Cholinesterase inhibitors in advanced Dementia with Lewy bodies: increase or stop? Sanjeet Pakrasi * , Alan Thomas, Urs P. Mosimann, David A. Cousins, Debbie Lett, David J. Burn, John T. O’Brien and Ian G. McKeith Institute for Ageing and Health, Wolfson Research Centre, Newcastle General Hospital, Westgate Road, Newcastle upon Tyne, UK SUMMARY Introduction There is little data on stopping cholinesterase inhibitors in Dementia with Lewy bodies (DLB). Equally, it is not known if increasing the dose of cholinesterase inhibitors may help neuropsychiatric symptoms in advanced DLB. Method We conducted an open label trial with donepezil involving 16 patients with LBD when the dose was reduced and treatment stopped over 4 weeks. Another 7 patients were given a trial of an increased dose of donepezil (15 mg) to resolve re- emergent neuropsychiatric symptoms. Results The slow discontinuation protocol was well tolerated in advanced DLB. Five of the seven patients given a trial of a higher dose of donepezil were rated as clinically improved after 12 weeks treatment. Conclusion Cholinesterase inhibitors can be discontinued slowly in advanced DLB. Increasing the dose of donepezil may be of benefit to some patients with DLB who experience a recurrence in their neuropsychiatric symptoms. Copyright # 2006 John Wiley & Sons, Ltd. key words — dementia; Lewy bodies; cholinesterase inhibitors; treatment; discontinuation; dose escalation INTRODUCTION Evidence suggests that cholinesterase inhibitors (ChEIs) are effective in the treatment of cognitive and neuropsychiatric symptoms in Dementia with Lewy bodies (DLB) and Parkinson’s disease with dementia (PDD) (McKeith et al., 2000). Unfortu- nately, symptoms can recur over time despite continued treatment. This may indicate that the ChEI is no longer effective and needs to be withdrawn. Withdrawal needs to be done cautiously since there is a report of acute cognitive and behavioural decline following abrupt cessation of donepezil treatment in DLB and PDD (Minett et al., 2003). Another option at this stage of dementia may be to increase the dose of donepezil, especially if it was believed that pharma- cological tolerance had developed. We describe a slow discontinuation protocol to stop donepezil in DLB designed to minimise withdrawal effects. We also report on a series of patients with DLB/PDD for whom the dose of donepezil was increased to treat re-emergent neuropsychiatric symptoms. METHOD We investigated the safety of a discontinuation protocol of donepezil in seven patients with DLB and nine with PDD (n ¼ 16). Details of patient INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY Int J Geriatr Psychiatry 2006; 21: 719–721. Published online 21 July 2006 in Wiley InterScience (www.interscience.wiley.com) DOI: 10.1002/gps.1547 *Correspondence to: Dr S. Pakrasi, Institute for Ageing and Health, Wolfson Research Centre, Newcastle General Hospital, Westgate Road, Newcastle upon Tyne NE4 6BE, UK. Tel: 01912563018. Fax: 01912195071. Contract/grant sponsor: FAPESP; contract/grant number: 99/ 04928-9. Contract/grant sponsor: CAPES; contract/grant number: BEX 0096/ 01-6. Copyright # 2006 John Wiley & Sons, Ltd. Received 16 August 2005 Accepted 8 December 2005