What happens when donepezil is suddenly withdrawn? An open label trial in dementia with Lewy bodies and Parkinson's disease with dementia.
BACKGROUND
This open label study was designed to assess the effects of donepezil treatment, its withdrawal and subsequent recommencement on cognitive functioning, behaviour and parkinsonian symptoms in patients with probable dementia with Lewy bodies (DLB) and with Parkinson's disease who subsequently developed dementia (PDD).


METHODS
Eight patients with DLB and 11 with PDD were treated with up to 10 mg of donepezil daily for 20 weeks followed by a 6-week withdrawal period. The primary outcome measures were the Mini-Mental State Examination (MMSE), the total Neuropsychiatric Inventory (NPI) and the Unified Parkinson's Disease Rating Scale III. Testing was conducted before dosing, at week 20, at a withdrawal visit and 3 months after recommencement on donepezil.


RESULTS
Patients with DLB and PDD showed a significant improvement in cognition with treatment, loss of this improvement on withdrawal and restoration of treatment gains on recommencement. Both groups also demonstrated favourable, behavioural changes with treatment, PDD patients in particular deteriorating significantly after withdrawal. The only NPI symptom domain that showed a consistent significant response to both treatment (positive) and withdrawal (negative) was hallucinations. The medication was well tolerated and parkinsonian features did not alter significantly over the testing sessions.


CONCLUSIONS
Our results suggest that treatment with donepezil improves cognition and hallucinations without increasing parkinsonian symptoms, and its sudden withdrawal is usually detrimental, producing acute cognitive and behavioural decline. Although recommencement on donepezil appears to reverse this deterioration we do not advise its abrupt discontinuation in this population.
Minett
Thaís S C
TS
Institute for Ageing and Health, Wolfson Research Centre, Newcastle General Hospital, Newcastle upon Tyne, UK.
Thomas
Alan
A
Wilkinson
Lucy M
LM
Daniel
Sarah L
SL
Sanders
Jonathan
J
Richardson
Jonathan
J
Littlewood
Elizabeth
E
Myint
Pat
P
Newby
Jane
J
McKeith
Ian G
IG
D002800:Cholinesterase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D003704:Dementia / Q000188:drug therapy / Q000209:etiology; D000077265:Donepezil; D004334:Drug Administration Schedule; D006801:Humans; D007189:Indans / Q000009:adverse effects / Q000627:therapeutic use*; D020961:Lewy Body Disease / Q000188:drug therapy*; D009483:Neuropsychological Tests; D018697:Nootropic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000188:drug therapy* / Q000523:psychology; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D016896:Treatment Outcome
D002800:Cholinesterase Inhibitors; D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D000077265:Donepezil