Oral Rivastigmine Research Articles

Treatment of Anticholinergic Delirium with Oral Rivastigmine: A Case Report

BackgroundAnticholinergic toxicity is commonly encountered in the emergency department. However, the availability of physostigmine, a central acetylcholinesterase inhibitor used to reverse anticholinergic delirium, has been significantly limited due to national drug shortages in the United States. Several articles have explored the viability of rivastigmine as an alternative treatment for these patients. Case ReportA 33-year-old male presented to the emergency department after a suspected suicide attempt. The patient was found with an empty bottle of diphenhydramine at the scene. On arrival, he was tachycardic, delirious, with dilated and nonreactive pupils and dry skin. As the clinical picture was highly suggestive of anticholinergic toxicity, the patient was treated with oral rivastigmine at a starting dose of 4.5mg to reverse his anticholinergic delirium. Though requiring a repeat dose, his delirium resolved without recurrence.Why Should an Emergency Physician Be Aware of This? Oral rivastigmine has been successfully applied here and in other case reports to reverse anticholinergic delirium with the benefit of prolonged agitation control. Emergency physicians may consider this medication in consultation with a specialist, with initial doses starting at 4.5 to 6 mg, if encountering anticholinergic delirium when physostigmine is not available.

Rivastigmine for the management of anticholinergic delirium

Introduction Anticholinergic agents are commonly taken in overdose, often causing delirium. The spectrum of anticholinergic delirium ranges from mild agitation to severe behavioural disturbance. Physostigmine is an effective treatment for anticholinergic delirium, but its availability is limited. As rivastigmine is readily available, it has been used to manage anticholinergic delirium; however, there is limited research investigating its use. Method This was a retrospective review of patients with anticholinergic delirium treated in two toxicology units with rivastigmine (oral capsule or transdermal patch) from January 2019 to June 2023. The primary outcome was the use of further parenteral treatment (sedation or physostigmine) for delirium post rivastigmine administration. Results Fifty patients were administered rivastigmine for the management of anticholinergic delirium. The median age was 36 years (interquartile range: 25–49 years) and 27 (54 per cent) were females. Features consistent with anticholinergic toxicity included tachycardia in 44 (88 per cent) and urinary retention requiring catheterisation in 40 (80 per cent). Forty-three patients (86 per cent) were treated with physostigmine before rivastigmine administration. Twenty-two were managed with transdermal rivastigmine (most commonly 9.5 mg/24 hour patch), and 28 with oral rivastigmine 6 mg. Further parenteral sedation and/or physostigmine treatment were required more often in patients given transdermal than oral rivastigmine [16/22 (73 per cent) versus 9/28 (32 per cent), P = 0.010)]. No patients had bradycardia or gastrointestinal symptoms following rivastigmine administration. One patient with a history of epilepsy had a seizure, 1.5 hours post physostigmine administration and 7 hours post transdermal rivastigmine. Discussion Rivastigmine has been increasingly used for the management of patients with anticholinergic delirium, due to the lack of availability of physostigmine. In this case series, rivastigmine transdermal patch appeared to be less effective than oral rivastigmine capsules, likely due to its slow onset of action and/or insufficient dose. Conclusion Rivastigmine can be used to treat anticholinergic delirium. In our case series oral rivastigmine appeared more effective than transdermal rivastigmine.

Improvement in delirium and visuospatial function after rivastigmine in antimuscarinic toxicity: a case report

Treatment of antimuscarinic toxicity has become more difficult in the United States due to an ongoing national shortage of physostigmine. Rivastigmine has emerged as an alternative, off-label therapy due to its similar mechanism of action as a reversible, centrally-acting acetylcholinesterase inhibitor. We present a case of a diphenhydramine overdose where the patient exhibited classic central antimuscarinic delirium characterized by inattention, floccillation, and deficits in spatial planning manifested by the inability to properly draw a clock. These symptoms rapidly resolved after treatment with oral rivastigmine.

Ocimum basilicum extract modulates Tau aggregation and improves memory function in a neurodegenerative rat model

The main objective of this study was evaluation of the neuroprotective potential effect of Ocimum basilicum on oxidative stress status in rat induced Alzheimer's disease. Fifty rats were divided into five groups (ten rats each). Rats were treated orally with AlCl3 to induced AD. Group 1 (control group). Group 2 (AD group): supplemented orally with AlCl3 (17mg/kg/day) for four weeks. Group 3 (OB/AD group) supplemented concomitantly with oral rivastigmine (3 mg/kg /day). Group 4 (OB/AD group) supplemented concomitantly with oral OB (250mg/kg/day) and Group 5 (OB/AD group) supplemented concomitantly with oral OB (500 mg/kg/day). The results showed that the plant leaves extract increased serum superoxide dismutase (SOD) with a significant decrease of a serum MDA and also the aggregation of tau protein expression was decreased . Histological changes were observed in brain tissues of AD rats. However, the high dosing of the plant leaves extract (500 mg/kg) was more powerful than the low treatment with low dose (250 mg/kg) by decreasing Tau protein expression. The results suggest that Ocimum basilicum can relieve symptoms and prevent the progression of AD severity by improving memory function. It can be concluded that OB leaves were alleviated the memory impairment and learning abilities due to antioxidants activity of flavonoids, tannins and terpenoids.

Case series profile of olanzapine post-injection delirium/sedation syndrome.

Olanzapine pamoate is an intramuscular depot injection for the treatment of schizophrenia. Approximately 1.4% of patients develop a serious adverse event called post-injection delirium/sedation syndrome (PDSS), characterised by drowsiness, anticholinergic and extrapyramidal symptoms. The objective is to investigate olanzapine PDSS presentations including clinical features and treatment approach. This is a retrospective review of olanzapine PDSS patients from three toxicology units and the NSW Poisons Information Centre between 2017 and 2022. Adult patients were included if they had intramuscular olanzapine then developed PDSS criteria. Clinical symptoms, treatment, timing and length of symptoms were extracted into a preformatted Excel database. There were 18 patients included in the series, with a median age of 49 years (interquartile range [IQR]: 38-58) and male predominance (89%). Median onset time post injection was 30 min (IQR: 11-38). PDSS symptoms predominate with drowsiness, confusion and dysarthria. Median length of symptoms was 24 h (IQR: 20-54). Most common treatment included supportive care without any pharmacological intervention (n = 10), benzodiazepine (n = 4) and benztropine (n = 3). In one case, bromocriptine and physostigmine followed by oral rivastigmine were given to manage antidopaminergic and anticholinergic symptoms respectively. This proposed treatment combination could potentially alleviate some of the symptoms but needs further studies to validate the findings. In conclusion, this case series supports the characterisation of PDSS symptomology predominantly being anticholinergic with similar onset (<1h) and duration (<72 h). Bromocriptine is proposed to manage PDSS if patients develop severe dopamine blockade and physostigmine followed by rivastigmine for anticholinergic delirium.

Comparative safety and efficacy of cognitive enhancers for Alzheimer’s dementia: a systematic review with individual patient data network meta-analysis

ObjectiveTo examine the comparative efficacy and safety of cognitive enhancers by patient characteristics for managing Alzheimer’s dementia (AD).DesignSystematic review and individual patient data (IPD) network meta-analysis (NMA) based on our...

Ginkgo biloba Extract (EGb761), Cholinesterase Inhibitors, and Memantine for the Treatment of Mild-to-Moderate Alzheimer's Disease: A Network Meta-Analysis.

Cholinesterase inhibitors (ChEIs) and memantine have been reported to provide modest benefits for cognition and aspects of functioning in Alzheimer's disease (AD). Ginkgo biloba extract (EGb761), a phytomedicine, is widely used and expected to be well-tolerated. A few trials have compared EGb761 with ChEIs, and the results were inconclusive. A network meta-analysis was conducted to evaluate the therapeutic benefits and tolerability of EGb761, three ChEIs (donepezil, galantamine, and rivastigmine), and memantine in mild-to-moderate AD patients. Electronic databases were searched through 30 June 2017. We included randomized double-blinded trials with a minimum treatment duration of 22 weeks for EGb761 240mg/day and 12weeks for ChEIs or memantine. The study patients included AD or probable AD patients without other types of dementia or neurological disorders. Cognition, function, and behavior symptoms were compared between treatments using the standardized mean difference (SMD). Clinical global impression, treatment discontinuation, and adverse events were compared between treatments using the relative risk (RR). Statistical pooling of the individual trial results was conducted using a frequentist approach. The probability of being the best for a treatment was estimated using surface under the cumulative ranking. EGb761 and memantine showed no therapeutic benefits in all study outcomes. For cognition, all ChEIs were significantly better than placebo (SMD from - 0.52 to - 0.26), and galantamine was better than rivastigmine in the oral and patch forms, EGb761, and memantine (SMD [95% confidence interval (CI)]: - 0.22 [- 0.40 to - 0.05]; - 0.26 [- 0.45 to - 0.07]; - 0.34 [- 0.56 to - 0.12]; and - 0.42 [- 0.71 to - 0.13], respectively). Compared to placebo, galantamine, the rivastigmine patch, and oral rivastigmine provided modest functional benefits (SMD, from 0.21 to 0.24), and galantamine provided behavioral benefits (SMD [95% CI]: - 0.15 [- 0.26 to - 0.04]). All ChEIs provided a better improvement in clinical global impression than placebo (RR from 1.20 to 1.69). The global impression ratings were more improved with donepezil than with galantamine (RR [95% CI]: 1.40 [1.09-1.80]) or with EGb761 (RR [95% CI]: 1.40 [1.06-1.85]), with a 96% probability of donepezil being more effective than the other study agents. Rivastigmine in oral and patch forms, galantamine, and donepezil had a higher risk of being discontinued than placebo (RR [95% CI]: 2.14 [1.49-3.06]; 2.04 [1.30-3.20]; 1.79 [1.28-2.49]; 1.49 [1.03-2.17], respectively). Discontinuation of EGb761 was not statistically lower than that of the ChEIs, in which donepezil had the lowest probability (38%) of being discontinued. EGb761 and memantine showed no treatment benefits compared to placebo and ChEIs. Galantamine provided the highest beneficial effect on cognition and behavioral symptoms. Donepezil provided a better clinical global impression and tolerability than the other ChEIs and EGb761, with a similar benefit for cognition as galantamine.

Comparison of cholinesterase inhibitor safety in real-world practice

IntroductionCholinesterase inhibitors (ChEIs) are widely used to treat mild to moderate Alzheimer's disease and related dementia. Clinical trials have focused on placebo comparisons, inadequately addressing within-class comparative safety. MethodsNew users of ChEIs in British Columbia were categorized into five study cohorts: low-dose donepezil, high-dose donepezil, galantamine, rivastigmine patch, and oral rivastigmine. Comparative safety of ChEIs assessed hazard ratios using propensity score adjusted Cox regression. ResultsCompared with low-dose donepezil, galantamine use was associated with a lower risk of mortality (adjusted hazard ratio: 0.84, 95% confidence interval: 0.60–1.18), cardiovascular serious adverse events (adjusted hazard ratio: 0.78, 95% confidence interval: 0.62–0.98), and entry into a residential care facility (adjusted hazard ratio: 0.72, 95% confidence interval: 0.59–0.89). DiscussionGiven the absence of randomized trial data showing clinically meaningful benefit of ChEI therapy in Alzheimer's disease, our study suggests preferential use of galantamine may at least be associated with fewer adverse events than treatment with donepezil or rivastigmine.

Alzheimer's disease medication and risk of all-cause mortality and all-cause hospitalization: A retrospective cohort study

IntroductionIdentifying Alzheimer's disease (AD) pharmacologic treatment options that effectively reduce the risk of mortality and hospitalization in real-world settings is critical. MethodsWe compared donepezil, galantamine, memantine, oral rivastigmine, and transdermal rivastigmine with regard to all-cause mortality and all-cause hospitalization risk among fee-for-service Medicare beneficiaries with AD (aged ≥ 65 years) using a retrospective cohort study design. Our primary analysis was based on intention to treat (ITT), but we also present as-treated analysis. ResultsIn our final study sample (N = 21,558), significant difference in survival among index AD medication groups were observed with donepezil being associated with better survival than memantine, and oral and transdermal forms of rivastigmine for both ITT and as-treated analysis. Difference in hazards of all-cause hospitalization among index AD medication groups was observed in ITT analysis but not in as-treated analysis. DiscussionSignificant differences exist in terms of mortality and hospitalization risk with different AD medication initiation in real-world setting.

The efficacy and safety of memantine for the treatment of Alzheimer’s disease

ABSTRACTIntroduction: Currently, five pharmacotherapeutic options are available to treat Alzheimer’s disease: memantine; the three cholinesterase inhibitors donepezil, galantamine, and rivastigmine; and combination treatments with memantine and one cholinesterase inhibitor. Selection of the best course of treatment is based upon the evidence gathered by systematic reviews and meta-analyses of randomized controlled trials.Areas covered: This article provides a risk–benefit analysis of these treatments using evidence from meta-analyses on their safety and their efficacy.Expert opinion: Memantine improves cognitive functions and behavioral disturbances more efficiently than the placebo, both as monotherapy and in combination with donepezil. Although memantine monotherapy and combination therapy are associated with a few individual adverse events such as somnolence, it is well-tolerated and its safety (all-cause discontinuation) is comparable or superior to that of the placebo (agitation). Pooled cholinesterase inhibitors are superior to the placebo in the improvement of cognitive functions, but not behavioral disturbances and they are not well-tolerated, as evaluated by the high discontinuation rate. Donepezil (10 mg/day) and oral rivastigmine and galantamine monotherapies carry the risk for some adverse events including gastrointestinal symptoms. Therefore, we consider that combined treatment with memantine and donepezil is the most useful treatment for Alzheimer’s disease.

Persistence and adherence to rivastigmine in patients with dementia: Results from a noninterventional, retrospective study using the National Health Insurance research database of Taiwan

IntroductionThe objective of the study was to assess adherence and persistence of patients treated with rivastigmine versus donepezil. MethodsPersistence was calculated as the time from the first prescription date of rivastigmine/donepezil until discontinuation/medication switch/end of available data, whichever occurred first. Adherence was calculated as proportion of days covered and medication possession ratio. ResultsA majority of patients persisted on 4.5 and 6 mg of rivastigmine for 429 and 468 days, respectively, versus 443 and 441 days for patients receiving 5 and 10 mg of donepezil daily, respectively. Patients who initially received 1.5 mg of oral rivastigmine required a shorter time to reach a stable dose compared with those who initiated treatment at a higher dose of rivastigmine. Patients at a stable dose of 4.5 or 6 mg of rivastigmine were observed to persist longer than those at a lower dose of rivastigmine and donepezil. DiscussionAlthough results indicate significant difference in persistence between rivastigmine and donepezil groups, clinical significance remains undetermined.

Comparative Effectiveness and Safety of Cognitive Enhancers for Treating Alzheimer's Disease: Systematic Review and Network Metaanalysis.

To examine the comparative effectiveness and safety of cognitive enhancers for Alzheimer's disease (AD). Systematic review and Bayesian network metaanalysis (NMA). MEDLINE, EMBASE, Cochrane Library, CINAHL, Ageline (inception-March 2016). Individuals with AD in randomized controlled trials (RCTs), quasi-RCTs, and nonrandomized studies. Any combination of donepezil, rivastigmine, galantamine, or memantine. Two reviewers independently screened titles, abstracts, and full-texts; abstracted data; and appraised risk of bias. Twenty thousand three hundred forty-three citations were screened, and 142 studies were included (110 RCTs, 21 non-RCTs, 11 cohort studies). NMA found that donepezil (Mini-Mental State Examination: mean difference (MD) = 1.39, 95% credible interval (CrI) = 0.53-2.24), donepezil+memantine (2.59, 95% CrI = 0.12-4.98), and transdermal rivastigmine (2.02, 95% CrI = 0.02-4.08) improved cognition more than placebo. NMA found that donepezil (Alzheimer's Disease Assessment Scale-cognitive: MD = -3.29, 95% CrI = -4.57 to -1.99) and galantamine (MD = -2.13, 95% CrI = -3.91 to -0.27) improved cognition more than placebo. NMA found that donepezil+memantine (MD = -5.23, 95% CrI = -8.72 to -1.56) improved behavior more than placebo. NMA found that donepezil (MD = -0.32, 95% CrI = -0.46 to -0.19), donepezil+memantine (MD = -0.57, 95% CrI = -0.95 to -0.21), oral rivastigmine (MD = -0.38, 95% CrI = -0.56 to -0.17), and galantamine (MD = -3.79, 95% CrI = -6.98 to -0.59) improved global status more than placebo. NMA found that galantamine decreased the odds of mortality (odds ratio = 0.56, 95% CrI = 0.36-0.87). No agent increased risk of serious adverse events, falls, or bradycardia. Some increased risk of headache (oral rivastigmine), diarrhea (oral rivastigmine, donepezil), nausea (oral rivastigmine, donepezil, galantamine), and vomiting (oral rivastigmine, donepezil, galantamine). An exhaustive review of the literature involving 142 studies demonstrated that cognitive enhancers in general have minimal effects on cognition according to minimal clinically important difference and global ratings. The drugs appear safe, but this must be interpreted cautiously because trial participants may have less comorbidity and fewer adverse effects than those treated with these drugs in clinical practice.

Overlap between frontotemporal dementia and Alzheimer’s disease: case report

The &lt;em&gt;frontal variant of Alzheimer’s disease&lt;/em&gt; (fv-AD) has been described in patients with prominent behavioral or executive dysfunctions. Subsequently, the spectrum of frontal variant Alzheimer’s disease has been enlarged to comprise patients with early personality and behavioral changes including disinhibition, apathy or compulsiveness. We describe the case of a patient with a history of memory loss and behavioral changes. The neuropsychological profile overlapped with the presence of behavioral disorders such as marked apathy, disinhibition, hostile behavior, agitation, irritability and hyperorality. The results of the neuropsychological examination leaned towards a diagnosis of frontotemporal circuit functional impairment, however, the 18-FDG PET study demonstrated a moderate-to-severe impairment in the bilateral parietal regions. On the basis of the neuropsychological profile and 18-FDG PET imaging, a diagnosis of a probable fv-AD was made, the patient started oral rivastigmine 3 mg/daily and subsequent assessments showed only modest worsening in the cognitive profile and a moderate improvement in behavioral symptoms.

Association between Anti-Dementia Treatment Persistence and Daily Dosage of the First Prescription: A Retrospective Analysis in Neuropsychiatric Practices in Germany.

High adherence and persistence are important for the efficacy of anti-dementia treatments. The goal of this study was to analyze the association between anti-dementia treatment persistence and daily dosage of the first prescription in patients treated in neuropsychiatric practices in Germany. This study included patients aged 60 years or over who were diagnosed with Alzheimer's disease and received anti-dementia prescriptions (galantamine, donepezil, memantine, and rivastigmine) for the first time between 2005 and 2014. The main outcome measure was the treatment persistence rate within 12 months after the index date as a function of the first dose. Cox proportional hazards regression models were used to estimate the relation between persistence and daily dosages after adjusting for age, gender, and residence in nursing homes. In this study, 2,442, 5,669, 4,416, 642, and 2,334 patients received galantamine, donepezil, memantine, oral rivastigmine, and patch rivastigmine, respectively. After 12 months of follow-up, continuation rates were similar for individuals using different doses of galantamine, donepezil, oral rivastigmine, and patch rivastigmine, but were significantly different for those taking memantine. Patients using 20 mg of memantine were less likely to discontinue their treatment than patients using 10 mg (HR = 0.88, 95% CI: 0.80-0.96). There was no significant association between daily dosages and persistence for the other drugs (HRs ranging from 0.86 to 1.15). There was no significant association between treatment persistence and daily dosages in patients with Alzheimer's disease in Germany who were treated with galantamine, donepezil, or rivastigmine.

Tolerability of Cholinesterase Inhibitors: A Population-Based Study of Persistence, Adherence, and Switching.

Cholinesterase inhibitors (ChEIs) are prescribed to dementia patients despite their poor tolerance. Low tolerability potentially reduces persistence and adherence, while inducing switching between medications. Comparisons of these utilization measures contribute to knowledge of the relative tolerability of these medications. The aim was to compare persistence, adherence, and switching between donepezil, galantamine, oral rivastigmine, and rivastigmine patch. A population-based cohort study, using British Columbia claims data (2009-2013), assessed ChEI new users aged 40 and older. We conducted survival analysis to compare persistence and Poisson regression to estimate switching rates. Good adherence, defined as a medication possession ratio of ≥80%, was modeled using log-binomial regression. Analyses were adjusted using propensity scores. Patients on galantamine had longer mean persistence and better adherence compared with patients on donepezil, with a hazard ratio for discontinuation of 0.91 [95% confidence interval (CI) 0.87-0.96] and a relative risk for good adherence of 1.01 (95% CI 1.002-1.03). Rivastigmine was associated with the shortest mean persistence [3.6months (95% CI 3.0-4.2) and 5.0 (95% CI 4.7-5.3) for oral and patch, respectively] and the highest mean switching rates. Comparing the two rivastigmine preparations, the patch was associated with decreased discontinuation compared with oral [hazard ratio 0.79 (95% CI 0.71-0.89)] and decreased switching [relative risk 0.63 (95% CI 0.46-0.87) during the first 6months of treatment]. Paradoxically, the patch was also associated with poorer adherence [relative risk for good adherence 0.94 (95% CI 0.91-0.98)] than the oral formulation. Based on estimates of persistence, adherence, and switching, galantamine was the best tolerated ChEI and rivastigmine the least.

Use of antidementia drugs and risk of pneumonia in older persons with Alzheimer’s disease

Introduction: Persons with Alzheimer’s disease are at an increased risk of pneumonia, but the comparative risks during specific antidementia treatments are not known. We compared the risk of pneumonia in the use of donepezil, rivastigmine (oral, transdermal), galantamine and memantine.Patients and methods: We used data from a nationwide cohort of community-dwelling individuals diagnosed with Alzheimer’s disease during 2005–2011 in Finland, who initiated monotherapy with acetylcholinesterase inhibitor or memantine (n = 65,481). The risk of hospitalization or death due to pneumonia was investigated with Cox proportional hazard models.Results: The risk of pneumonia was higher in persons using rivastigmine patch (n = 9709) (adjusted hazard ratio (HR) 1.15, 95% confidence interval (CI) 1.04–1.27) and memantine (n = 11,024) (HR 1.59, 95% CI 1.48–1.71) compared with donepezil users (n = 26,416) whereas oral rivastigmine (n = 7384) (HR 1.08, 95% CI 0.98–1.19) and galantamine (n = 10,948) (HR 0.91, 95% CI 0.83–1.00) were not associated with an increased risk. These results did not change when adjusting for comorbid conditions, use of psychotropic drugs or with inverse probability of treatment weighting.Discussion: The increased risk of pneumonia in this fragile group of aged persons should be taken into account. Memantine is associated with the highest risk in the comparison of antidementia drugs.KEY MessagePneumonia risk is increased in persons with Alzheimer’s disease who use memantine or rivastigmine patches.

Differential metformin dose-dependent effects on cognition in rats: role of Akt.

Epidemiological evidence suggests that individuals with diabetes mellitus are at greater risk of developing Alzheimer's disease, and controversy overwhelms the usefulness of the widely prescribed insulin-sensitizing drug, metformin, on cognition. Through the scopolamine-induced memory deficit model, we investigated metformin influence on cognitive dysfunction and explored underlying mechanisms. Sixty adult male Wistar rats were randomly assigned into 5 groups (12 rats each) to receive either normal saline, scopolamine 1mg/kg intraperitoneally once daily, scopolamine + oral metformin (100mg/kg/day), scopolamine + oral metformin (300mg/kg/day) or scopolamine + oral rivastigmine (0.75mg/kg/day) for 14days. Cognitive behaviours were tested using Morris water maze and passive avoidance tasks. Biochemically, brain oxidative (malondialdehyde) and inflammatory (TNF-α) markers, nitric oxide, Akt, phospho-Akt, phospho-tau and acetyl cholinesterase activity in hippocampal and cortical tissues were assessed. The lower dose of metformin (100mg/kg) ameliorated scopolamine-induced impaired performance in both Morris water maze and passive avoidance tasks, and was associated with significant reduction of inflammation and to a lesser extent oxidative stress versus rivastigmine. Given the role of total Akt in regulation of abnormal tau accumulation and degradation, our finding that metformin 100 decreased the elevated total Akt while increasing its phosphorylated form explains its beneficial modulatory effect on phosphorylated tau in both tissues, and could further clarify its protection against memory impairment. Metformin, only in the average human antidiabetic dose, offers a protective effect against scopolamine-induced cognitive impairment, while no deleterious effect was observed with the higher dose, which may support a bonus effect of metformin in type 2 diabetic patients.

Characteristics of Pediatric Exposures to Antidementia Drugs Reported to a Poison Control System

To characterize pediatric exposures to the antidementia drugs donepezil, memantine, rivastigmine, and galantamine by reviewing a poison control system's database. A retrospective review of a statewide poison control system's database identified cases of pediatric (less than 19years of age) exposures to antidementia drugs over an 11-year period. Data collected included age, sex, drug(s) involved, route of exposure, reason for exposure, symptoms, and interventions. There were 189 cases identified (53% male, median age: 2.3years, 99% unintentional exposures). Donepezil was the most commonly reported exposure (106 cases), followed by memantine (57), galantamine (18), oral rivastigmine (16), and transdermal rivastigmine (3). Coingestants were reported in 68 (36%) cases. Symptoms were reported in 38 (20%) cases. Gastrointestinal symptoms were most common (n=21) followed by central nervous system depression (n=15). Oral rivastigmine was associated with higher rates of symptoms. No bradycardia, seizures, or fasciculations were reported. Eighty-nine cases (47%) were evaluated at a health care facility, and 13 (7%) were admitted to a hospital. Oral rivastigmine exposures were associated with increased rate of health care facility evaluation. Activated charcoal was administered in 28 cases. Atropine was given only once, for drooling. There were no serious outcomes or deaths in this series. Reported pediatric exposures to antidementia drugs resulted in minimal morbidity and no mortality. Oral rivastigmine exposures were found to be associated with more symptoms and health care facility evaluations.

Rivastigmine for gait stability in patients with Parkinson's disease (ReSPonD): a randomised, double-blind, placebo-controlled, phase 2 trial

Falls are a frequent and serious complication of Parkinson's disease and are related partly to an underlying cholinergic deficit that contributes to gait and cognitive dysfunction in these patients. Gait dysfunction can lead to an increased variability of gait from one step to another, raising the likelihood of falls. In the ReSPonD trial we aimed to assess whether ameliorating this cholinergic deficit with the acetylcholinesterase inhibitor rivastigmine would reduce gait variability. We did this randomised, double-blind, placebo-controlled, phase 2 trial at the North Bristol NHS Trust Hospital, Bristol, UK, in patients with Parkinson's disease recruited from community and hospital settings in the UK. We included patients who had fallen at least once in the year before enrolment, were able to walk 18 m without an aid, had no previous exposure to an acetylcholinesterase inhibitor, and did not have dementia. Our clinical trials unit randomly assigned (1:1) patients to oral rivastigmine or placebo capsules (both taken twice a day) using a computer-generated randomisation sequence and web-based allocation. Rivastigmine was uptitrated from 3 mg per day to the target dose of 12 mg per day over 12 weeks. Both the trial team and patients were masked to treatment allocation. Masking was achieved with matched placebo capsules and a dummy uptitration schedule. The primary endpoint was difference in step time variability between the two groups at 32 weeks, adjusted for baseline age, cognition, step time variability, and number of falls in the previous year. We measured step time variability with a triaxial accelerometer during an 18 m walking task in three conditions: normal walking, simple dual task with phonemic verbal fluency (walking while naming words beginning with a single letter), and complex dual task switching with phonemic verbal fluency (walking while naming words, alternating between two letters of the alphabet). Analysis was by modified intention to treat; we excluded from the primary analysis patients who withdrew, died, or did not attend the 32 week assessment. This trial is registered with ISRCTN, number 19880883. Between Oct 4, 2012 and March 28, 2013, we enrolled 130 patients and randomly assigned 65 to the rivastigmine group and 65 to the placebo group. At week 32, compared with patients assigned to placebo (59 assessed), those assigned to rivastigmine (55 assessed) had improved step time variability for normal walking (ratio of geometric means 0.72, 95% CI 0.58-0.88; p=0.002) and the simple dual task (0.79; 0.62-0.99; p=0.045). Improvements in step time variability for the complex dual task did not differ between groups (0.81, 0.60-1.09; p=0.17). Gastrointestinal side-effects were more common in the rivastigmine group than in the placebo group (p<0.0001); 20 (31%) patients in the rivastigmine group versus three (5%) in the placebo group had nausea and 15 (17%) versus three (5%) had vomiting. Rivastigmine can improve gait stability and might reduce the frequency of falls. A phase 3 study is needed to confirm these findings and show cost-effectiveness of rivastigmine treatment. Parkinson's UK.

Acquired Localized Hypertrichosis Induced by Rivastigmine.

Hypertrichosis is the excessive hair growth in any area of the skin surface. Acquired localized hypertrichosis may be secondary to multiple causes and there is a secondary form due to several drugs, which is usually reversible with discontinuation of the causative agent. Rivastigmine is a reversible and competitive inhibitor of acetylcholinesterase and butyrylcholinesterase used for symptomatic treatment of Alzheimer dementia and Parkinson's disease. It has an adequate safety profile and cutaneous side effects are unusual. Irritant contact dermatitis, allergic dermatitis, baboon syndrome, and cutaneous rash due to rivastigmine have been reported. We report on a Caucasian 80-year-old male with personal history of Alzheimer's disease. The patient started therapy with oral rivastigmine one month prior to clinical presentation of localized hypertrichosis on both forearms. Norgalanthamine has been shown to promote hair growth activity via the proliferation of dermal papilla. Acetylcholinesterase inhibitors can induce hair growth.