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Sudeep S Gill - One of the best experts on this subject based on the ideXlab platform.
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antidepressants for agitation and psychosis in dementia
Cochrane Database of Systematic Reviews, 2011Co-Authors: Dallas Seitz, Sudeep S Gill, Nathan Herrmann, Nikesh Adunuri, Andrea Gruneir, Paula A RochonAbstract:Background Agitation and psychosis are common among older adults with dementia and are challenging to manage. At the present time, little is known about the efficacy and safety of antidepressant medications when used to treat these symptoms. Objectives To assess the safety and efficacy of antidepressants in treating psychosis and agitation in older adults with Alzheimer's disease, vascular, or mixed dementia. Search methods We searched the Cochrane Dementia and Cognitive Improvement Group’s Specialized Register which included Cochrane Central Register of Controlled Trials (The Cochrane Library 2009, Issue 3), MEDLINE (January 1950 to October 2009), EMBASE (1980 - October 2009), CINAHL (all dates - October 2009) and PsycINFO (1806 to October 2009). Selection criteria Randomized, controlled trials of antidepressants (selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, trazodone, and other antidepressants), compared to either placebo or comparator medications (Typical or aTypical Antipsychotics, anticonvulsants, benzodiazepines, cholinesterase inhibitors, memantine or other medications) for treatment of agitation or psychosis in older adults with dementia. Data collection and analysis Two authors independently assessed trial quality and extracted trial data. We collected information on efficacy as measured by dementia neuropsychiatric symptom rating scales and adverse effects. Study authors were contacted for additional information. Main results Nine trials including a total of 692 individuals were included in the review. Five studies compared SSRIs to placebo and two studies were combined in a meta-analysis for the outcome of change in Cohen-Mansfield Agitation Inventory (CMAI) scores. There was a significant difference between antidepressants and placebo on measures of agitation as reported on the change in CMAI total score (mean difference (MD), -0.89, 95% CI, -1.22 to -0.57) although the results were heavily weighted by one large study. There were no significant differences in change in behavioral symptoms of dementia for SSRIs compared to placebo in the one study that reported on changes in the Neuropsychiatric Inventory and Behavioral Pathology in Dementia scales. One study comparing citalopram to placebo found a significant difference in NPS as measured on the Neurobehavioral Rating Scale (NBRS) after controlling for baseline severity NBRS score although the unadjusted mean difference was not statistically significant (MD - 7.70, 95% CI: -16.57 to 1.17). There was no difference in the rates of trial withdrawals due to adverse events for SSRIs compared to placebo for four studies reporting this outcome (relative risk (RR), 1.07, 95% CI: 0.55 to 2.11) or in the number of trial withdrawals due to any cause in the three studies reporting this outcome (RR, 0.91, 95% CI, 0.65 to 1.26). One study compared the SSRI citalopram to the aTypical antipsychotic risperidone and found no difference in NBRS scores, trial withdrawals due to any cause or trial withdrawals due to adverse events although the rates of adverse events as measured on the UKU side effect scale total score were lower for citalopram (MD -2.82, 95% CI: -4.94 to -0.70). Three studies compared SSRIs to Typical Antipsychotics. In meta-analysis of two studies there was no statistically significant differences in changes in CMAI total scores (MD, 4.66, 95% CI: -3.58 to 12.90). There was also no difference in trial withdrawals due to any cause or due to adverse events for SSRIs compared to Typical Antipsychotics. One study of trazodone compared to placebo did not find any significant difference in change in CMAI total scores (MD, 5.18, 95% CI, -2.86 to 13.22) or trial withdrawals due to any cause (RR, 1.06, 95% CI, 0.54 to 2.09). Two studies comparing trazodone to haloperidol also failed to detect any difference in change in CMAI total scores (MD, 3.28, 95% CI, -3.28 to 9.85) or trial withdrawals due to any cause (RR, 0.79, 95% CI, 0.43 to 1.46). Authors' conclusions Currently there are relatively few studies of antidepressants for the treatment of agitation and psychosis in dementia. The SSRIs sertraline and citalopram were associated with a reduction in symptoms of agitation when compared to placebo in two studies. Both SSRIs and trazodone appear to be tolerated reasonably well when compared to placebo, Typical Antipsychotics and aTypical Antipsychotics. Future studies involving more subjects are required to determine if SSRIs, trazodone, or other antidepressants are safe and effective treatments for agitation and psychosis in dementia.
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ATypical Antipsychotics and parkinsonism.
JAMA Internal Medicine, 2005Co-Authors: Paula A Rochon, Kathy Sykora, Susan Garfinkel, Muhammad Mamdani, Sudeep S Gill, Geoffrey M Anderson, Sharon-lise T. Normand, Therese A Stukel, Ping LiAbstract:Background ATypical antipsychotic agents are thought to be less likely than older Typical agents to produce parkinsonism. This has not been well documented. We compared the risk of development of incident parkinsonism among older adults dispensed aTypical relative to Typical Antipsychotics. Methods Retrospective cohort study of all adults 66 years and older in Ontario. We used Cox proportional hazards models to study the association between the type, potency, and dose of antipsychotic dispensed and the development of parkinsonism during 1 year of follow-up. Results All 25 769 older adults prescribed Antipsychotics were observed for 11 573 person-years, and 449 events of parkinsonism were identified. Relative to individuals dispensed an aTypical antipsychotic, those dispensed a Typical agent were 30% more likely (adjusted hazard ratio [HR], 1.30; 95% confidence interval [CI], 1.04-1.58) and those exposed to neither agent were 60% less likely (HR, 0.40; 95% CI, 0.29-0.43) to experience development of parkinsonism. Furthermore, those dispensed lower-potency Typical agents were no different (HR, 0.75; 95% CI, 0.48-1.15), and those dispensed higher-potency Typical Antipsychotics were at close to a 50% greater risk (HR, 1.44; 95% CI, 1.13-1.84) of development of parkinsonism relative to aTypical Antipsychotics. Relative to those dispensed a high-dose aTypical antipsychotic, those dispensed a Typical antipsychotic were at similar risk for parkinsonism (Wald χ 2 = 0.14, P = .7). Conclusions The risk of development of parkinsonism associated with the use of high-dose aTypical Antipsychotics was similar to that associated with the use of Typical Antipsychotics. Caution should be used when prescribing aTypical antipsychotic therapy at high doses.
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aTypical antipsychotic drugs and risk of ischaemic stroke population based retrospective cohort study
Journal of Neurology Neurosurgery and Psychiatry, 2005Co-Authors: Sudeep S Gill, Kathy Sykora, Paula A Rochon, Sharon-lise T. Normand, Nathan Herrmann, Philip E Lee, Nadia Gunraj, Jerry H Gurwitz, Connie Marras, Walter P WodchisAbstract:To compare the incidence of admissions to hospital for stroke among older adults with dementia receiving aTypical or Typical Antipsychotics. Design: Population based retrospective cohort study. Setting: Ontario, Canada. patients: 32 710 older adults (⩾65 years) …
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aTypical antipsychotic drugs and risk of ischaemic stroke population based retrospective cohort study
BMJ, 2005Co-Authors: Sudeep S Gill, Kathy Sykora, Paula A Rochon, Sharon-lise T. Normand, Nathan Herrmann, Philip E Lee, Nadia Gunraj, Jerry H Gurwitz, Connie Marras, Walter P WodchisAbstract:Abstract Objective To compare the incidence of admissions to hospital for stroke among older adults with dementia receiving aTypical or Typical Antipsychotics. Design Population based retrospective cohort study. Setting Ontario, Canada. Patients 32 710 older adults (≤ 65 years) with dementia (17 845 dispensed an aTypical antipsychotic and 14 865 dispensed a Typical antipsychotic). Main outcome measures Admission to hospital with the most responsible diagnosis (single most important condition responsible for the patient9s admission) of ischaemic stroke. Observation of patients until they were either admitted to hospital with ischaemic stroke, stopped taking Antipsychotics, died, or the study ended. Results After adjustment for potential confounders, participants receiving aTypical Antipsychotics showed no significant increase in risk of ischaemic stroke compared with those receiving Typical Antipsychotics (adjusted hazard ratio 1.01, 95% confidence interval 0.81 to 1.26). This finding was consistent in a series of subgroup analyses, including ones of individual aTypical antipsychotic drugs (risperidone, olanzapine, and quetiapine) and selected subpopulations of the main cohorts. Conclusion Older adults with dementia who take aTypical Antipsychotics have a similar risk of ischaemic stroke to those taking Typical Antipsychotics.
Nathan Herrmann - One of the best experts on this subject based on the ideXlab platform.
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antidepressants for agitation and psychosis in dementia
Cochrane Database of Systematic Reviews, 2011Co-Authors: Dallas Seitz, Sudeep S Gill, Nathan Herrmann, Nikesh Adunuri, Andrea Gruneir, Paula A RochonAbstract:Background Agitation and psychosis are common among older adults with dementia and are challenging to manage. At the present time, little is known about the efficacy and safety of antidepressant medications when used to treat these symptoms. Objectives To assess the safety and efficacy of antidepressants in treating psychosis and agitation in older adults with Alzheimer's disease, vascular, or mixed dementia. Search methods We searched the Cochrane Dementia and Cognitive Improvement Group’s Specialized Register which included Cochrane Central Register of Controlled Trials (The Cochrane Library 2009, Issue 3), MEDLINE (January 1950 to October 2009), EMBASE (1980 - October 2009), CINAHL (all dates - October 2009) and PsycINFO (1806 to October 2009). Selection criteria Randomized, controlled trials of antidepressants (selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, trazodone, and other antidepressants), compared to either placebo or comparator medications (Typical or aTypical Antipsychotics, anticonvulsants, benzodiazepines, cholinesterase inhibitors, memantine or other medications) for treatment of agitation or psychosis in older adults with dementia. Data collection and analysis Two authors independently assessed trial quality and extracted trial data. We collected information on efficacy as measured by dementia neuropsychiatric symptom rating scales and adverse effects. Study authors were contacted for additional information. Main results Nine trials including a total of 692 individuals were included in the review. Five studies compared SSRIs to placebo and two studies were combined in a meta-analysis for the outcome of change in Cohen-Mansfield Agitation Inventory (CMAI) scores. There was a significant difference between antidepressants and placebo on measures of agitation as reported on the change in CMAI total score (mean difference (MD), -0.89, 95% CI, -1.22 to -0.57) although the results were heavily weighted by one large study. There were no significant differences in change in behavioral symptoms of dementia for SSRIs compared to placebo in the one study that reported on changes in the Neuropsychiatric Inventory and Behavioral Pathology in Dementia scales. One study comparing citalopram to placebo found a significant difference in NPS as measured on the Neurobehavioral Rating Scale (NBRS) after controlling for baseline severity NBRS score although the unadjusted mean difference was not statistically significant (MD - 7.70, 95% CI: -16.57 to 1.17). There was no difference in the rates of trial withdrawals due to adverse events for SSRIs compared to placebo for four studies reporting this outcome (relative risk (RR), 1.07, 95% CI: 0.55 to 2.11) or in the number of trial withdrawals due to any cause in the three studies reporting this outcome (RR, 0.91, 95% CI, 0.65 to 1.26). One study compared the SSRI citalopram to the aTypical antipsychotic risperidone and found no difference in NBRS scores, trial withdrawals due to any cause or trial withdrawals due to adverse events although the rates of adverse events as measured on the UKU side effect scale total score were lower for citalopram (MD -2.82, 95% CI: -4.94 to -0.70). Three studies compared SSRIs to Typical Antipsychotics. In meta-analysis of two studies there was no statistically significant differences in changes in CMAI total scores (MD, 4.66, 95% CI: -3.58 to 12.90). There was also no difference in trial withdrawals due to any cause or due to adverse events for SSRIs compared to Typical Antipsychotics. One study of trazodone compared to placebo did not find any significant difference in change in CMAI total scores (MD, 5.18, 95% CI, -2.86 to 13.22) or trial withdrawals due to any cause (RR, 1.06, 95% CI, 0.54 to 2.09). Two studies comparing trazodone to haloperidol also failed to detect any difference in change in CMAI total scores (MD, 3.28, 95% CI, -3.28 to 9.85) or trial withdrawals due to any cause (RR, 0.79, 95% CI, 0.43 to 1.46). Authors' conclusions Currently there are relatively few studies of antidepressants for the treatment of agitation and psychosis in dementia. The SSRIs sertraline and citalopram were associated with a reduction in symptoms of agitation when compared to placebo in two studies. Both SSRIs and trazodone appear to be tolerated reasonably well when compared to placebo, Typical Antipsychotics and aTypical Antipsychotics. Future studies involving more subjects are required to determine if SSRIs, trazodone, or other antidepressants are safe and effective treatments for agitation and psychosis in dementia.
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aTypical antipsychotic drugs and risk of ischaemic stroke population based retrospective cohort study
Journal of Neurology Neurosurgery and Psychiatry, 2005Co-Authors: Sudeep S Gill, Kathy Sykora, Paula A Rochon, Sharon-lise T. Normand, Nathan Herrmann, Philip E Lee, Nadia Gunraj, Jerry H Gurwitz, Connie Marras, Walter P WodchisAbstract:To compare the incidence of admissions to hospital for stroke among older adults with dementia receiving aTypical or Typical Antipsychotics. Design: Population based retrospective cohort study. Setting: Ontario, Canada. patients: 32 710 older adults (⩾65 years) …
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aTypical antipsychotic drugs and risk of ischaemic stroke population based retrospective cohort study
BMJ, 2005Co-Authors: Sudeep S Gill, Kathy Sykora, Paula A Rochon, Sharon-lise T. Normand, Nathan Herrmann, Philip E Lee, Nadia Gunraj, Jerry H Gurwitz, Connie Marras, Walter P WodchisAbstract:Abstract Objective To compare the incidence of admissions to hospital for stroke among older adults with dementia receiving aTypical or Typical Antipsychotics. Design Population based retrospective cohort study. Setting Ontario, Canada. Patients 32 710 older adults (≤ 65 years) with dementia (17 845 dispensed an aTypical antipsychotic and 14 865 dispensed a Typical antipsychotic). Main outcome measures Admission to hospital with the most responsible diagnosis (single most important condition responsible for the patient9s admission) of ischaemic stroke. Observation of patients until they were either admitted to hospital with ischaemic stroke, stopped taking Antipsychotics, died, or the study ended. Results After adjustment for potential confounders, participants receiving aTypical Antipsychotics showed no significant increase in risk of ischaemic stroke compared with those receiving Typical Antipsychotics (adjusted hazard ratio 1.01, 95% confidence interval 0.81 to 1.26). This finding was consistent in a series of subgroup analyses, including ones of individual aTypical antipsychotic drugs (risperidone, olanzapine, and quetiapine) and selected subpopulations of the main cohorts. Conclusion Older adults with dementia who take aTypical Antipsychotics have a similar risk of ischaemic stroke to those taking Typical Antipsychotics.
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aTypical Antipsychotics and risk of cerebrovascular accidents
American Journal of Psychiatry, 2004Co-Authors: Nathan Herrmann, Muhammad Mamdani, Krista L LanctotAbstract:OBJECTIVE: Randomized controlled trials have suggested that at least one aTypical antipsychotic may be associated with an increased risk of stroke in older people with dementia. This study examined the association between aTypical antipsychotic use and stroke in the elderly. METHOD: The authors conducted a retrospective population-based cohort study of patients over the age of 66 by linking administrative health care databases. Three cohorts—users of Typical Antipsychotics, risperidone, and olanzapine—were identified and compared. RESULTS: Subjects treated with Typical Antipsychotics (N=1,015) were compared with those given risperidone (N=6,964) and olanzapine (N=3,421). Model-based estimates adjusted for covariates hypothesized to be associated with stroke risk revealed relative risk estimates of 1.1 (95% CI=0.5–2.3) for olanzapine and 1.4 (95% CI=0.7–2.8) for risperidone. CONCLUSIONS: Olanzapine and risperidone use were not associated with a statistically significant increased risk of stroke compared wi...
Paula A Rochon - One of the best experts on this subject based on the ideXlab platform.
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antidepressants for agitation and psychosis in dementia
Cochrane Database of Systematic Reviews, 2011Co-Authors: Dallas Seitz, Sudeep S Gill, Nathan Herrmann, Nikesh Adunuri, Andrea Gruneir, Paula A RochonAbstract:Background Agitation and psychosis are common among older adults with dementia and are challenging to manage. At the present time, little is known about the efficacy and safety of antidepressant medications when used to treat these symptoms. Objectives To assess the safety and efficacy of antidepressants in treating psychosis and agitation in older adults with Alzheimer's disease, vascular, or mixed dementia. Search methods We searched the Cochrane Dementia and Cognitive Improvement Group’s Specialized Register which included Cochrane Central Register of Controlled Trials (The Cochrane Library 2009, Issue 3), MEDLINE (January 1950 to October 2009), EMBASE (1980 - October 2009), CINAHL (all dates - October 2009) and PsycINFO (1806 to October 2009). Selection criteria Randomized, controlled trials of antidepressants (selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, trazodone, and other antidepressants), compared to either placebo or comparator medications (Typical or aTypical Antipsychotics, anticonvulsants, benzodiazepines, cholinesterase inhibitors, memantine or other medications) for treatment of agitation or psychosis in older adults with dementia. Data collection and analysis Two authors independently assessed trial quality and extracted trial data. We collected information on efficacy as measured by dementia neuropsychiatric symptom rating scales and adverse effects. Study authors were contacted for additional information. Main results Nine trials including a total of 692 individuals were included in the review. Five studies compared SSRIs to placebo and two studies were combined in a meta-analysis for the outcome of change in Cohen-Mansfield Agitation Inventory (CMAI) scores. There was a significant difference between antidepressants and placebo on measures of agitation as reported on the change in CMAI total score (mean difference (MD), -0.89, 95% CI, -1.22 to -0.57) although the results were heavily weighted by one large study. There were no significant differences in change in behavioral symptoms of dementia for SSRIs compared to placebo in the one study that reported on changes in the Neuropsychiatric Inventory and Behavioral Pathology in Dementia scales. One study comparing citalopram to placebo found a significant difference in NPS as measured on the Neurobehavioral Rating Scale (NBRS) after controlling for baseline severity NBRS score although the unadjusted mean difference was not statistically significant (MD - 7.70, 95% CI: -16.57 to 1.17). There was no difference in the rates of trial withdrawals due to adverse events for SSRIs compared to placebo for four studies reporting this outcome (relative risk (RR), 1.07, 95% CI: 0.55 to 2.11) or in the number of trial withdrawals due to any cause in the three studies reporting this outcome (RR, 0.91, 95% CI, 0.65 to 1.26). One study compared the SSRI citalopram to the aTypical antipsychotic risperidone and found no difference in NBRS scores, trial withdrawals due to any cause or trial withdrawals due to adverse events although the rates of adverse events as measured on the UKU side effect scale total score were lower for citalopram (MD -2.82, 95% CI: -4.94 to -0.70). Three studies compared SSRIs to Typical Antipsychotics. In meta-analysis of two studies there was no statistically significant differences in changes in CMAI total scores (MD, 4.66, 95% CI: -3.58 to 12.90). There was also no difference in trial withdrawals due to any cause or due to adverse events for SSRIs compared to Typical Antipsychotics. One study of trazodone compared to placebo did not find any significant difference in change in CMAI total scores (MD, 5.18, 95% CI, -2.86 to 13.22) or trial withdrawals due to any cause (RR, 1.06, 95% CI, 0.54 to 2.09). Two studies comparing trazodone to haloperidol also failed to detect any difference in change in CMAI total scores (MD, 3.28, 95% CI, -3.28 to 9.85) or trial withdrawals due to any cause (RR, 0.79, 95% CI, 0.43 to 1.46). Authors' conclusions Currently there are relatively few studies of antidepressants for the treatment of agitation and psychosis in dementia. The SSRIs sertraline and citalopram were associated with a reduction in symptoms of agitation when compared to placebo in two studies. Both SSRIs and trazodone appear to be tolerated reasonably well when compared to placebo, Typical Antipsychotics and aTypical Antipsychotics. Future studies involving more subjects are required to determine if SSRIs, trazodone, or other antidepressants are safe and effective treatments for agitation and psychosis in dementia.
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ATypical Antipsychotics and parkinsonism.
JAMA Internal Medicine, 2005Co-Authors: Paula A Rochon, Kathy Sykora, Susan Garfinkel, Muhammad Mamdani, Sudeep S Gill, Geoffrey M Anderson, Sharon-lise T. Normand, Therese A Stukel, Ping LiAbstract:Background ATypical antipsychotic agents are thought to be less likely than older Typical agents to produce parkinsonism. This has not been well documented. We compared the risk of development of incident parkinsonism among older adults dispensed aTypical relative to Typical Antipsychotics. Methods Retrospective cohort study of all adults 66 years and older in Ontario. We used Cox proportional hazards models to study the association between the type, potency, and dose of antipsychotic dispensed and the development of parkinsonism during 1 year of follow-up. Results All 25 769 older adults prescribed Antipsychotics were observed for 11 573 person-years, and 449 events of parkinsonism were identified. Relative to individuals dispensed an aTypical antipsychotic, those dispensed a Typical agent were 30% more likely (adjusted hazard ratio [HR], 1.30; 95% confidence interval [CI], 1.04-1.58) and those exposed to neither agent were 60% less likely (HR, 0.40; 95% CI, 0.29-0.43) to experience development of parkinsonism. Furthermore, those dispensed lower-potency Typical agents were no different (HR, 0.75; 95% CI, 0.48-1.15), and those dispensed higher-potency Typical Antipsychotics were at close to a 50% greater risk (HR, 1.44; 95% CI, 1.13-1.84) of development of parkinsonism relative to aTypical Antipsychotics. Relative to those dispensed a high-dose aTypical antipsychotic, those dispensed a Typical antipsychotic were at similar risk for parkinsonism (Wald χ 2 = 0.14, P = .7). Conclusions The risk of development of parkinsonism associated with the use of high-dose aTypical Antipsychotics was similar to that associated with the use of Typical Antipsychotics. Caution should be used when prescribing aTypical antipsychotic therapy at high doses.
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aTypical antipsychotic drugs and risk of ischaemic stroke population based retrospective cohort study
Journal of Neurology Neurosurgery and Psychiatry, 2005Co-Authors: Sudeep S Gill, Kathy Sykora, Paula A Rochon, Sharon-lise T. Normand, Nathan Herrmann, Philip E Lee, Nadia Gunraj, Jerry H Gurwitz, Connie Marras, Walter P WodchisAbstract:To compare the incidence of admissions to hospital for stroke among older adults with dementia receiving aTypical or Typical Antipsychotics. Design: Population based retrospective cohort study. Setting: Ontario, Canada. patients: 32 710 older adults (⩾65 years) …
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aTypical antipsychotic drugs and risk of ischaemic stroke population based retrospective cohort study
BMJ, 2005Co-Authors: Sudeep S Gill, Kathy Sykora, Paula A Rochon, Sharon-lise T. Normand, Nathan Herrmann, Philip E Lee, Nadia Gunraj, Jerry H Gurwitz, Connie Marras, Walter P WodchisAbstract:Abstract Objective To compare the incidence of admissions to hospital for stroke among older adults with dementia receiving aTypical or Typical Antipsychotics. Design Population based retrospective cohort study. Setting Ontario, Canada. Patients 32 710 older adults (≤ 65 years) with dementia (17 845 dispensed an aTypical antipsychotic and 14 865 dispensed a Typical antipsychotic). Main outcome measures Admission to hospital with the most responsible diagnosis (single most important condition responsible for the patient9s admission) of ischaemic stroke. Observation of patients until they were either admitted to hospital with ischaemic stroke, stopped taking Antipsychotics, died, or the study ended. Results After adjustment for potential confounders, participants receiving aTypical Antipsychotics showed no significant increase in risk of ischaemic stroke compared with those receiving Typical Antipsychotics (adjusted hazard ratio 1.01, 95% confidence interval 0.81 to 1.26). This finding was consistent in a series of subgroup analyses, including ones of individual aTypical antipsychotic drugs (risperidone, olanzapine, and quetiapine) and selected subpopulations of the main cohorts. Conclusion Older adults with dementia who take aTypical Antipsychotics have a similar risk of ischaemic stroke to those taking Typical Antipsychotics.
Walter P Wodchis - One of the best experts on this subject based on the ideXlab platform.
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aTypical antipsychotic drugs and risk of ischaemic stroke population based retrospective cohort study
Journal of Neurology Neurosurgery and Psychiatry, 2005Co-Authors: Sudeep S Gill, Kathy Sykora, Paula A Rochon, Sharon-lise T. Normand, Nathan Herrmann, Philip E Lee, Nadia Gunraj, Jerry H Gurwitz, Connie Marras, Walter P WodchisAbstract:To compare the incidence of admissions to hospital for stroke among older adults with dementia receiving aTypical or Typical Antipsychotics. Design: Population based retrospective cohort study. Setting: Ontario, Canada. patients: 32 710 older adults (⩾65 years) …
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aTypical antipsychotic drugs and risk of ischaemic stroke population based retrospective cohort study
BMJ, 2005Co-Authors: Sudeep S Gill, Kathy Sykora, Paula A Rochon, Sharon-lise T. Normand, Nathan Herrmann, Philip E Lee, Nadia Gunraj, Jerry H Gurwitz, Connie Marras, Walter P WodchisAbstract:Abstract Objective To compare the incidence of admissions to hospital for stroke among older adults with dementia receiving aTypical or Typical Antipsychotics. Design Population based retrospective cohort study. Setting Ontario, Canada. Patients 32 710 older adults (≤ 65 years) with dementia (17 845 dispensed an aTypical antipsychotic and 14 865 dispensed a Typical antipsychotic). Main outcome measures Admission to hospital with the most responsible diagnosis (single most important condition responsible for the patient9s admission) of ischaemic stroke. Observation of patients until they were either admitted to hospital with ischaemic stroke, stopped taking Antipsychotics, died, or the study ended. Results After adjustment for potential confounders, participants receiving aTypical Antipsychotics showed no significant increase in risk of ischaemic stroke compared with those receiving Typical Antipsychotics (adjusted hazard ratio 1.01, 95% confidence interval 0.81 to 1.26). This finding was consistent in a series of subgroup analyses, including ones of individual aTypical antipsychotic drugs (risperidone, olanzapine, and quetiapine) and selected subpopulations of the main cohorts. Conclusion Older adults with dementia who take aTypical Antipsychotics have a similar risk of ischaemic stroke to those taking Typical Antipsychotics.
Joseph T Coyle - One of the best experts on this subject based on the ideXlab platform.
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The NMDA receptor glycine modulatory site: a therapeutic target for improving cognition and reducing negative symptoms in schizophrenia
Psychopharmacology, 2004Co-Authors: Joseph T Coyle, Guochuan TsaiAbstract:Numerous clinical studies demonstrate that subanaesthetic doses of dissociative anaesthetics, which are non-competitive antagonists at the NMDA receptor, replicate in normal subjects the cognitive impairments, negative symptoms and brain functional abnormalities of schizophrenia. Post-mortem and genetic studies have identified several abnormalities associated with schizophrenia that would interfere with the activation of the glycine modulatory site on the NMDA receptor. Placebo controlled clinical trials with agents that directly or indirectly activate the glycine modulatory site consistently reduce negative symptoms and frequently improve cognition in patients with chronic schizophrenia, who are receiving concurrent Typical Antipsychotics. Thus, there is convincing evidence that the glycine modulatory site on the NMDA receptor is a valid therapeutic target for improving cognition and associated negative symptoms in schizophrenia.
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glutamatergic mechanisms in schizophrenia
Annual Review of Pharmacology and Toxicology, 2003Co-Authors: Guochuan Tsai, Joseph T CoyleAbstract:Schizophrenia is a chronic, severely disabling brain disorder with symptomatic onset in early adulthood. Typical antipsychotic medications that block dopamine D2 receptors are most effective in treating the psychosis but have limited effects on the negative symptoms and cognitive impairments. Considerable research has demonstrated that noncompetitive NMDA receptor antagonists, the dissociative anaesthetic like phencyclidine and ketamine, reproduce the cardinal symptomatic features of schizophrenia. Postmortem studies reveal variable alterations in glutamate receptors and their modulators in schizophrenia. Several clinical trials indicate agents that enhance NMDA receptor function via the glycine modulatory site reduce negative and variably improve cognitive function in schizophrenics receiving Typical Antipsychotics. Thus, hypofunction of a subpopulation of cortico-limbic NMDA receptors may participate in the pathophysiology of schizophrenia.
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converging evidence of nmda receptor hypofunction in the pathophysiology of schizophrenia
Annals of the New York Academy of Sciences, 2003Co-Authors: Guochuan Tsai, Joseph T Coyle, Donald C GoffAbstract:Numerous clinical studies demonstrate that subanesthetic doses of dissociative anesthetics, which are noncompetitive antagonists at the NMDA receptor, replicate in normal subjects the cognitive impairments, negative symptoms, and brain functional abnormalities of schizophrenia. Postmortem and genetic studies have identified several abnormalities associated with schizophrenia that would interfere with the activation of the glycine modulatory site on the NMDA receptor. Placebo-controlled clinical trials with agents that directly or indirectly activate the glycine modulatory site consistently reduce negative symptoms and frequently improve cognition in patients with chronic schizophrenia who are receiving concurrent Typical Antipsychotics. Thus, there is convincing evidence that hypofunction of a subset of NMDA receptors may contribute to the symptomatic features of schizophrenia.
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ionotropic glutamate receptors as therapeutic targets in schizophrenia
Current Drug Targets - Cns & Neurological Disorders, 2002Co-Authors: Joseph T Coyle, Guochuan Tsai, Donald C GoffAbstract:Evidence implicating dysfunction of glutamatergic neurotransmission rests largely on the finding that antagonists of the NMDA subtype of glutamate receptor, especially the dissociative anesthetics like ketamine, can reproduce the full range of symptoms as well as the physiologic manifestation of schizophrenia such as hypofrontality, impaired prepulse inhibition and enhanced subcortical dopamine release. To test the hypothesis that schizophrenia may result from NMDA receptor hypofunction a number of clinical trials have examined the effects of agents that act on the glycine modulatory site on the NMDA receptor. Glycine, D-serine, and the partial agonist, D-cycloserine, have been shown to improve cognition and decrease negative symptoms in schizophrenic subjects receiving Typical Antipsychotics. Results with D-cycloserine suggest that clozapine may enhance glycine modulatory site occupancy. Preliminary results with an allosteric modulator of the AMPA subtype of glutamate receptor suggest enhanced cognitive functions in subjects treated with clozapine.
