Recommendations for research
The guideline committee has made the following recommendations for research. The committee's full set of research recommendations is detailed in the full guideline.
What is the effectiveness of combination treatment with a cholinesterase inhibitor and memantine for people with Parkinson's disease dementia if treatment with a cholinesterase inhibitor alone is not effective or no longer effective?
The guideline committee felt that cholinesterase inhibitors, memantine and combination therapy with both treatments are all reasonable clinical options, but noted that some people do not tolerate cholinesterase inhibitors well due to side effects. The evidence base for memantine was considerably weaker than for cholinesterase inhibitors, and therefore there would be value in either additional trials of memantine compared with placebo (in people for whom cholinesterase inhibitors are not an option), or non-inferiority studies compared with cholinesterase inhibitors.
In clinical practice, memantine is often added to a cholinesterase inhibitor when it is no longer proving effective, but there is no evidence base for this and randomised trials to establish whether there is additional benefit would be valuable. Both of these questions could potentially be answered in a single study with 3 arms of memantine monotherapy, cholinesterase inhibitor monotherapy and combination treatment.
For people with Parkinson's disease, what is the most effective pharmacological treatment for orthostatic hypotension?
Particular interventions and comparisons of interest are:
midodrine compared with fludrocortisone (primary comparison)
The guideline committee felt that orthostatic hypotension was an important practical problem, common in people with Parkinson's disease and a contributor to falls and injuries. The current best pharmacological treatment is not yet established and research in this area would help to determine this. The randomised controlled trials that have previously been undertaken have only provided low-quality evidence (because of both small sample sizes and weaknesses in the trial designs) and cover only a subset of the comparisons of interest, making future research in this area of value.
What is the effectiveness of rivastigmine compared with atypical antipsychotic drugs for treating psychotic symptoms (particularly hallucinations and delusions) associated with Parkinson's disease?
Rivastigmine is commonly used to treat Parkinson's disease psychosis because it has shown some effectiveness in improving behavioural symptoms in people with Parkinson's disease dementia. At present, no evidence exists to support the efficacy of rivastigmine in treating people with Parkinson's disease whose symptoms are predominantly psychotic. It would be beneficial to undertake primary research in this area to determine the most effective treatment options for managing Parkinson's disease psychosis.
What is the best first-line treatment for rapid eye movement sleep behaviour disorder (RBD) in people with Parkinson's disease?
The guideline committee highlighted the importance of minimising RBD, for both people with Parkinson's disease and their carers, particularly because of potential safety concerns. Only 1 paper was found to address optimal management, and this involved people in whom first-line treatment had failed. With multiple possible treatment options and no current evidence on what the most effective first-line treatment is, research (in the form of randomised controlled trials) in this area would be beneficial.
Does physiotherapy started early in the course of Parkinson's disease, as opposed to after motor symptom onset, confer benefits in terms of delaying symptom onset and/or reducing severity?
The guideline committee felt that physiotherapy was beneficial for those earlier in the course of the disease as it may delay or lessen problems associated with symptoms, as well as for those who have developed symptoms and problems. At present, no substantial evidence exists to support the efficacy of physiotherapy as an early intervention to prevent the onset or reduce severity of motor symptoms, because most of the trials have been conducted in people who have already developed motor symptoms.
If physiotherapy were shown to have a beneficial effect in either delaying the onset or decreasing the severity of symptoms, this would have a substantial beneficial impact on the quality of life of people with Parkinson's disease and their family and carers. Relevant trials would not compare physiotherapy with no physiotherapy, but rather early physiotherapy (at the time of diagnosis) with physiotherapy offered at the current standard times in the UK.