- Email: [email protected]
P1-409 The risk of dementia in sertraline treated elderly patients with depression and cognitive impairment
Poster Session P l: Therapeutics and Therapeutic Strategies- Therapeutic Strategies, Behavioral Symptoms CD45RB may be beneficial for mitigating microgliosis associated with neurodegenerafive diseases.
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THE RISK OF DEMENTIA IN SERTRALINE TREATED ELDERLY PATIENTS WITH DEPRESSION AND COGNITIVE IMPAIRMENT
Gregory H. Peltou .1 , D.P. Devanand 1, Maggie Padilla 1, Nicole Juszczak 2 , Cheng-Sheng Chen 2, Karen Marder 3, Steven E Roose 1, Harold A. Sackeim 1, Yaakov Stern 4. tColumbia U. and New York State
Psychiatric Inst., New York, NY,, USA; 2New York State Psychiatric Inst., New York, NY,, USA; 3Columbia U. and Sergievsky Center, New York, NY, USA; 4Columbia U., New York State Psychiatric Inst., and Sergievsky Center, New York, NY,, USA. Contact e-mail: [email protected] Background: Epidemiological studies suggest depression increases? the risk of future dementia in the elderly cognitively impaired subject without dementia (DEP-CI). Objective(s): Determine whether effective antidepressant treatment alters cognitive performance in these subjects, and whether persistent depression or cognitive deficits predicts future dementia. Methods:39 elderly DEP-CI patients from a memory disorders center and a late-life depression clinic received a comprehensive medical, psychiatric and neuropsychological evaluation before and immediately after open-label treatment with sertraline up to 200 mg/day for 12 weeks. Follow-up evaluation was conducted 12-months later. Results: Of the 39 patients starting the study, 13 dropped during the acute trial, 2 diagnosed with dementia during the trial, and 2 refused follow-up. In the remaining 22 patients followed for an average of 12 months, 12 converted to dementia (54% all probable AD). There was no significant difference in age (mean 71.7 410.8 years old), education (12.6 4- 4.9 years), or 30-item Folstein MMSE (26.5 4- 2.8) between patients followed and dropouts. Among the patients followed, independent samples t-tests revealed no significant difference in age, education, or gender. Similarly, diagnostic subtype of depression (major depression or dysthymia) and antidepressant treatment response rate were not different between groups. No neuropsychological measure at baseline or at end of the acute trial predicted future dementia. In ROC analyses, we determined the optimal antidepressant response to discriminate between future converters and non-converters. We found that a >60% decrease in 24-item HAMD (mean HAMD after treatment < 7) significantly reduced the risk of developing dementia in the next 12 months (p = 0.021). In backward stepwise logistic regression, controlling for age and family history of depression, lower total HAMD scores significantly predicted a reduced risk of future dementia. Conclusions: Elderly DEP-CI patients are at a significantly increased risk of progressing to dementia, irrespective of severity or type of baseline depression, change in cognitive performance after treatment, or antidepressant response, using conventional criteria. However, if a patient with DEP-CI can achieve a >60% reduction of depressed mood symptoms (or absolute HAMD < 6) after sertraline treatment, these data suggest there may be a delay in the diagnosis of dementia, by 12 months of follow-up.
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SAFETY, PHARMACOKINETICS (PK), AND PHARMACODYNAMICS (PD) OF ASCENDING MULTIPLE DOSES OF SRA-333 IN HEALTHY SUBJECTS
Sangeeta V. Raje* l, Anna Plotka I , Virginia Parks 2, Alain Patat 2, Didier Chassard 3. t Wyeth Research, Collegeville, PA, USA; 2Wyeth
Research, Paris, France; 3Aster, Paris, France. Contact e-mail: [email protected] Background: SRA-333 is a new potent and silent 5HTIA antagonist that increases glutamatergic and cholinergic neurotransmission during cognitive processes. SRA-333 is proposed for the treatment of cognitive deficits associated with Alzheimer's disease. Objectives: This was a randomized, doubleblind, placebo-controlled, sequential-, ascending-, multiple-dose study in 41 young adults and 8 elderly subjects to assess the safety, tolerability, PI<, and PD of SRA-333. Methods: Doses of 0.1, 0.25, 0.5, 1, and 5 mg every 12 hours (ql2h) (young) and 0.5 mg ql2h (elderly) were administered for 14
$215
days in cohorts of 8 subjects (6 active and 2 placebo). Assessments consisted of safety evaluations (vital signs, ECG, and laboratory test results) up to 48 hours after the last dose range of 0.1 to 5 rag. A complete PK profile was performed on days 1 and 14. Cognitive assessment was performed using the Cognitive Drug Research battery (Reading, UK), which explored attention, sensori-motor tasks, and working and episodic memory. Results: SRA-333 was safe and well tolerated up to a daily dose of 10 mg for 14 days. No consistent, severe, or dose-related adverse events were observed. No clinically significant changes were recorded in vital signs, ECGs, or routine laboratory tests. No clinically relevant cognitive impairment was observed. SRA-333 was rapidly absorbed (tmax --~ lh) and eliminated (half-life _~ 6h). Plasma concentrations exhibited approximately linear dose-proportionality over the dose range studied. Mean steady state AUC 0-~2hwas within 20% of the single-dose AUC 0 - 0o indicating linear drug accumulation with repeated administration. Steady-state Cmax and AUC were moderately higher (48% and 42%, respectively) in the elderly subjectsin comparison to the young subjects. No gender related PK differences were observed. Conclusions: In summary, SRA-333 was safe and well-tolerated up to a daily dose of 10 mg for 14 days. Its pharmacokinetic profile allowed a twice-daily dosing regimen.
P•P•-411•
CURRENT DEMENTIA KNOWLEDGE AND PRACTICES REPORTED BY PRIMARY CARE PHYSICIANS
Richard Fortinsky*, Ianita Zlateva, Chaewon Song. University of
Connecticut Health Center, Farmington, CT, USA. Contact e-mail: fortinsky@ nsol. uchc.edu Background: Primary care physicians today face: diagnosing increasing numbers of patients with memory loss; growing options for treating dementia symptoms with medications; and growing demands to link dementia patients and their family caregivers with community services. Timely information on physicians' dementia care expertise and limitations will help optimize primary care for patients and families. Objective: Summarize primary care physicians' reported dementia care practices in terms of diagnosis, medication treatment, and community service referrals. Methods: Six hundred licensed primary care physicians in Connecticut, USA were randomly selected to receive mailed self-administered questionnaires. A total of 309 survey forms were returned (52% response rate); of these, 175 physicians had active ambulatory care practices at the time of the survey (study sample). Questionnaires were completed between May and October 2003. Results: More than one-third of study sample members were women (35%), mean age = 47 (+ 10 years), 60% were general internists, and 30% were family physicians. Diagnosis results: 68% referred to another physician for diagnostic help only in difficult cases, most often either a neurologist or geriatrician. Most reported that it was very important (64%) or somewhat important (31%) to make a diagnosis early in the course of memory loss. Medication treatment results: 90% prescribed donepezil in the previous year for dementia patients living home, 50% prescribed rivastigmine, 35% prescribed gaiantamine, and 34% prescribed vitamin E. Cholinesterase inhibitors were prescribed based on: scientific evidence of efficacy (61%), favorable side effect profile (54%), dosage interval (41%), and because a sample was available (33%). Community service referral results: In the previous year, physicians were most likely to refer patients and family caregivers to home health agencies (86%), adult day care programs (85%), assisted living facilities (69%), and nursing homes (62%); only 29% referred to the local Alzheimer's Association (29%) or a family support group (28%). Only 15% reported being "very confident" about advice they provide about community services. Conclusions: Primary care physicians have made progress in dementia diagnosis practices, very frequently prescribe cholinesterase inhibitors for clinically sound reasons, but continue to report limitations linking dementia patients and family caregivers with community resources.
~
THE RISK OF DEMENTIA IN SERTRALINE TREATED ELDERLY PATIENTS WITH DEPRESSION AND COGNITIVE IMPAIRMENT
Gregory H. Peltou .1 , D.P. Devanand 1, Maggie Padilla 1, Nicole Juszczak 2 , Cheng-Sheng Chen 2, Karen Marder 3, Steven E Roose 1, Harold A. Sackeim 1, Yaakov Stern 4. tColumbia U. and New York State
Psychiatric Inst., New York, NY,, USA; 2New York State Psychiatric Inst., New York, NY,, USA; 3Columbia U. and Sergievsky Center, New York, NY, USA; 4Columbia U., New York State Psychiatric Inst., and Sergievsky Center, New York, NY,, USA. Contact e-mail: [email protected] Background: Epidemiological studies suggest depression increases? the risk of future dementia in the elderly cognitively impaired subject without dementia (DEP-CI). Objective(s): Determine whether effective antidepressant treatment alters cognitive performance in these subjects, and whether persistent depression or cognitive deficits predicts future dementia. Methods:39 elderly DEP-CI patients from a memory disorders center and a late-life depression clinic received a comprehensive medical, psychiatric and neuropsychological evaluation before and immediately after open-label treatment with sertraline up to 200 mg/day for 12 weeks. Follow-up evaluation was conducted 12-months later. Results: Of the 39 patients starting the study, 13 dropped during the acute trial, 2 diagnosed with dementia during the trial, and 2 refused follow-up. In the remaining 22 patients followed for an average of 12 months, 12 converted to dementia (54% all probable AD). There was no significant difference in age (mean 71.7 410.8 years old), education (12.6 4- 4.9 years), or 30-item Folstein MMSE (26.5 4- 2.8) between patients followed and dropouts. Among the patients followed, independent samples t-tests revealed no significant difference in age, education, or gender. Similarly, diagnostic subtype of depression (major depression or dysthymia) and antidepressant treatment response rate were not different between groups. No neuropsychological measure at baseline or at end of the acute trial predicted future dementia. In ROC analyses, we determined the optimal antidepressant response to discriminate between future converters and non-converters. We found that a >60% decrease in 24-item HAMD (mean HAMD after treatment < 7) significantly reduced the risk of developing dementia in the next 12 months (p = 0.021). In backward stepwise logistic regression, controlling for age and family history of depression, lower total HAMD scores significantly predicted a reduced risk of future dementia. Conclusions: Elderly DEP-CI patients are at a significantly increased risk of progressing to dementia, irrespective of severity or type of baseline depression, change in cognitive performance after treatment, or antidepressant response, using conventional criteria. However, if a patient with DEP-CI can achieve a >60% reduction of depressed mood symptoms (or absolute HAMD < 6) after sertraline treatment, these data suggest there may be a delay in the diagnosis of dementia, by 12 months of follow-up.
•
SAFETY, PHARMACOKINETICS (PK), AND PHARMACODYNAMICS (PD) OF ASCENDING MULTIPLE DOSES OF SRA-333 IN HEALTHY SUBJECTS
Sangeeta V. Raje* l, Anna Plotka I , Virginia Parks 2, Alain Patat 2, Didier Chassard 3. t Wyeth Research, Collegeville, PA, USA; 2Wyeth
Research, Paris, France; 3Aster, Paris, France. Contact e-mail: [email protected] Background: SRA-333 is a new potent and silent 5HTIA antagonist that increases glutamatergic and cholinergic neurotransmission during cognitive processes. SRA-333 is proposed for the treatment of cognitive deficits associated with Alzheimer's disease. Objectives: This was a randomized, doubleblind, placebo-controlled, sequential-, ascending-, multiple-dose study in 41 young adults and 8 elderly subjects to assess the safety, tolerability, PI<, and PD of SRA-333. Methods: Doses of 0.1, 0.25, 0.5, 1, and 5 mg every 12 hours (ql2h) (young) and 0.5 mg ql2h (elderly) were administered for 14
$215
days in cohorts of 8 subjects (6 active and 2 placebo). Assessments consisted of safety evaluations (vital signs, ECG, and laboratory test results) up to 48 hours after the last dose range of 0.1 to 5 rag. A complete PK profile was performed on days 1 and 14. Cognitive assessment was performed using the Cognitive Drug Research battery (Reading, UK), which explored attention, sensori-motor tasks, and working and episodic memory. Results: SRA-333 was safe and well tolerated up to a daily dose of 10 mg for 14 days. No consistent, severe, or dose-related adverse events were observed. No clinically significant changes were recorded in vital signs, ECGs, or routine laboratory tests. No clinically relevant cognitive impairment was observed. SRA-333 was rapidly absorbed (tmax --~ lh) and eliminated (half-life _~ 6h). Plasma concentrations exhibited approximately linear dose-proportionality over the dose range studied. Mean steady state AUC 0-~2hwas within 20% of the single-dose AUC 0 - 0o indicating linear drug accumulation with repeated administration. Steady-state Cmax and AUC were moderately higher (48% and 42%, respectively) in the elderly subjectsin comparison to the young subjects. No gender related PK differences were observed. Conclusions: In summary, SRA-333 was safe and well-tolerated up to a daily dose of 10 mg for 14 days. Its pharmacokinetic profile allowed a twice-daily dosing regimen.
P•P•-411•
CURRENT DEMENTIA KNOWLEDGE AND PRACTICES REPORTED BY PRIMARY CARE PHYSICIANS
Richard Fortinsky*, Ianita Zlateva, Chaewon Song. University of
Connecticut Health Center, Farmington, CT, USA. Contact e-mail: fortinsky@ nsol. uchc.edu Background: Primary care physicians today face: diagnosing increasing numbers of patients with memory loss; growing options for treating dementia symptoms with medications; and growing demands to link dementia patients and their family caregivers with community services. Timely information on physicians' dementia care expertise and limitations will help optimize primary care for patients and families. Objective: Summarize primary care physicians' reported dementia care practices in terms of diagnosis, medication treatment, and community service referrals. Methods: Six hundred licensed primary care physicians in Connecticut, USA were randomly selected to receive mailed self-administered questionnaires. A total of 309 survey forms were returned (52% response rate); of these, 175 physicians had active ambulatory care practices at the time of the survey (study sample). Questionnaires were completed between May and October 2003. Results: More than one-third of study sample members were women (35%), mean age = 47 (+ 10 years), 60% were general internists, and 30% were family physicians. Diagnosis results: 68% referred to another physician for diagnostic help only in difficult cases, most often either a neurologist or geriatrician. Most reported that it was very important (64%) or somewhat important (31%) to make a diagnosis early in the course of memory loss. Medication treatment results: 90% prescribed donepezil in the previous year for dementia patients living home, 50% prescribed rivastigmine, 35% prescribed gaiantamine, and 34% prescribed vitamin E. Cholinesterase inhibitors were prescribed based on: scientific evidence of efficacy (61%), favorable side effect profile (54%), dosage interval (41%), and because a sample was available (33%). Community service referral results: In the previous year, physicians were most likely to refer patients and family caregivers to home health agencies (86%), adult day care programs (85%), assisted living facilities (69%), and nursing homes (62%); only 29% referred to the local Alzheimer's Association (29%) or a family support group (28%). Only 15% reported being "very confident" about advice they provide about community services. Conclusions: Primary care physicians have made progress in dementia diagnosis practices, very frequently prescribe cholinesterase inhibitors for clinically sound reasons, but continue to report limitations linking dementia patients and family caregivers with community resources.