The efficacy, safety, and tolerability of donepezil for the treatment of young adults with Down syndrome.

The objective of our study was to assess the efficacy and safety of donepezil in young adults with Down syndrome (DS) but no evidence of Alzheimer disease (AD). A 12-week, randomized, double-blind, placebo-controlled study with a 12-week, open-label extension was conducted. The intervention consisted of donepezil (5-10 mg/day) in young adults (aged 18-35 years) with DS, but no AD. The primary measure was the Severe Impairment Battery (SIB) test and secondary measures were the Vineland Adaptive Behavior Scales (VABS), the Rivermead Behavioral Memory Test for Children, and the Clinical Evaluation of Language Fundamentals, Third Edition. At baseline, 123 subjects were randomly assigned treatment with donepezil or placebo. During the double-blind phase, SIB scores improved significantly from baseline in both groups, with no significant between-group differences. During the open-label phase, SIB scores in the original donepezil group remained stable; the original placebo group showed an improvement similar to that seen in the double-blind phase. VABS scores improved for donepezil, but not placebo, during the double-blind phase (observed cases, P = 0.03; last observation carried forward, P = 0.07). Post hoc responder analyses were significant for donepezil using three of five response definitions (P < or = 0.045). Adverse event rates were comparable to AD studies. In this first large-scale, multicenter trial of a pharmacological agent for DS, donepezil appears safe. Efficacy interpretation was limited for the primary measure due to apparent learning/practice and ceiling effects. Outcomes in post hoc analyses suggested efficacy in some, but not all subjects, consistent with phenotypic variability of DS. Additional studies are required to confirm potential benefits of donepezil in this population.

The effect of desflurane versus propofol anesthesia on postoperative delirium in elderly obese patients undergoing total knee replacement: A randomized, controlled, double-blinded clinical trial.

STUDY OBJECTIVE: The goal of this study was to investigate the incidence of delirium, wake-up times and early post-operative cognitive decline in one hundred obese elderly patients undergoing total knee arthroplasty. DESIGN: Prospective randomized trial. SETTINGS: Operating room, postoperative recovery area, hospital wards. PATIENTS: 100 obese patients (ASA II and III) undergoing primary total knee replacement under general anesthesia with a femoral nerve block catheter. INTERVENTION: Patients were prospectively randomized to maintenance anesthesia with either propofol or desflurane. MEASUREMENTS: The primary endpoint assessed by a blinded investigator was delirium as measured by the Confusion Assessment Method. Secondary endpoints were wake-up times and a battery of six different tests of cognitive function. MAIN RESULTS: Four of the 100 patients that gave informed consent withdrew from the study. Of the remaining 96 patients, 6 patients did not complete full CAM testing. Preoperative pain scores, durations of surgery and anesthesia, and amount of intraoperative fentanyl were not different between groups. One patient in the propofol group developed delirium compared to zero in desflurane. One patient in desflurane group developed a confused state not characterized as delirium. Fifty percent of the patients exhibited a 20% decrease in the results of at least one cognitive test on the first 2days after surgery, with no difference between groups. There were no differences in the time to emergence from anesthesia, incidence of postoperative nausea and vomiting, and length of postanesthesia care unit (PACU) stay between the two groups. CONCLUSIONS: In conclusion we found a low incidence of delirium but significant cognitive decline in the first 48h after surgery. In this relatively small sample size of a hundred patients there was no difference in the incidence of postoperative delirium, early cognitive outcomes, or wake up times between the desflurane or propofol group.

Folic acid supplementation in dementia: a preliminary report.

Recent work on high plasma homocysteine levels in patients at risk for developing Alzheimer's disease has led to the hypothesis that folic acid supplementation might reduce risk in such patients. The authors report on the effects of folic acid 10 mg/day versus placebo on 11 patients (only 7 completers) with dementia and low-normal folic acid levels. This is the first study evaluating folic acid or placebo in patients with dementia. Subjects had low-normal baseline folic acid levels. The magnitude of change between baseline and second testing was not statistically significant between the 2 groups. However, there was a trend for the folate group to perform worse on two specific cognitive measures, suggesting a possible trend toward worsening of some cognitive abilities after the folic acid. The folic acid in very high doses was well tolerated. Larger studies are necessary before empirically administering folic acid to patients already suffering from dementia.

Safety of antidepressants in the elderly.

Until the 1980s, the two major classes of antidepressants, the tricyclics and the monoamine oxidase inhibitors (MAOIs), were effective but had severe side effects, requiring monitoring by psychiatrists. The past several years have brought new classes of antidepressants that are safer for the patient to take and far easier for the non-psychiatrist to prescribe. Whilst this is of enormous value, it leaves the physician with the dilemma of which one to prescribe. These new antidepressants cannot safely be used interchangeably. This paper will discuss each of the antidepressants presently available, with particular emphasis on safety in the elderly. Drug interactions, side effects and particular challenges to the older patient will be described. The authors will then advise a general strategy for prescribing antidepressants.

Topiramate: Effects on cognition in patients with epilepsy, migraine headache and obesity.

This paper reviews the clinical implications of topiramate (TPM)-induced cognitive deficits in patients with epilepsy, migraine headache, obesity, and in normal populations, followed by reviews of the literature describing the reversal of such deficits upon medication discontinuation. It also discusses animal investigations of TPM's role of neuroprotection in brain injury. TPM's most intolerable adverse effects (AEs) are on verbal fluency and reaction time, resulting in high discontinuation rates in patients taking it for epilepsy and migraine headache. However, because TPM is so effective in the treatment of epilepsy and migraine headache, its use is expected to continue. There appears to be greater tolerance of TPM's cognitive AEs when it is used in the treatment of obesity, perhaps because of the lower doses required. Research attempting to predict the populations most vulnerable to the cognitive effects caused by TPM is ongoing. Studies suggest that one such population may include patients with a past psychiatric history. Slow titration and administration of the lowest possible doses may decrease risk of cognitive deficits.

Safety and efficacy of anticonvulsants in elderly patients with psychiatric disorders: oxcarbazepine, topiramate and gabapentin.

Few controlled studies are available to guide the clinician in treating potentially assaultive elderly individuals with psychiatric disorders. Safety concerns limit the use of benzodiazepines and antipsychotic medications in the elderly individual, making anticonvulsants an attractive alternative. This paper reviews three specific anticonvulsants for this purpose: gabapentin, oxcarbazepine and topiramate, describing safety and efficacy in elderly patients with severe agitation from psychosis or dementia. Gabapentin, renally excreted, with a half-life of 6.5-10.5 h, may cause ataxia. Oxcarbazapine, hepatically reduced, may cause hyponatremia, and topiramate may cause significant cognitive impairment. Nonetheless, these are important medications to consider in the treatment of agitation.

Role of psychiatric comorbidity on cognitive function during and after the menopausal transition.

While cognitive complaints are common during the menopausal transition, measurable cognitive decline occurs infrequently, often due to underlying psychiatric or neurological disease. To clarify the nature, etiology and evidence for cognitive and memory complaints during midlife, at the time of the menopausal transition, we have critically reviewed the evidence for impairments in memory and cognition associated with common comorbid psychiatric conditions, focusing on mood and anxiety disorders, attention-deficit disorder, prolonged stress and decreased quantity or quality of sleep. Both the evidence for a primary effect of menopause on cognitive function and contrarily the effect of cognition on the menopausal transition are examined. Impairment in specific aspects of executive function is explored. Evaluation and treatment strategies for the symptomatic menopausal woman distressed by changes in her day-to-day cognitive function with or without psychiatric comorbidity are presented.

Safety and tolerability of mood-stabilising anticonvulsants in the elderly.

The authors review current research on the safety and tolerability of anticonvulsant medications used for individuals over the age of 60 years with affective disorders, agitation and other psychiatric disorders. Three anticonvulsants currently approved in the US for treatment of bipolar affective disorder are reviewed: valproate, lamotrigine and extended-release carbamazepine. The authors discuss the pharmacokinetics, pharmacodynamics, drug-drug interactions and the impact of ageing for each drug. There are few studies of anticonvulsant medications in elderly patients with bipolar disorder or other psychiatric conditions. Therefore, the authors summarise adverse events of greatest prevalence and/or greatest severity based on data derived predominately from studies of geriatric patients with epilepsy and/or other non-psychiatric indications. Guidelines are offered for the safe use of these medications in the elderly, based on research literature.

The effect of oxybutynin treatment on cognition in children with diurnal incontinence.

PURPOSE: Oxybutynin is a powerful anticholinergic drug already known to impair cognition in the elderly. The impact of this drug on cognitive functioning in the pediatric population is unknown. We report the results of a study designed to assess the effect of oxybutynin on cognitive function in children. MATERIALS AND METHODS: A total of 25 patients presenting with the primary symptom of daytime enuresis were recruited for this nonrandomized trial. All subjects initially received 4 weeks of behavior modification, followed by an additional 4 weeks of behavior modification either alone or with oxybutynin for continued treatment of enuresis. Neuropsychological testing was performed at baseline (4 weeks) and after additional therapy (8 weeks). RESULTS: Patient demographics included a male-to-female ratio of 11:14 and a mean age of 7.2 +/- 1.8 years. A total of 10 patients were assigned to the control group receiving behavior modification, and 15 patients were assigned to the treatment group receiving behavior modification plus oxybutynin. The oxybutynin treated patients had a lower overall performance at baseline pretreatment testing. However, performance in this group improved following treatment with oxybutynin. CONCLUSIONS: Oxybutynin, a commonly used pharmacological agent in pediatric urology, was not associated with cognitive impairment following treatment. However, we observed lower baseline cognitive functioning in patients whose parents chose oxybutynin over behavior modification alone. This finding may represent a selection bias. However, it also supports the need for a multidisciplinary approach to the treatment of patients with dysfunctional voiding, as some may have cognitive difficulties that have not previously been explored.

Orange juice-induced hyperkalemia in schizophrenia.

Some fruit juices have very high potassium content. However, only several cases of juice-induced hyperkalemia have been reported that involved non-psychiatric, diabetic outpatients with renal compromise. We present a highly unusual case of a 66-year-old non-diabetic, schizophrenic woman with psychogenic polydipsia and normal renal function who developed hyperkalemia secondary to excessive orange juice consumption while an inpatient. In addition to demonstrating this previously undescribed medical comorbidity of schizophrenia, this case highlights the need for careful attention when communicating with both nursing and patients when managing psychogenic polydipsia.

Is dopamine administration possibly a risk factor for delirium?

OBJECTIVE: We explored the possibility that the administration of intravenous dopamine increases the risk for delirium as manifested by need for haloperidol. DESIGN: This study was based on a retrospective analysis. To examine the contribution of dopamine in the prediction of need for haloperidol, a multivariate logistic regression model was used. SETTING: University hospital. PATIENTS: All inpatient admissions to Stanford University Hospital over a 1-year period (n = 21,844). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Dopamine administration was associated with nearly a tripling of the odds of subsequent need of the antipsychotic drug (chi-square = 108, df = 1, p =.0001, odds ratio = 2.89), even after intensive care unit admission and diagnostic related group weight were considered as indicators of severity of illness. Even when analysis was limited to patients seen in the intensive care unit setting (n = 3,308), dopamine administration remained a very strong risk factor for haloperidol and hence possibly for delirium. The increased risk of need for haloperidol in patients administered dopamine is evident in every age group after age 20. CONCLUSIONS: The retrospective nature of this study, the inexact method to assess acuity, and, most of all, the use of haloperidol as an indicator of the presence of delirium preclude concluding that dopamine is directly a risk factor for delirium, much less a causal risk factor. However, the association is potent enough to suggest this possibility strongly and thus supports the need for prospective studies to examine the relationship between dopamine and delirium and to consider possible prophylactic treatment against delirium in those given dopamine.