Vch-a-1200-feb2011: atypical antipsychotic agents

VCH-A-1220
Atypical Antipsychotic Agents - Guideline for use as part of the
management strategy of behavioural and psychological symptoms of
dementia (BPSD)

Site Applicability

Practice Level
Physicians, Pharmacists, Nurse Practitioners
Practice Guideline
Purpose: The purpose of this guideline is to support clinicians in making informed decisions surrounding the
use of atypical antipsychotic drugs as part of the management of aggression or agitation in patients with
dementia in acute or residential care. Information on the reported risks and benefits of atypical antipsychotic use
in this population has been consolidated and interpreted in the context of best practice recommendations.
Scope: Recommendations have been provided for the initial patient assessment on admission, the initial use of
non-pharmacologic therapy at index episode of aggression or agitation, indication for drug therapy, involvement
and documentation of informed consent of family/substitute decision-maker, initiation, careful titration and
monitoring of drug therapy, documentation of effectiveness by 8 weeks, and documentation of review with a
purpose to discontinue by 3 to 6 months when appropriate

Need to Know
Summary:

Goals: To support clinicians in drug-therapy decision making by providing current evidence with respect to
reported risks and benefits. To encourage judicious and evidence-based use of drug therapy when
instituted. To improve sharing of information with all care providers and family/substitute decision-makers.
Key Points:

Conduct patient assessment on admission to unit and before initiating drug therapy: Document
baseline alertness, sedation, cognitive function, ADLs. Discourage telephone orders for initiating drug
therapy & ensure work-up for contributing or reversible factors (such as: delirium, pain, discomfort, infection,
loneliness, fear, boredom, drug side effects or interactions, environmental stress).

Non-drug interventions are considered first line before drug therapy by expert opinion: Given that
not every patient will benefit from drug therapy & the possibility for harm, develop a patient/resident-
centered psychosocial care plan & continue to optimize non-drug therapy even if drug therapy is initiated.

Recognize that the evidence base for drug therapy is modest: Debate exists surrounding magnitude of
drug benefit due to inconsistent study results (including a high placebo response rate when drug effect is
measured by clinicians) and limited applicability to all dementia subtypes encountered in clinical practice. At
best, 1 in 5 patients will demonstrate benefit with drug therapy, at worst, 1 in 14 (that is, a number needed to
treat that ranges from 5 to 14). Currently, however, atypical antipsychotics have a larger body of evidence
in the management of BPSD than other drug therapies. Atypical antipsychotics are more likely to improve
Note: This is a controlled document. A printed or external copy may not reflect the current, electronic version on the Vancouver Coastal Health Authority (VCHA)
Intranet. The VCHA electronic version is always the current version.
This clinical practice guideline has been prepared as a guide to assist and support practice for staff working at VCHA. It is not a substitute for proper training,
experience and the exercise of professional judgment. Approval has been granted from VCHA to share this version of the document with external agencies.
VCH Professional Practice – Promoting & Advancing Best Practice VCH-A-1220
aggressive rather than non-aggressive symptoms & are unlikely to benefit wandering, exit-seeking,
disruptive vocalizations. There is no evidence for improvement in other important patient-centered
outcomes such as: functional or cognitive abilities, quality of life, caregiver time needed.
Discuss the risks and monitor throughout drug therapy: Health Canada warnings between 2002 and
2005 report of an increased risk of mortality (largely due to cardiovascular events and infection) &
cerebrovascular events based on results of drug studies. It has been estimated (when one considers the
increased risk of mortality), that at best, 1 in 9 patients will benefit from drug therapy, at worst, 1 in 25 (that
is, a number needed to treat that ranges from 9 to 25). Although many uncertainties remain, it is
recommended that possible risks be discussed with all involved in care of patient prior to initiating drug
therapy. Be vigilant for side effects that can emerge during drug therapy: extrapyramidal side effects (may
affect 1 in 20 patients), tardive dyskinesia, anticholinergic toxicity, somnolence, abnormal gait, confusion &
cognitive decline, falls, hypotension, ECG changes, peripheral edema, respiratory & urinary tract infections,
metabolic changes.
Collaborate in team huddle prior to initiating drug therapy: Ensure optimization of psychosocial plan &
identify as a team the urgency/time line for initiating drug therapy. Current guidelines suggest that drug
therapy may be considered when there is a significant risk of harm to patient or others or when agitation or
aggressive symptoms are persistent, recurrent, or severe enough to cause significant suffering and distress,
or significant interference with care. Identify target symptom & provide documentation in chart. Share the
decision making with family/substitute decision maker.

Unknown which atypical antipsychotic optimizes safety and efficacy: Currently only risperidone has
Health Canada approval for short-term use for aggression ± psychosis. Risperidone, olanzapine have
stronger evidence base than quetiapine but quetiapine is often chosen preferentially in Lewy Body Dementia
& Parkinson’s Disease Dementia due to an increased risk of extrapyramidal side effects in these patients.

Start with an appropriately low dose: Consider risperidone 0.25 mg per day, olanzapine 2.5 mg per day,
quetiapine 12.5-25 mg per day as starting doses. Some side effects appear dose related & target doses
remain poorly defined therefore aim for lowest effective maintenance dose.

Make a decision regarding effectiveness by 8 weeks: Monitor & document impact of drug therapy on
symptoms using a behavioural chart. Follow frequency of symptoms, severity of symptoms, functional
status, quality of life, & include healthcare provider/family/substitute decision-maker/patient (where possible)
input.
Review for drug taper after a 3 to 6 month period of behavioural stability: The optimal duration of
therapy is unknown due to relatively short duration of studies. Individualize treatment duration taking into
account: patient’s functional status, target symptom, duration/persistence/severity of symptoms.
Review of complete guideline is recommended for all physicians, nurse-practitioners and pharmacists
involved at all levels of drug-therapy decision making for more complete information on key points
Patient assessment on admission to unit
• person-centered, sound admission process 1 • document baseline alertness, sedation, cognitive function, ADLs 2 Patient assessment on first episode
• assess, identify, and manage potentially reversible or contributing factors (eg delirium, pain, discomfort, infections, metabolic, neuropsychiatric, loneliness, fear, boredom, polypharmacy, drug interactions, environmental stress) 2-5 • ensure appropriate tests ordered (e.g. chemistry, hematology, microbiology, radiology) • ensure physical assessment; discourage telephone orders to initiate drug therapy Note: This is a controlled document. A printed or external copy may not reflect the current, electronic version on the Vancouver Coastal Health Authority (VCHA)
Intranet. The VCHA electronic version is always the current version.
This clinical practice guideline has been prepared as a guide to assist and support practice for staff working at VCHA. It is not a substitute for proper training,
experience and the exercise of professional judgment. Approval has been granted from VCHA to share this version of the document with external agencies.
VCH Professional Practice – Promoting & Advancing Best Practice VCH-A-1220
• gather information from family/substitute decision-maker and several staff members across different • behaviour analysis via ABC approach: Antecedants, Behaviours, Consequences 3,4 • see also VCH Least Restraint and Maximizing Freedom: Residential Care guideline (currently in draft) Initiate appropriate non-pharmacologic intervention
• first line intervention ahead of drug therapy in clinical practice guidelines 2,3 • evidence suggests poor adherence to this recommendation 6,7 • further study required to strengthen evidence base for specific interventions 2,5 • in urgent situations, may initiate non-pharmacologic and drug therapy together 3 • individualize a psychosocial care plan that emphasizes “interest, social activity, comfort” 2 • continue to optimize non-pharmacologic interventions even if drug therapy is initiated 2 • consult pharmacist to assess for possible medication-related contributors to onset of or change in behavioural or psychological symptoms as soon as possible • see also VCH Least Restraint and Maximizing Freedom: Residential Care guideline (currently in draft) Current evidence base for efficacy
• available data: inconsistent results, small RCTs with methodologic limitations, short duration generally up to 12 weeks, prominent placebo response rates (30-40%), highly selected patients 2,8-10 • majority of data involves patients with Alzheimer’s and Vascular Dementia; evidence may be less • debate regarding clinical significance of trial outcomes 8,11,13,14 • currently, larger evidence base exists for antipsychotics than for other pharmacologic interventions 9,11,13; • evidence base is more robust for aggressive than non-aggressive symptoms (e.g. agitation, hallucinations, delusions); many trials measured global behavioural disturbance therefore it is difficult to separate out the effects on specific symptoms 2,15-18 • some behaviours unlikely to respond: wandering, exit-seeking, disruptive vocalizations 3 “should not be viewed as broad spectrum agents” 19 • NNT= 6 commonly referenced in professional presentations but may range from 5-14 8 (derived from a small number of diverse RCTs demonstrating nominal statistical significance on symptom scales; it is possible that careful patient selection by experienced clinicians caring for patients with severe target symptoms unresponsive to non-pharmacologic intervention may reduce this NNT sponsored, outpatient RCT) showed for every 10 patients treated ~ 2 will • given the modest benefit afforded by these agents, concordance with prescribing guidelines does not • no RCT evidence of benefit on functional abilities, QOL, caregiving time needed 18 • do not improve cognitive deficits of dementia; may further cognitive impairment, confusion 8,18,20,22 • incomplete reporting of harms in RCTs 23,24 • risk associated with longer-term use (> 10-12 weeks) unknown EPS (NNH = 20), TD, anticholinergic toxicity, somnolence (NNH = 10), abnormal gait (NNH=13), confusion, falls, hypotension, ECG abnormalities, peripheral edema (NNH = 20), UTIs (NNH = 25), RTIs, metabolic including worsening hyperglycemia, weight gain, cognitive decline (i.e. ↓ 0.7 of an MMSE point over 6-12 weeks) • in CATIE-AD, discontinuation due to intolerance, ADRs, death favoured placebo over all 3 drugs (risperidone, olanzapine, quetiapine) 20 Note: This is a controlled document. A printed or external copy may not reflect the current, electronic version on the Vancouver Coastal Health Authority (VCHA)
Intranet. The VCHA electronic version is always the current version.
This clinical practice guideline has been prepared as a guide to assist and support practice for staff working at VCHA. It is not a substitute for proper training,
experience and the exercise of professional judgment. Approval has been granted from VCHA to share this version of the document with external agencies.
VCH Professional Practice – Promoting & Advancing Best Practice VCH-A-1220
• increased risk of mortality (largely due to CV events eg heart failure, sudden death and infection e.g. NNH = 100 by independent meta-analysis 26 (15 short-term RCTs over 10-12 weeks) 3.5% vs 2.3% pooled results for risperidone, olanzapine, quetiapine, aripiprazole unclear if pre-existing risk factors affect risk insufficient information on cause of death nonrandomized data suggest risk may be similar 27,28 or possibly higher 29-32 with typical (compared to atypical) antipsychotics • increased risk of cerebrovascular events (CVAEs) Health Canada warning October 2002 33 (risperidone), March 2004 34 (olanzapine) NNH = 71 by independent meta-analysis 35 (11 short-term RCTs) 2.2% vs 0.8% pooled results for risperidone, olanzapine only overall rate of CVAEs may not indicate increased risk of serious events (eg stroke) unclear if pre-existing risk factors affect risk causative pathophysiology unknown; association requires further clarification 35 several methodologic issues identified, conflicting observational data 35 • short-term RCTs suggest atypicals are less likely to cause EPS or exacerbate TD than typicals (however comparisons only exist for haloperidol); no additional therapeutic advantages have been established 16 o short-term RCTs cannot provide adequate data on risk of movement disorders with long-term use observational data over the longer term suggests this advantage may be lost at higher doses 36,37 in CATIE-AD, the incidence of parkinsonism or EPS was 12% for both the olanzapine group (mean dose 5.5 mg per day) and the risperidone group (mean dose 1 mg per day) versus 2% for the quetiapine group (mean dose 56.5 mg per day) 20; the quetiapine dose utilized was lower than that of earlier trials 8 • direct RCT comparisons between typical and atypical agents are limited, therefore the differential effects of these agents on adverse events such as CVAEs and mortality is uncertain 16 o an analysis of the impact of regulatory warnings on prescription rates demonstrated after the first Health Canada warning in October 2002 (for risperidone) a subsequent increase in quetiapine use and typical antipsychotic use 38, however given the minimal within-class and between-class comparisons this is not an evidence-based strategy for minimizing specific risks rather, individualized decision making taking into account each patient’s risk factors for particular adverse events is recommended 16 “the same drugs may not be equally effective and/or safe in all elderly patients” 2 Drug decision making
• team huddle prior to initiating drug therapy to coordinate care with other health-care professionals 16,23,39 • considerable debate regarding the threshold for prescribing atypical antipsychotics in BPSD 40-42, current guidelines suggest that antipsychotics be used when: there is a significant risk of harm to the patient or others or when agitation or aggressive symptoms are persistent, recurrent, or severe enough to cause significant suffering and distress, or significant interference with care 2,3,43,44 • a 2004 expert consensus document did not recommend their use in panic disorder, generalized anxiety disorder, nonpsychotic major depression, hypochondriasis, irritability, hostility, sleep disturbance, neuropathic pain, severe nausea, motion sickness in the absence of a major psychiatric syndrome 45 • “likelihood of helping vs harming” has been estimated at NNT = 9-25 when one balances the evidence of efficacy with the evidence for increased mortality 26 (see earlier limitation of NNT); however this estimate will not help a clinician identify which patient is likely to respond and which patient is at risk for harm Note: This is a controlled document. A printed or external copy may not reflect the current, electronic version on the Vancouver Coastal Health Authority (VCHA)
Intranet. The VCHA electronic version is always the current version.
This clinical practice guideline has been prepared as a guide to assist and support practice for staff working at VCHA. It is not a substitute for proper training,
experience and the exercise of professional judgment. Approval has been granted from VCHA to share this version of the document with external agencies.
VCH Professional Practice – Promoting & Advancing Best Practice VCH-A-1220
• consider role of non-antipsychotic agents where appropriate (see references 3,4,16); optimize treatment of comorbid neuropsychiatric symptoms (eg depression, anxiety) with evidence-based therapies • identify target symptom, ensure documentation • identify whether target symptoms are likely to respond to drug therapy; and consider that not all • identify dementia subtype where possible and consider: majority of RCTs included patients with Alzheimer’s and Vascular Dementia 11,12 Lewy Body and Parkinson’s Disease Dementia subtypes are considered to be more vulnerable to extrapyramidal side effects 3,45,46 • determine urgency/time line for initiating drug therapy some symptoms resolve without drug therapy over a period of days to weeks 15 may consider a period of observation unless symptoms are extremely distressing 16,47 • involve family/substitute decision-maker in decision making regarding treatment options; adequately inform of risks/benefits, obtain and document consent 2,16 • assess risk factors for stroke, MI, ECG abnormalities, aspiration pneumonia, other infection 2 Which atypical
• insufficient data to guide which drug optimizes safety and efficacy 23,48 • currently risperidone is the only agent approved by Health Canada for: “short-term symptomatic management of inappropriate behaviour due to aggression and/or psychosis” in dementia 49 • specifically, a Cochrane review finds evidence for risperidone and olanzapine in the management of aggression; and risperidone for psychosis 11 • risperidone, olanzapine have stronger evidence base than quetiapine 4,10-13 • in CATIE-AD, median time to discontinuation due to lack of efficacy favoured olanzapine (22.1 weeks) and risperidone (26.7 weeks) over quetiapine (9.1 weeks) and placebo (9 weeks) 20; the quetiapine dose utilized was lower than that of earlier trials 8 • multiple analyses find insufficient RCT evidence to evaluate quetiapine 8,10-14 however, quetiapine generally recommended in Lewy Body Dementia and Parkinson’s Disease Dementia over other antipsychotics 3,45; hypothesized to decrease the risk of neuroleptic malignant syndrome and movement ADRs in the “EPS-vulnerable” patient 46 Which dose
• some ADRs appear to be dose related (hypotension, gait disturbances, EPS, somnolence, anticholinergic side effects) 2,16,23,36,50,51 • start with an appropriately low dose 52,53 • aim for the lowest effective maintenance dose 3,4,16 • may consider target doses but recognize these ranges are not universally accepted given the limited number of trials assessing optimal dosing 16 ; except for CATIE-AD 20 most RCTs used fixed dosing o • generally given as a one time daily dose (at bedtime for olanzapine, quetiapine) or divided into a twice daily dose 54; half life is sufficient such that dividing the dose more than twice a day or targeting specific hours of the day with maintenance dosing is probably unnecessary • optimal dose for quetiapine inadequately studied and complicated by one RCT suggesting a minimum effective dose of 200 mg per day on measures of agitation 55 • recognize it is not known if dosing modifies the risk of CVAEs, mortality 51 Note: This is a controlled document. A printed or external copy may not reflect the current, electronic version on the Vancouver Coastal Health Authority (VCHA)
Intranet. The VCHA electronic version is always the current version.
This clinical practice guideline has been prepared as a guide to assist and support practice for staff working at VCHA. It is not a substitute for proper training,
experience and the exercise of professional judgment. Approval has been granted from VCHA to share this version of the document with external agencies.
VCH Professional Practice – Promoting & Advancing Best Practice VCH-A-1220
• the safety and efficacy of single doses (PRN dosing) has not been evaluated or compared in clinical trials to other PRN agents (such as typical antipsychotics or benzodiazepines), and the onset of action of atypical antipsychotics has not been clearly defined 41,56 o in practice this strategy has been used by our expert panel in select situations: to determine the need for a maintenance dose 52,57, during the dose titration phase in conjunction with regular dosing 57, in advance of unavoidable activities know to trigger significantly aggressive or agitated behaviour 52, and for anticipated but intermittent behaviours 52 if employed, ensure effective documentation systems in place: specify indication for PRN doses (e.g. specific behaviour) and include documentation via ABC approach (Antecedants, Behaviours, Consequences); regular assessment of ongoing PRN orders are recommended in order to ensure appropriateness and to determine if a modification to maintenance dose is needed 52,57 quetiapine is commonly utilized over other atypicals as a PRN agent when insomnia is present as part of the BPSD picture 53 however its use as a sedative for primary insomnia outside the setting of agitated and aggressive behaviours is generally not recommended 45 Monitoring
• consider the following parameters when assessing effectiveness 16: healthcare provider, caregiver, family/substitute decision-maker, and patient (where possible) input • document impact on symptoms using an observational chart 4; for example, see the • consider follow-up intervals: 1 week after initiation; 10 days after dose change 45 • some symptoms improve in the first 2 to 4 weeks of drug therapy 16; our content expert panel suggests making a decision regarding effectiveness by 8 weeks o some symptoms may respond earlier than others to drug therapy 52 no rationale for extending therapy outside length of RCTs (10 to 12 weeks) if no benefit 8 document when and what benefit is observed in the chart • the median time to discontinuation due to treatment failure in CATIE-AD (outpatient RCT) ranged from 5 • be vigilant for treatment-emergent and dose-related ADRs (see Risks and Which Dose) • periodic physical assessments should include an assessment for movement-related ADRs (eg EPS, TD) • monitoring for metabolic ADRs such as hyperglycemia (observational evidence exits for worsening hyperglycemia in the elderly with diabetes 58), dyslipidemia (olanzapine associated with ↓ HDL in CATIE-AD 59), weight gain (olanzapine, quetiapine in particular associated with weight gain in women in CATIE-AD 59) has been recommended 16 however the clinical relevance of these surrogate markers in this patient population has not been determined o consider that changes in weight may occur independently of metabolic alterations and may reflect, rather, a change in the individual’s functional status while on drug therapy; for example, a patient with poor baseline nutritional status may gain weight if BPSD symptoms and, subsequently, oral intake improves; conversely, a patient with weight loss should be assessed for worsening BPSD symptoms or excess somnolence which may be negatively affecting oral intake • reduce dose or discontinue if evidence of substantial QT prolongation on ECG 42:; the benefit of baseline or routine monitoring has not been determined Duration of therapy
• risk and benefit of long-term use outside the scope of short-term RCTs (up to 12 weeks) is not known 15 • longer term trials (up to 12 months) have not shown consistent benefit 20,22,60 Note: This is a controlled document. A printed or external copy may not reflect the current, electronic version on the Vancouver Coastal Health Authority (VCHA)
Intranet. The VCHA electronic version is always the current version.
This clinical practice guideline has been prepared as a guide to assist and support practice for staff working at VCHA. It is not a substitute for proper training,
experience and the exercise of professional judgment. Approval has been granted from VCHA to share this version of the document with external agencies.
VCH Professional Practice – Promoting & Advancing Best Practice VCH-A-1220
• for some patients, symptoms wax and wane, and may attenuate over time particularly in the case of Alzheimer’s Dementia where hallucinations tend to resolve over a period of a few months, but delusions, aggression, and agitation may be more persistent 61 • documentation of ongoing evaluation and the need for medication continuation should be regularly 43,54, national 3,62, and international 16,39,44,63,64 guidelines recommend periodic attempts to taper and discontinue after a period of symptomatic remission • in practice, efforts to stop or dose reduce appear to be infrequent 6,65 • a few RCTs indicate successful drug withdrawal after a period of behavioural stability 60,66-70 • recognize it is not known if duration of therapy modifies the risk of CVAEs, mortality • there is considerable uncertainty regarding optimal treatment duration current Canadian guidelines recommend 3-6 months 3,62; this also reflects the range of opinion of our content expert panel: some recommend 3 months of behavioural stability to be an appropriate goal for taper assessment, others 6 months appropriate length of therapy should be individualized and may depend on the patient’s functional status, the target symptom, and the duration, persistence, and severity of symptoms • anecdotal clinical experience suggests some patients require maintenance therapy 68 • even if benefit is documented, review patient at periodic intervals
Expected Client/Family/Substitute Decision-Maker Outcomes
Judicious use of atypical agents with the aim to optimize treatment of significant behavioural and psychologic symptoms Reduced risk of unnecessary drug exposure, therefore avoidance of adverse events Improved sharing of information of risks and benefits of treatment with family/substitute decision-maker and care providers Documentation
• Patient admission: document baseline alertness, sedation, cognitive function, ADLs
• Non-pharmacologic: document psychosocial care plan
• Drug decision making: identify and document dementia subtype where possible; identify and
document target symptoms; specify indication for PRN doses • Informed consent: document that possible risks and benefits have been explained to all care providers
• Monitoring: document impact on symptoms using an observational chart ; document what and when
benefit is observed; document decision regarding effectiveness by 8 weeks • Duration: document assessment for taper every 3 to 6 months
Related Documents
VCH Least Restraint and Maximizing Freedom: Residential Care (Currently in Draft)
References
1. Personal Communication. Smith, C. Nurse Practitioner. Home Health. Powell River 2. Salzman C et al. Elderly patients with dementia-related symptoms of severe agitation and aggression: consensus statement on treatment options, clinical trials methodology, and policy. J Clin Psychiatry 2008;69:889-98 Note: This is a controlled document. A printed or external copy may not reflect the current, electronic version on the Vancouver Coastal Health Authority (VCHA)
Intranet. The VCHA electronic version is always the current version.
This clinical practice guideline has been prepared as a guide to assist and support practice for staff working at VCHA. It is not a substitute for proper training,
experience and the exercise of professional judgment. Approval has been granted from VCHA to share this version of the document with external agencies.
VCH Professional Practice – Promoting & Advancing Best Practice VCH-A-1220
3. CCSMH. National Guidelines for Senior’s Mental Health: the assessment and treatment of mental health issues in long-term care homes (focus on mood and behaviour symptoms). Can J Geriatrics 2006:9:S59-64 4. Passmore M et al. Alternatives to atypical antipsychotics for the management of dementia-related 5. Ayalon L et al. Effectiveness of nonpharmacological interventions for the management of neuropsychiatric symptoms in patients with dementia: a systematic review. Arch Intern Med 2006;166:2182-8 6. Dhawan N et al. Documentation of antipsychotic use and indications for newly diagnosed, nonaggressive dementia patients. Primary Care Companion J Clin Psychiatry 2008;10:97-102 7. Kunik M et al. Documentation, assessment, and treatment of aggression in patients with newly diagnosed dementia. Alzheimer Dis Assoc Disorders 2007;21:115-21 8. Schneider L et al. Efficacy and adverse effects of atypical antipsychotics for dementia. Am J Geriatric 9. Herrmann N, Lanctot K. Pharmacologic management of neuropsychiatric symptoms of Alzheimer disease. Can J Psychiatry 2007;52:630-46 10. Canadian Agency for Drugs and Technologies in Health. Novel antipsychotics for agitation in dementia. March 2003. www.cadth.ca. Accessed May 5, 2008 11. Ballard C et al. Atypical antipsychotics for aggression and psychosis in Alzheimer's Disease. Cochrane 12. Carson S et al. A systematic review of the efficacy and safety of atypical antipsychotics in patients with psychological and behavioural symptoms in dementia. J Am Geriatric Soc 2006;54:354-61 13. Sink K et al. Pharmacologic treatment of neuropsychiatric symptoms of dementia. JAMA 2005;5:596-608 14. Lee P et al. Atypical antipsychotic drugs in the treatment of behavioural and psychological symptoms of 15. Ballard C, Howard R. Neuroleptic drugs in dementia: benefits and harm. Nat Rev Neuro 2006;7:492-500 16. Jeste D et al. ANCP White Paper: update on use of antipsychotic drugs in elderly persons with dementia. Neuropsychopharmacology 2008;33:957-70 17. Ballard C. Agitation and psychosis in dementia. Am J Geriatric Psychiatry 2007;15:913-7 18. Sultzer D et al. Clinical symptom responses to atypical antipsychotic medications in Alzheimer's disease: phase 1 outcomes from the CATIE-AD effectiveness trial. Am J Psychiatry 2008;165:844-54 19. Suh G et al. The use of atypical antipsychotics in dementia: rethinking Simpson's paradox. Internat 20. Schneider L et al. Effectiveness of atypical antipsychotic drugs in patients with Alzheimer's Disease. N 21. Briesacher B et al. The quality of antipsychotic drug prescribing in nursing homes. Arch Intern Med 22. Ballard C et al. Quetiapine and rivastigmine and cognitive decline in Alzheimer’s Disease. BMJ 23. Van Iersel M et al. Antipsychotics for behavioural and psychological problems in elderly people with 24. Lee P et al. Published randomized controlled trials of drug therapy for dementia often lack complete data on harm. J Clin Epidemiol 2008;61:1152-60 25. Health Canada website. www.hc-sc.gc.ca/dhp-mps/medeff/advisories-avis/prof/2005/atyp- antipsycho_hpc-cps_e.html. Accessed May 1, 2008 26. Schneider L et al. Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials. JAMA 2005;294:1934-43 Note: This is a controlled document. A printed or external copy may not reflect the current, electronic version on the Vancouver Coastal Health Authority (VCHA)
Intranet. The VCHA electronic version is always the current version.
This clinical practice guideline has been prepared as a guide to assist and support practice for staff working at VCHA. It is not a substitute for proper training,
experience and the exercise of professional judgment. Approval has been granted from VCHA to share this version of the document with external agencies.
VCH Professional Practice – Promoting & Advancing Best Practice VCH-A-1220
27. Trifiro G et al. All-cause mortality associated with atypical and typical antipsychotics in demented outpatients. Pharmacoepidemiol Drug Saf 2007;16:538-44 28. Kales H et al. Mortality risk in patients with dementia treated with antipsychotics versus other psychiatric medications. Am J Psychiatry 2007;164:1568-76 29. Wang P et al. Risk of death in elderly users of conventional vs atypical antipsychotic medications. N 30. Schneeweiss S et al. Risk of death associated with the use of conventional versus atypical antipsychotic drugs among elderly patients. CMAJ 2007;176:627-32 31. Gill S et al. Antipsychotic drug use and mortality in older adults with dementia. Ann Intern Med 32. Liperoti R et al. All-cause mortality associated with atypical and conventional antipsychotics among nursing home residents with dementia: a retrospective cohort study. J Clin Psychiatry 2009;70:1340-7 33. Health Canada website. www.hc-sc.gc.ca/dhp-mps/medeff/advisories-avis/prof/2002/risperdal_hpc- 34. Health Canada website. www.hc-sc.gc.ca/dhp-mps/medeff/advisories-avis/prof/2004/zyprexa_hpc- 35. Herrmann N, Lanctot K. Do atypical antipsychotics cause stroke? CNS Drugs 2005:19:91-103 36. Rochon P et al. Atypical antipsychotics and parkinsonism. Arch Intern Med 2005;165:1882-8 37. Lee P et al. Antipsychotic medications and drug-induced movement disorders other than parkinsonism: a population-based cohort study in older adults. J Am Geriatr Soc 2005:53:1374-9 38. Valiyeva E et al. Effect of regulatory warnings on antipsychotic prescription rates among elderly patients with dementia: a population-based time-series analysis. CMAJ 2008:179:438-46 39. American Geriatrics Society and American Association for Geriatric Psychiatry. Consensus statement on improving the quality of mental health care in U.S. nursing homes: management of depression and behavioral symptoms associated with dementia. J Am Geriatric Soc 2003;51:1287-98 40. CBC News in Depth. www.cbc.ca/news/background/seniorsdrugs/off-limits.html. Accessed May 8, 41. Ames D et al. For debate: should novel antipsychotics ever be used to treat the behavioural and psychological symptoms of dementia (BPSD)? Int Psychogeriatric 2005;17:3-29 42. Schneeweiss S, Avorn J. Antipsychotic agents and sudden cardiac death—how should we manage the 43. BC Guidelines and Protocols Advisory Committee. Cognitive impairment in the elderly. Revised January 30, 2008. www.health.gov.bc.ca. Accessed May 8, 2008 44. Lyketsos C et al. Position statement of the American Association for Geriatric Psychiatry regarding principles of care for patients with dementia resulting from Alzheimer’s Disease. Am J Geriatric Psychiatry 2006;14:561-72 45. Alexopoulos G et al. Expert consensus guidelines for using antipsychotic agents in older patients. J 46. Friedman J. Atypical antipsychotics in the EPS-vulnerable patient. Psychoneuroendocrinology 47. Ballard C, O’Brien J. Treating behavioural and psychological signs in Alzheimer’s disease. BMJ 48. Agency for Healthcare Research and Quality. Efficacy and comparative effectiveness of off-label use of atypical antipsychotics. January 2007. www.ahrq.com. Accessed May 17, 2008 49. Canadian Pharmacists Association. 2009 Compendium of Pharmaceuticals and Specialties. www.pharmacists.ca/content/products/ecps_english.cfm Note: This is a controlled document. A printed or external copy may not reflect the current, electronic version on the Vancouver Coastal Health Authority (VCHA)
Intranet. The VCHA electronic version is always the current version.
This clinical practice guideline has been prepared as a guide to assist and support practice for staff working at VCHA. It is not a substitute for proper training,
experience and the exercise of professional judgment. Approval has been granted from VCHA to share this version of the document with external agencies.
VCH Professional Practice – Promoting & Advancing Best Practice VCH-A-1220
50. McKeith I, Cummings J. Behavioural changes and psychological symptoms in dementia disorders. 51. Nelson J. Increased risk of cerebrovascular adverse events and death in elderly demented patients treated with atypical antipsychotics. J Clin Psychiatry 2005;66:1071 52. Passmore M. Psychiatrist MSJ. 53. Chan P. Psychiatrist VA and Residential 54. Donnelly M. Behavioural and psychological disturbances in Alzheimer disease. BCMJ 2005;47:487-93 55. Zhong K et al. Quetiapine to treat agitation in dementia. Curr Alz Res 2007;41:81-93 56. Philip N et al. Patterns of quetiapine use in psychiatric inpatients: an examination of off-label use. Ann 57. Drance E. Medical Director, VC Mental Health, Older Adult Mental Health 58. Lipscombe L et al. Antipsychotic drugs and hyperglycemia in older patients with diabetes. Arch Intern 59. Zheng L et al. Metabolic changes associated with second-generation antipsychotic use in Alzheimer’s Disease patients: the CATIE-AD study. Am J Psychiatry 2009:166:583-90 60. Ballard C et al. A randomised, blinded, placebo-controlled trial in dementia patients continuing or stopping neuroleptics. PLoS Medicine 2008;5:587-99 61. Ballard C. Management of agitation and aggression associated with Alzheimer’s disease: controversies and possible solutions. Curr Opin Psychiatry 2009;22:532-40 62. Third Canadian Consensus Conference on the Diagnosis and Treatment of Dementia. Approved Recommendations July 2007. www.cccdtd.ca. Accessed May 6, 2008 63. Centers for Medicare and Medicaid Services. Interpretive guidelines for long-term care facilities. In: State Operations Manual. Baltimore,MD:Centers for Medicare and Medicaid Services. Appendix PP. Revised August 17,2008 www.cms.hhs.gov/manuals/downloads/som107ap_pp_guidelines_ltcf.pdf. Accessed May 8, 2008 64. National Institute for Health and Clinical Excellence. The NICE-SCIE guidelines on supporting people with dementia and their carers in health and social care. National Clinical Practice Guideline Number 42. www.nice.uk.org. Accessed May 10, 2008 65. Rochon P et al. Variation in nursing home antipsychotic prescribing rates. Arch Intern Med 66. Cohen-Mansfield J et al. Withdrawal of haloperidol, thioridazine, and lorazepam in the nursing home. 67. Bridges-Parlet S et al. Withdrawal of neuroleptic medications form institutionalised dementia patients. J 68. Ballard C et al. A 3-month, randomized, placebo-controlled, neuroleptic discontinuation study in 100 people with dementia. J Clin Psychiatry 2004;65:114-9 69. Van Reekum R et al. A randomized, placebo-controlled trial of the discontinuation of long-term antipsychotics in dementia. Int Psychogeriatric 2002;14:197-210 70. Ruth S et al. Effect of antipsychotic withdrawal on behaviour and sleep/wake activity in nursing home residents with dementia. J Am Geriatric Soc 2004;52:1737-43 Note: This is a controlled document. A printed or external copy may not reflect the current, electronic version on the Vancouver Coastal Health Authority (VCHA)
Intranet. The VCHA electronic version is always the current version.
This clinical practice guideline has been prepared as a guide to assist and support practice for staff working at VCHA. It is not a substitute for proper training,
experience and the exercise of professional judgment. Approval has been granted from VCHA to share this version of the document with external agencies.
VCH Professional Practice – Promoting & Advancing Best Practice VCH-A-1220

Developed By
Dr Jane de Lemos, PharmD, Regional Coordinator, Professional Practice, VCH-PHC Pharmacy Dr Peter Chan, Psychiatrist VA and Residential Dr Liz Drance, Medical Director, VC Mental Health, Older Adult Mental Health Dr Mike Passmore, Geriatric Psychiatrist, PHC/FHA Dr Cait O’Sullivan (Lead) PharmD Clinical Pharmacist, Powell River
Endorsed By
Regional Pharmacy and Therapeutics Committee Health Authority Medical Advisory Council (HAMAC) VCH Professional Practice Directors: • Monica Redekopp, Richmond Health Services • Johanne Fort, Vancouver – Community Services • Lorraine Blackburn (Acting), Vancouver – Acute Services
Final Sign-off & Approved for Posting By
Susan Wannamaker, Chief Nursing Officer & Executive Lead Professional Practice - VCH
Date of Creation/Review/Revision
Original publication date: February, 2011 Review /revision date(s): February, 2014 Note: This is a controlled document. A printed or external copy may not reflect the current, electronic version on the Vancouver Coastal Health Authority (VCHA)
Intranet. The VCHA electronic version is always the current version.
This clinical practice guideline has been prepared as a guide to assist and support practice for staff working at VCHA. It is not a substitute for proper training,
experience and the exercise of professional judgment. Approval has been granted from VCHA to share this version of the document with external agencies.
VCH Professional Practice – Promoting & Advancing Best Practice

Source: http://www.bcpga.bc.ca/2013/Atypical_Antipsychotics_Agents.pdf