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Need for Higher Regulation of Second Generation Antipsychotics Prescribing for Behavioral & Psychological Symptoms of Dementia Caitlyn Cardetti Advisor: Dr. Dawn Albertson
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Need for Higher Regulation of SGA Prescribing for BPSD

Jan 13, 2015

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Page 1: Need for Higher Regulation of SGA Prescribing for BPSD

Need for Higher Regulation of Second Generation

Antipsychotics Prescribing for Behavioral & Psychological

Symptoms of DementiaCaitlyn Cardetti

Advisor: Dr. Dawn Albertson

Page 2: Need for Higher Regulation of SGA Prescribing for BPSD

The Elderly• Fastest growing age group.• Often excluded from clinical trials.• Most likely age group to use

prescription drugs.

1 2 3-4 5+

Risk of Polypharmacy with AgeAges 20-59 Age 60+

Number of Prescription Drugs

Page 3: Need for Higher Regulation of SGA Prescribing for BPSD

The Aging Body & Drugs

Page 4: Need for Higher Regulation of SGA Prescribing for BPSD

Behavioral & Psychological Symptoms of Dementia (BPSD)

• Symptoms include but are not limited to:• Agitation• Irritability• Anxiety

• Commonly treated with off label use of second generation antipsychotics (SGA)• FGA vs. SGA

Page 5: Need for Higher Regulation of SGA Prescribing for BPSD

Purpose• Identify appropriateness of SGA as treatment for BPSD• Efficacy• Possible Adverse Drug Effects (ADE)

• Specific issues concerning the elderly• Exacerbation of Age-Associated Diseases• Drug Interactions

Page 6: Need for Higher Regulation of SGA Prescribing for BPSD

Methodology• Use of broad search terms in PubMed database• Preliminary search found only 3 of 9 SGA to be

effective for treatment of BPSD• Olanzapine• Risperidone• Aripiprazole

• Each drug individually searched inwith the following categories:• Adverse Drug Effects (ADE)• Age-Associated Diseases• Polypharmacy

Page 7: Need for Higher Regulation of SGA Prescribing for BPSD

Exacerbation of Age-Associated Diseases• Cardiovascular Disease• Olanzapine – favorable QTc profile• Risperidone – increased risk of stroke, possible risk of QT

prolongation• Aripiprazole – possible risk of QT prolongation

• Diabetes• Olanzapine – associated with increased glucose levels• Risperidone – associated with a few cases of

hyperglycemia• Aripiprazole – no data

Page 8: Need for Higher Regulation of SGA Prescribing for BPSD

Drug Interactions• Donezepil (Aricept)• Treatment for mild to moderate Alzheimer’s Disease• Possible indication of increased movement disorders with

olanzapine

• Antidiuretics• Drugs that limit formation of urine• No literature available

• Beta Blockers• Drugs commonly prescribed for HTN• Olanzapine is inhibited by a common beta blocker

• Statins• Medication that lowers cholesterol• Possible increased risk of muscle breakdown

when used with SGA

114%

214%

3-431%

5+42%

Polypharmacy in those Age 60+

Page 9: Need for Higher Regulation of SGA Prescribing for BPSD

Conclusion & Recommendations• Increase resources available for doctors when

prescribing• Need for further studies in exacerbation of age-associated

diseases and drug interactions

Olanzapine

Risperidone

Aripiprazole

Donezepil - ? ?Antidiuretics

? ? ?Beta Blockers

- ? ?Statins - - -

Olanzapine

Risperidone

Aripiprazole

CV Disease

+ - -/?Diabetes - - ?

Page 10: Need for Higher Regulation of SGA Prescribing for BPSD

Conclusions & Recommendations• Update the Beers Criteria

Page 11: Need for Higher Regulation of SGA Prescribing for BPSD

Conclusions & Recommendations• Update the Beers Criteria

Page 12: Need for Higher Regulation of SGA Prescribing for BPSD

Conclusions & Recommendations• Create standard guidelines for prescribing• Assurance that non-pharmacological interventions were

tried but failed• Evaluations for drug profiles based on patient’s current

health condition• Recommendations for follow-ups

Page 13: Need for Higher Regulation of SGA Prescribing for BPSD

References• Cerejeira, J., Largarto, L., & Mukaetova-Ladinska, E. B. (2012). Behavioral and psychological

symptoms of dementia. Frontiers of Neurology, 3(73), doi: 10.3389/fneur.2012.00073.• Maher, A., Maglione, M., Bagley, S., Suttorp, M., Hu, J., Ewing, B., Wang, Z., Timmer, M., &

Shekelle, P.G. (2011). Efficacy and comparative effectiveness of atypical antipsychotic medications for off-label uses in adults: A systematic review and meta-analysis. Journal of American Medical Association, 306(12), 1359-69. Retrieved from http://www.ncbi.nlm.nih.gov.ezproxy.mnsu.edu/pubmed/21954480

• Department of Health and Human Services, Administration of Aging. (2011). Aging statistics. Retrieved from website: http://www.aoa.gov/AoARoot/Aging_Statistics/index.aspx

• Chen, Y., Briesacher, B., Field, T., Tjia, J., Lau, D., & Gurwitz, J. (2011). Unexplained variation across u.s. nursing homes in antipsychotc prescribing rates. Archives of Internal Medicine, 170(1), 89-95. doi: 10.1001/archinternmed.2009/469

• Gu Q, Dillon CF, Burt VL. Prescription drug use continues to increase: U.S. prescription drug data for 2007-2008. NCHS data brief, no 42. Hyattsville, MD: National Center for Health Statistics. 2010.

• Agency for Healthcare Research and Quality, Effective Health Care Program. (2011). Off-label use of atypical antipsychotics: An update. comparative effectiveness review no. 43 (Publication No. 11-EHC087-EF). Retrieved from AHRQ Publication website: http://www.effectivehealthcare.ahrq.gov/search-for-guides-reviews-and-reports/?pageaction=displayproduct&productid=786

• Jeste M.D., D., Dolder, Pharm.D., C., Nayak M.A., G., & Salzman M.D., C. (2005). Atypical antipsychotics in elderly patients with dementia or schizophrenia: Review of recent literature. Harvard Review of Psychiatry, 13, 340-351. doi: 10.1080|10673220500433247

Page 14: Need for Higher Regulation of SGA Prescribing for BPSD

References• (2012). American geriatrics society updated beers criteria for potentially inappropriate

medication use in older adults. Journal of American Geriatrics Society, doi: 10.1111/j.1532-5415/2012.03923/x

• De Deyn, P., Katz, I., Brodaty, H., Lyons, B., Greenspan, A., & Burns, A. (2005). Management of agitation, aggression, and psychosis associated with dementia: A pooled analysis including three randomized, placebo-controlled double-blind trials in nursing home residents treated with risperidone. Journal of Clinical Neurology and Neurosurgery, doi: 10.1016/j/clineuro.2005.03.013

• McShane, R., Keene, J., Gedling, K., Fairburn, C., Jacoby, R., & Hope, T. (1997). Do neuroleptic drugs hasten cognitive decline in dementia? Prospective study with necropsy follow up. British Medical Journal,315(7076), 266-270. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2125727/

• Ballard C, Lana MM, Theodoulou M, Douglas S, McShane R, et al. (2008) A Randomised, Blinded, Placebo-Controlled Trial in Dementia Patients Continuing or Stopping Neuroleptics (The DART-AD Trial) . PLoS Med 5(4): e76. doi:10.1371/journal.pmed.0050076Strait, J. B., & Lakatta, E. G. (2012). Aging-associated cardiovascular changes and their relationship to heart failure. Heart Failure Clinics, 8(1), 143-164. doi: 0.1016/j.hfc.2011.08.01

• Glassman, A., & Bigger Jr., J. (2001). Antipsychotic drugs: prolonged qtc interval, torsade de pointes, and sudden dath . American Journal of Psychiatry,158(11), 1774-82. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/11691681

• Lindborg, S., Beasley, C., Alaka, K., & Taylor, C. (2003). Effects of intramsucular olaznapine vs. haloperiodol and placebo on qtc intervals in acutely agitated patients. Psychiatry Research Journal, 119(1-2), 113-23. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/12860365

Page 15: Need for Higher Regulation of SGA Prescribing for BPSD

References• Gulisano, M., Cali, P., Cavanna, A., Eddy, C., Rickards, H., & Rizzo, R. (2011). Cardiovascular

safety of aripiprazole and pimozide in young patients with tourette snydrome. Journal of Neurological Sciences, 32(6), 1213-7. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/21732066

• tminan, M., Streiner, D., & Ronchon, P. (2003). Exploring the association between atypical neuroleptic agents and diabetes mellitus in older adults.Pharmacotherapy, 23(11), 1411-5. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/14620387

• Kroner Pharm.D., B.C.P.S., B. (2002). Common drug pathways and interactions. Diabetes Spectrum, 15(4), 249-255. doi: 10.2337/diaspect.15.4.249

• Nirogi, R., Bjyrapuneni, G., Kandikere, V., Benade, V., Muddana, N., Saralaya, R., Irappanavar, S., Ponnamaneni, R., & Mukkanti, K. (2012). Concurrent administration of atypical antipsychotics and donepezil: drug interaction study in rats. European Journal of Drug Metabolism and Pharmacokinetics, Retrieved from http://www.ncbi.nlm.nih.gov.ezproxy.mnsu.edu/pubmed/22302541

• van den Heuvel, O., Bet, P., van Dam, E., & Eeckhout, A. (2006). The syndrome of inappropriate antidiuretic hormone secretion (siadh) during treatment with the antipsychotic agents haloperidol and quetiapine.Ned Tijdschr Geneeskd, 150(35), 1944-8. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/16999280

• Atalay, A., Turnhan, N., & Aki, O. (2007). A challenging case of syndrome of inappropriate secretion of antidiuretic hormone in an elderly patient secondary to quetiapine. Southern Medical Journal, 100(8), 832-3. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/17713312

Page 16: Need for Higher Regulation of SGA Prescribing for BPSD

References• Webber, M., Mahmud, W., Lightfoot, J., & Shekhar, A. (2004). Rhabdomyolysis

and compartment syndrome with coadministration of risperidone and simvastatin. Journal of Psychopharmacology,18(3), 432-4. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/15358990

• Patier, J., Ferrere, F., Moreno-Cobo, M., & Echaniz, A. (2007). Rhabdomyolysis caused by association of simvastatin and risperidone. Medicina clinica ,129(11), 439. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/17927942

• Vivves, S., Batlle, M., Motane, E., & Ribera, J. (2008). Rhabdomyolysis and renal failure secondary to interaction between simvastatin, ciclosporin a and risperidone in an allogeneic stem cell transplantation patient. Medicina clinica , 131(17), 676. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/19087798

• Walder, A., & Baumann, P. (2009). Mood stabilizer therapy and pravastatin: higher risk for adverse skin reactions?. Acta Medica, 52(1), 15-18. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/19754002

• Ohaski, K., Hamamura, T., Lee, Y., Fujiwara, Y., Suzuki, H., & Kuroda, S. (2000). Clozapine- and olanzapine-induced fos exression in the rat medial prefrontal cortex is mediated by beta-adrenoceptors. Neuropsychopharmacology,23(2), 162-9. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/10882842