Student Forum Is It Time to Call It Quits on Low-Dose Quetiapine? Amie Taggart Blaszczyk, Kelley A. McGinnis, Heidi N. Michaels, Tony N. Nguyen The mandate of the Centers for Medicare & Medicaid Services to decrease the use of antipsychotics in long-term care facilities requires creative solutions. Low-dose quetiapine is used for a multitude of behavioral disorders and sleep problems in the nursing facility population. Yet, at doses of 25 mg per day or less, it doesn’t have strong affinity (if any) for the dopamine-2 (D2) receptor, but it does maintain affinity for the histamine-1 and alpha-1 receptors. This begs the question: If it’s not antagonizing the D2 receptor, could the use of something with similar receptor-affinity produce the same result, allowing discontinuation of the antipsychotic altogether? Using knowledge of receptor affinities and the pharmacologic action of low-dose quetiapine, consultant pharmacists may have one additional tool in their armamentarium of fighting inappropriate antipsychotic use. Key words: Antipsychotic agents, Alzheimer’s disease, Dementia, Psychotic disorders, Quetiapine. Abbreviations: AD = Alzheimer’s disease, BPSD = Behavioral or Psychological Symptoms Associated with Dementia, CATIE = Clinical Antipsychotic Trials of Intervention Effectiveness, CGI = Clinical Global Impression. Consult Pharm 2015;30:287-90.
Introduction In March 2012, the Centers for Medicare & Medicaid Services (CMS) launched a quality initiative aimed at decreasing off-label use of antipsychotics in nursing facilities by 15% by the end of 2013.1 This was in reaction to a 2011 report from the Office of the Inspector General that found that 14% of elderly nursing facility residents had Medicare claims for second-generation (atypical) antipsychotic drugs, and that 83% of these claims were associated with off-label use. Antipsychotics are frequently prescribed for residents with dementia who have behavioral or psychological symptoms associated with dementia (BPSD).2,3 The use of the word “agitation” is often used as a catch-all term for these types of behaviors. In September 2014, CMS announced reaching its initial goal of a greater than 15% reduction in antipsychotic use in long-term nursing facility residents, with all 50 states showing at least some improvement.1 The National Partnership to Improve Dementia Care is a coalition whose goal is to support efforts to reduce antipsychotic use through enhanced training for providers, publicly available data on antipsychotic use, and the formation of a behavioral health committee for dementia care practice.1,4 Considering the complexity of the rationale for antipsychotic therapy, a one-size-fits-all solution for reducing antipsychotic use is not feasible. Therefore, the mandates from CMS on decreasing antipsychotic use in long-term care requires creative solutions from the entire health care team—including the consultant pharmacist. The consultant pharmacist has the training and knowledge to understand how receptor affinities and pharmacologic actions of medications can influence necessity within a disease state, as well as the knowledge of adverse effects. This paper will focus on the receptor affinities of quetiapine and how consultant pharmacists may be able to recommend agents with similar receptor affinities and pharmacologic effects to elicit the same response, but without the use of an antipsychotic.
The Consultant Pharmacist may 2015 Vol. 30, No. 5
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Student Forum Review of Quetiapine Quetiapine is a second-generation antipsychotic indicated for the treatment of schizophrenia and bipolar disorder. This medication is rapidly absorbed orally, with blood concentrations peaking at one to two hours, demonstrates linear pharmacokinetics up to a dose of 375 mg twice daily, and is eliminated through hepatic metabolism by cytochrome P450 3A4.5 Quetiapine antagonizes multiple receptors: alpha 1 and 2, dopamine (D2), histamine (H1), muscarinic, and serotonin (5HT1A, -1D, -2A, and -2D). As the dopamine hypothesis of schizophrenia suggests, antipsychotic efficacy is through antagonism of the D2 receptor.6 However, quetiapine has a low affinity for the D2 receptor, requiring higher doses for clinical effects of D2 antagonism.7-9 Experts in the field have even noted a need for doses exceeding approved doses for the treatment of schizophrenia.10 A fixed-dose trial in schizophrenic patients failed to show a statistically significant improvement in the Clinical Global Impression (CGI) scale between those taking quetiapine 25 mg twice daily versus 150 mg three times daily. However, there was a statistically significant improvement in CGI in patients taking 225 mg twice daily compared with 25 mg twice daily.11 The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) research group compared several second-generation antipsychotics with perphenazine in schizophrenic patients. The quetiapine dosing in this trial ranged from 200 mg to 800 mg per day, with a mean modal dose of 543.4 mg per day, again supporting a need for higher dosing for antipsychotic effects.9 Case studies and case series have reported that using higherthan-approved doses of quetiapine may be necessary and effective in treatment resistance.11 Since quetiapine’s affinity for the D2 receptor is much lower than the affinity for the alpha-1, H1, and 5HT-2A receptors, side effects manifesting from antagonism of these receptors can be present at much lower doses (12.5 mg to 100 mg).11,12 While the prevalence of specific antipsychotic prescribing in facilities varies from region to region, quetiapine, even at low doses, is one of the most
288
commonly prescribed antipsychotics for a variety of psychiatric indications (both on-label and off-label) in elderly nursing facility residents.2 Aside from the burden of cost, clinical “antipsychotic effects” at low doses are questionable. Given the receptor affinities of low-dose quetiapine for H1 and 5HT-2A, the question could be posed: Is effectiveness derived from the sedative and mood properties of quetiapine, rather than the antipsychotic (D2 receptor antagonism) properties? And, if so, are there safer alternatives with similar receptor affinities? Both the patient’s and staff ’s safety, as well as the provider’s and facility’s liability, are considerations when evaluating a change in therapy. Behavioral disturbances that may harm the patient or staff, such as aggression, wandering into off-limit areas, and disturbing or scary hallucinations, can occur when a patient is not adequately treated. However, there is also the concern for anticholinergic effects, increased fall risk, changes in cognition, and increased cardiovascular risk associated with the use of antipsychotics, especially in patients with dementia, which may be an unnecessary risk.13 Nonpharmacologic alternatives or tapering down antipsychotic therapy in patients on low-dose quetiapine is a reasonable consideration. Studies have suggested a potential benefit in cognition following antipsychotic withdrawal, and though safer alternatives in the geriatric population exist, none is without risk.14 CATIE-AD (Alzheimer’s disease [AD]), a randomized placebo-controlled trial that enrolled outpatients with AD and psychosis, aggression or agitation, failed to show clinical benefit in patients treated with quetiapine compared with a placebo group.15 The average final dose in the quetiapine arm was 56.5 mg/day, an increase from 34.1 mg/day initially. The time to discontinuation for lack of efficacy was not different between the quetiapine and placebo groups (median time: 9.1 weeks versus 9.0 weeks, respectively). Not all residents, families, staff, or facilities are amenable to antipsychotic therapy being discontinued, especially when there is a perception of benefit. However, given the receptors quetiapine likely antagonizes at low doses, providers and families may be amenable to switching to an agent that behaves the same way as those same receptors.
The Consultant Pharmacist may 2015 Vol. 30, No. 5
Is It Time to Call It Quits on Low-Dose Quetiapine?
Antidepressants
Melatonin
Antidepressants with evidence supporting a benefit of improving behavioral disturbances include trazodone and mirtazapine.16-19 While the use of an antidepressant to help with problematic behaviors may seem like an easy switch, these agents are not benign from a side effect standpoint. They would also require additional documentation for their use, especially in those without a concomitant depression diagnosis. Trazodone is an antidepressant that, at low doses, antagonizes 5HT-2A, H1, and alpha-1 receptors.20 This accounts for the sedative-hypnotic effects seen when used at low doses. Antidepressant effects of trazodone are not typically seen until doses are greater than 100 mg.20 In one study, trazodone showed an ability to manage agitation and aggressive behavior associated with psychosis in a cohort of depressed elderly patients.16 Though not statistically different from placebo, another study showed similar efficacy with trazodone when compared with haloperidol in older adults with dementia.17 As is the case with quetiapine, there is a potential increased risk of orthostatic hypotension in the older patient population, secondary to its antagonism of the alpha-1 receptor.21 Mirtazapine can be an option for agitation in AD and, because of its 5HT-2C and H1 antagonism, has shown to improve sleep and appetite, but may require a risk-versusbenefit discussion when used in patients with diabetes, metabolic syndrome, hyperlipidemia, and obesity.19,20,22,23 Since agitation may be related to insomnia or untreated depression, the potential for minimizing agitation may be easily resolved, or at least modulated, with the bedtime use of mirtazapine.19 Advantages include minor side effects (mild hypotension, headache), improved appetite without affecting weight substantially, and potential for regulating sleep through its target on the HPA axis and melatonin.24
If agitation being treated is related to sundowning, evidence exists for the administration of melatonin.25 In one study, patients receiving nightly melatonin at a dose of 6 mg to 9 mg had fewer documented behavioral changes.26 Another trial monitored AD patients for three weeks and found reduced agitation and daytime sleepiness with bedtime melatonin use at a dose of 1 mg to 3 mg.27
Implications and Strategies for the Consultant Pharmacist While pharmacokinetic evidence exists to support a trial of no therapy or an alternative therapy for behavioral symptoms associated with dementia for patients being treated with low-dose quetiapine, the next step would be to convey this to the person with the power to change therapy: the prescriber. The consultant pharmacist’s note should gather information from as many sources as possible to make the case for a trial discontinuation and/or switch. The nursing facility typically has all the information necessary to make a good decision; however, this information may reside in several different places (e.g., nurse’s medication administration record or behavior flow sheet) or can be gained by talking to the care aide. The consultant pharmacist is in the unique position to collate all this information into a note that gives the prescriber all the necessary information to make an informed decision, including references to primary literature. While an understanding of dissociation constants, receptor affinities, and pharmacologic effects are part of the training of pharmacists, providers may need help interpreting how this information affects the clinical manifestations of the pharmacotherapy they prescribe. The use of low-dose quetiapine is seemingly “lowhanging fruit” for consultant pharmacists seeking to make an impact on the use of antipsychotics in the long-term care facility. Knowledge of receptor affinities and pharmacologic effects, as well as appropriate data-gathering and collating within a medical note, can potentially be an effective strategy for decreasing the use of low-dose quetiapine.
The Consultant Pharmacist may 2015 Vol. 30, No. 5
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Student Forum
Amie Taggart Blaszczyk, PharmD, CGP, BCPS, FASCP, is associate professor and division head, Geriatrics, Texas Tech University Health Sciences Center-Dallas/Fort Worth, Dallas, Texas. Kelley A. McGinnis is a 2015 PharmD candidate, Texas Tech University Health Sciences Center-Dallas/Fort Worth. Heidi N. Michaels is a 2015 PharmD candidate, Texas Tech University Health Sciences CenterDallas/Fort Worth. Tony N. Nguyen is a 2015 PharmD candidate, Texas Tech University Health Sciences Center-Dallas/Fort Worth. For correspondence: Amie Taggart Blaszczyk, PharmD, CGP, BCPS, FASCP, Texas Tech University Health Sciences Center-Dallas/Fort Worth, 5920 Forest Park Road, Suite 500, Dallas, TX 75235; E-mail: [email protected]. Disclosure: No funding was received for the development of this manuscript. The authors have no potential conflicts of interest. © 2015 American Society of Consultant Pharmacists, Inc. All rights reserved. Doi:10.4140/TCP.n.2015.287. References 1. Data show National Partnership to Improve Dementia Care exceeds goals to reduce unnecessary antipsychotic medications in nursing homes. Baltimore, MD: Centers for Medicare & Medicaid Services; September 19, 2014. Available at http://www.cms.gov/ Newsroom/MediaReleaseDatabase/Fact-sheets/2014-Fact-sheetsitems/2014-09-19.html. Accessed: April 1, 2015. 2. Levinson DR. Medicare Atypical Antipsychotic Drug Claims for Elderly Nursing Home Residents. Department of Health and Human Services Office of Inspector General Report (OEI-07-08-00150). May 4, 2011. Available at https://oig.hhs.gov/oei/reports/oei-07-08-00150. pdf. Accessed September 8, 2014. 3. Briesacher BA, Limcangco MR, Simoni-Wastila L et al. The quality of antipsychotic drug prescribing in nursing homes. Arch Intern Med 2005;165:1280-5. 4. Bonner A. Improving dementia care and reducing unnecessary use of antipsychotic medications in nursing homes. Baltimore, MD: Centers for Medicare & Medicaid Services; January 1, 2013. Available at https://doh.sd.gov/news/documents/cms_dementia_care.pdf. Accessed September 11, 2014. 5. DeVane CL, Nemeroff CB. Clinical pharmacokinetics of quetiapine an atypical antipsychotic. Clin Pharmacokinet 2001;40:509-22. 6. Nemeroff CB, Kinkead B, Goldstein J. Quetiapine: preclinical studies, pharmacokinetics, drug interactions, and dosing. J Clin Psychiatry 2002;63 Suppl 13:5-11. 7. Richelson E, Souder T. Binding of antipsychotic drugs to human brain receptors: focus on newer generation compounds. Life Sci 2000;68:29-39. 8. Gefvert O, Lundberg T, Wieselgren I-M et al. D2 and 5HT2A receptor occupancy of different doses of quetiapine in schizophrenia: a PET study. Eur Neuropsychopharmacol 2001;11:105-10.
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9. Lieberman JA, Stroup TS, McEvoy JP et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 2005;353:1209-23. 10. Citrome L, Jaffe A, Levine J et al. Dosing of quetiapine in schizophrenia: how clinical practice differs from registration studies. J Clin Psychiatry 2005;66:1512-6. 11. Sparshatt A, Jones S, Taylor D. Quetiapine dose-response relationship in schizophrenia. CNS Drugs 2008;22:49-68. 12. American Geriatrics Society. Guide to the management of psychotic disorders and neuropsychiatric symptoms of dementia in older adults. Available at http://dementia.americangeriatrics.org/table6.php. Accessed December 15, 2014. 13. Weeke P, Jensen A, Folke F et al. Antipsychotics and associated risk of out-of-hospital cardiac arrest. Clin Pharmacol Ther 2014;96:490-7. 14. Targum SD. Treating psychotic symptoms in elderly patients. Prim Care Companion J Clin Psychiatry 2001;3:156-63. 15. Schneider LS, Tariot PN, Dagerman KS et al. Effectiveness of atypical antipsychotic drugs in patients with Alzheimer’s disease. N Engl J Med 2006;355:1525-38. 16. Sultzer DL, Gray KF, Gunay I et al. Does behavioral improvement with haloperidol or trazodone treatment depend on psychosis or mood symptoms in patients with dementia? J Am Geriatr Soc 2001;49:1294-300. 17. Seitz DP, Adunuri N, Gill SS et al. Antidepressants for agitation and psychosis in dementia. Cochrane Database Syst Rev 2011:CD008191. 18. Mendelson WB. A review of the evidence for the efficacy and safety of trazodone in insomnia. J Clin Psychiatry 2005;66:469-76. 19. Cakir S, Kulaksizoglu IB. The efficacy of mirtazapine in agitated patients with Alzheimer’s disease: a 12-week open-label pilot study. Neuropsychiatr Dis Treat 2008;4:963-6. 20. Stahl SM. Antidepressants. In Stahl SM, ed. Stahl’s Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. 3rd ed. New York, NY: Cambridge University Press; 2008. 21. Schwab W, Messinger-Rapport B, Franco K. Psychiatric symptoms of dementia: treatable, but no silver bullet. Cleve Clin J Med 2009;76:167-74. 22. Thase ME. Antidepressant treatment of the depressed patient with insomnia. J Clin Psych 1999;60 Suppl 17:28-31; discussion 46-8. 23. Nutt D. Mirtazapine: pharmacology in relation to adverse effects. Acta Psychiatr Scand 1997:96 Suppl 391:31-7. 24. Roose SP, Nelson JC, Salzman C et al. Mirtazapine in the Nursing Home Study Group. Open-label study of mirtazapine orally disintegrating tablets in depressed patients in the nursing home. Curr Med Res Opin 2003;19:737-46. 25. Srinivasan V, Kaur C, Pandi-Perumal S et al. Melatonin and its agonist ramelteon in Alzheimer’s disease: possible therapeutic value. Int J Alzheimers Dis 2010;2011:741974. 26. Cardinali DP, Brusco LI, Liberczuk C et al. The use of melatonin in Alzheimer’s disease. Neuro Endocrinol Lett 2002;23 Suppl 1:20-3. 27. Cohen-Mansfield J, Garfinkel D, Lipson S. Melatonin for treatment of sundowning in elderly persons with dementia—a preliminary study. Arch Gerontol Geriatr 2000;31:65-76.
The Consultant Pharmacist may 2015 Vol. 30, No. 5
Introduction In March 2012, the Centers for Medicare & Medicaid Services (CMS) launched a quality initiative aimed at decreasing off-label use of antipsychotics in nursing facilities by 15% by the end of 2013.1 This was in reaction to a 2011 report from the Office of the Inspector General that found that 14% of elderly nursing facility residents had Medicare claims for second-generation (atypical) antipsychotic drugs, and that 83% of these claims were associated with off-label use. Antipsychotics are frequently prescribed for residents with dementia who have behavioral or psychological symptoms associated with dementia (BPSD).2,3 The use of the word “agitation” is often used as a catch-all term for these types of behaviors. In September 2014, CMS announced reaching its initial goal of a greater than 15% reduction in antipsychotic use in long-term nursing facility residents, with all 50 states showing at least some improvement.1 The National Partnership to Improve Dementia Care is a coalition whose goal is to support efforts to reduce antipsychotic use through enhanced training for providers, publicly available data on antipsychotic use, and the formation of a behavioral health committee for dementia care practice.1,4 Considering the complexity of the rationale for antipsychotic therapy, a one-size-fits-all solution for reducing antipsychotic use is not feasible. Therefore, the mandates from CMS on decreasing antipsychotic use in long-term care requires creative solutions from the entire health care team—including the consultant pharmacist. The consultant pharmacist has the training and knowledge to understand how receptor affinities and pharmacologic actions of medications can influence necessity within a disease state, as well as the knowledge of adverse effects. This paper will focus on the receptor affinities of quetiapine and how consultant pharmacists may be able to recommend agents with similar receptor affinities and pharmacologic effects to elicit the same response, but without the use of an antipsychotic.
The Consultant Pharmacist may 2015 Vol. 30, No. 5
287
Student Forum Review of Quetiapine Quetiapine is a second-generation antipsychotic indicated for the treatment of schizophrenia and bipolar disorder. This medication is rapidly absorbed orally, with blood concentrations peaking at one to two hours, demonstrates linear pharmacokinetics up to a dose of 375 mg twice daily, and is eliminated through hepatic metabolism by cytochrome P450 3A4.5 Quetiapine antagonizes multiple receptors: alpha 1 and 2, dopamine (D2), histamine (H1), muscarinic, and serotonin (5HT1A, -1D, -2A, and -2D). As the dopamine hypothesis of schizophrenia suggests, antipsychotic efficacy is through antagonism of the D2 receptor.6 However, quetiapine has a low affinity for the D2 receptor, requiring higher doses for clinical effects of D2 antagonism.7-9 Experts in the field have even noted a need for doses exceeding approved doses for the treatment of schizophrenia.10 A fixed-dose trial in schizophrenic patients failed to show a statistically significant improvement in the Clinical Global Impression (CGI) scale between those taking quetiapine 25 mg twice daily versus 150 mg three times daily. However, there was a statistically significant improvement in CGI in patients taking 225 mg twice daily compared with 25 mg twice daily.11 The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) research group compared several second-generation antipsychotics with perphenazine in schizophrenic patients. The quetiapine dosing in this trial ranged from 200 mg to 800 mg per day, with a mean modal dose of 543.4 mg per day, again supporting a need for higher dosing for antipsychotic effects.9 Case studies and case series have reported that using higherthan-approved doses of quetiapine may be necessary and effective in treatment resistance.11 Since quetiapine’s affinity for the D2 receptor is much lower than the affinity for the alpha-1, H1, and 5HT-2A receptors, side effects manifesting from antagonism of these receptors can be present at much lower doses (12.5 mg to 100 mg).11,12 While the prevalence of specific antipsychotic prescribing in facilities varies from region to region, quetiapine, even at low doses, is one of the most
288
commonly prescribed antipsychotics for a variety of psychiatric indications (both on-label and off-label) in elderly nursing facility residents.2 Aside from the burden of cost, clinical “antipsychotic effects” at low doses are questionable. Given the receptor affinities of low-dose quetiapine for H1 and 5HT-2A, the question could be posed: Is effectiveness derived from the sedative and mood properties of quetiapine, rather than the antipsychotic (D2 receptor antagonism) properties? And, if so, are there safer alternatives with similar receptor affinities? Both the patient’s and staff ’s safety, as well as the provider’s and facility’s liability, are considerations when evaluating a change in therapy. Behavioral disturbances that may harm the patient or staff, such as aggression, wandering into off-limit areas, and disturbing or scary hallucinations, can occur when a patient is not adequately treated. However, there is also the concern for anticholinergic effects, increased fall risk, changes in cognition, and increased cardiovascular risk associated with the use of antipsychotics, especially in patients with dementia, which may be an unnecessary risk.13 Nonpharmacologic alternatives or tapering down antipsychotic therapy in patients on low-dose quetiapine is a reasonable consideration. Studies have suggested a potential benefit in cognition following antipsychotic withdrawal, and though safer alternatives in the geriatric population exist, none is without risk.14 CATIE-AD (Alzheimer’s disease [AD]), a randomized placebo-controlled trial that enrolled outpatients with AD and psychosis, aggression or agitation, failed to show clinical benefit in patients treated with quetiapine compared with a placebo group.15 The average final dose in the quetiapine arm was 56.5 mg/day, an increase from 34.1 mg/day initially. The time to discontinuation for lack of efficacy was not different between the quetiapine and placebo groups (median time: 9.1 weeks versus 9.0 weeks, respectively). Not all residents, families, staff, or facilities are amenable to antipsychotic therapy being discontinued, especially when there is a perception of benefit. However, given the receptors quetiapine likely antagonizes at low doses, providers and families may be amenable to switching to an agent that behaves the same way as those same receptors.
The Consultant Pharmacist may 2015 Vol. 30, No. 5
Is It Time to Call It Quits on Low-Dose Quetiapine?
Antidepressants
Melatonin
Antidepressants with evidence supporting a benefit of improving behavioral disturbances include trazodone and mirtazapine.16-19 While the use of an antidepressant to help with problematic behaviors may seem like an easy switch, these agents are not benign from a side effect standpoint. They would also require additional documentation for their use, especially in those without a concomitant depression diagnosis. Trazodone is an antidepressant that, at low doses, antagonizes 5HT-2A, H1, and alpha-1 receptors.20 This accounts for the sedative-hypnotic effects seen when used at low doses. Antidepressant effects of trazodone are not typically seen until doses are greater than 100 mg.20 In one study, trazodone showed an ability to manage agitation and aggressive behavior associated with psychosis in a cohort of depressed elderly patients.16 Though not statistically different from placebo, another study showed similar efficacy with trazodone when compared with haloperidol in older adults with dementia.17 As is the case with quetiapine, there is a potential increased risk of orthostatic hypotension in the older patient population, secondary to its antagonism of the alpha-1 receptor.21 Mirtazapine can be an option for agitation in AD and, because of its 5HT-2C and H1 antagonism, has shown to improve sleep and appetite, but may require a risk-versusbenefit discussion when used in patients with diabetes, metabolic syndrome, hyperlipidemia, and obesity.19,20,22,23 Since agitation may be related to insomnia or untreated depression, the potential for minimizing agitation may be easily resolved, or at least modulated, with the bedtime use of mirtazapine.19 Advantages include minor side effects (mild hypotension, headache), improved appetite without affecting weight substantially, and potential for regulating sleep through its target on the HPA axis and melatonin.24
If agitation being treated is related to sundowning, evidence exists for the administration of melatonin.25 In one study, patients receiving nightly melatonin at a dose of 6 mg to 9 mg had fewer documented behavioral changes.26 Another trial monitored AD patients for three weeks and found reduced agitation and daytime sleepiness with bedtime melatonin use at a dose of 1 mg to 3 mg.27
Implications and Strategies for the Consultant Pharmacist While pharmacokinetic evidence exists to support a trial of no therapy or an alternative therapy for behavioral symptoms associated with dementia for patients being treated with low-dose quetiapine, the next step would be to convey this to the person with the power to change therapy: the prescriber. The consultant pharmacist’s note should gather information from as many sources as possible to make the case for a trial discontinuation and/or switch. The nursing facility typically has all the information necessary to make a good decision; however, this information may reside in several different places (e.g., nurse’s medication administration record or behavior flow sheet) or can be gained by talking to the care aide. The consultant pharmacist is in the unique position to collate all this information into a note that gives the prescriber all the necessary information to make an informed decision, including references to primary literature. While an understanding of dissociation constants, receptor affinities, and pharmacologic effects are part of the training of pharmacists, providers may need help interpreting how this information affects the clinical manifestations of the pharmacotherapy they prescribe. The use of low-dose quetiapine is seemingly “lowhanging fruit” for consultant pharmacists seeking to make an impact on the use of antipsychotics in the long-term care facility. Knowledge of receptor affinities and pharmacologic effects, as well as appropriate data-gathering and collating within a medical note, can potentially be an effective strategy for decreasing the use of low-dose quetiapine.
The Consultant Pharmacist may 2015 Vol. 30, No. 5
289
Student Forum
Amie Taggart Blaszczyk, PharmD, CGP, BCPS, FASCP, is associate professor and division head, Geriatrics, Texas Tech University Health Sciences Center-Dallas/Fort Worth, Dallas, Texas. Kelley A. McGinnis is a 2015 PharmD candidate, Texas Tech University Health Sciences Center-Dallas/Fort Worth. Heidi N. Michaels is a 2015 PharmD candidate, Texas Tech University Health Sciences CenterDallas/Fort Worth. Tony N. Nguyen is a 2015 PharmD candidate, Texas Tech University Health Sciences Center-Dallas/Fort Worth. For correspondence: Amie Taggart Blaszczyk, PharmD, CGP, BCPS, FASCP, Texas Tech University Health Sciences Center-Dallas/Fort Worth, 5920 Forest Park Road, Suite 500, Dallas, TX 75235; E-mail: [email protected]. Disclosure: No funding was received for the development of this manuscript. The authors have no potential conflicts of interest. © 2015 American Society of Consultant Pharmacists, Inc. All rights reserved. Doi:10.4140/TCP.n.2015.287. References 1. Data show National Partnership to Improve Dementia Care exceeds goals to reduce unnecessary antipsychotic medications in nursing homes. Baltimore, MD: Centers for Medicare & Medicaid Services; September 19, 2014. Available at http://www.cms.gov/ Newsroom/MediaReleaseDatabase/Fact-sheets/2014-Fact-sheetsitems/2014-09-19.html. Accessed: April 1, 2015. 2. Levinson DR. Medicare Atypical Antipsychotic Drug Claims for Elderly Nursing Home Residents. Department of Health and Human Services Office of Inspector General Report (OEI-07-08-00150). May 4, 2011. Available at https://oig.hhs.gov/oei/reports/oei-07-08-00150. pdf. Accessed September 8, 2014. 3. Briesacher BA, Limcangco MR, Simoni-Wastila L et al. The quality of antipsychotic drug prescribing in nursing homes. Arch Intern Med 2005;165:1280-5. 4. Bonner A. Improving dementia care and reducing unnecessary use of antipsychotic medications in nursing homes. Baltimore, MD: Centers for Medicare & Medicaid Services; January 1, 2013. Available at https://doh.sd.gov/news/documents/cms_dementia_care.pdf. Accessed September 11, 2014. 5. DeVane CL, Nemeroff CB. Clinical pharmacokinetics of quetiapine an atypical antipsychotic. Clin Pharmacokinet 2001;40:509-22. 6. Nemeroff CB, Kinkead B, Goldstein J. Quetiapine: preclinical studies, pharmacokinetics, drug interactions, and dosing. J Clin Psychiatry 2002;63 Suppl 13:5-11. 7. Richelson E, Souder T. Binding of antipsychotic drugs to human brain receptors: focus on newer generation compounds. Life Sci 2000;68:29-39. 8. Gefvert O, Lundberg T, Wieselgren I-M et al. D2 and 5HT2A receptor occupancy of different doses of quetiapine in schizophrenia: a PET study. Eur Neuropsychopharmacol 2001;11:105-10.
290
9. Lieberman JA, Stroup TS, McEvoy JP et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 2005;353:1209-23. 10. Citrome L, Jaffe A, Levine J et al. Dosing of quetiapine in schizophrenia: how clinical practice differs from registration studies. J Clin Psychiatry 2005;66:1512-6. 11. Sparshatt A, Jones S, Taylor D. Quetiapine dose-response relationship in schizophrenia. CNS Drugs 2008;22:49-68. 12. American Geriatrics Society. Guide to the management of psychotic disorders and neuropsychiatric symptoms of dementia in older adults. Available at http://dementia.americangeriatrics.org/table6.php. Accessed December 15, 2014. 13. Weeke P, Jensen A, Folke F et al. Antipsychotics and associated risk of out-of-hospital cardiac arrest. Clin Pharmacol Ther 2014;96:490-7. 14. Targum SD. Treating psychotic symptoms in elderly patients. Prim Care Companion J Clin Psychiatry 2001;3:156-63. 15. Schneider LS, Tariot PN, Dagerman KS et al. Effectiveness of atypical antipsychotic drugs in patients with Alzheimer’s disease. N Engl J Med 2006;355:1525-38. 16. Sultzer DL, Gray KF, Gunay I et al. Does behavioral improvement with haloperidol or trazodone treatment depend on psychosis or mood symptoms in patients with dementia? J Am Geriatr Soc 2001;49:1294-300. 17. Seitz DP, Adunuri N, Gill SS et al. Antidepressants for agitation and psychosis in dementia. Cochrane Database Syst Rev 2011:CD008191. 18. Mendelson WB. A review of the evidence for the efficacy and safety of trazodone in insomnia. J Clin Psychiatry 2005;66:469-76. 19. Cakir S, Kulaksizoglu IB. The efficacy of mirtazapine in agitated patients with Alzheimer’s disease: a 12-week open-label pilot study. Neuropsychiatr Dis Treat 2008;4:963-6. 20. Stahl SM. Antidepressants. In Stahl SM, ed. Stahl’s Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. 3rd ed. New York, NY: Cambridge University Press; 2008. 21. Schwab W, Messinger-Rapport B, Franco K. Psychiatric symptoms of dementia: treatable, but no silver bullet. Cleve Clin J Med 2009;76:167-74. 22. Thase ME. Antidepressant treatment of the depressed patient with insomnia. J Clin Psych 1999;60 Suppl 17:28-31; discussion 46-8. 23. Nutt D. Mirtazapine: pharmacology in relation to adverse effects. Acta Psychiatr Scand 1997:96 Suppl 391:31-7. 24. Roose SP, Nelson JC, Salzman C et al. Mirtazapine in the Nursing Home Study Group. Open-label study of mirtazapine orally disintegrating tablets in depressed patients in the nursing home. Curr Med Res Opin 2003;19:737-46. 25. Srinivasan V, Kaur C, Pandi-Perumal S et al. Melatonin and its agonist ramelteon in Alzheimer’s disease: possible therapeutic value. Int J Alzheimers Dis 2010;2011:741974. 26. Cardinali DP, Brusco LI, Liberczuk C et al. The use of melatonin in Alzheimer’s disease. Neuro Endocrinol Lett 2002;23 Suppl 1:20-3. 27. Cohen-Mansfield J, Garfinkel D, Lipson S. Melatonin for treatment of sundowning in elderly persons with dementia—a preliminary study. Arch Gerontol Geriatr 2000;31:65-76.
The Consultant Pharmacist may 2015 Vol. 30, No. 5
