Balanced information for better care

Preventing overuse of antipsychotic drugs in nursing home care Safer alternatives

Antipsychotic medications (APMs) are frequently overused in patients with dementia1 FIGURE 1. APMs are often prescribed for nursing home patients with dementia who

have no indication for their use1

40%

Use not indicated

Proportion of patients with non-aggressive behavioral problems who are prescribed an antipsychotic drug

23%

Proportion of patients with no behavioral problems who are prescribed an antipsychotic drug

Do not prescribe an APM for these problems: • insomnia • wandering • restlessness • social isolation

APMs (including quetiapine [Seroquel]) are poorly effective in treating insomnia and can cause side effects such as tardive dyskinesia and metabolic complications even at low doses.2

• mild anxiety, nervousness • inattention or indifference • fidgeting • uncooperativeness • shouting

2

Preventing overuse of antipsychotic drugs in nursing home care

Avoid routine use of APMs to manage dementia-related behavioral disturbances • Their effect size is small • Side effects are common • They increase the risk of death 3,4,5 These medications are NOT approved by the FDA to treat behavioral and psychological symptoms of dementia (BPSD); risks often outweigh benefits in these patients.

For every 100 patients with dementia treated with an atypical antipsychotic for 10-12 weeks, 1 will die as a result.3

FIGURE 2. In a meta-analysis of 15 randomized trials, patients given an atypical

antipsychotic drug had higher rates of deaths than patients given placebo3 4.0% 3.5% Death rate

3.0% 2.5% 2.0% 1.5% 1.0%

54% Placebo

0.5%

Atypical antipsychotic

relative increase in mortality

0.0%

These results are based on a meta-analysis of clinical trials of aripiprazole, olanzapine, quetiapine, and ripseridone.3 Other studies, which led to the FDA black box warning, found a 60-70% increased risk of death.5

Risks and side effects of antipsychotic medications in the elderly include: • death

• pneumonia

• stroke

• parkinsonian effects

• falls

• diabetes

• QTc prolongation, arrhythmia

• constipation

Balanced information for better care

3

Set realistic treatment goals when managing behavioral problems in older patients Recognizing the difference between acute and non-acute behavioral and psychological symptoms of dementia is key in planning management. Re-assess symptoms frequently, as they are likely to fluctuate over time. FIGURE 3. An algorithm for managing behavioral problems in older patients with dementia6,7,8

Identify the problem behavior to be addressed. Record intensity, frequency, and consequences. Rule out reversible causes

RE

ES

REASS

• physical agression • violent behavior • hallucinations or delusions that are distressing to the patient • self-harm

N

Non-acute BPSD (common) Drug therapy rarely required • Focus on non-drug interventions. • Avoid APMs if possible. • SSRIs may have a limited role: — avoid fluoxetine (Prozac), citalopram (Celexa), paroxetine (Paxil). — consider sertraline (Zoloft), escitalopram (Lexapro).

APMs may sometimes be appropriate to manage acute problems of severe BPSD, but are seldom appropriate for non-acute BPSD. 4

Preventing overuse of antipsychotic drugs in nursing home care

LARLY

Drug therapy may be required for:

GU

Acute BPSD (rare)

RE

Y

Are the symptoms: — severely disruptive? — dangerous? — distressing?

AS

SS

SR

LY AR

SE

EG UL

Initiate non-drug approaches

Rule out reversible causes of the behavioral and psychological symptoms6 CLINICAL CONDITIONS Examples: • acute infection (e.g., UTI, pneumonia) • dehydration • pain • hypoxia • constipation

PSYCHOLOGICAL • loneliness • frustration • inability to easily communicate •u  nfamiliarity with setting and people

DRUGINDUCED Examples: • anticholinergics (e.g., oxybutynin [Ditropan], solifenacin [Vesicare]) • benzodiazepines (e.g., alprazolam [Xanax], diazepam [Valium], lorazepam [Ativan], clonazepam [Klonopin])

ENVIRONMENTAL • discomfort from being in one position for too long • disrupted routines • inappropriate lighting • sensory deficits • noise

Sometimes, acute BPSD may be a manifestation of delirium, an acute and reversible condition.

Balanced information for better care

5

Non-drug approaches are the mainstay of managing behavioral problems in older patients • They can often produce satisfactory clinical outcomes with much lower risk than sedating medications.9 • Continue in parallel with any drug treatment. Difficult behavior may be an attempt to communicate an unmet need.10 Addressing that need may be more effective and safer than sedating the patient. Agitation can come from underlying problems as diverse as pain, infection, or abdominal symptoms. Let the patient know you’re aware of their discomfort, and look for a cause.

There is solid evidence that staff training can improve behavioral symptoms and reduce the need for antipsychotic medication in patients with dementia.9-12 TABLE 1. Effective environmental modifications supported by evidence10

6

Reduce excessive stimulation

• Eliminate or reduce use of paging systems. • Monitor television and radio volume; provide earphone amplifiers for the hearing impaired. • Use soft but adequate lighting. • Provide quiet space, and alternative spaces during group activities.

Address boredom

• Offer recreational activities and exercise programs. • Provide freedom to go outdoors by securing enclosed walking paths. • Create opportunities for escorted walking with staff as companions.

Support normal sleep/wake cycles

• On admission, ask each patient (or a family member) what time they prefer to go to bed and get up. • Avoid routine use of hypnotics. • Reduce or eliminate caffeine intake.

Preventing overuse of antipsychotic drugs in nursing home care

Drugs are sometimes necessary to manage a specific acute dangerous behavior especially if there is a risk of harm to the patient or others, and potential benefits outweigh the risks. If an antipsychotic medication must be used to target a specific behavior that does not respond to non-drug approaches, do so cautiously:7,8

1 2 3

Identify and document the behavior being targeted.\

Start the drug on a trial basis of limited duration, generally under 7 days. Start at the lowest dose and gradually titrate to response. Monitor for side effects. TABLE 2. Starting and maximum does of antipsychotic medications in older patients

4 5

Drug

Starting dose

Maximum dose

aripiprazole

2–5 mg

15 mg

olanzapine

1.25–5 mg

10 mg

quetiapine

12.5–25 mg

300 mg

risperidone

0.25–0.5 mg

2 mg

paliperidone

1.5 mg

3–6 mg

Evaluate the effect of the drug trial on targeted behaviors; discontinue if result is unsatisfactory in terms of poor efficacy or side effects. Attempt gradual dose reduction regularly, monitoring for recurrence of severe symptoms. • Massachusetts policy requires a nursing facility to attempt APM dose reduction in two separate quarters, then annually, unless clinically contraindicated. • Taper slowly, unless abrupt cessation is necessary. • Reduce dose by 25%-50% every 2 weeks. Stop after 2 weeks on minimum dose.

6

Continuing an antipsychotic drug may be required if a patient’s symptoms are dangerous, highly distressing, or seriously disruptive, or are due to mania or psychosis. If the drug must be continued, review benefits and side effects at least every 3 months.

Balanced information for better care

7

Antipsychotic medications vary in their side effects TABLE 3. APMs with highest rates of specific side effects13,14

Metabolic effects Weight gain

olanzapine (Zyprexa) +++

quetiapine (Seroquel) ++

risperidone (Risperdal) ++

Diabetes, hyperglycemia

olanzapine +++

quetiapine ++

Extrapyramidal symptoms

haloperidol (Haldol) +++

phenothiazines +++

Sedation

olanzapine ++

quetiapine ++

lurasidone (Latuda) ++

QTc prolongation

quetiapine ++

ziprasidone (Geodon) ++

iloperidone ++

Orthostatic hypotension

paliperidone ++

quetiapine ++

risperidone ++

paliperidone (Invega) ++

iloperidone (Fanapt) ++

Neurologic effects

Cardiovascular effects

+++ = high incidence or severity, ++ = moderate incidence or severity. This is not an exhaustive list and represents the drugs most likely to cause the particular adverse effect. More detailed information on the side effect profile of each drug can be found in the evidence document accompanying this brochure.

Restrict the use of p.r.n. antipsychotic medication to the management of episodic or rapidly changing aggression, or frank psychosis.7,8 • Document the specific circumstances warranting p.r.n. use, including the symptoms to trigger administration, dose, frequency, duration, and maximum dose for any 24-hour period. • Scheduling drug-free days can help minimize overall psychotropic load. • Seek consent from the patient’s family or guardian whenever possible.

8

Preventing overuse of antipsychotic drugs in nursing home care

Screen for side effects at drug initiation and at regular intervals TABLE 4. Guidelines for screening patients prescribed ANY antipsychotic medication

What to assess

baseline

4 weeks

8 weeks

12 weeks quarterly

annually

Weight (BMI)

X

X

X

Waist circumference

X

Blood pressure

X

X

X

Fasting plasma glucose, or A1c

X

X

X

Fasting lipid profile

X

X

X

FBC, urea, and electrolytes

X

Metabolic effects X

X X

X

Neurologic effects Extrapyramidal symptoms

every assessment

Sedation

every assessment

Cardiovascular effects QTc prolongation

X

Orthostatic hypotension

X

with dose increase or addition of other QT prolonging drugs every assessment

Anticholinergic effects Constipation, blurred vision, dry mouth, sedation, urinary retention

every assessment

Some behaviors do not respond well to any medication. In general, antipsychotic drugs are less likely to be helpful when:8 • the behavior is intermittent, e.g., significant physical aggression once per week versus 4-5 times every day. • the behavior is situation-specific, e.g., resisting showering versus resisting all care.

Balanced information for better care

9

Avoid benzodiazepines and similar drugs (e.g., zolpidem) in managing BPSD Benzodiazepines can cause or exacerbate a range of problems:15-18 • cognitive impairment

• respiratory suppression

• falls and accidents

• aspiration

• paradoxical agitation

• death

• physical dependence A small dose of a short-acting benzodiazepine may occasionally be required for an activity that causes anxiety, e.g., bathing.

Antidepressants may be beneficial in BPSD, but results are mixed and effect sizes are small.19,20 SSRIs (especially sertraline and citalopram) have shown moderate efficacy in reducing agitation in patients with dementia.19-21 However, citalopram causes QTc prolongation and should be avoided in the elderly; escitalopram may be used instead. Trazodone, while widely used for BPSD, lacks good evidence to support its use in patients with dementia.13

Antipsychotic medications may have a limited role in some patients with depression. Do not routinely use antipsychotic medications for most depressed patients. • APMs as ‘add-on therapy’ in depression may slightly increase the rate of remission but with little benefit in quality of life; adverse effects are substantial.22 Patients with psychotic depression warrant specialist referral; in these circumstances, an antipsychotic is sometimes combined with an antidepressant, such as an SSRI or venlafaxine.23

10

Preventing overuse of antipsychotic drugs in nursing home care

In summary 3 Antipsychotic medications are often overused in older patients in nursing homes, but they increase the risk of death and can cause substantial side effects. 3 In managing behavioral and psychological symptoms in patients with dementia, rule out any reversible clinical, psychological, or environmental triggers. 3 Identify specific target behaviors and set realistic treatment goals. 3 Initiate non-drug interventions first in most patients, and continue these even if drug treatment is required. 3 If an antipsychotic medication must be used to manage a specific, identified dangerous behavior not responding to non-drug approaches, do so cautiously. 3 Regularly re-assess and re-evaluate the need for ongoing antipsychotic medication use; discontinue if the targeted behavior is not improving. 3 Screen for specific side effects at baseline and at regular intervals.

References: (1) Crystal S, Olfson M, Huang C, Pincus H, Gerhard T. Broadened Use Of Atypical Antipsychotics: Safety, Effectiveness, And Policy Challenges. Health Affairs. September 1, 2009 2009;28(5):w770-w781. (2) Agency for Healthcare Research and Quality. Off-Label Use of Atypical Antipsychotics: An Update, Comparative Effectiveness Review No. 43. 2011. (3) Schneider LS, Dagerman KS, Insel P. Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials. JAMA. Oct 19 2005;294(15):1934-1943. (4) Mittal V, Kurup L, Williamson D, Muralee S, Tampi RR. Risk of cerebrovascular adverse events and death in elderly patients with dementia when treated with antipsychotic medications: a literature review of evidence. American journal of Alzheimer’s disease and other dementias. Feb 2011;26(1):10-28. (5) FDA. Public Health Advisory: Deaths with Antipsychotics in Elderly Patients with Behavioral Disturbances. 2005. (6) Kapusta P RL, Bareham J, Jensen B. Behavior management in dementia. Can Fam Physician. 2011;57(12):1420-1422. (7) Centres for Medicare an Medicaid Services. State Operations Manual, Appendix PP-Guidance to Surveyors for Long Term Care Facilities. www.cms.gov/Regulations-and-Guidance/Guidance/Manuals/downloads/som107ap_pp_guidelines_ltcf.pdf. (8) The Royal Australian and New Zealand College of Psychiatrists Faculty of Psychiatry of Old Age. The Use of Antipsychotics in Residential Aged Care, Clinical Recommendations. www.bpac.org.nz/a4d/resources/docs/RANZCP_Clinical_recommendations.pdf. 2011. (9) Brodaty H, Arasaratnam C. Meta-analysis of nonpharmacological interventions for neuropsychiatric symptoms of dementia. Am J Psychiatry. 2012 2012;169(9):946-95. (10) Avorn J, Soumerai S, Everitt D, Ross-Degnan D, Beers M, Sherman D, et al. A randomized trial of a program to reduce the use of psychoactive drugs in nursing homes. New England Journal of Medicine 1992;327(3):168–73. (11) Fossey J, Ballard C, Juszczak E, James I, Alder N, Jacoby R, et al. Effect of enhanced psychosocial care on antipsychotic use in nursing home residents with severe dementia: cluster randomised trial. British Medical Journal 2006;332(7544):756–61. (12) Wehry, Susan. OASIS 1.3. Training Manual for Trainers 2012. Statewide Initiative to Safely Reduce the Off-Label Use of Antipsychotics. Mass Senior Care Foundation; 2013. (13) Taylor D. PC, Kapur S. The Maudsley prescribing guidelines in psychiatry, 11th Edn. UK:Wiley-Blackwell; 2012. (14) PharmacistsLetter., PrescribersLetter. Comparison of Atypical Antipsychotics PL Detail-Document #281006. Stockton, CA: Therapeutic Research Center; October, 2012. (15) Rabins PV, Blacker D, Rovner BW, et al. American Psychiatric Association practice guidelines: treatment of patient’s with Alzheimer’s disease and other dementias. Psychiatry online 2007. (16) Glass J, Lanctot KL, Herrmann N, Sproule BA, Busto UE. Sedative hypnotics in older people with insomnia: meta-analysis of risks and benefits. BMJ Clinical research. Nov 19 2005;331(7526):1169. (17) Burrett-Jerrott SE SS. Cognitive and sedative effects of benzodiazepine use. Curr Pharm Des. 2002;8:45-58. (18) Bianchi MT, Thomas RJ, Ellenbogen JM. Hypnotics and mortality risk. Journal of clinical sleep medicine. 2012;8(4):351-352. (19) Seitz DP, Adunuri N, Gill SS, Gruneir A, Herrmann N, Rochon P. Antidepressants for agitation and psychosis in dementia. Cochrane database of systematic reviews (Online). 2011(2):CD008191. (20) 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. American journal of Alzheimer’s disease and other dementias. May 2011;26(3):169-183. (21) Porsteinsson AP, Drye LT, Pollock BG, et al. Effect of citalopram on agitation in Alzheimer disease: the CitAD randomized clinical trial. JAMA. Feb 19 2014;311(7):682-691. (22) Spielmans GI, Berman MI, Linardatos E, Rosenlicht NZ, Perry A, Tsai AC. Adjunctive atypical antipsychotic treatment for major depressive disorder: a meta-analysis of depression, quality of life, and safety outcomes. PLoS medicine. 2013;10(3):e1001403. (23) Tang M, Osser DN. The psychopharmacology algorithm project at the Harvard South Shore Program: 2012 update on psychotic depression. Journal of Mood Disorders. 2012;2(4):167-179.

Balanced information for better care

11

About this publication These are general recommendations only; specific clinical decisions should be made by the treating physician based on an individual patient’s clinical condition. More detailed information on this topic is provided in a longer evidence document at alosafoundation.org.

The Independent Drug Information Service (IDIS) is supported by the Massachusetts Department of Public Health and the PACE Program of the Department of Aging of the Commonwealth of Pennsylvania.

This material is provided by the Alosa Foundation, a nonprofit organization which is not affiliated with any pharmaceutical company. IDIS is a service of the Alosa Foundation.

This material was produced by Jerry Avorn, M.D., Professor of Medicine, Harvard Medical School; Eran Metzger, M.D., Assistant Professor of Psychiatry, Harvard Medical School; Michael A. Fischer, M.D., M.S., Associate Professor of Medicine, Niteesh K. Choudhry, M.D., Ph.D., Associate Professor of Medicine, Harvard Medical School; Eimir Hurley, BSc (Pharm), MBiostat, Program Director, Alosa Foundation. Drs. Avorn, Choudhry, and Fischer are all physicians at the Brigham and Women’s Hospital in Boston, while Dr. Metzger is the Chief of Psychiatry at Hebrew SeniorLife. None of the authors accepts any personal compensation from any drug company. Medical writer: Stephen Braun.

Copyright 2014 by the Alosa Foundation. All rights reserved.