• Abstract and Figures
• Public Full-text

Ambulatory Geriatrics Curriculum for Internal Medicine Residents

Module on BPSD: Agitation and Behavioral Problems in Dementia

A. Introduction to Module: In 2012, 5.4 million Americans are diagnosed with Alzheimer’s Disease. Lifetime risk of experiencing BPSD i s nearly 100%. BPSD is associated with increased morbidity and nursing home placement and is potentially tre atable. The information in this curriculum has been created to help the general internist have a structured appro ach to the evaluation and management of BPSD.

B. Learning Objectives:

At the conclusion of this module, learners will be able to: 1. Define BPSD 2. Evaluate BPSD 3. Discuss the Guidelines for Management of BPSD • Nonpharmacologic Interventions • Pharmacologic Interventions

Curriculum, Resources and Handout for Residents: Behavioral and Psychological Symptoms of Dementia I. What Is BPSD? Non-cognitive manifestations of dementia

B(ehavioral)______Behavioral Symptoms P(sychological)______“Agitation” Mood Symptoms Related to resistiveness to care Psychotic Symptoms Physical vs Verbal Sleep Disturbances Aggressive vs Nonaggressive S(ymptoms)______Hitting, biting, yelling vs pacing, wandering, hoarding D (ementia)______Psychological Symptoms Mood Symptoms Psychotic Symptoms Sleep Disturbances

II. Why Is BPSD Important? 1 in 8 Americans > 65 yrs of age has AD (ie 5.4 million) 1. Lifetime risk is nearly 100% 2. Associated with increased morbidity and nursing home placement 3. Potentially treatable

III. REVIEW UNFOLDING CLINICAL CASE WITH ANSWERS AND APPENDIX

Developed by Christine Chang, MD December 2014 10-18-15 PART A: You are seeing Mrs. Robbin Green, a 78-year-old with mild Alzheimer’s disease (MMSE 23 of 30), hypertension, osteoarthritis, and urinary incontinence who comes to the office with her daughter for “acting up” for past 2 weeks. Daughter reports that she repeats stories and packs her bags several times a day, stating that she is “going home.” She is up frequently at night, pacing and wandering. The other day, she struck her home attendant. Medications: donepezil 5 mg daily, hydrochlorothiazide 25 mg daily, lisinopril 10 mg daily, baby aspirin, tolterodine LA 2 mg, and acetaminophen 500 mg once daily.

1. How would you approach this case?

Evaluation of BPSD 1. Obtain a History - clear description of the behavior from the patient & others • Temporal onset, course • Associated circumstances • Relationship to key environmental factors • In context of the patient’s medical, family and social history

2. Careful Physical & Neurologic Exam Assess Mental Status Pay attention to: • Appearance and Behavior • Speech • Mood • Thoughts and Perceptions • Cognitive Function • Attention

3. Lab Studies • CBC, metabolic panel and drug levels in all cases of new onset BPSD • Brain imaging, EKG, CXR, and urinalysis based on the history and exam

R/O Delirium • Acute Conditions such as acute infection like pneumonia and UTI, angina, endocrine abnormality, electrolyte imbalance, pain and constipation • Medication Toxicity or adverse effects of medications due to new or existing medications

R/O Environmental Causes 1) Make sure basic physical needs are met 2) Environmental Precipitant • Disruptions in routine-new or sick caregiver • Over Stimulation • Under Stimulation

After medical, environmental, and care giving causes are excluded, it can be concluded that the primary cause is progression of the dementia

Developed by Christine Chang, MD December 2014 10-18-15 PART A continued: Daughter reports that patient has been more incontinent these days but has had no fevers, chills, flank pain or hematuria. Pt has been eating a little less as well but reports no nausea, vomiting, diarrhea or constipation. ROS is otherwise negative. There are no new medications and no changes in the care giving environment.

Physical exam is unremarkable except for Temp 100.1, mild suprapubic tenderness without guarding or rebound or CVA tenderness. Neurological exam is non-focal though technically difficult. She is oriented only to person and easily distracted. Labs are unremarkable except for urine with positive nitrites and leukocyte esterase, and CBC with mild leukocytosis with left shift.

2. What is the most appropriate treatment? Treat UTI and employ NonPharmacologic Interventions

PART B: Mrs. Green is seen as an urgent visit 2 months later for being more agitated. Daughter reports that the patient has been screaming and scratching the new home attendant mainly during bathing. Daughter normally tries to help the home attendant with her mother’s care but has been busier these days as her grandchildren have been visiting. Daughter/pt denies fever, chills, cough, shortness of breath, pain, urinary or bowel symptoms. She has been eating and sleeping as usual. No other symptoms reported nor are there any new medications. Physical exam is unremarkable. Repeat MMSE remains 23/30 3. What is the most appropriate approach? a. Start haloperidol 0.5 mg at night b. Start risperidone 1 mg at night c. Increase donepezil to 10 mg d. Start citalopram 10 mg daily e. Review NonPharmacologic, patient-centered Interventions

Guideline for Management of BPSD 2012 Non-pharmacologic mgt of BPSD by Gitlin LN, Kales HC, Lyketsos CG1

2013 Management of the Behavioral and Psychological Symptoms of Dementia. NaRCAD (the National Resource Center for Academic Detailing) with support from a grant from the Agency for Healthcare Research and Quality 2

Nonpharmacologic Interventions First Why? • 40% of BPSD symptoms spontaneously resolve; “they come and go” • Placebo response can be quite substantial • No FDA approved medications for psychosis in AD

4 Effective Nonpharmacologic Interventions (Review Appendix A) 1-18 1. CG Interventions 2. Unmet Needs Interventions 3. Behavioral Interventions 4. Psychosocial Interventions

Developed by Christine Chang, MD December 2014 10-18-15 PART C: In a visit one year later, Mrs. Green is brought in for an urgent visit by her daughter with complaints of trouble sleeping for the past month. Mrs. Green confirms trouble falling sleep but is unable to provide a more comprehensive history. Daughter reports that her mother is usually active in the daytime, but for the last month has caught her napping in the daytime. Patient denies being sad or depressed and appetite and weight are stable. Physical exam and lab studies were within normal limits. PHQ9 was negative.

4. What is your first intervention? For Sleep-wake Cycle Disturbance >1 Month a. Prescribe zolpidem 5 mg Evaluation for Potential underlying causes of Insomnia 1. Obtain a complete Medication list with timing b. Recommend melatonin 1.5 mg • Diuretic (nocturia) c. Prescribe triazolam 0.125 mg • Stimulants/sympathomimetic d. Prescribe trazodone 25 mg (nicotine, caffeine, bronchodilators) e. Prescribe mirtazapine 7.5 mg • Anticholinergics, sedating (sinemet, analgesics) f. Counsel about non-pharmacologic interventions • SSRI can decrease REM to promote sleep 2. Complete a Sleep Diary to assess for patterns or triggers for insomnia 3. R/O depression + other psychiatric conditions

Review Appendix B21-23 REVIEW: McCurry SM et al. “Nighttime insomnia treatment and education f or Alzheimer's disease: a RCT.” JAGS. 2005 (Appendix B)21-23

5. What is your next approach if your first intervention fails?

REVIEW Appendix C-Hypnotics Recommend: E-trazodone a. Prescribe diphenhydramine 25 mg 2007 APA 31 + GRS 8 32 recommends 22,23: • Trazodone 303 b. Prescribe zolpidem 5 mg • Zolpidem and zaleplon • Mirtazapine c. Prescribe melatonin 1.5 mg REM-dys-control à clonazepam and cholinesterase inhibitors (e 29,30 d. Increase donepezil to 10 mg g, rivastigmine, pramipexole, melatonin ) Avoid: e. Prescribe trazodone 25 mg • Benzodiazepines • Antihistamines especially diphenhydramine f. Prescribe mirtazapine 7.5 mg

Key Points 21-33 • Pharmacologic treatment of the demented elder with insomnia should be reserved for those deemed to have primary insomnia and who have not responded to more conservative, nonpharmacologic interventions. • If the decision is made to treat with medication, the lowest possible effective dose should be used for a time-limited trial, and ‘‘as needed’’ dosing should be the rule. Use of these medications should be tapered Developedor discontinued by Christine gradually,Chang, MD mindful of potential for rebound insomnia after discontinuation. Of the choices December 2014 10-18-15listed, trazodone is considered the safest and least addictive. • Prescribed treatments should continue to be used in concert with non-pharmacologic and sleep hygiene measures. Part D: For the next 6 months, Mrs. Green’s course is unremarkable as the donepezil 10 mg with the intermittent trazodone 25mg has helped. During today’s visit, Mrs. Green reports feeling depressed about her loss of function and memory. She is no longer interested in going outdoors or watching some of her favorite TV shows. Patient reports anorexia and has lost 4.5 kg (10 lb) in past four months. Pt reports no suicidal ideation. On exam, patient affect appears flatten. PHQ9= 15 (c/w moderate-severe depression) but MMSE remains 23 which is unchanged. Physical exam is otherwise unremarkable. Lab work up including chemistries, CBC and TSH are negative. 6. What are the differential diagnoses?

2013 Management of the Behavioral and Psychological Symptoms of Dementia. National Resource Center for Academic Detailing with support from a grant from the Agency for Healthcare 7. How would you treat this patient? Research and Quality 2

a. Enrollment in Adult Day Health Care Center NON-EMERGENT vs EMERGENT BPSD 34-39

33, 40-48 b. Caregiver education and training in coping skills. Consider Antidepressants –1st line: SSRIs  Citalopram  Sertraline c. Prescribe nortriptyline 25 mg (improved depressive symptoms & ADLS w/o improving cognition)

d. Prescribe citalopram 10 mg Avoid fluoxetine and paroxetine (cyt 2D6 INH)

e. ECT (Electroconvulsive Therapy)

PART E: Mrs. Green’s returns 2 weeks later and reports that the initial treatment was unhelpful.

Developed by Christine Chang, MD December 2014 10-18-15 8. What would you do next? If a first agent has failed an adequate therapeutic dose for 3-6 weeks, 33-47 a. Switch to another agent in same class consider alternatives : b. Switch to another agent in another class  Bupropion (Dop/NE reuptake INH)  Mirtazapine 47 (SNA) c. Titrate dose of initial medication  Venlafaxine 43 (SNRI) d. Add methylphenidate 5 mg daily  Cymbalta (SNRI)  Tricyclic agents (desipramine + nortriptyline)

*Switch vs add- on but WATCH for Serotonin Syndrome:  MAOI + tramadol, DM, codeine, methadone + sumatryptan  Cyt3A4 deceases with AGE (grapefruit juice or azithromycin)  Cyt2D6 decreased in 5-10% Caucasian SLOW metabolizers  Bacterial endotoxin lipopolysaccharide

For partial responders to an antidepressant, consider augmentation strategies—watch for psychostimulant effect  Methylphenidate 49 ????  Modafinil??

If depression remains and patient is in danger of serious weight loss or suicidal ideas despite several antidepressant trials, consider

PART F: Mrs. Green responds well to citalopram 20ElectroConvulsive mg which you Therapycontinue 50 for the next 12 months. Over the next 2 years, daughter reports that Mrs. Green gradually*No RCT requires in geriatric more patients assistance with dementia with all of her ADLs despite addition of memantine 10 mg twice a day. She has developed urinary incontinence over past six months. The daughter has hired Carol to help with Mrs. Green’s care six months ago. Today daughter reports that Mrs. Green has been more and more resistant to personal care including bathing, shower and toileting over past two months. In few instances she became physically aggressive toward her daughter and her aide Carol. The daughter and Carol have employed appropriate non-pharmacologic interventions without much success. Again there are no new medications, no change in the care giving environment. Her physical exam and laboratory workup are negative. Delirium has been ruled out. Pain is optimized.

2013 Management of the behavioral and psychological symptoms of 9. When would you consider any medications? dementia. National Resource Center for Academic Detailing with support from a grant from the AHRQ 2

When pt is a danger to self and others after NPI has failed FOR EMERGENT BPSD 34-39, 60 Antipsychotics:  Use faster acting, higher risk medications  Limited evidence for longer term efficacy (≥6 months)  Genetic variability: T allele vs C allele of 5HT2A T102C polymorphism

NONemergent BPSD 2, 34-39, 51-54, 61, 67

• Aggression: consider risperidone 51, 54-56, abilify, ?olanzepine vs SSRI 40-48, prazosin 61, propranolol 65 • Psychosis: Consider risperidone 51,54-56 • PD/LBD: Consider Cholinesterase inhibitors, Namenda66, Quetiapine and Clozapine • FTD: Consider SSRIs • Bipolar-mood lability-hypersexual: consider carbamazepine 68. Developed by Christine Chang, MD Oral/depot progesterone, or anti-estrogen leuprolide, SSRI December 2014 Avoid valproic acid 67 10-18-15 10. What medication would you consider in treating her symptoms? a. Time-limited trial of haloperidol 0.5 mg Review Appendix D (BPSD TX guidelines) 2, 34-39, 51-54, 60, 61, 67 b. Time-limited trial of risperidone 0.5 mg Appendix E (Pharmacologics) c. Time-limited trial of olanzapine 5 mg Appendix F (Black Box warning) 71-73 d. Time-limited trial of valproate 250 mg e. Start a trial of prazosin 1mg daily Risperidone has modest but significant improvement in aggression 51, 54- 56(dose 2 mg, over 6-12 weeks of treatment)

Haldol might be effective in treating aggression in patients with dementia but side effects limits its use (extrapyramidal symptoms) 56-58

Part G: Mrs. Green does not respond to the risperidone 0.5 mg so you titrate it to 1mg and the symptoms subside. You continue this for 4 weeks and eventually you are able to wean it off74.

Always remember to wean antipsychotics if possible when BPSD improves given Black Box warning 71-73

TAKE HOME POINTS: • Always obtain a thorough history about the “disturbance” • Rule out delirium and other environmental factors contributing to the disturbance • Use nonpharmacologic interventions for BPSD first • Consider “targeted,” time-limited pharmacologic trials for severe or persistent BPSD symptoms given m odest evidence of efficacy and moderate potential for harm

Appendix A: 4 Effective Nonpharmacologic Interventions 1-20 1. CG education Interventions about 1. Disease, prognosis, realistic expectations Developed by Christine Chang, MD December 2014 10-18-15 2. 5 Techniques to minimize development of BPSD 1) Maintain a structured daily routine of meaningful activities 2) Environmental modifications-safe, comfortable, orienting 3) Communication Techniques-speak slowly, clearly, in nonconfrontational manner 4) Encourage independence in ADLs • Correct sensory impairments • Simplify routines, set up, limit choices • Finger foods, Velcro, snaps 5) Patient –Centered Care ie Person-Centered Showers and Towel Baths12 (www.bathingw ithoutabattle.unc.edu) 13 http://www.alz.org/care/alzheimers-dementia-bathing.asp14 Suggests the following: • Create environment based on patient comfort and preference • Cover with towels to maintain warmth and modesty • Use no-rinse soap and warm water • Use gentle massage to cleanse • Modify shower spray

2. Unmet Needs Interventions- make sure hunger, thirst, pain, boredom are addressed as pt may “act out” when they are unable to communicate their needs

3. Behavioral Interventions a. 3 R’s (Repeat, Reassure, Redirect)  Positive reinforcement (by praising, encouraging or reassuring) to encourage desirable behavior s  Distraction technique-redirection b. Be a Sleuth: Do the “ABC’s” and Avoid triggers –look at the Antecedant Behaviors that lead to a particular Consequence and AVOID itIdentify the precipitating factor and avoid the triggers

4. Psychosocial Interventions a. 5 Techniques to minimize development of BPSD (above) b. Preferred Calming Music c. Aromatherapy-lavender d. Thermal bath e. Bright Light and Pet Therapy f. Snoezelen-Multisensory: light, sound, aroma, massage g. Exercise and Structured activity therapies ***Physical restraints should be avoided *alz.org-caregiver centerget supportTraining and Resources * http://www.agingbraincare.org/. Look under Tools, then ABC Care Protocols. The nonpharmacologic protocols are available in the Care Protocols upon registration20.

Appendix B: Non-pharmacologic Interventions for Insomnia: McCurry SM et al. Nightti me insomnia treatment and education for Alzheimer's disease: a RCT. JAGS. 200521— employs 4 of t he 6 traditional techniques for insomnia mgt: sleep hygiene, stimulus control, sleep restriction and circadian rhy thm manipulators (No Cognitive Behavioral Therapy (CBT) or “relaxation”)

Developed by Christine Chang, MD December 2014 10-18-15 1. Follow Structured sleep and rising times that were not to deviate no more than 30 minutes from the se lected times (circadian) 2. Encouraged patients not to nap after 1 PM and limit naps to 30 minutes or less (sleep hygiene, circ adian, sleep restriction) 3. Walk for 30 minutes, exercise daily (circadian) 4. Bright light tx at dawn/dusk (circadian) 5. Eliminate triggers for nighttime awakenings ie control night time pain, give nightly snack, take activat ing meds in the AM (stimulus control) 6. Reduce light/noise levels in their sleeping areas (stimulus control) 7. Switch to decaffeinated drinks and reduce evening fluid consumption (stimulus control) 8. If nocturia affected sleep, encourage toileting schedules at night, use of incontinence pads, exclude urinary tract infections (stimulus control)

Appendix C:

APPROVED Hypnotics for INSOMNIA NON-APPROVED for INSOMNIA 1. BZO R Agonists 1. Sedating Antidepressant BZO Trazodone * Temezepam, Triazolam Mirtazapine Non-BZO Doxepin 10 Zolpidem* 2. Antipsychotics Zaleplon* 3. Anticonvulsants Eszopiclone NONPRESCRIPTION AGENTS 2. Melatonin R Agonist 1. Sedating Antihistamines Ramelteon 2. Melatonin 3. Tryptophan-milk/honey 3. Orexin R blocker 4. Valeria, Kava, St. John’s Wort Suvorexant-Belsomra

Appendix D: 2013 Management of the Behavioral and Psychological Symptoms of Dementia. NaRCAD (the National Resource Center for Academic Detailing) with support from a grant from the Agency for Healthcare Research and Quality 2,34-39, 51-54, 61-64, 67 • Nonpharmacologics • Pharmacologics: – FOR EMERGENT BPSD 34-39 60 • Antipsychotics: • Use faster acting, higher risk medications • Limited evidence for longer term efficacy (≥6 months) – NONemergent BPSD 2, 31-36, 48-51, 58,-61, 64 • Memantine • Carbamazepine • Citalopram • Prazosin

Appendix E: Possible medication for Agitation, Aggression, and Psychotic symptoms in BPSD. (Medications listed are not FDA approved to treat BPSD and are off-label recommendations) Class Startin Theraputic Comments g Dose Dose Antipsychotics Black Box warning Watch for: Extrapyramidal effects, tardive diskinesia, neuroleptic malignant syndrome, hypotension, QTc prolongation and torsades de pointes, anticholinergic side effects (ie Constipation, xerostomia, and somnolence), agranulocytosis, blurred vision, May Lowers seizure threshold Developed by Christine Chang, MD December 2014 10-18-15 Haloperidol 0.5-2mg *Class effect as above. Watch esp for Extrapyramidal effects can occur with doses 56-58 q2-12 hrs >4.5 mg/d *More effective for treating aggressive agitation * Available as Oral, IV , IM, subcutaneous Risperidone 0.25-0.5 1-2mg *Class effect as above and EPS with doses > 1 mg/day 51, 54-56 mg * Clinical experience suggest better results in patients with hypoactive delirium *Risperidone and olanzepine effective for aggressive agitation but risperidone may be more helpful for psychotic symptoms. * Available as tablet, rapidly dissolving tablet, liquid concentrate, IM Olanzapine 2.5-5 mg 5-15 mg *Class effect as above. Watch especially for hyperglycemia and cerebrovascular events in patients with dementia. *Risperidone and olanzepine effective for aggressive agitation. *Literature suggests that older age, preexisting dementia, and hypoactive delirium are associated with poor response *Available as tablet, rapidly dissolving tablet, IM injection Quetiapine 12.5- 100–200 mg *Class effect as above. Watch especially for orthostatic, and hyperglycemia. 25mg * Preferred in patients with Parkinson disease or Lewy body dementia due to its lower risk of extrapyramidal adverse effects *Ophthalmologic exam recommended every 6 months *Available as tablet Aripiprazole 2.5-5 mg 5-15mg *Class effect as above. Watch especially for increased cerebrovascular events in dementia, hyperglycemia and weight gain *Clinical experience suggests better results in hypoactive delirium *No adjustment needed with age, renal or hepatic impairment *Available as Tablet, disintegrating tablet, liquid concentrate, IM (convert to oral ASAP) * Ziprasidone and clozapine are both poorly tolerated in older adult. Might consider in rare refractory cases. Note. CBCs = complete blood cell counts EPS = extrapyramidal symptoms IM = intramuscular Anticonvulsants Starting Therapeutic Comments dose dose Carbamazepine 50-100mg 200-1000mg *Main side effects are sedation, ataxia, nausea 68 *Monitor for hyponatremia and pancytopenia Divalproex 125- 250-1000mg *Main side effects nausea and sedation. sodium 70 250mg *Monitor for Liver function abnormality, thrombocytopenia, pancreatitis. * NOT recommended in most recent guidelines and Cochrane review 2004, 2009

Appendix F: Black Box Warning for Typical and Atypical Antipsychotics 71-73 http://www.fda.gov/cder/drug/infopage/antipsychotics/default.htm April 2005

• Increased risk of mortality. Rate of death was 1.6 to 1.7 times that of placebo in 6-12 wks of use • Death appeared to be heart related or from infections (eg, pneumonia) • Diabetes mellitus, hyperglycemia, ketoacidosis, and hyperosmolar states Bibliography: 1 Gitlin LN, Kales HC, Lyketsos CG. Nonpharmacologic management of behavioral symptoms in dementia. JAMA. 2012 Nov 21;308(19):2020-9. doi: 10.1001/jama.2012.36918.

2 Osser, David; Fischer, Michael. Management of the behavioral and psychological symptoms of dementia. NaRCAD (the National Resource Center for Academic Detailing) with support from a grant from the Agency for Healthcare Research and Quality to the Division of Pharmacoepidemiology and Pharmacoeconomics of the Brigham and Women’s Hospital Department of Medicine. December 28, 2013

3 Gitlin LN, Winter L, Dennis MP, Hodgson N, Hauck WW. A biobehavioral home-based intervention and the well-being of patients with dementia and their caregivers: the COPE randomized trial. JAMA. 2010 Sep 1;304(9):983-91.

Developed by Christine Chang, MD December 2014 10-18-15 4 Gitlin LN, Winter L, Dennis MP, Hodgson N, Hauck WW. Targeting and managing behavioral symptoms in individuals with dementia: a randomized trial of a nonpharmacological intervention. J Am Geriatr Soc. 2010 Aug;58(8):1465-74.

5 Cohen-Mansfield J, Thein K, Marx MS, Dakheel-Ali M, Freedman L. Efficacy of nonpharmacologic interventions for agitation in advanced dementia: a randomized, placebo-controlled trial. J Clin Psychiatry. 2012 Sep;73(9):1255-61. doi: 10.4088/JCP.12m07918.

6 Eun-Hi Kong, Lois K. Evans and James P. Guevara. Nonpharmacological intervention for agitation in dementia: A systematic review and meta-analysis. Aging & Mental Health. July 2009, 512–520

7 Bird M, Jones RH, Korten A, Smithers H. A controlled trial of a predominantly psychosocial approach to BPSD: treating causality. Int Psychogeriatr. 2007 Oct;19(5):874-91. Epub 2007 Jan 19. Links

8 Ayalon L, Gum AM, Feliciano L, Areán PA. Effectiveness of nonpharmacological interventions for the management of neuropsychiatric symptoms in patients with dementia: a systematic review. Arch Intern Med. 2006 Nov 13;166(20):2182-8. Review

9 McGonigal-Kenny ML, Schutte DL. Nonpharmacologic management of agitated behaviors in persons with Alzheimer disease and other chronic dementing conditions. J Gerontol Nurs. 2006 Feb;32(2):9-14. Review

10 Livingston G, Johnston K, Katona C, et al. Systematic review of psychological approaches to the management of neuropsychiatric symptoms of dementia. Am J Psychiatry. 2005;162(11):1996-2021

11 Cohen-Mansfield, J. Nonpharmacologic interventions for inappropriate behaviors in dementia: A review, summary, and critique. Am J Geriatr Psychiatry 2001; 9(4): 361-381.

12 Sloane PD, Hoeffer B, Mitchell CM, McKenzie DA, Barrick AL, Rader J, Stewart BJ, Talerico KA, Rasin JH, Zink RC, Koch GG. Effect of person-centered showering and the towel bath on bathing-associated aggression, agitation, and discomfort in nursing home residents with dementia: a randomized, controlled trial. J Am Geriatr Soc. 2004 Nov; 52(11):1795-804.

13 http://www.bathingwithoutabattle.unc.edu/

14http://www.alz.org/care/alzheimers-dementia-bathing.asp

15 Husebo BS, Ballard C, Aarsland D. Pain treatment of agitation in patients with dementia: a systematic review. Int J Geriatr Psychiatry. 2011 Oct;26(10):1012-8. doi: 10.1002/gps.2649. Epub 2011 Feb 9.

16 Laura N. Gitlin, Helen C. Kales, Constantine G. Lyketsos. Managing Behavioral Symptoms in Dementia Using Nonpharmacologic Approaches: An Overview. JAMA. 2012 November 21; 308(19): 2020–2029.

17 Staedtler AV1, Nunez D. “Nonpharmacological therapy for the management of neuropsychiatric symptoms of Alzheimer's disease: linking evidence to practice. Worldviews on Evidence-Based Nursing Volume 12, Issue 2, 2015 Apr;12 (2):108-15. doi: 10.1111/wvn.12086. Epub 2015 Mar 21.

18 Caregiver- and Patient-Directed Interventions for Dementia An Evidence-Based Analysis. Ont Health Technol Assess Ser. 2008; 8(4): 1–98.

19 Hermans, DG. Htay, U Hla. McShane, R. Non-pharmacological interventions for wandering of people with dementia in the domestic setting. [Systematic Review] Cochrane Dementia and Cognitive Improvement Group Cochrane Database of Systematic Reviews. 4, 2007.

20http://www.agingbraincare.org/. Look under Tools, then ABC Care Protocols. The nonpharmacologic protocols are available in the Care Protocols upon registration.

21 McCurry SM, Gibbons LE, Logsdon RG, Vitiello MV, Teri L Nighttime insomnia treatment and education for Alzheimer's disease: a randomized, controlled trial. Journal of the American Geriatrics Society. 53(5): 793-802, 2005 May

22 Paniagua MA, Paniagua EW. .The demented elder with insomnia. Clin Geriatr Med. 2008 Feb;24(1):69-81, vii. Review.

23 Bliwise DL. Sleep disorders in Alzheimer's disease and other dementias. Clin Cornerstone. 2004;6 Suppl 1A:S16-28. Review.

24 Buscemi N, Vandermeer B, Friesen C, Bialy L, Tubman M, Ospina M, Klassen TP, Witmans M. “The Efficacy and Safety of Drug Treatments for Chronic Insomnia in Adults: A Meta-analysis of RCTs. J Gen Intern Med. 2007 Sep; 22(9):1335-50. Epub 2007 Jul 10.

25 McCrae CS, McGovern R, Lukefahr R, Stripling AM.Research Evaluating Brief Behavioral Sleep Treatments for Rural Elderly (RESTORE): a preliminary examination of effectiveness.Am J Geriatr Psychiatry. 2007 Nov; 15(11):979-82.

26 Morgenthaler T; Kramer M; Alessi C et al. Practice parameters for the psychological and behavioral treatment of insomnia: an update. An American Academy of Sleep Medicine report. SLEEP 2006;29(11): 1415-1419.

27 Morin CM, Bootzin RR, Buysse DJ, Edinger JD, Espie CA, Lichstein KL. Psychological and behavioral treatment of insomnia: update of the recent evidence (1998-2004). Sleep. 2006 Nov 1; 29 (11): 1398-414

Developed by Christine Chang, MD December 2014 10-18-15 28 National Institutes of Health State-of-the Science Conference Statement. Manifestations and Management of Chronic Insomnia in Adults. Bethesda, Md; August 18, 2005:1-18.

29 Pandi-Perumal SR, Zisapel N, Srinivasan V, Cardinali DP. Melatonin and sleep in aging population. Exp Gerontol. 2005 Dec; 40 (12):911-25.

30 Cardinali DP, Furio AM, Brusco LI. Clinical aspects of melatonin intervention in Alzheimer's disease progression. Curr Neuropharmacol. 2010 Sep;8(3):218-27

31 American Psychiatric Association. Practice guideline for the treatment of Alzheimer’s disease and other dementias of later life. Am J Psychiatry. 1997; 154 (5 Suppl): 1–39.

32 Geriatric Review Syllabus; 8th edition. Chapter 35: Behavioral Problems in Dementia, p 296-304.

33 Martinon-Torres, G. Fioravanti, M. Grimley Evans, J. Trazodone for agitation in dementia. [Systematic Review] Cochrane Dementia and Cognitive Improvement Group Cochrane Database of Systematic Reviews. 4, 2007.

34 Corbett A, Smith J, Creese B, Ballard C. Treatment of behavioral and psychological symptoms of Alzheimer's disease. Curr Treat Options Neurol. 2012 Apr;14(2):113-25. doi: 10.1007/s11940-012-0166-9.

35 Sadowsky CH, Galvin JE. Guidelines for the management of cognitive and behavioral problems in dementia. J Am Board Fam Med. 2012 May-Jun;25(3):350-66.

36 Wang PS, Brookhart MA, Setoguchi S, Patrick AR, Schneeweiss S. Psychotropic medication use for behavioral symptoms of dementia. Curr Neurol Neurosci Rep. 2006 Nov; 6 (6): 490-5.

37 Franco KN, Messinger-Rapport B. Pharmacological treatment of neuropsychiatric symptoms of dementia: a review of the evidence. J Am Med Dir Assoc. 2006 Mar; 7(3): 201-2.

38 Sink KM, Holden KF, Yaffe K. Pharmacological treatment of neuropsychiatric symptoms of dementia: a review of the evidence. JAMA. 2005 Feb 2; 293(5): 596- 608. Review.

39 Locca JF, Büla CJ, Zumbach S, Bugnon O. Pharmacological treatment of behavioral and psychological symptoms of dementia (BPSD) in nursing homes: development of practice recommendations in a Swiss canton. J Am Med Dir Assoc. 2008 Jul; 9(6):439-48.

40 Henry G, Williamson D, Tampi RR. Efficacy and tolerability of antidepressants in the treatment of behavioral and psychological symptoms of dementia, a literature review of evidence. Am J Alzheimers Dis Other Demen. 2011 May;26(3):169-83

41 Banerjee, Sube MD et al. Sertraline or mirtazapine for depression in dementia (HTA-SADD): a randomised, multicentre, double-blind, placebo-controlled trial. The Lancet, July 2011 (378): 403 – 411

42 Seitz DP, Adunuri N, Gill SS, Gruneir A, Herrmann N, Rochon P. Antidepressants for agitation and psychosis in dementia. Cochrane Database Syst Rev. 2011 Feb 16;(2):CD008191

43 Bains, J; Birks, JS; Dening, TD. Antidepressants for treating depression in dementia. EBM Reviews – Cochrane Database of Systematic Reviews 4, 2006

44 Oslin DW, Ten Have TR, Streim JE, Datto CJ, Weintraub D, DiFilippo S, Katz IR Probing the safety of medications in the frail elderly: evidence from a randomized clinical trial of sertraline and venlafaxine in depressed nursing home residents. Evid Based Ment Health. 2004 May; 7 (2): 47. 45 Lyketsos CG, DelCampo L, et al. Treating depression in Alzheimer disease: efficacy and safety of sertraline therapy, and the benefits of depression reduction: the DIADS. Arch Gen Psychiatry. 2003 Jul;60(7):737-46.)

46 Pollock BG, Mulsant BH, et al. Comparison of Citalopram, Perphenazine, and placebo for the acute treatment of psychosis and behavioral disturbances in hospitalized, demented patients. Am J Psychiatry 2002; 159:460-465

47 Raji MA, Brady SR. Mirtazapine for treatment of depression and comorbidities in Alzheimer disease. Ann Pharmacother. 2001 Sep; 35 (9): 1024-7.

48 Kołaczkowski M1, Marcinkowska M, Bucki A, Pawłowski M, Mitka K, Jaśkowska J, Kowalski P, Kazek G, Siwek A, Wasik A, Wesołowska A, Mierzejewski P,Bienkowski P. Novel Arylsulfonamide Derivatives with 5-HT6/5-HT7 Receptor Antagonism Targeting Behavioral and Psychological Symptoms of Dementia. J Med Chem. 2014 Jun 12;57(11):4543-57. doi: 10.1021/jm401895u. Epub 2014 May 23.

49 Prasad R. Padala, M.D.; William J. Burke, M.D.; Subhash C. Bhatia, M.D.; Frederick Petty, Ph.D., M.D.Treatment of Apathy With Methylphenidate. The Journal of Neuropsychiatry and Clinical Neurosciences 2007;19:81-83

50 Ujkaj M, Davidoff DA, Seiner SJ, Ellison JM, Harper DG, Forester BP. Safety and efficacy of electroconvulsive therapy for the treatment of agitation and aggression in patients with dementia. Am J Geriatr Psychiatry. 2012 Jan;20(1):61-72.

51 Ballard C, Waite J, Birk J, “Atypical antipsychotics for aggression and psychosis in Alzheimer’s disease. “Cochrane Database of Systematic Reviews 2006, Issue 1. Art. No.: CD003476.DOI:10.1002/14651858.CD003476.pub2.

Developed by Christine Chang, MD December 2014 10-18-15 52 Alexopoulos GS, Streim J, Carpenter D, et.al. Expert consensus guideline series : Using antipsychotic agents in older patients. J Clin Psychiatry 2004; 65(suppl 2):1-105.

53 ACP Journal Club Review: Limited evidence supports the use of atypical antipsychotic drugs in behavioral and psychological symptoms of dementia [Therapeutics] ACP Journal Club. v142(1):15, January/February, 2005.

54 Rabinowitz J, Katz IR, De Deyn PP, Brodaty H, Greenspan A, Davidson M Behavioral and psychological symptoms in patients with dementia as a target for pharmacotherapy with risperidone. [Clinical Trial. Comparative Study. Journal Article. Randomized Controlled Trial. Research Support, Non-U.S. Gov't] The Journal of clinical psychiatry. 65(10):1329-34, 2004 Oct.

55 Rabinowitz J, Katz I, De Deyn PP, Greenspan A, Brodaty H Treating behavioral and psychological symptoms in patients with psychosis of Alzheimer's disease using risperidone. [Journal Article. Randomized Controlled Trial] International psychogeriatrics / IPA. 19(2):227-40, 2007 Apr.

56 EBM Reviews - Cochrane Central Register of Controlled Trials Suh GH, Greenspan AJ, Choi SK Comparative efficacy of risperidone versus haloperidol on behavioural and psychological symptoms of dementia. [Comparative Study. Journal Article. Randomized Controlled Trial. Research Support, Non-U.S. Gov't] International journal of geriatric psychiatry. 21(7):654-60, 2006 Jul.

57 Longergan E, Luxenberg J, et al. Haloperidol for agitation in dementia. Cochrane Database of Systematic Reviews. 4, 2007

58 Lonegan E, Luxenberg J, colford J: Haloperidol for agitation in dementia. Cochrane Database Syst Rev 2002.

59 Lee PE, Gill SS, Freedman M, Brondskill SE, Hillmer MP, Rochon PA. Atypical antipsychotic drugs in the treatment of behavioural and psychological symptoms of dementia: systematic review. BMJ 2004; 329; 75

60 Schneider LS, Tariot PN, Dagerman KS, Davis SM, Hsiao JK, Ismail MS, Lebowitz BD, Lyketsos CG, Ryan JM, Stroup TS, Sultzer DL, Weintraub D, Lieberman JA; CATIE-AD Study Group. Effectiveness of atypical antipsychotic drugs in patients with Alzheimer's disease. N Engl J Med. 2006 Oct 12; 355(15): 1525-38.

61 Lucy Y. Wang, MD,1,2,* Jane B. Shofer, MS,2 Kirsten Rohde, RN,1 Kim L. Hart, PA-C,1 David J. Hoff, PA-C,1 Yun H. McFall, RPh,1 Murray A. Raskind, MD,1,2 and Elaine R. Peskind, MD1,2 . PRAZOSIN FOR THE TREATMENT OF BEHAVIORAL SYMPTOMS IN ALZHEIMER’S DISEASE PATIENTS WITH AGITATION AND AGGRESSION. Am J Geriatr Psychiatry. 2009 September; 17 (9) : 744–751.

62 Miller LJ. Michael E. DeBakey. The use of cognitive enhancers in behavioral disturbances of Alzheimer's disease. Consult Pharm. 2007 Sep;22 (9):754-62.

63 Tangwongchai S, Thavichachart N, Senanarong V, Poungvarin N, Phanthumchinda K, Praditsuwan R, Nidhinandana S, Chankrachang S. Galantamine for the Treatment of BPSD in Thai Patients With Possible Alzheimer's Disease With or Without Cerebrovascular Disease. Am J Alzheimers Dis Other Demen. 2008 Dec-2009 Jan;23(6):593-601

64 Howard, Robert J, Juszcak, Edmund, et.al. Donepezil for Treatment of Agitation in Alzheimer’s Disease. N Engl J Med 2007; 357; 14 (1382-1392)

65 Peskind ER, Tsuang DW, Bonner LT, Pascualy M, Riekse RG, Snowden MB, Thomas R, Raskind MA. Propranolol for disruptive behaviors in nursing home residents with probable or possible Alzheimer disease: a placebo-controlled study. Alzheimer Dis Assoc Disord. 2005 Jan-Mar;19(1):23-8.

66 Maidment ID, Fox CG, Boustani M, Rodriguez J, Brown RC, Katona CL. Efficacy of memantine on behavioral and psychological symptoms related to dementia: a systematic meta-analysis. Ann Pharmacother. 2008 Jan; 42(1): 32-8.

67 McShane, R, A Areosa Sastre, N Minakaran, Memantine for dementia: Cochrane Database of Systematic Reviews 2007 Issue 4.

68 Konovalov S, Muralee S, Tampi RR. Anticonvulsants for the treatment of behavioral and psychological symptoms of dementia: a literature review. Int Psychogeriatr. 2008 Apr; 20(2):293-308.

69 Kim Y, Wilkins KM, Tampi RR. Use of gabapentin in the treatment of behavioural and psychological symptoms of dementia: a review of the evidence. Drugs Aging. 2008; 25(3): 187-96

70 Lonergan, ET, J Luxenberg, Valproate preparations for agitation in dementia: Cochrane Database of Systematic Reviews 2007 Issue 4

71 Blackbox warning: http://www.fda.gov/cder/drug/infopage/antipsychotics/default.ht m.

72 Schneider LS, Dagerman KS, Insel P. Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials. JAMA 2005; 294:1934-43.

73 Van Iersel MB, Zuidema SU, Koopmans RT, Verhey FR, Olde Rikkert MG. Antipsychotics for behavioural and psychological problems in elderly people with dementia: a systematic review of adverse events. Drugs Aging. 2005; 22 (10): 845-58. Review. 74 Declercq T, Petrovic M, Azermai M, Vander Stichele R, De Sutter AI, van Driel ML, Christiaens T.Withdrawal versus continuation of chronic antipsychotic drugs for behavioral and psychological symptoms in older people with dementia. Cochrane Database Syst Rev.2013 Mar 28;3:CD007726.

Developed by Christine Chang, MD December 2014 10-18-15 75 Ruths S, Straand J, Nygaard HA, Aarsland D. Stopping antipsychotic drug therapy in demented nursing home patients: a randomized, placebo-controlled study--the Bergen District Nursing Home Study (BEDNURS). Int J Geriatr Psychiatry. 2008 Sep;23(9):889-95

76 Tampi RR1, Tampi DJ. Efficacy and Tolerability of Benzodiazepines for the Treatment of Behavioral and Psychological Symptoms of Dementia: A Systematic Review of Randomized Controlled Trials Am J Alzheimers Dis Other Demen. 2014 Mar 6.

77 Woodward MR, Harper DG, Stolyar A, Forester BP, Ellison JM. Dronabinol for the Treatment of Agitation and Aggressive Behavior in Acutely Hospitalized Severely Demented Patients with Noncognitive Behavioral Symptoms. Am J Geriatr Psychiatry. 2013 Apr 15. S1064-7481(12)00094-2.

Developed by Christine Chang, MD December 2014 10-18-15

Load more

  14

Copy Link