BPSD - Devon Partnership NHS Trust

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ACETYL-CHOLINESTERASE INHIBITORS (If not already prescribed for management of AD) Intervention Rationale (Where stated, doses derived from published studies) DPT use approved Donepezil (Off-license use) Meta-analysis demonstrated a small by significant overall advantage of AChEIs over placebo with regard to the treatment of BPSD in Alzheimer’s Disease, although no short term benefit for treatment of clinically significant agitation with donepezil observed in 12 week RCT. Current evidence appears to demonstrate that AChEIs have their greatest effects on depression and dysphoria, apathy, indifference and anxiety and are probably not an effective treatment for the management of agitation or aggression in Alzheimer’s dementia. YES Galantamine (Off-license use) Rivastigmine (Off-license use) Evidence equivocal at doses of 16-24mg/day. In placebo controlled trials, Rockwood et al (2001) reported no statistically significant difference in behavioural symptoms between groups (n=386). Cummings et al (2004) post hoc analysis of Tariot et al (2000) reported slight improvement (NPI) observed with galantamine (p=0.04) at 16 & 24mg/day but not 8mg/d (n=978) Not approved because available evidence equivocal and increased treatment cost cannot be justified due to lack of evidence demonstrating increased efficacy compared with donepezil. Reported doses prescribed 1.5-4.5mg bd (6-12mg/day). Evidence equivocal (most studies open-label and behaviour a secondary end-point). Metaanalysis reported rivastigmine may be tolerated and effective for BPSD (6- 12mg/d) (Finkel et al, 2004) Not approved because available evidence equivocal and increased treatment cost cannot be justified due to lack of evidence demonstrating increased efficacy compared with donepezil. NO NO NMDA ANTAGONIST Memantine Systemic metaanalysis suggested that memantine (10mg bd) decreases (Off-license use) NPI scores and may have a role in BPSD (reducing agitation/aggression) but effect size small. Could be considered for management of severe symptoms of agitation/aggression and psychosis in people who have failed to respond to other medication and who are otherwise prone to a rapid decline. Maidment et al (2008). However, a randomised DB PC trial (Fox et al 2012) reported no improvement in significant agitation in people with moderate to severe AD, suggesting that memantine should not be routinely prescribed to treatment agitation in AD. YES ANTIDEPRESSANTS Intervention Rationale (Where stated, doses derived from published studies) DPT use approved Mirtazapine (Off-license use) Citalopram (Off-license use) Trazadone (Off-license use) Limited evidence available. One 12 week open-label study reported mirtazapine (15-30mg/day) could be a well-tolerated treatment option for the management of agitation in people with Alzheimer’s Disease (AD). YES Whilst not clinically effective for the treatment of depression in people with AD, mirtazapine may act to improve general behavioural and psychological Banerjee (2013) symptoms in dementia rather than depression Limited, but encouraging, evidence available. More studies needed. Trazadone most widely used antidepressant prescribed for people presenting with BPSD despite lack of robust evidence to support efficacy. NO NO PG 14 – Pharmacological Management of BPSD Approved by Drug and Therapeutics Committee: September 2013 Review date: September 2015 Page 8 of 10
BENZODIAZEPINES Intervention Rationale (Where stated, doses derived from published studies) Diazepam 1-2 mg up to 3 times a day (increase if necessary to (Off-license use) Max 15mg/24 in divided doses) Licensed for anxietyshort term use only for acute & severe distress and/or where sedation is required T1/2 ~32 hours (21-50) longer in older adults No systemic reviews of RCTs examining the usefulness of benzodiazepines in the management symptoms associated with dementia (including anxiety) were identified. Lorazepam (Off-license use) NB 5mg diazepam ~equiv to 0.5mg lorazepam Usual max dose= 2mg/24hours (in divided doses) Short term use for only for acute & severe distress and/or where sedation is required Licensed for anxiety T1/2 ~12 hours (8-25) Similar in older adults No systemic reviews of RCTs examining the usefulness of benzodiazepines in the management symptoms associated with dementia (including anxiety) were identified May cause/hasten cognitive decline Paradoxical disinhibition may occur Contribute to falls and hip fractures Accumulation leading to excessive sedation/adverse effects and/or tolerance over time DPT use approved YES ONLY for short term use for acute & severe distress and/or where sedation is required ANTI-CONVULSANTS: Intervention Rationale (Where stated, doses derived from published studies) Carbamazepine Uncontrolled studies & case reports have reported improvement in (Off-license use) presenting hostility & aggression in people with dementia who had not responded to antipsychotics as well as short term efficacy for agitation, however a review of placebo controlled RCTs to date provides equivocal information about efficacy for BPSD, and the safety and tolerability of therapeutic doses in people with dementia/older adults still needs to be established. DPT use approved NO Valproate (Off-license use) Adverse effects include: Impairment of balance & increased risk of falls, Drug interactions, Impaired cognition, Blood dyscraisias, Hyponatraemia, Hepatic dysfunction, Serious skin reactions Despite positive treatment responses documented in case reports, retrospective chart reviews and open-label studies, the existing d/b, p/c, RCTs do not support the proposal that valproate is effective in the management of agitation, aggression or other BPSD in people with dementia. NO Adverse effects include: GI side effects, Impaired cognition, Hepatotoxicity- monitor liver function before & during treatment Oxcarbazepine No evidence to demonstrate efficacy NO Gabapentin Limited data reporting treatment well tolerated and effective, but NO evidence weak (small open-label &case reports only) and incomplete. Pregabalin No available published evidence reporting use or efficacy for BPSD NO Lamotrigine Topiramate Limited data reporting treatment well tolerated and effective, but evidence very weak (case reports only). Limited data (non-random retrospective study n=15). Reduction in Cohen-Mansfield Agitation Inventory noted but evidence very weak. NO PG 14 – Pharmacological Management of BPSD Approved by Drug and Therapeutics Committee: September 2013 Review date: September 2015 Page 9 of 10
Page 1 and 2: Prescribing Guideline Pharmacologic
Page 3 and 4: No further intervention needed at t
Page 5 and 6: Initiation of medication (by, or on
Page 7: Appendix 1 Decision aid for special

BPSD - Devon Partnership NHS Trust

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