Sigma-1 receptor agonist fluvoxamine for postoperative delirium in older adults: report of three cases

<p>Abstract</p> <p>Background</p> <p>Postoperative delirium is a topic of great importance in the geriatric surgical specialty. Although antipsychotic drugs are the medications most frequently used to treat this syndrome, these drugs are associated with a variety of adverse events, including sedation, extrapyramidal side effects, and cardiac arrhythmias. Drug treatment for postoperative delirium requires careful consideration of the balance between the effective management of symptoms and potential adverse effects.</p> <p>Methods</p> <p>We report on a Japanese woman (an 86-year-old (open reduction and internal fixation of the right femoral neck fracture), and two Japanese men (an 86-year-old (abdominal aortic aneurysm stent grafting), and a 77-year-old (right upper lobectomy due to lung tumour)) in which the selective serotonin reuptake inhibitor and sigma-1 receptor agonist fluvoxamine was effective in ameliorating the postoperative delirium of these patients.</p> <p>Results</p> <p>Delirium Rating Scale scores in these patients dramatically decreased after treatment with fluvoxamine.</p> <p>Conclusions</p> <p>Doctors should consider fluvoxamine as an alternative approach to treating postoperative delirium in older patients in order to avoid the risk of side effects and increased mortality by antipsychotic drugs.</p

A pilot study of rivastigmine in the treatment of delirium after stroke: A safe alternative

<p>Abstract</p> <p>Background</p> <p>Delirium is a common disorder in the early phase of stroke. Given the presumed cholinergic deficiency in delirium, we tested treatment with the acetylcholinesterase inhibitor rivastigmine.</p> <p>Methods</p> <p>This pilot study was performed within an epidemiological study. In 527 consecutive stroke patients presence of delirium was assessed during the first week with the confusion assessment method. Severity was scored with the delirium rating scale (DRS). Sixty-two patients developed a delirium in the acute phase of stroke. Only patients with a severe and persistent delirium (defined as a DRS of 12 or more for more than 24 hours) were enrolled in the present study. In total 26 fulfilled these criteria of whom 17 were treated with orally administered rivastigmine with a total dose between 3 and 12 mg a day. Eight patients could not be treated because of dysphagia and one because of early discharge.</p> <p>Results</p> <p>No major side effects were recorded. In 16 patients there was a considerable decrease in severity of delirium. The mean DRS declined from 14.8 on day one to 8.5 after therapy and 5.6 after tapering. The mean duration of delirium was 6.7 days (range; 2–17).</p> <p>Conclusion</p> <p>Rivastigmine is safe in stroke patients with delirium even after rapid titration. In the majority of patients the delirium improved after treatment. A randomized controlled trial is needed to establish the usefulness of rivastigmine in delirium after stroke.</p> <p>Trial registration</p> <p>Nederlands Trial Register NTR1395</p

Improving delirium care in the intensive care unit: The design of a pragmatic study

<p>Abstract</p> <p>Background</p> <p>Delirium prevalence in the intensive care unit (ICU) is high. Numerous psychotropic agents are used to manage delirium in the ICU with limited data regarding their efficacy or harms.</p> <p>Methods/Design</p> <p>This is a randomized controlled trial of 428 patients aged 18 and older suffering from delirium and admitted to the ICU of Wishard Memorial Hospital in Indianapolis. Subjects assigned to the intervention group will receive a multicomponent pharmacological management protocol for delirium (PMD) and those assigned to the control group will receive no change in their usual ICU care. The primary outcomes of the trial are (1) delirium severity as measured by the Delirium Rating Scale revised-98 (DRS-R-98) and (2) delirium duration as determined by the Confusion Assessment Method for the ICU (CAM-ICU). The PMD protocol targets the three neurotransmitter systems thought to be compromised in delirious patients: dopamine, acetylcholine, and gamma-aminobutyric acid. The PMD protocol will target the reduction of anticholinergic medications and benzodiazepines, and introduce a low-dose of haloperidol at 0.5-1 mg for 7 days. The protocol will be delivered by a combination of computer (artificial intelligence) and pharmacist (human intelligence) decision support system to increase adherence to the PMD protocol.</p> <p>Discussion</p> <p>The proposed study will evaluate the content and the delivery process of a multicomponent pharmacological management program for delirium in the ICU.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00842608">NCT00842608</a></p

Relationship between atomoxetine plasma concentration, treatment response and tolerability in attention-deficit/hyperactivity disorder and comorbid oppositional defiant disorder

The purpose of this study was to examine whether atomoxetine plasma concentration predicts attention-deficit/hyperactivity disorder (ADHD) or oppositional defiant disorder (ODD) response. This post-hoc analysis assessed the relationship between atomoxetine plasma concentration and ADHD and ODD symptoms in patients (with ADHD and comorbid ODD) aged 6–12 years. Patients were randomly assigned to atomoxetine 1.2 mg/kg/day (n = 156) or placebo (n = 70) for 8 weeks (Study Period II). At the end of 8 weeks, ODD non-remitters (score >9 on the SNAP-IV ODD subscale and CGI-I > 2) with atomoxetine plasma concentration <800 ng/ml at 2 weeks were re-randomized to either atomoxetine 1.2 mg/kg/day or 2.4 mg/kg/day for an additional 4 weeks (Study Period III). ODD remitters and non-remitters with plasma atomoxetine ≥800 ng/ml remained on 1.2 mg/kg/day atomoxetine for 4 weeks. Patients who received atomoxetine, completed Study Period II, and entered Study Period III were included in these analyses. All the groups demonstrated improvement on the SNAP-IV ODD and ADHD-combined subscales (P < .001). At the end of Study Periods II and III, ODD and ADHD improvement was significantly greater in the remitter group compared with the non-remitter groups. Symptom improvement was numerically greater in the non-remitter (2.4 mg/kg/day compared with the non-remitter 1.2 mg/kg/day) group. Atomoxetine plasma concentration was not indicative of ODD and ADHD improvement after 12 weeks of treatment. ADHD and ODD symptoms improved in all the groups with longer duration on atomoxetine. Results suggest atomoxetine plasma concentration does not predict ODD and ADHD symptom improvement. However, a higher atomoxetine dose may benefit some patients

Use of neuroleptics in a general hospital

BACKGROUND: This study investigates the clinical use of neuroleptics within a general hospital in acutely ill medical or surgical patients and its relation with dementia three months after admission compared with control subjects. METHODS: Cases were defined as every adult patient to whom a neuroleptic medication was prescribed during their hospitalization in our Hospital from February 1(st), to June 30(th), 1998. A control matched by age and sex was randomly selected among patients who had been admitted in the same period, in the same department, and had not received neuroleptics drugs (205 cases and 200 controls). Demographic, clinical and complementary data were compared between cases and controls. Crude odds ratios estimating the risk of dementia in non previously demented subjects compared with the risk in non-demented control subjects were calculated. RESULTS: 205 of 2665 patients (7.7%) received a neuroleptic drug. The mean age was 80.0 ± 13.6 years and 52% were females. They were older and stayed longer than the rest of the population. Only 11% received a psychological evaluation before the prescription. Fifty two percent were agitated while 40% had no reason justifying the use of neuroleptic drug. Three months after neuroleptic use 27% of the surviving cases and 2.6% of the surviving controls who were judged non-demented at admission were identified as demented. CONCLUSIONS: The most common reason for neuroleptic treatment was to manage agitation symptomatically in hospitalised patients. Organic mental syndromes were rarely investigated, and mental status exams were generally absent. Most of neuroleptic recipients had either recognised or unrecognised dementia