Galantamine treatment in Alzheimer's disease: response and long-term outcome in a routine clinical setting (original) (raw)
Related papers
European Journal of Neurology, 2004
In clinical trials, short-term galantamine treatment produces consistent positive effects on global ratings, cognitive tests, and assessments of activities of daily living and behavior in patients with mild-to-moderate Alzheimer's disease (AD), providing the rationale for longer-term, open-label treatment. In this continuation trial following enrollment in previous 12-month trials, patients received galantamine 24 mg/day for a total of 24 months (total exposure up to 36 months). Primary efficacy measures were the ADAS-cog/11 and DAD. Adverse events (AEs) were coded to WHO preferred terms, including AEs begun in previous trials. Initial improvement in cognitive function was followed by a gradual decline, as measured by increased ADAS-cog/11 scores. At 36 months, ADAS-cog/11 scores increased by a mean (SEM) of 12.4 (0.80) points (P < 0.001) versus a projected 22-point increase for untreated patients. Functional abilities, as measured by the DAD, had decreased significantly at each time point versus baseline (P < 0.001). The most common treatment-emergent AEs were agitation (16.1%), insomnia (12.4%), fall (11.2%), and urinary tract infection (10.2%). AEs were mainly mild to moderate, appropriate for an elderly population, with few judged treatment related. Galantamine 24 mg/day is safe and effective for long-term treatment of mild-to-moderate AD. Potential exists for prolonged benefit with galantamine therapy versus lack of treatment for the long-term.
Effects of galantamine in a 2-year, randomized, placebo-controlled study in Alzheimer's disease
Neuropsychiatric Disease and Treatment, 2014
Background: Currently available treatments for Alzheimer's disease (AD) can produce mild improvements in cognitive function, behavior, and activities of daily living in patients, but their influence on long-term survival is not well established. This study was designed to assess patient survival and drug efficacy following a 2-year galantamine treatment in patients with mild to moderately severe AD. Methods: In this multicenter, double-blind study, patients were randomized 1:1 to receive galantamine or placebo. One primary end point was safety; mortality was assessed. An independent Data Safety Monitoring Board monitored mortality for the total deaths reaching prespecified numbers, using a time-to-event method and a Cox-regression model. The primary efficacy end point was cognitive change from baseline to month 24, as measured by the Mini-Mental State Examination (MMSE) score, analyzed using intent-to-treat analysis with the 'last observation carried forward' approach, in an analysis of covariance model. Results: In all, 1,024 galantamine-and 1,021 placebo-treated patients received study drug, with mean age ∼73 years, and mean (standard deviation [SD]) baseline MMSE score of 19 (4.08). A total of 32% of patients (661/2,045) completed the study, 27% (554/2,045) withdrew, and 41% (830/2,045) did not complete the study and were discontinued due to a Data Safety Monitoring Board-recommended early study termination. The mortality rate was significantly lower in the galantamine group versus placebo (hazard ratio [HR] =0.58; 95% confidence interval [CI]: 0.37; 0.89) (P=0.011). Cognitive impairment, based on the mean (SD) change in MMSE scores from baseline to month 24, significantly worsened in the placebo (−2.14 [4.34]) compared with the galantamine group (−1.41 [4.05]) (P,0.001). Functional impairment, based on mean (SD) change in the Disability Assessment in Dementia score (secondary end point), at month 24 significantly worsened in the placebo (−10.81 [18.27]) versus the galantamine group (−8.16 [17.25]) (P=0.002). Incidences of treatment-emergent adverse events were 54.0% for the galantamine and 48.6% for the placebo group. Conclusion: Long-term treatment with galantamine significantly reduced mortality and the decline in cognition and daily living activities, in mild to moderate AD patients. Identification: This study is registered at ClinicalTrials.gov (NCT00679627).
Can We Predict the Response to Galantamine in Alzheimer`s Disease Patients?
Romanian Journal of Neurology
Although considerate progress was obtained by adding imagistic and laboratory test, clinical examination remains the core of the diagnosis for Alzheimer`s disease. After 20 years of experience with anticholinergic drugs we know that only one third of the patients respond to the treatment; the treatment is more efficient in the initial stages of the neurocognitive decline. It is important to evaluate the efficacy of drugs as soon as possible. We examined patients with mild and moderate Alzheimer`s disease referred through our outpatient clinic. They fulfilled the NINCDS-ADRDA criteria for Alzheimer`s disease and they scored at baseline 21 to 26 points on MMSE. The patients were treated with Galantamine, 8 mg/day for the first month and then 16 mg/day. We evaluated the patients after 2 and 6 months of treatment; we performed MMSE and ADAS-Cog in order to see if a more complex evaluation would be helpful. We considered that the treatment was efficient if MMSE score did not decrease aft...
The dramatic effects of Galantamine in a patient with early-onset Alzheimer's disease
Psychiatria Danubina, 2010
We discuss the case of a 51 year old former mid-wife presented to the NHS Luton and Bedfordshire psychiatric services with a 2 year history of increasing forgetfulness with significant impairment to her daily function. She was diagnosed with non-familial early-onset Alzheimer's Disease (EOAD) and started on 8mg daily of the acetylcholinesterase inhibitor Galantamine. The information for this study was gathered from patient notes, consultant, collateral and personal accounts. Periodic outpatient consultations at the NHS Luton and Bedfordshire psychiatric services were used to monitor Mrs LF's global, functional and behavioral progress. These were supplemented with the mini mental state examination (MMSE) at each outpatient appointment. The graph of MMSE scores illustrates severe decline in scores, followed eventually by increase in score to sustained improvement while continuing on galantamine. Functionally, this lady has successfully negotiated a divorce, moved into her own ...
Dose and plasma concentration of galantamine in Alzheimer's disease - clinical application
Alzheimer's Research & Therapy, 2013
Introduction: Patients with Alzheimer's disease (AD) are currently treated with cholinesterase inhibitors, such as galantamine, without actual knowledge of its concentration in plasma. Our objective was to analyse potential relationships between galantamine concentration, galantamine dose, socio-demographic characteristics, body weight, body mass index (BMI), and treatment response.
Medical Journal of Indonesia, 2007
Penelitian ini bertujuan menilai efektivitas dan keamanan Acetylcholinesterase Inhibitor Galantamine pada penderita Alzheimer dan Alzheimer's Disease (AD) yang disertai dengan penyakit serebrovaskular (AD+CVD atau Mixed Dementia). Galantamine diberikan selama 6 bulan pada 28 penderita AD dan AD + CVD. Evaluasi kognitif dilakukan dengan menggunakan Mini Mental State Examination (MMSE), Restricted Reminding (RR), Neuropsycholgy Assessment, evaluasi fungsi global dengan Clinical Dementia Rating (CDR), evaluasi perubahan perilaku dengan Neuropsychiatric Inventory (NPI). Hasil penelitian pada 28 penderita AD dan AD + CVD, Galantamine memberikan perbaikan fungsi kognitif yang bermakna secara klinis maupun statistik setelah terapi 6 bulan dibandingkan data dasar awal (skor MMSE p<0.05, skor RR p<0.05, NA p<0.05), perbaikan fungsi global (CDR p<0.05) dan perbaikan gejala perilaku (NPI p<0.05). Efek samping ringan (32%) mual-mual dan anokresia terjadi saat titrasi dosis obat dan dapat diatasi dengan domperidone. Disimpulkan bahwa Galantamine efektif memberikan perbaikan fungsi kognitif, fungsi global, gejala perilaku dan aman serta dapat ditoleransi dengan baik.
International Journal of Clinical Practice, 2006
The objective is to evaluate the efficacy of galantamine when a slow titration regimen is employed in Thai Alzheimer's disease (AD) patients with or without cerebrovascular disease and vascular dementia (VaD).A 6-month, multicentre, open-label, uncontrolled trial was undertaken in 75 AD patients. Eligible patients received an initial galantamine dose of 8 mg/day and escalated over 5–8 weeks to maintenance doses of 16 or 24 mg/day. Primary efficacy measures were AD Assessment Scale-cognitive subscale (ADAS-cog) and the Clinician's Interview-Based Impression of Change-Plus version (CIBIC-plus). The Behavioural Pathology in AD Rating Scale (BEHAVE AD), the AD Cooperative Study Activities of Daily Living Inventory and Pittsburgh Sleep Quality Index were the secondary efficacy variables. Analyses were based on the intent-to-treat population.Treatment with galantamine showed significant improvement in cognition on the ADAS-cog and CIBIC-plus at month 6. Galantamine showed favourable effects on activities of daily living. Behavioural symptoms and sleep quality were also significantly improved (p < 0.05). Galantamine was well tolerated. The adverse events were mild-to-moderate intensity. The most frequent adverse events commonly reported were nausea (16.4%), dizziness (9.6%) and vomiting (6.8%).The results of this study may be consistent with galantamine being an effective and safe treatment for mild-to-moderate AD patients with or without cerebrovascular disease and VaD. Flexible dose escalation of galantamine was well tolerated. The daily maintenance dose of galantamine was 16 mg/day, followed by a back up dose of 24 mg/day.
The Lancet Neurology, 2009
Background The effi cacy of galantamine has been shown in patients with mild, moderate, and advanced moderate Alzheimer's disease (AD). Here we report its effi cacy in patients with severe AD. Methods Between December, 2003, and March, 2007, patients aged 84 (SD 6) years with severe AD (mini-mental state examination [MMSE] score 5-12 points), in a nursing home setting were randomly assigned to receive galantamine (n=207), titrated initially to 24 mg/day, or placebo (n=200). Co-primary effi cacy measures for cognitive function and ability to undertake normal daily activities were the severe impairment battery (SIB) and the seven-item minimum data set-activities of daily living (MDS-ADL), respectively. Adverse events, vital signs, laboratory parameters, and electrocardiograms were monitored. This trial is registered with ClinicalTrials.gov, number NCT00216593. Findings 168 of 207 (81%) patients in the galantamine group and 161 of 200 (81%) in the placebo group completed the study. Mean SIB scores increased (improved) by 1•9 (95% CI-0•1 to 3•9) points with galantamine and decreased (worsened) by 3•0 (-5•6 to-0•5) points with placebo (between-group least squares mean diff erence 4•36, 1•3 to 7•5; p=0•006). Mean MDS-ADL self-performance score worsened by 1•2 (0•6 to 1•8) points and 1•6 (0•8 to 2•3) points, respectively (between-group least squares mean diff erence-0•41,-1•3 to 0•5; p=0•383). Nominally signifi cant between-group diff erences in favour of galantamine occurred for the SIB domains of memory (p=0•006), praxis (p=0•010), and visuospatial ability (p=0.002), and for the MDS-ADL subitem locomotion on unit (p=0•021). 183 of 207 patients (88%) who received galantamine and 177 of 200 (89%) who received placebo had adverse events, which were mostly mild to moderate. Eight patients (4%) in the galantamine group and 21 patients (11%) in the placebo group died. ECG abnormalities were similar between the two groups. Interpretation Galantamine can be started and used safely in elderly patients with severe AD. Galantamine improved cognitive function but failed to signifi cantly improve the co-primary parameter of overall activities of daily living. Funding Janssen-Cilag EMEA.
Neuropsychiatric disease and treatment, 2017
Long-term maintenance of cognitive function is an important goal of treatment for Alzheimer's disease (AD), but evidence about the long-term efficacy of cholinesterase inhibitors is sparse. To evaluate the long-term efficacy and safety of galantamine for AD in routine clinical practice, we conducted a 72-week post-marketing surveillance study. The effect of galantamine on cognitive function was estimated in comparison with a simulated disease trajectory. Patients with mild-to-moderate AD received flexible dosing of galantamine (16-24 mg/day) during this study. Cognitive function was assessed by the mini mental state examination (MMSE) and the clinical status was determined by the Clinical Global Impression-Improvement (CGI-I). Changes of the MMSE score without treatment were estimated in each patient using Mendiondo's model. Generalized linear mixed model analysis was performed to compare the simulated MMSE scores with the actual scores. Of the 661 patients who were enrolled...