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Citalopram for Agitation in AD (CitAD): Pharmacokinetic Studies, Subgroup Analyses, and Effect on Other Neuropsychiatric Symptoms
2016 AAGP Annual Meeting 5
Johns Hopkins University, Baltimore, MD University of Pennsylvania School of Medicine, Philadelphia, PA
6
Abstract: The media recently drew attention to the unsettling trial of Henry Rayhons, a 78-year old man in Iowa accused of having sex with his wife while she was living in a nursing home with dementia. Staff members there believed she was mentally incapable of consenting to sex. The state charged Mr. Rayhons with sexual abuse in the third-degree, a felony, for which he was eventually found not guilty. This case highlights the challenge for our society to balance individuals’ rights to engage in one of life’s primal pleasures and acts of self-expression, with the clinical, legal, and ethical obligations to protect vulnerable individuals who may be unable to consent due to cognitive impairment. A panel, comprised of two geriatric psychiatrists, a geriatrician-ethicist, and an attorney-physician, will summarize the currently available information and published guidelines on how to assess whether a person living with dementia has the capacity to consent to sexual intimacy. We will consider whether sexual intimacy is able to fit within the current framework of competency and decision-making abilities, and explore how “consent” is conceptualized in other essential acts of self-expression, such as voting. We will review how laws and policies allowing law enforcement to bring charges of domestic abuse or sexual assault without the victim’s consent will need to be reevaluated and adjusted in the context of cases like that of Mr. Rayhons. We will illustrate the importance of having open dialogue with patients and families on patients’ sexual preferences, akin to discussions on end-of-life care. We will discuss ways for health professionals to communicate patients’ wishes on intimacy to law enforcement when there is a question of consent. Faculty Disclosures: Gregory Dolin Nothing to disclose Jason Karlawish Nothing to disclose Eitan Z. Kimchi Nothing to disclose Daniel D. Sewell Consultant: ActivCare, Inc—Advisory Board Member Research Support: Hartford Foundation—Associate Director of the UC San Diego Hartford Center of Excellence in Geriatric Psychiatry
CITALOPRAM FOR AGITATION IN AD (CitAD): PHARMACOKINETIC STUDIES, SUBGROUP ANALYSES, AND EFFECT ON OTHER NEUROPSYCHIATRIC SYMPTOMS Session 412 Constantine G. Lyketsos1; Bruce G. Pollock2; Lon Schneider3; Anton P. Porsteinsson4 1
Johns Hopkins Medicine, Baltimore, MD University of Toronto, Toronto, ON, Canada 3 UCLA, Los Angeles, CA 4 University of Rochester, Rochester, NY 2
Abstract: Introduction: Citalopram for Agitation in AD (CitAD) was carried out by a collaborative of 8 universities that worked together implementing earlier clinical trials targeting neuropsychiatric symptoms (NPS) in Alzheimer’s disease (AD). CitAD findings were cited by Neurology Today as a Top 10 Advance in Neurology for 2014. Furthermore, NIA highlighted the importance of CitAD findings in its 2014 Annual Report. Methods: CitAD was a 9-week, multi-center, randomized, placebo-controlled clinical trial that evaluated the efficacy and safety of citalopram at a target dose of 30 mg per day for agitation in AD. CitAD enrolled 186 participants with AD, Mini-Mental State Examination (MMSE) scores 5–28, and clinically significant agitation requiring pharmacologic therapy (agitation score >4 on the Neuropsychiatric Inventory (NPI) at baseline). The study achieved 91% participant retention, with 80% remaining on therapy over all 9 weeks.
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Am J Geriatr Psychiatry 24:3, Supplement 1
2016 AAGP Annual Meeting Results: As previously reported, citalopram at 30 mg daily was effective for agitation in patients with AD, with significant reductions in three measures of agitation: mADCS-CGIC, NBRS, and Cohen-Mansfield Agitation Inventory. About 40% of patients on citalopram had moderate or marked reduction in agitation, compared with 26% on placebo. We report here that in addition to agitation, citalopram improved affective symptoms and delusions. Compared with placebo, participants on citalopram declined more on MMSE and exhibited prolongation of the QTc interval. The adverse effects on MMSE and QTc were closely linked to R-citalopram blood concentrations, but efficacy was linked closely to S-citalopram concentrations. Few pre-specified predictors of response could be identified, but patients with nursing home residence did not benefit from citalopram, while an index of symptoms suggested a subgroup of patients who benefitted the most. For example, patients with predominately affective symptomatology did better on citalopram (52% substantial clinical improvement) vs. placebo (14%). Discussion: Citalopram at a dose of 30 mg/day is effective for agitation in patients with AD and leads to broad improvement in NPS, including delusions. Adverse effects on cognition and cardiac conduction appear to be primarily linked to R-citalopram, suggesting that S-citalopram might be both safer and more effective. Finally, citalopram appears to be most effective for a subgroup of patients with agitation, especially those with prominent affective symptoms. Faculty Disclosures: Constantine G. Lyketsos Consultant: Astra-Zeneca, Glaxo-Smith Kline, Eisai, Novartis, Forest, Supernus, Adlyfe, Takeda, Wyeth, Lundbeck, Merz, Lilly, Pfizer, Genentech, Elan, NFL Players Association, NFL Benefits Office, Avanir, Zinfandel, BMS, Abvie, Janssen, Orion, Otsuka, Servier, Astellas—Several consulting projects Research Support: NIMH, NIA, Associated Jewish Federation of Baltimore, Weinberg Foundation, Forest, Glaxo-Smith-Kline, Eisai, Pfizer, Astra-Zeneca, Lilly, Ortho-McNeil, Bristol-Myers, Novartis, National Football League, Elan, Functional Neuromodulation—Several research projects Other: Pfizer, Forest, Glaxo-Smith Kline, Health Monitor—Honorarium or travel support Bruce G. Pollock Nothing to disclose Anton P. Porsteinsson Research Support: AstraZeneca—To my institution Research Support: Avanir—To my institution Research Support: Biogen—To my institution Research Support: Eisai—To my institution Research Support: Ely Lilly—To my institution Research Support: Merck—To my institution Research Support: Roche—To my institution Research Support: Transition Therapeutics—To my institution Research Support: Toyama—To my institution Consultant: Lundbeck—Advisory Board Consultant: Merck—Advisory Board Consultant: Functional Neuromodulation—DSMB Consultant: NYPI—DSMB Consultant: Quintiles—DSMB Lon Schneider No Answer
PSYCHIATRIC CARE FROM A DISTANCE—CURRENT CHALLENGES AND FUTURE IMPLICATIONS Session 413 Ipsit V. Vahia1; Rujvi Kamat1; Shilpa Srinivasan2; Ching Yu3 1
University of California, San Diego, CA University of South Carolina School of Medicine, Columbia, SC 3 McGill University, Montreal, QC, Canada 2
Am J Geriatr Psychiatry 24:3, Supplement 1
S37
Johns Hopkins University, Baltimore, MD University of Pennsylvania School of Medicine, Philadelphia, PA
6
Abstract: The media recently drew attention to the unsettling trial of Henry Rayhons, a 78-year old man in Iowa accused of having sex with his wife while she was living in a nursing home with dementia. Staff members there believed she was mentally incapable of consenting to sex. The state charged Mr. Rayhons with sexual abuse in the third-degree, a felony, for which he was eventually found not guilty. This case highlights the challenge for our society to balance individuals’ rights to engage in one of life’s primal pleasures and acts of self-expression, with the clinical, legal, and ethical obligations to protect vulnerable individuals who may be unable to consent due to cognitive impairment. A panel, comprised of two geriatric psychiatrists, a geriatrician-ethicist, and an attorney-physician, will summarize the currently available information and published guidelines on how to assess whether a person living with dementia has the capacity to consent to sexual intimacy. We will consider whether sexual intimacy is able to fit within the current framework of competency and decision-making abilities, and explore how “consent” is conceptualized in other essential acts of self-expression, such as voting. We will review how laws and policies allowing law enforcement to bring charges of domestic abuse or sexual assault without the victim’s consent will need to be reevaluated and adjusted in the context of cases like that of Mr. Rayhons. We will illustrate the importance of having open dialogue with patients and families on patients’ sexual preferences, akin to discussions on end-of-life care. We will discuss ways for health professionals to communicate patients’ wishes on intimacy to law enforcement when there is a question of consent. Faculty Disclosures: Gregory Dolin Nothing to disclose Jason Karlawish Nothing to disclose Eitan Z. Kimchi Nothing to disclose Daniel D. Sewell Consultant: ActivCare, Inc—Advisory Board Member Research Support: Hartford Foundation—Associate Director of the UC San Diego Hartford Center of Excellence in Geriatric Psychiatry
CITALOPRAM FOR AGITATION IN AD (CitAD): PHARMACOKINETIC STUDIES, SUBGROUP ANALYSES, AND EFFECT ON OTHER NEUROPSYCHIATRIC SYMPTOMS Session 412 Constantine G. Lyketsos1; Bruce G. Pollock2; Lon Schneider3; Anton P. Porsteinsson4 1
Johns Hopkins Medicine, Baltimore, MD University of Toronto, Toronto, ON, Canada 3 UCLA, Los Angeles, CA 4 University of Rochester, Rochester, NY 2
Abstract: Introduction: Citalopram for Agitation in AD (CitAD) was carried out by a collaborative of 8 universities that worked together implementing earlier clinical trials targeting neuropsychiatric symptoms (NPS) in Alzheimer’s disease (AD). CitAD findings were cited by Neurology Today as a Top 10 Advance in Neurology for 2014. Furthermore, NIA highlighted the importance of CitAD findings in its 2014 Annual Report. Methods: CitAD was a 9-week, multi-center, randomized, placebo-controlled clinical trial that evaluated the efficacy and safety of citalopram at a target dose of 30 mg per day for agitation in AD. CitAD enrolled 186 participants with AD, Mini-Mental State Examination (MMSE) scores 5–28, and clinically significant agitation requiring pharmacologic therapy (agitation score >4 on the Neuropsychiatric Inventory (NPI) at baseline). The study achieved 91% participant retention, with 80% remaining on therapy over all 9 weeks.
S36
Am J Geriatr Psychiatry 24:3, Supplement 1
2016 AAGP Annual Meeting Results: As previously reported, citalopram at 30 mg daily was effective for agitation in patients with AD, with significant reductions in three measures of agitation: mADCS-CGIC, NBRS, and Cohen-Mansfield Agitation Inventory. About 40% of patients on citalopram had moderate or marked reduction in agitation, compared with 26% on placebo. We report here that in addition to agitation, citalopram improved affective symptoms and delusions. Compared with placebo, participants on citalopram declined more on MMSE and exhibited prolongation of the QTc interval. The adverse effects on MMSE and QTc were closely linked to R-citalopram blood concentrations, but efficacy was linked closely to S-citalopram concentrations. Few pre-specified predictors of response could be identified, but patients with nursing home residence did not benefit from citalopram, while an index of symptoms suggested a subgroup of patients who benefitted the most. For example, patients with predominately affective symptomatology did better on citalopram (52% substantial clinical improvement) vs. placebo (14%). Discussion: Citalopram at a dose of 30 mg/day is effective for agitation in patients with AD and leads to broad improvement in NPS, including delusions. Adverse effects on cognition and cardiac conduction appear to be primarily linked to R-citalopram, suggesting that S-citalopram might be both safer and more effective. Finally, citalopram appears to be most effective for a subgroup of patients with agitation, especially those with prominent affective symptoms. Faculty Disclosures: Constantine G. Lyketsos Consultant: Astra-Zeneca, Glaxo-Smith Kline, Eisai, Novartis, Forest, Supernus, Adlyfe, Takeda, Wyeth, Lundbeck, Merz, Lilly, Pfizer, Genentech, Elan, NFL Players Association, NFL Benefits Office, Avanir, Zinfandel, BMS, Abvie, Janssen, Orion, Otsuka, Servier, Astellas—Several consulting projects Research Support: NIMH, NIA, Associated Jewish Federation of Baltimore, Weinberg Foundation, Forest, Glaxo-Smith-Kline, Eisai, Pfizer, Astra-Zeneca, Lilly, Ortho-McNeil, Bristol-Myers, Novartis, National Football League, Elan, Functional Neuromodulation—Several research projects Other: Pfizer, Forest, Glaxo-Smith Kline, Health Monitor—Honorarium or travel support Bruce G. Pollock Nothing to disclose Anton P. Porsteinsson Research Support: AstraZeneca—To my institution Research Support: Avanir—To my institution Research Support: Biogen—To my institution Research Support: Eisai—To my institution Research Support: Ely Lilly—To my institution Research Support: Merck—To my institution Research Support: Roche—To my institution Research Support: Transition Therapeutics—To my institution Research Support: Toyama—To my institution Consultant: Lundbeck—Advisory Board Consultant: Merck—Advisory Board Consultant: Functional Neuromodulation—DSMB Consultant: NYPI—DSMB Consultant: Quintiles—DSMB Lon Schneider No Answer
PSYCHIATRIC CARE FROM A DISTANCE—CURRENT CHALLENGES AND FUTURE IMPLICATIONS Session 413 Ipsit V. Vahia1; Rujvi Kamat1; Shilpa Srinivasan2; Ching Yu3 1
University of California, San Diego, CA University of South Carolina School of Medicine, Columbia, SC 3 McGill University, Montreal, QC, Canada 2
Am J Geriatr Psychiatry 24:3, Supplement 1
S37