A double‐blind,placebo‐controlled study of prucalopride in elderly patients with chronic constipation

Background Constipation affects up to 50% of the elderly; this study evaluates the efficacy, safety, and tolerability of the selective 5‐HT₄ agonist prucalopride in chronically constipated elderly patients. Methods Three hundred chronic constipation patients aged ≥65 years were randomized to prucalopride (1, 2, or 4 mg once daily) or placebo for 4 weeks. The primary endpoint was the percentage of patients with ≥3 spontaneous complete bowel movements (SCBM) per week. Secondary endpoints included the percentage with an increase of ≥1 SCBM per week, BM frequency, constipation‐related symptoms, quality of life (QoL), safety, and tolerability. Key Results More patients achieved ≥3 SCBM per week with prucalopride than with placebo. This difference was largest and significant during the first week of 4 mg prucalopride (P ≤ 0.05). Significantly more patients in each prucalopride group achieved an increase of ≥1 SCBM per week from baseline vs placebo (e.g. 60% with 1 mg prucalopride vs 34% with placebo at week 4; P ≤ 0.05). More patients had improvement in PAC‐QOL satisfaction score of ≥1 with 1 mg prucalopride than with placebo (P ≤ 0.05); the same was true for PAC‐SYM stool symptoms (1 and 4 mg prucalopride; P ≤ 0.05). Treatment‐emergent adverse events were similar between groups: the most frequently reported with prucalopride were headache and gastrointestinal events. There were no clinically significant differences between prucalopride and placebo for vital signs, laboratory assessments, or ECG variables. Conclusions & Inferences Prucalopride, in the dose‐range tested (1–4 mg once daily), has beneficial effects on bowel movements, symptoms, and QoL, and is safe and well‐tolerated in elderly patients with chronic constipation.     

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.     

Risperidone therapy for post-operative delirium in elderly patients

In elderly patients, post‐operative delirium can complicate the treatment of any underlying condition that requires surgical intervention. Two elderly patients who underwent surgical procedures for neoplasia developed symptoms of nocturnal delirium soon after recovery from general anesthesia. Risperidone therapy was initiated in both patients (0.5 mg/day in Case 1 and 0.2 mg/day in Case 2 ) and their mental states rapidly stabilized, enabling treatment of the underlying condition and resulting in good post‐operative progress. Both patients were discharged from hospital without symptoms. To the best of the author's knowledge, this is the first report of the successful use of risperidone in the treatment of post‐operative delirium.     

Efficacy of transcranial direct current stimulation on postoperative delirium in elderly patients undergoing lower limb major arthroplasty: A randomized controlled trial

BackgroundPostoperative delirium (POD) is a common and severe postoperative complication in elderly patients undergoing major surgery linked to increased morbidity and mortality. It is reported that transcranial direct current stimulation (tDCS) effectively enhances cognitive function and improves impaired consciousness.ObjectiveThis study aimed to evaluate the efficacy of tDCS on POD in elderly patients undergoing lower limb major arthroplasty, including total hip arthroplasty (THA) or total knee arthroplasty (TKA).MethodsPatients aged ≥65 years scheduled for THA or TKA were randomly assigned to receive 2 mA tDCS for 20 min active-tDCS (n = 61) or sham-tDCS (n = 61). The primary outcome was the incidence of POD during the first 3 postoperative days.ResultsAll 122 patients (median age, 70 years; 80 women [65.6%]) completed the trial. The incident delirium risk was 4.9% (n = 3) vs. 19.7% (n = 12) in active-tDCS and sham-tDCS groups, respectively (relative risk, 0.250; 95% CI, 0.074 to 0.842; P = 0.013). Compared to the sham-tDCS group, the anxiety and depression scores of patients in the active-tDCS group were lower at 2 h and one day after surgery (P < 0.001 for each), and pain scores of patients in the active-tDCS group were lower during the first three days after surgery (P < 0.05).ConclusionOne session of anodal tDCS over the left dorsolateral prefrontal cortex may decrease the incidence of POD in elderly patients undergoing lower limb major arthroplasty.     

Predicting post-operative delirium in elderly patients undergoing surgery for hip fracture

Background: Delirium in elderly patients with hip fracture has a significant negative influence on the disease course. Awareness of risk factors for postoperative delirium (POD) may lead to the development of effective preventive strategies. The aims of this study were: to find patients’ features that are predictors of POD, and; to develop a model predicting the risk for POD. Patients and methods: Seventy‐seven elderly patients (81.9 years of age, SD 7.5 years) were non‐delirious prior to surgery and enrolled in the study. Delirium was diagnosed by Confusion Assessment Method and Algorrhithm. Patients’ characteristics as potential predictors of POD were analyzed by logistic regression analysis on SAS software. Results: Postoperative delirium was diagnosed in 37 patients. Use of multiple (>3) medications, lower scores on cognitive tests (<20 on Set Test and <24 on Mini‐mental Status Exam), albumin level less than 3.5 g/dL, hematocrit level less than 33% and age over 81 years were predictors of POD. A logistic regression formula including these predictors weighed by their parameter estimates can be used to calculate the probability of POD. The model had a good fit and a good predictive power. A Delirium Predicting Scale was derived based on parameter estimates of these predictors. Patients can be classified as low‐, intermediate‐ or high‐risk for POD. Conclusions: A logistic regression model, which includes patients’ age, medication history, cognitive performance measured by Set Test and Mini‐Mental Status Exam, albumin and hematocrit levels, can be used to predict risk for POD after surgical repair of fractured hip in elderly patients.     

Gender differences in challenging behaviors, management and outcomes in elderly patients with delirium

BACKGROUND: Gender differences have been reported in some common mental disorders. However, few studies have monitored gender differences in individuals with delirium. OBJECTIVE: To explore gender differences in challenging behaviors, management and outcomes in age-matched elderly patients with delirium.DESIGN, TIME AND SETTING: A retrospective cohort study was performed in the Bankstown-Lidcombe Hospital, Sydney, Australia, from October 2008 to April 2009. METHODS: Patients, aged 65-90 years, diagnosed with delirium according to the International Classification of Diseases (ICD)-10 in the Psychogeriatric Unit of Bankstown Lidcombe Hospital from January 2002 to October 2008 were reviewed. All the patients were measured according to the Confusion Assessment Method upon admission. Those who developed delirium during hospitalization were excluded.MAIN OUTCOME MEASURES: Cause of delirium, wandering, aggression, duration of delirium, physical restraint, use of antipsychotic medicine, recovery from delirium, discharge back home, length of stay, one-to-one nursing care, falls and absconding rate.RESULTS: The 131 age-matched delirious patients comprised 54 males and 77 females. The behavioral disorders of wandering [odds ration (OR) = 2.612, 95% confidence interval (CI) = 1.26 -5.413, P = 0.009] and aggression (OR = 2.243, 95% CI = 1.028 - 4.891, P= 0.04) were more frequent in males than in females. More males received one-to-one nursing care (OR = 4.114, 95% CI = 1.355 - 12.491, P = 0.008), were more likely to receive antipsychotic medications (OR = 2.24, 95% CI = 1.095-4.583, P = 0.021) and more likely to be physically restrained (OR = 2.07, 95% CI = 1.02-1.02, P = 0.043) compared with female patients. All absconding patients (3/131, 2.3%) were male. In addition, male patients displayed a greater falling rate compared with females (OR = 4.57, 95% CI= 1.519-13.722, P = 0.004).CONCLUSION: There are gender differences in challenging behaviors, management and outcomes in elderly delirious patients. Males with delirium display more challenging behaviors that require physical restraint and pharmacological management including wandering and aggression; males also abscond and have a higher rate of falls compared with female patients.     

A randomized,double‐blind,placebo‐controlled trial evaluating cysteamine in Huntington's disease

Background : Cysteamine has been demonstrated as potentially effective in numerous animal models of Huntington's disease. Methods : Ninety‐six patients with early‐stage Huntington's disease were randomized to 1200 mg delayed‐release cysteamine bitartrate or placebo daily for 18 months. The primary end point was the change from baseline in the UHDRS Total Motor Score. A linear mixed‐effects model for repeated measures was used to assess treatment effect, expressed as the least‐squares mean difference of cysteamine minus placebo, with negative values indicating less deterioration relative to placebo. Results : At 18 months, the treatment effect was not statistically significant — least‐squares mean difference, ‐1.5 ± 1.71 (P = 0.385) — although this did represent less mean deterioration from baseline for the treated group relative to placebo. Treatment with cysteamine was safe and well tolerated. Conclusions : Efficacy of cysteamine was not demonstrated in this study population of patients with Huntington's disease. Post hoc analyses indicate the need for definitive future studies. © 2017 International Parkinson and Movement Disorder Society     

A randomized,double‐blind,placebo‐controlled trial of camicinal in Parkinson's disease

Background : Delayed gastric emptying may impair l ‐dopa absorption, contributing to motor fluctuations. We evaluated the effect of camicinal (GSK962040), a gastroprokinetic, on the absorption of l ‐dopa and symptoms of PD. Methods : Phase II, double‐blind, placebo‐controlled trial. Participants were randomized to receive camicinal 50 mg once‐daily (n = 38) or placebo (n = 20) for 7 to 9 days. Results: l ‐dopa exposure was similar with coadministration of camicinal compared to placebo. Median time to maximum l ‐dopa concentration was reduced, indicating more rapid absorption of l ‐dopa. Camicinal resulted in significant reduction in OFF time (–2.31 hours; 95% confidence interval: –3.71, –0.90), significant increase in ON time (+1.88 hours; 95% confidence interval: 0.28, 3.48) per day, and significant decrease in mean total MDS‐UPDRS score (–12.5; 95% confidence interval: –19.67, ‐5.29). Camicinal treatment was generally well tolerated. Conclusions : PD symptom improvement with camicinal occurred in parallel with more rapid absorption of l ‐dopa. This study provides evidence of an improvement of the motor response to l ‐dopa in people with PD treated with camicinal 50 mg once‐daily compared with placebo, which will require further evaluation. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.     

A randomized,double‐blind,placebo‐controlled trial of pridopidine in Huntington's disease

We examined the effects of 3 dosages of pridopidine, a dopamine‐stabilizing compound, on motor function and other features of Huntington's disease, with additional evaluation of its safety and tolerability. This was a randomized, double‐blind, placebo‐controlled trial in outpatient neurology clinics at 27 sites in the United States and Canada. Two hundred twenty‐seven subjects enrolled from October 24, 2009, to May 10, 2010. The intervention was pridopidine, either 20 (n=56), 45 (n=55), or 90 (n=58) mg daily for 12 weeks or matching placebo (n=58). The primary outcome measure was the change from baseline to week 12 in the Modified Motor Score, a subset of the Unified Huntington's Disease Rating Scale Total Motor Score. Measures of safety and tolerability included adverse events and trial completion on the assigned dosage. After 12 weeks, the treatment effect (relative to placebo, where negative values indicate improvement) of pridopidine 90 mg/day on the Modified Motor Score was ?1.2 points (95% confidence interval [CI], ?2.5 to 0.1 points; P = .08). The effect on the Total Motor Score was ?2.8 points (95% CI, ?5.4 to ?0.1 points; nominal P = .04). No significant effects were seen in secondary outcome measures with any of the active dosages. Pridopidine was generally well tolerated. Although the primary analysis did not demonstrate a statistically significant treatment effect, the overall results suggest that pridopidine may improve motor function in Huntington's disease. The 90 mg/day dosage appears worthy of further study. Pridopidine was well tolerated. © 2013 International Parkinson and Movement Disorder Society     

Twice‐daily,low‐dose pramipexole in early Parkinson's disease: A randomized,placebo‐controlled trial

To compare the safety and efficacy of low dosages of pramipexole given twice daily (bid) in early Parkinson's disease (PD) with those of a standard 3 times daily (tid) regimen in a randomized, double‐blind, placebo controlled trial involving 311 early PD patients not receiving dopaminergic treatment. Subjects were randomly assigned and followed on assigned treatment for 12 weeks with pramipexole at dosages of 0.5 mg bid, 0.75 mg bid, or 0.5 mg tid, or matching placebo. All subjects were dosed 3 times daily, with placebo if necessary, to maintain blinding. The primary outcome was the change from baseline to Week 12 in the Unified Parkinson Disease Rating Scale (UPDRS) total score (Parts I–III). All active dosages had similar antiparkinson efficacy showing reductions of 4–5 UPDRS points relative to placebo (p < 0.0001) for each comparison. Somnolence, fatigue, nausea, constipation, and peripheral edema were more common in the active treatment groups than in the placebo group, but their frequency did not vary by dosage. In this fixed dosage, randomized study pramipexole administered twice daily at a total daily dosage of 1.0–1.5 mg daily was of comparable efficacy and tolerability to a dosage of 0.5 mg tid over a 12‐week treatment period in early PD. © 2010 Movement Disorder Society     

Efficacy of risperidone in the treatment of delirium in elderly patients

Background:  Despite increasing recognition of delirium as a serious complication of physical illness, little has been reported in this area. Interest has been raised in treatment options other than haloperidol, such as atypical antipsychotic agents.
Methods:  A 2-week open-label trial of risperidone for the treatment of delirium was conducted to assess the efficacy and tolerance of this medication in elderly patients. Twenty-two patients with DSM-IV-defined delirium were investigated. All patients had the hyperactive–hyperalert variant of delirium. Patients received a fixed dose of risperidone (mean 1.5 ± 0.7 mg; range 0.5–3 mg). Delirium was assessed using the Delirium Rating Scale (DRS) at baseline and on Days 1, 3, 5, 7, and 14 after the initiation of risperidone treatment. Clinical and demographic data, as well as risperidone therapy related information, were collected.
Results:  Delirium resolved in all patients over the course of treatment. The mean period over which delirium resolved was 4.0 ± 2.9 days. The mean DRS score at baseline was 20.7 ± 3.0. The DRS score improved from baseline to Day 1 of treatment and continued to improve until the study end-point. Mild side-effects were present in 27.3% of patients. Stepwise logistic regression identified a decrease of 2 points or higher on the DRS on Day 1 associated with side-effects. There were no significant differences in the response to treatment with the different doses of risperidone used.
Conclusion:  Our findings indicate that low-dose risperidone (0.5–3.0 mg/day) is effective and safe for the treatment of delirium in elderly patients, and that an early response on Day 1 of treatment may be associated with side-effects in these patients.     

Use of aripiprazole for delirium in the elderly: a short review

The effects and tolerability of antipsychotics in delirium treatment remain controversial. Compared to other antipsychotics, aripiprazole differs in pharmacological activity because it exerts its effect as a dopamine D₂ partial agonist. The guidelines of the American Psychiatric Association rank aripiprazole highly among antipsychotics with regard to safety, and this drug is likely to be useful for delirium treatment. Here, we reviewed the efficacy and safety of aripiprazole for delirium. The results of our literature review on the efficacy and safety of delirium treatments suggest that aripiprazole is an effective treatment option for delirium in the elderly. Aripiprazole is as effective as other antipsychotics in improving delirium symptoms, and it is safer because it is less likely to cause extrapyramidal symptoms, excessive sedation, and weight gain. However, these findings are based on only a few clinical studies of elderly patients with delirium. Therefore, further investigations are necessary.