Rationalisation of antipsychotic drug use in older people
The study will use positron emission tomography (PET) imaging of brain dopamine receptors to investigate disease-specific mechanisms underpinning antipsychotic drug sensitivity in later life, and combine this with data on clinical outcome measures to inform and guide prescribing.
The research will focus upon two groups of patients who are extremely susceptible to antipsychotic drug side effects - schizophrenia-like psychosis with onset after the age of 60 years and Alzheimer’s disease with behavioural or psychotic symptoms.
Why carry out the research?
There are approximately 700,000 people in the UK with dementia and up to 50% of these are prescribed antipsychotic medication for the treatment of behavioural and psychotic symptoms. Whilst the drugs have been shown to reduce symptoms, their use is associated with a range of side effects, including falls, sedation and problems with movement co-ordination.
People with schizophrenia-like illnesses with onset in later life represent the largest diagnostic group presenting to older adult mental health services after dementia and depression and are exquisitely sensitive to the motor side effects of antipsychotic drugs.
The mechanisms underlying disease-specific differences in side effect profile are poorly understood and under-researched. There is an urgent clinical need to establish why this is the case, to inform treatment strategies, reduce morbidity and improve quality of life.
Brain imaging techniques that allow the action of antipsychotic drugs at dopamine receptor sites have played a crucial role in optimising dosage strategies in young people with schizophrenia and the current study aims to use a similar approach in older people, to determine the relationship between drug dosage, plasma levels and action at dopamine receptor sites.
How is the research being undertaken?
A pilot study has been funded by Guy's and St Thomas’ charity, to test an imaging protocol that has been specifically adapted for use in older people. Eight people with dementia will be recruited to the study and will have PET imaging of brain dopamine receptors before and after treatment with the antipsychotic drug amisulpride.
The main study has been funded by the National Institute for Health Research. 40 people with dementia, 40 people with schizophrenia-like psychosis with onset >60 years and 20 healthy older participants will be recruited and will be involved in one of the following:
Brain imaging before and after 4 days treatment with a low (starter) dose of amisulpride in 20 healthy older people and 20 participants from each patient group.
Brain imaging before and after 4-10 weeks treatment with amisulpride in 20 participants from each patient group
Patients participating in both arms of the trial will have blood sampling of amisulpride levels prior to each dose increase and clinical assessment to measure symptoms and side effects.
This information will be combined with imaging data to determine the minimal clinically effective dose, optimum dose range and threshold dopamine receptor occupancy for motor side effects in each patient group.
Where is it happening?
Participants will be recruited via the South London and Maudsley NHS Foundation Trust.
Who is involved?
Dr Suzanne Reeves, Clinical Senior Lecturer in the Department of Old Age Psychiatry, is the Chief Investigator.
Chloe Clark-Papasavas, is a PhD student and investigator based at the Institute of Psychiatry.
Professor Robert Howard and Professor Stephen Jackson are investigators at the Institute of Psychiatry and King's College Hospital respectively.
Dr Paul Marsden and Dr Joel Dunn are investigators based at St Thomas’ Hospital, overseeing PET imaging.
What is the timescale?
Recruitment for the pilot study is currently underway. We anticipate that recruitment for the main study will begin in July/August 2011 and continue for 4 years.
To find out more
Dr Suzanne Reeves