As well as examining the evidence for starting patients on drug treatments, Cochrane Reviews also look at the relative benefits of stopping or continuing once someone has started taking them. This is the case with a February 2021 review of the effects of withdrawing or continuing two common classes of drug treatment for people with dementia. We asked lead author, Carole Parsons from Queen’s University Belfast in Northern Ireland to tell us what they found.
Monaz: Hello, I'm Monaz Mehta, editor in the Cochrane Editorial and Methods department. As well as examining the evidence for starting patients on drug treatments, Cochrane Reviews also look at the relative benefits of stopping or continuing once someone has started taking them. This is the case with a February 2021 review of the effects of withdrawing or continuing two common classes of drug treatment for people with dementia. We asked lead author, Carole Parsons from Queen's University Belfast in Northern Ireland to tell us what they found.
Carole: Dementia is a progressive syndrome characterised by deterioration in memory, thinking and behaviour, and by impaired ability to perform daily activities. The two classes of drug that we wanted to assess in this review are cholinesterase inhibitors (such as donepezil, galantamine and rivastigmine) and memantine, but we found no currently available evidence to influence clinical practice regarding withdrawal or continuation of memantine.
In our review, we wanted to find out more about the effects of withdrawal or continuation on cognitive, neuropsychiatric and functional outcomes, rates of institutionalisation, adverse events, dropout from trials, mortality, quality of life and carer‐related outcomes for people with dementia. We divided the effects into three time periods: short term, which was the first two months; medium term between three and 11 months and long-term, after a year or more.
We included six randomised trials which compared withdrawal versus continuation of cholinesterase inhibitors. These included nearly 700 patients with dementia due to Alzheimer's disease. We also found a seventh trial that investigated discontinuing either the cholinesterase inhibitor donepezil or memantine, but we could not use this in our meta-analysis because data were not available on the drugs separately.
Turning to the results, we found that discontinuing cholinesterase inhibitors may be associated with worse cognitive function in the short and medium term, compared to continuing treatment. Data from one longer‐term study also suggest that discontinuing the drug is probably associated with worse cognitive function at 12 months.
We found that discontinuation may make little or no difference to functional status in the short or medium term, but after 12 months, it probably results in greater functional impairment than continuing treatment.
Discontinuation of a cholinesterase inhibitor may be associated with a worsening of neuropsychiatric symptoms over the short and medium term, while data from one study suggest that discontinuing may result in little to no change in neuropsychiatric status at 12 months.
In conclusion, discontinuing cholinesterase inhibitors may result in worse cognitive, neuropsychiatric and functional status than continuing treatment, but this is supported by limited evidence, almost all of low or very low certainty. As all participants had dementia due to Alzheimer's disease, our findings are also not transferable to other dementia types.
Although certainty is low, this small body of evidence is consistent in suggesting that discontinuing cholinesterase inhibitors may be associated with worse outcomes than continuing treatment at least over the short term, indicating that clinicians should approach discontinuation of cholinesterase inhibitors with caution. If withdrawal is to be attempted, careful re‐evaluation of the cognitive, functional and neuropsychiatric status of the patient is advisable. In making decisions regarding discontinuing these drugs, clinicians should consider the evidence from existing trials, or the lack thereof, along with other important individualised patient‐centred considerations, including patient and carer preferences and values, changing goals of care as individuals approach the end of life, and potential adverse events.
Finally, there is a pressing need for more well‐designed, randomised, placebo‐controlled trials examining withdrawal of cholinesterase inhibitors and memantine, in which continuation of the medication is the control intervention. The eligibility criteria for these trials also need to be wide enough to provide evidence for people with a range of severities of dementia and in community and institutional care settings.
Monaz: If you would like to find out more about the trials that have already been done and watch for future updates of the review should the new studies become available, simply go online to Cochrane Library dot com and search 'withdrawal of cholinesterase inhibitors' to find it.