturbed behavior at admission than those with a PPD. However, these symptoms abated more rapidly for the SIP group during admission. Although positive symptom scores were equally high at admission for both groups, there was a more rapid abatement of these symptoms in the SIP group. Finally, negative symptoms were lower in the SIP group at admission and at Days 50/51, although the decline in symptoms was comparable in both groups.     

An update on medication management of women with schizophrenia in pregnancy

Introduction: Women with schizophrenia and their babies are at high risk of adverse outcomes in pregnancy and childbirth. A better understanding of the specific risks conferred by the illness itself and by the treatment provided will help guide more effective care of these women.

Areas covered: Herein, the authors review genetic, demographic, socioeconomic, nutritional and lifestyle risks associated with schizophrenia in pregnancy. They also cover specific risks associated with typical antipsychotic medications, specific risks associated with atypical antipsychotic medications, risks associated with polypharmacy and risks of developmental delay in children exposed to antipsychotic medications in utero.

Expert opinion: Our understanding of the risks that women with schizophrenia face in pregnancy from their illness and from the treatment they receive continues to evolve. As our ability to analyze data progresses, the risks conferred by antipsychotic medication treatment appear to lessen in clinical and statistical significance, whilst the true risks to these women and their babies from their experience of disadvantage continue to set them aside from the general population. Reducing polypharmacy and providing comprehensive and supportive care can minimize harm to women with schizophrenia and their babies.     

A clinical evaluation of risperidone in the treatment of schizophrenia: a 10-week, open-label, multicenter trial

The efficacy and safety of risperidone have previously been demonstrated in controlled clinical trials in hospitalized chronic schizophrenia patients who met strict research criteria. The present study was designed to evaluate the efficacy and safety of risperidone in a heterogeneous patient population. Patients were enrolled in the study if they had a diagnosis of schizophrenia (DSM-III-R) with or without acute exacerbation. Of the 945 patients from 158 psychiatric centers who entered this phase IV study, 558 completed the 10-week trial. During week 1, the dose of risperidone was titrated to 6 mg/day, maintained there for 1 week, and then adjusted over a 4-week period as clinically necessary; the dose was then fixed for the final 4-week period. The mean dose of risperidone at endpoint was 5.9 mg/day. Patients were evaluated at baseline and at weeks 2, 6, and 10, using Clinical Global Impression scale, Psychotic Symptoms Assessment scale, and Global Assessment of Functioning scale. Significant improvement in mean scores was found on each of these measures at endpoint. Comparable results were obtained at week 10 in treatment-resistant and non-treatment-resistant patients. Risperidone was generally well tolerated and the severity of extrapyramidal symptoms was significantly reduced at endpoint. Received: 17 April 1996/Final version: 31 December 1996