Use of neuroendocrine effects in discrimination between CNS-active drugs in the rat

Different psychotropic drugs were investigated in order to determine their effect on the release of prolactin and corticosterone and their influence on the tuberoinfundibular dopamine (TIDA) neuron activity. The results were used in a principal component analysis, which grouped the psychotropic drugs into different clusters. In the plot showing these clusters the anxiolytic drugs were found to be grouped together and differ from the antidepressant drugs by their potent ability to increase plasma corticosterone. The antipsychotic drugs formed a separate group being clustered together. Typical neuroleptic and atypical antipsychotic drugs could be separated within the cluster by their different effects on plasma prolactin and corticosterone and on TIDA neuron activity. The results indicate that the neuroendocrine profiles of antidepressant and anxiolytic drugs are different from those of antipsychotic drugs and that the neuroendocrine measurements could be a useful tool in the early classification of psychotropic drugs. © 1993 Wiley-Liss, Inc.     

Clinical experience of quetiapine in 24 elderly patients with delirium

Background: A recent study reported that patients with delirium responded well to the administration of atypical antipsychotic agents. In the present study we administered quetiapine to patients with delirium and obtained good results. Methods: This study included 24 patients (10 men, 14 women), referred to the psychiatry department during admission to other hospital departments, who were diagnosed as having delirium according to the diagnostic and statistical manual of mental disorders (4th edition) (DSM‐IV) between April 2001 and September 2002. The mean age of the patients was 76.5 years (men 71.0 years; women 80.5 years). An initial dose of quetiapine was established at 25–50 mg/day. Depending on the symptoms, the dose and frequency were increased as required. According to Trzepacz's delirium rating scale (DRS), the treatment response was evaluated prior to the administration of quetiapine and 1, 3, 5 and 7 days after administration began. Results: Prior to the administration of quetiapine, the mean DRS score was 18.1. The mean scores were 12.2, 10.8, 9.7 and 8.9 after 1, 3, 5 and 7 days of quetiapine administration, respectively. These values were significantly lower than the value before administration (P < 0.001). Seven days after the administration of quetiapine commenced, the total DRS score was lower than the cutoff point (12) in 20 patients (83.3%). In 18 patients (75.0%), delirium was clinically relieved. Doses ranged from 25 mg/day to 125 mg/day, with a mean dose of 54.7 mg/day. With respect to the administration method, the majority of patients (i.e. 13 patients) received quetiapine once per day (after dinner). Somnolence was observed in three patients as a side‐effect of quetiapine administration. However, this side‐effect improved after 1–2 days, without decreasing the dose. Conclusions: Quetiapine may be useful for controlling delirium and concerning side‐effects and extrapyramidal symptoms were not recorded in the present study. Thus, it is appropriate to trial quetiapine in the treatment of delirium.     

Atypical antipsychotics to treat the neuropsychiatric symptoms of dementia

Neuropsychiatric symptoms are common in older adults with dementia and can be associated with a rapid decline in cognitive and functional status. This article reviews the current literature supporting the use of atypical antipsychotic medications in this population. Among the currently available atypical antipsychotics, risperidone and olanzapine have been the most widely studied in double-blind, randomized, placebo-controlled clinical trials. Despite the common use of other atypical antipsychotic medications, their efficacy and safety in older adults with dementia has not been as extensively studied. Some controversy surrounds the use of atypical antipsychotic agents in older adults with the suggestion that they may increase the incidence of stroke or even death. Despite the potential for increased risk of harm from the use of these medications, atypical antipsychotics are often effective in treating troublesome neuropsychiatric symptoms refractory to other treatments. Whenever possible, these atypical antipsychotic drug treatments should be combined with non-pharmacological treatments to limit the need and dose of antipsychotic drugs and constant monitoring for potential harms should be maintained. The choice of which atypical antipsychotic agent can be guided by the nature and severity of the target symptom and the medication least likely to cause harm to the patient.     

Treatment of Alzheimer’s disease across the spectrum of severity

Alzheimer’s disease (AD) is the most common cause of dementia affecting nearly 18 million people around the world and 4.5 million in the US. It is a progressive neurodegenerative condition that is estimated to dramatically increase in prevalence as the elderly population continues to grow. As the cognitive and neuropsychiatric signs and symptoms of AD progresses in severity over time, affected individuals become increasingly dependent on others for assistance in performing all activities of daily living. The burden of caring for someone affected by the disorder is great and has substantial impact on a family’s emotional, social and financial well-being. In the US, the currently approved medications for the treatment of mild to moderate stages of AD are the cholinesterase inhibitors (ChEIs). Cholinesterase inhibitors have shown modest efficacy in terms of symptomatic improvement and stabilization for periods generally ranging from 6 to 12 months. There are additional data that have emerged, which suggest longer-term benefits. For the moderate to severe stages of AD, memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist is in widespread use and has shown modest benefit as monotherapy and in combination with ChEIs. The cost effectiveness of the currently available therapeutic agents for AD has undergone great scrutiny and remains controversial, especially outside the US. Neuropsychiatric symptoms such as agitation and psychosis are common in AD. Unfortunately, in the US there are no Food and Drug Administration (FDA)-approved agents for the treatment of these symptoms, although atypical antipsychotics have shown some efficacy and have been widely used. However, the use of these agents has recently warranted special caution due to reports of associated adverse effects such as weight gain, hyperlipidemia, glucose intolerance, cerebrovascular events, and an increased risk for death. Alternative agents used to treat neuropsychiatric symptoms include serotonergic antidepressants, benzodiazepines, and anticonvulsant medications.     

Tardive dyskinesia in children treated with atypical antipsychotic medications.

Recent years have witnessed increased antipsychotic treatment of children despite limited long‐term safety data in children. In this study, motor side effects associated with the use of antipsychotic drugs in children were examined in a sample of pediatric psychiatric patients. Child and adolescent psychiatric patients receiving antipsychotics (most were on atypicals) for 6 months or longer (n = 118) were compared with antipsychotic‐naïve patients (n = 80) with similar age, sex ratio, and diagnoses. Only 19% of patients on antipsychotics had ever experienced psychotic symptoms. Eleven children (9%) on antipsychotics exhibited dyskinesia, when compared with 0 in the naïve group (P = 0.003, Fisher's exact test). Nine of 62 African–American children (15%) on antipsychotics exhibited dyskinesia, when compared with only 4% (2 of 52) of European–American children (P = 0.003, Fisher's exact test). Children treated with antipsychotic drugs might experience a significant risk of dyskinesia even when treated only with atypical antipsychotics. Ethnicity might also be a risk factor for dyskinesia in children. Side‐effect profile of the atypical antipsychotic drugs in children may be much different than that in adults. © 2007 Movement Disorder Society     

To What Extent Do Local Nursing Home Prescribing Patterns Relate to Psychotropic Prescribing in Assisted Living?

ObjectiveIn nursing homes (NHs), psychoactive medication use has received notable attention, but less is known about prescribing in assisted living (AL). This study examined how antipsychotic and antianxiety medication prescribing in AL compares with NHs.DesignObservational, cross-sectional AL data linked to publicly reported NH measures.Setting and ParticipantsRandom sample of 250 AL communities and the full sample of 3371 NHs in 7 states.MethodsWe calculated the percentage of residents receiving antipsychotics and antianxiety medications. For each AL community, we calculated the distance to NHs in the state. Linear models estimated the relationship between AL prescribing and that of the closest and farthest 5 NHs, adjusting for AL characteristics and state fixed effects.ResultsThe prescribing rate of potentially inappropriate antipsychotics (i.e., excluding for persons with recorded schizophrenia and Tourette syndrome) and of antianxiety medications (excluding for those on hospice) in AL was 15% and 21%, respectively. Unadjusted mean antipsychotic prescribing rates were nominally higher in AL than NHs (14.8% vs 14.6%; P = .056), whereas mean antianxiety prescribing was nominally lower in AL (21.2% vs 22.6%; P = .032). In adjusted analyses, AL rates of antipsychotic use were not associated with NH rates. However, being affiliated with an NH was associated with a lower rate of antipsychotic use [b = −0.03; 95% confidence interval (CI) −0.50 to −0.001; P = .043], whereas antianxiety rates were associated with neighboring NHs’ prescribing rates (b = 0.43; 95% CI 0.16–0.70; P = .002).Conclusions and ImplicationsThis study suggests reducing antipsychotic medication use in NHs may influence AL practices in a way not accounted for by local NH patterns. And, because antianxiety medications have not been the focus of national campaigns, they may be more subject to local prescribing behaviors. It seems advantageous to consider prescribing in AL when efforts are implemented to change NH prescribing, as there seems to be related influence whether by affiliation or region.     

中药预防抗精神病药物所致高血糖的研究

目的　研究中药对抗精神病药物所致高血糖的作用。方法　将 110例男性精神病患者随机分为 2组 ,对照组 5 7例单服抗精神病药物 ,研究组 5 3例在服用抗精神病药物的同时加服中药滋阴汤。两组均于治疗前及治疗后 1,2个月测定空腹血糖 ,并行统计学处理。结果两组在治疗 1,2个月时血糖存在显著性差异 (P <0 .0 5 ) ,治疗结束时对照组中有 2例患者血糖值超过正常值的最高限。结论　中药能预防抗精神病药物所致的血糖增高。     

Outcomes and Costs of Risperidone versus Olanzapine in Patients with Chronic Schizophrenia or Schizoaffective Disorders: A Markov Model

OBJECTIVE: To compare expected outcomes and costs of care in patients with chronic schizophrenia or schizoaffective disorders who are treated with risperidone versus olanzapine. METHODS: A Markov model was developed to examine outcomes and costs of care in patients with chronic schizophrenia or schizoaffective disorders receiving risperidone or olanzapine. The time frame of interest was 1 year. The model focused particular attention on the likelihood of therapy switching and discontinuation as a result of treatment-emergent side effects, as the efficacy of these two agents is similar. Measures of interest included the incidence of relapse and selected side effects including extrapyramidal symptoms (EPS), prolactin-related disorders and diabetes, expected change in body weight, and the percentage of patients remaining on initial therapy at the end of 1 year. Costs of antipsychotic therapy and psychiatric and nonpsychiatric services also were examined. RESULTS: At 1 year, the rate of EPS was estimated to be slightly higher for risperidone, as was the incidence of symptomatic prolactin-related disorders. The expected incidence of diabetes mellitus, while low, was slightly higher for olanzapine. Approximately 25% and 4% of olanzapine and risperidone patients, respectively, were projected to experience an increase in body weight > or = 7%. The estimated percentage of patients remaining on initial therapy at the end of 1 year was higher for risperidone than olanzapine (76.9% vs. 45.6%, respectively). Expected mean total costs of care per month of therapy were $2163 for risperidone and $2316 for olanzapine. Results from sensitivity analyses suggest that the probability of therapy discontinuation following weight gain >5 kg would have to be lower than 0.1 for the number of patients remaining on therapy at the end of 1 year to be the same for risperidone and olanzapine. CONCLUSIONS: Compared with risperidone, treatment with olanzapine may result in greater increases in body weight, higher rates of therapy discontinuation, and higher costs of medical-care services.     

心境障碍病人176例住院用药状况调查分析

目的:了解心境障碍病人住院用药情况,为临床合理用药提供参考。方法:对确诊的176例心境障碍病人应用各种精神药物的分布及频率进行调查统计。结果: 接受抗抑郁药治疗的107例病人中,使用第2代抗抑郁药占78. 5 % (84 /107 )。接受抗精神病药治疗占全部病人的57. 4 % ( 101 176),其中第2代抗精神病药占26. 1 % (46 /176)。合并用心境稳定剂占45. 5 % (80 /176 ),其中碳酸锂居首位。合并丁螺环酮和苯二氮艹卓类药分别占20. 5 % (36 /176)和39. 2 % (69 /176)。结论: 处方方式逐渐以第2代抗精神病药和抗抑郁药占主流,锂盐仍然为一线情感稳定剂。