- Email: [email protected]
P1-430 Drug utilisation review of cholinesterase inhibitors (CHEI) in the province of Quebec, Canada
Poster Session P l: Therapeutics and Therapeutic Strategies- Therapeutic Strategies, Behavioral Symptoms years. Controls were matched for age, gender, diagnosis, dementia severity, living arrangement and medication. The interventions were conducted once per week for 1 hour run by a clinical psychogeriatric team. Outcome measures were patients' cognitive and functional status as welt as BPSD and caregivers' subjective burden and depression measured by validated scales. Data were obtained 6, 12 mad 24 months after baseline. Results: There were no significant differences between the intervention and control group neither after 6, 12 nor after 24 months treatment. Conclusions: The lack of a positive impact in alleviating caregiver burden or BPSD after intensive psychological interventions may result from extensive care in the routine clinical management including individual counselling for patients and families. The effect of "treatment as usual" needs to be taken into account when comparing an intervention and control group, as well as the dosage of the intervention.
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PATTERNS OF NEUROPSYCHIATRIC SYMPTOMS IN ALZHEIMER'S DEMENTIA, MIXED DEMENTIA, AND VASCULAR DEMENTIA
Sohel S achak *1 , Howard Feldman ~, Young Zhu 1, Joan Amatniek 1, Atul Mahableshwarkar I . 1Janssen Pharmaceutica, Titusville, NJ, USA;
2Vancouver Hospital and Health Sciences Center, Vancouver, BC, Canada. Contact e-mail: [email protected], com
Background: Both risk factors and clinical features of Alzheimer's disease (AD), AD+ Vascular Dementia (VaD), and VaD, overlap. Behavioral and neuropsychological symptoms are common in both. The longitudinal elucidation of similarity and difference is still required. However it may be that these disorders are different in respect to the patterns of neuropsychiatric symptoms. Gaining this insight may allow for more effective treatment of each condition. Objective: To compare the neuropsychiatric symptom patterns presented in AD, mixed (AD+VaD), and VaD. Methods: An analysis of AD (N = 978), mixed (N = 184), and VaD (N = 155), subjects at baseline from two randomized, placebo-controlled trials was conducted. Patients with a baseline MMSE of 10-22 were included. The 10 items of the neuropsychiatric inventory mean scores were analyzed. Analysis of variance was used to compare NPI item mean scores between the three groups. Percentage of baseline NPI item scores > 0 was compared using Chi-square test. Factor analysis was conducted to see where the similarities and differences in patterns between these groups lie. Results: Mean ages were 78.86 4- 7.62 (AD), 77.01 4- 6.62 (Mixed), and 74.41 3z 7.24 (VaD). There was a greater percentage of females in the AD population (63.91) mixed (55.43) or VaD (44.52) Mean NPI scores at baseline were 11.91 ± 12.68, 11.43 4I1.63, and 13.07 -4- 13,02 for the AD, mixed, and VaD groups respectively. Patients with AD showed significantly more aberrant motor behavior and less irritability while VaD patients had significantly more apathy and elation, and fewer delusions. Other NPI items are similar between groups. In most cases, the mixed group had mean item scores between the other two groups. Percent of NPI item scores > 0 between groups were similar. Conclusions: Important similarities and differences in neuropsychiatric symptoms are seen between AD, VaD and mixed patients. Future studies will investigate whether there is a differential in responsiveness to neuropsychiatric symptoms within groups treated with galantamine.
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FOUR-WEEKLY DOSE ESCALATION PROVIDES IMPROVED GASTROINTESTINAL TOLERABILITY WITH RIVASTIGMINE TREATMENT
Fraser Inglis*. Glasgow Memory Clinic, Clydebank, United Kingdom.
Contact e-mail: info @memoryclinic.com
Background: The cholinesterase inhibitors are known to be associated with cholinergic events that mainly affect the gastrointestinal (GI) system and occur mostly during the dose titration phase of treatment. Slower dose escalation schedules can significantly reduce the incidence of nausea and vomiting associated with rivastigmine. Objective(s): To determine the effects of a 4-weekly dose escalation on the GI tolerability of rivastigmine. Methods: Data from three recent studies using 4-weekly rivastigmine dose
$221
escalation schedules were reviewed: a double-blind, placebo-controlled study of fivastigmine 3-12 mg/day in moderate to severe Alzheimer's disease (AD) (n = 218) [1]; a 26-week, open-label study of rivastigmine 3-12 rag/day in mixed dementia (n = 80) [2]; and a 22-month, open-label study comparing rivastigmine 3-6 mg/day and aspirin 100 rag/day in vascular dementia (VaD) (n = 16) [3]. No formal meta-analyses were possible due to the different trial designs and patient populations. However, rates of nausea and vomiting were tabulated and compared with those reported in published regulatory studies using rapid dose titration schedules [4,5]. Results: Rates of nausea and vomiting in rivastigmine-treated patients in the moderate to severe AD study were 26% and 21%, respectively. In the mixed dementia study, rates of nausea and vomiting were 29% and 14%, respectively. All patients completed the VaD study and there were no reports of vomiting; five patients reported nausea but all cases were mild and resolved spontaneously within 1-2 weeks. These findings compare favorably with regulatory studies involving rapid titration, in which rates of nausea and vomiting were 50-54% and 33-34%, respectively. Conclusions: Rivastigmine was well tolerated using a 4-weekly dose escalation schedule. Besides administering rivastigmine with a full meal, the GI tolerability of this potent agent may be further improved by using a minimum 4-weekly dose escalation schedule. References: [1] Blesa et al. Presented at the ADPD congress, Spain, 2003. [21 Rosler et al. Presented at the ACNP congress, Puerto Rico, 2002. [3] Moretti et al. J Neurol Sci 2002; 203-2-4:141-6. [4] Corey-Bloom et al. Int J Geriatr Psychopharmacol 1998; 1:55-63. [5] Rosler et al. BMJ 1999; 318:633-40.
~ D R U G UTILISATION REVIEW OF CHOLINESTERASE INHIB1TORS (CHEI) IN THE PROVINCE OF QUEBEC, CANADA Fadi Massoud* 1, Marc Dorais 1, Claudie Charbonneau 2, Brnrdicte Lescrauwaet 2, Jean-Marc Boucher 1, Jacques LeLorier 1. ~Centre
Hospimlier de l'Universitd de Montrdal (CHUM), Montreal, PQ, Canada; 2Pfizer Canada, Montreal, PQ, Canada. Contact e-mail: [email protected]
Background: three ChE1 are available for the treatment of Alzheimer's disease: donepezil, rivastigmine, and galantarnine. Objective(s): to examine the variables associated with ChEI dispensation and persistence on therapy. Methods: we reviewed the utilization of ChEI in the Rrgie de l'Assurance Maladie du Qurbec (RAMQ) database which includes most individuals over 65 in the province of Quebec. This database contains demographic variables, detailed information on &rugs prescribed and medical services dispensed. The recruitment period includes all subjects receiving at least one dispensation of ChEI between January 1st 2000 and June 30 th 2003. The index date corresponds to the first dispensation of ChEI during the recruitment period. We used descriptive statistics, Kaplan-Meier curves, and Cox Regression analyses. Results: 18,748 patients were included. Mean age was 79.2 (standard deviation (SD)=6.8), and 68% were women. The index drug was donepezil in 81% of patients, rivastigmine in 11% and galantamine in 8%. Mean Cin'onic Disease Scure (CDS) was 0.7 (SD = 1.4). Mean number of total drug dispensations in the year prior to the index date was 64 (SD = 88). For the same period, the mean number of hospitalizations was 0.8 (SD = 1.6) and the mean number of days of hospitalization was 2.5 (SD = 6.2). At the index date, 74% of the prescriptions were made by a general practitioner (GP), 15% by a neurologist, 5% by a geriatrician, and l% by a psychiatrist. Fifty percent of patients were still taking their index medication 216 days after initiation. Strong risk factors for discontinuing therapy were increasing age (being >_ 90 yielded a rate ratio (RR) of 1,47, 95% confidence interval (CI) (1.24-1.75)), taking less medications (having < 20 prescribed dispensations in the previous year yielded a RR of 1.29 95%CI(1.17-1.42)). Mild risk factors for discontinuing therapy were index prescription by a GP rather than a specialist (RR 1.10 95%CI (1.01-1.18)), and being prescribed donepezil rather than galantamine (RR 1.13 95%CI (1.03-1.23)). Conclusions: most individuals being prescribed ChEI are receiving donepezil. They are in general good health and use relatively little medical resources. These medications are well tolerated, and fifty percent of patients were still taking their index medication 216 days after initiation.
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PATTERNS OF NEUROPSYCHIATRIC SYMPTOMS IN ALZHEIMER'S DEMENTIA, MIXED DEMENTIA, AND VASCULAR DEMENTIA
Sohel S achak *1 , Howard Feldman ~, Young Zhu 1, Joan Amatniek 1, Atul Mahableshwarkar I . 1Janssen Pharmaceutica, Titusville, NJ, USA;
2Vancouver Hospital and Health Sciences Center, Vancouver, BC, Canada. Contact e-mail: [email protected], com
Background: Both risk factors and clinical features of Alzheimer's disease (AD), AD+ Vascular Dementia (VaD), and VaD, overlap. Behavioral and neuropsychological symptoms are common in both. The longitudinal elucidation of similarity and difference is still required. However it may be that these disorders are different in respect to the patterns of neuropsychiatric symptoms. Gaining this insight may allow for more effective treatment of each condition. Objective: To compare the neuropsychiatric symptom patterns presented in AD, mixed (AD+VaD), and VaD. Methods: An analysis of AD (N = 978), mixed (N = 184), and VaD (N = 155), subjects at baseline from two randomized, placebo-controlled trials was conducted. Patients with a baseline MMSE of 10-22 were included. The 10 items of the neuropsychiatric inventory mean scores were analyzed. Analysis of variance was used to compare NPI item mean scores between the three groups. Percentage of baseline NPI item scores > 0 was compared using Chi-square test. Factor analysis was conducted to see where the similarities and differences in patterns between these groups lie. Results: Mean ages were 78.86 4- 7.62 (AD), 77.01 4- 6.62 (Mixed), and 74.41 3z 7.24 (VaD). There was a greater percentage of females in the AD population (63.91) mixed (55.43) or VaD (44.52) Mean NPI scores at baseline were 11.91 ± 12.68, 11.43 4I1.63, and 13.07 -4- 13,02 for the AD, mixed, and VaD groups respectively. Patients with AD showed significantly more aberrant motor behavior and less irritability while VaD patients had significantly more apathy and elation, and fewer delusions. Other NPI items are similar between groups. In most cases, the mixed group had mean item scores between the other two groups. Percent of NPI item scores > 0 between groups were similar. Conclusions: Important similarities and differences in neuropsychiatric symptoms are seen between AD, VaD and mixed patients. Future studies will investigate whether there is a differential in responsiveness to neuropsychiatric symptoms within groups treated with galantamine.
•
FOUR-WEEKLY DOSE ESCALATION PROVIDES IMPROVED GASTROINTESTINAL TOLERABILITY WITH RIVASTIGMINE TREATMENT
Fraser Inglis*. Glasgow Memory Clinic, Clydebank, United Kingdom.
Contact e-mail: info @memoryclinic.com
Background: The cholinesterase inhibitors are known to be associated with cholinergic events that mainly affect the gastrointestinal (GI) system and occur mostly during the dose titration phase of treatment. Slower dose escalation schedules can significantly reduce the incidence of nausea and vomiting associated with rivastigmine. Objective(s): To determine the effects of a 4-weekly dose escalation on the GI tolerability of rivastigmine. Methods: Data from three recent studies using 4-weekly rivastigmine dose
$221
escalation schedules were reviewed: a double-blind, placebo-controlled study of fivastigmine 3-12 mg/day in moderate to severe Alzheimer's disease (AD) (n = 218) [1]; a 26-week, open-label study of rivastigmine 3-12 rag/day in mixed dementia (n = 80) [2]; and a 22-month, open-label study comparing rivastigmine 3-6 mg/day and aspirin 100 rag/day in vascular dementia (VaD) (n = 16) [3]. No formal meta-analyses were possible due to the different trial designs and patient populations. However, rates of nausea and vomiting were tabulated and compared with those reported in published regulatory studies using rapid dose titration schedules [4,5]. Results: Rates of nausea and vomiting in rivastigmine-treated patients in the moderate to severe AD study were 26% and 21%, respectively. In the mixed dementia study, rates of nausea and vomiting were 29% and 14%, respectively. All patients completed the VaD study and there were no reports of vomiting; five patients reported nausea but all cases were mild and resolved spontaneously within 1-2 weeks. These findings compare favorably with regulatory studies involving rapid titration, in which rates of nausea and vomiting were 50-54% and 33-34%, respectively. Conclusions: Rivastigmine was well tolerated using a 4-weekly dose escalation schedule. Besides administering rivastigmine with a full meal, the GI tolerability of this potent agent may be further improved by using a minimum 4-weekly dose escalation schedule. References: [1] Blesa et al. Presented at the ADPD congress, Spain, 2003. [21 Rosler et al. Presented at the ACNP congress, Puerto Rico, 2002. [3] Moretti et al. J Neurol Sci 2002; 203-2-4:141-6. [4] Corey-Bloom et al. Int J Geriatr Psychopharmacol 1998; 1:55-63. [5] Rosler et al. BMJ 1999; 318:633-40.
~ D R U G UTILISATION REVIEW OF CHOLINESTERASE INHIB1TORS (CHEI) IN THE PROVINCE OF QUEBEC, CANADA Fadi Massoud* 1, Marc Dorais 1, Claudie Charbonneau 2, Brnrdicte Lescrauwaet 2, Jean-Marc Boucher 1, Jacques LeLorier 1. ~Centre
Hospimlier de l'Universitd de Montrdal (CHUM), Montreal, PQ, Canada; 2Pfizer Canada, Montreal, PQ, Canada. Contact e-mail: [email protected]
Background: three ChE1 are available for the treatment of Alzheimer's disease: donepezil, rivastigmine, and galantarnine. Objective(s): to examine the variables associated with ChEI dispensation and persistence on therapy. Methods: we reviewed the utilization of ChEI in the Rrgie de l'Assurance Maladie du Qurbec (RAMQ) database which includes most individuals over 65 in the province of Quebec. This database contains demographic variables, detailed information on &rugs prescribed and medical services dispensed. The recruitment period includes all subjects receiving at least one dispensation of ChEI between January 1st 2000 and June 30 th 2003. The index date corresponds to the first dispensation of ChEI during the recruitment period. We used descriptive statistics, Kaplan-Meier curves, and Cox Regression analyses. Results: 18,748 patients were included. Mean age was 79.2 (standard deviation (SD)=6.8), and 68% were women. The index drug was donepezil in 81% of patients, rivastigmine in 11% and galantamine in 8%. Mean Cin'onic Disease Scure (CDS) was 0.7 (SD = 1.4). Mean number of total drug dispensations in the year prior to the index date was 64 (SD = 88). For the same period, the mean number of hospitalizations was 0.8 (SD = 1.6) and the mean number of days of hospitalization was 2.5 (SD = 6.2). At the index date, 74% of the prescriptions were made by a general practitioner (GP), 15% by a neurologist, 5% by a geriatrician, and l% by a psychiatrist. Fifty percent of patients were still taking their index medication 216 days after initiation. Strong risk factors for discontinuing therapy were increasing age (being >_ 90 yielded a rate ratio (RR) of 1,47, 95% confidence interval (CI) (1.24-1.75)), taking less medications (having < 20 prescribed dispensations in the previous year yielded a RR of 1.29 95%CI(1.17-1.42)). Mild risk factors for discontinuing therapy were index prescription by a GP rather than a specialist (RR 1.10 95%CI (1.01-1.18)), and being prescribed donepezil rather than galantamine (RR 1.13 95%CI (1.03-1.23)). Conclusions: most individuals being prescribed ChEI are receiving donepezil. They are in general good health and use relatively little medical resources. These medications are well tolerated, and fifty percent of patients were still taking their index medication 216 days after initiation.