The long-term use of widely-prescribed anti-psychotic drugs is associated with a significant deterioration in the verbal fluency of people with Alzheimer’s and offers no long-term benefit for most patients, according to new research
The neuroleptics which came under analysis in the study were thioridazine (Melleril), chlorpromazine (Largactil), haloperidol (Serenace), trifluoperazine (Stelazine) and risperidone (Risperdal).
The research, published in the open access journal, Public Library of Science Medicine and funded by leading UK charity, the Alzheimer’s Research Trust, is significant for up to 60% of patients with Alzheimer’s disease in nursing homes who are prescribed the drugs, also known as neuroleptics, as a treatment for behavioural symptoms such as aggression.
The new research, carried out by researchers at Kings College London and at the Universities of Oxford and Newcastle, will help inform the All-Party Parliamentary Group on Dementia inquiry into the use of anti-psychotics in care homes, which is due to be published in April.
The study noted a deterioration in patients’ verbal fluency and cognitive ability six months after treatment was started.
Professor Clive Ballard, Professor of Age Related Disorders at King’s College London, and lead researcher on the project, said:
“It is very clear that even over a six month period of treatment, there is no benefit from neuroleptics in treating the behaviour in people with Alzheimer’s disease when the symptoms are mild. For people with more severe behavioural symptoms, balancing the potential benefits against adverse effects is more difficult, but this study provides an important evidence base to inform this decision-making process. The considerable risks of maintenance therapy highlight the urgency of further work to find, develop and implement safer and more effective treatment approaches for neuropsychiatric symptoms in people with Alzheimer’s disease.”
Rebecca Wood, Chief Executive of the Alzheimer’s Research Trust, said:
“These results are deeply troubling and highlight the urgent need to develop better treatments. 700,000 people are affected by dementia in the UK, a figure that will double in the next 30 years. The Government needs to make Alzheimer’s research funding a priority.
“Only £11 is spent on UK research into Alzheimer’s for every person affected by the disease, compared to £289 for cancer patients.”
Rita Clark, from Cleveland, whose husband has been living with Alzheimer’s for the past seven years, said: “My husband developed a range of side effects while receiving anti-psychotic drugs. Since the drugs have been withdrawn, the side effects have gone and he generally seems much better and more settled. I’m not saying it’s the same for everyone, but in my husband’s case, withdrawing the drugs has led to a clear improvement in his quality of life.”
This is the largest neuroleptic withdrawal study of Alzheimer’s patients and the only long-term one of its type.
Source:Alzheimer’s Research Trust
About the research
• The grant “Neuroleptics: do they accelerate cognitive decline and exacerbate neuronal loss?” was funded by the Alzheimer’s Research Trust. It began in July 2001 and ran until June 2006
• 165 participants with Alzheimer’s disease living in nursing homes in Oxfordshire, Newcastle, Edinburgh and London, who had been taking neuroleptic drugs for at least 3 months, took part in a long-term randomized double-blind placebo controlled neuroleptic withdrawal trial
• The neuroleptics in the study were thioridazine (Melleril), chlorpromazine (Largactil), haloperidol (Serenace), trifluoperazine (Stelazine) and risperidone (Risperdal). Patients continued to take their prescribed neuroleptic drug for 12 months or took a matched placebo
• Additional follow up was completed a minimum of 12 months after initial enrolment (range 24-54 months) to determine the impact of continuing or discontinuing neuroleptics on mortality. The results of this study will be published shortly.
About Alzheimer’s
• There is no cure, fully-effective treatment or prevention for Alzheimer’s
• Alzheimer’s disease is the most common cause of dementia, accounting for around two thirds of dementia in the elderly
About neuroleptics
• Neuroleptics are sedative drugs, also known as major tranquilisers or anti-psychotics. They are not licensed for the treatment of dementia, but are prescribed to some people with dementia to control agitation, delusions, anxiety, hallucinations, sleep disturbance, and aggressive behaviour
• Originally used to treat schizophrenia, neuroleptics are prescribed to up to 60% of people with Alzheimer’s living in residential or nursing homes (Reference: McGrath AM, Jackson GA. Survey of prescribing in residents of nursing homes in Glasgow. BMJ 1996;314:611-2 and Margallo-Lana M, Swann A, O’Brien J, Fairbairn A, Reichelt K, et al (2001) Prevalence and pharmacological management of behavioral and psychological symptoms amongst dementia sufferers living in care environments. Int J Geriatric Psych 16: 39-44).
About anti-Alzheimer’s drugs
• There are three drugs licensed for the treatment of mild to moderate Alzheimer’s disease, known as cholinesterase inhibitors: donepezil (Aricept), galantamine (Reminyl), rivastigmine (Exelon). In November 2006, despite evidence of benefits to patients, the National Institute for Health and Clinical Excellence (NICE) recommended the restriction of these drugs to only those in the moderate stages of the disease
• A fourth drug, Memantine (Ebixa), is the first licensed for the moderately-severe to severe stages of Alzheimer’s. Again, despite evidence of benefits to some patients, it is not recommended by NICE for prescription on the NHS except for as part of clinical research trials.
Alzheimer’s Research Trust position on neuroleptic treatment for people with Alzheimer’s
Cumulative evidence now suggests that neuroleptics should be reviewed and discontinued in Alzheimer’s patients with a Neuropsychiatric Inventory score of less than or equal to 14, given the potential adverse events of ongoing neuroleptic treatment. In other words dementia patients on long-term neuroleptic treatment with mild behaviour problems would generally be better off having the drug withdrawn.
The situation is more complex for those experiencing severe behavioural symptoms which can be distressing both for the patient and carer and sometimes dangerous. If continuing treatment, this should be monitored carefully and the modest benefits weighed against the potential incredibly serious side-effects shown by this study.
This data further adds to the serious safety concerns with long-term use and we encourage clinicians to try to replace neuroleptics with safer management approaches. Many studies have demonstrated that psychological management approaches can replace neuroleptic therapy without significant worsening of behavioural symptoms. Evidence is emerging that cholinesterase inhibitors or memantine may be safer and effective alternatives for some symptoms.
For now we suggest these drugs should only continue to be prescribed long-term to dementia patients experiencing severe behavioural problems and only as a last resort when non-drug methods have been tried and failed.
