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Autonomic disturbance and pain. While most people are troubled by these problems in the later stages of their, certain non-motor conditions can develop throughout the course of the condition (eg depression, anxiety, ) or even precede it (eg sleep disturbance, depression, anxiety). A recent study reported on the non-motor problems experienced by a group of 149 people with followed for 15–18 years. They found the occurrence rates were: falls 81% (with 23% suffering fractures), cognitive decline 84% (48% fulfilling criteria for dementia), hallucinations 50%, depression 50%, choking 50%, symptomatic postural hypotension 35%, and urinary incontinence 41%. There have previously been few therapeutic studies examining the effects of treatments for non-motor disorders. However, there is now a real desire to increase research into the non-motor features of as their effect on people’s well-being has been recognised.
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The non-motor features of considered in the scope of this guideline and thus undergoing literature review were:. Depression, dementia and psychosis are frequent problems in and some research has been performed on their treatment.
Therefore, these topics were included in the scope of this guideline. Other important mental health issues in include anxiety and apathy, but little work has been done in these areas specific to PD so they were not included in the scope. Standard treatment therefore applies in these areas; see guidance entitled: ‘Anxiety: management of anxiety (panic disorder, with or without agoraphobia, and generalised anxiety disorder) in adults in primary, secondary and community care’.
Depression Depression affects around 40–50% of people with. It is usually mild to moderate but can be severe, and symptoms of depression can predate motor manifestations. The relationship of depression to the pathology of is unclear but the inconsistent relationship between mood changes and the severity of motor symptoms indicates that depression should not simply be considered a reaction to motor disability.
There are difficulties in diagnosing mild depression in people with as the clinical features of depression overlap with the motor features of PD. The characteristic features of depression are low mood, loss of interest and enjoyment, and fatigue. This is accompanied by various combinations of:. Disturbance of cognitive function and thought processes. The disturbance of cognitive functions and thought processes may result in poor concentration and memory, excessive worry, feelings of worthlessness, hopelessness and guilt, negative views of self and life, and thoughts of suicide. Psychological and physical symptoms of anxiety are also common.
The development of depression creates an added burden for people with and their carers and has been shown to be an important determinant of. Factors relevant to the aetiology of depression that need to be considered are:. Methodology A and two randomised controlled trials, (published after the review’s search date) were found which addressed the effectiveness of antidepressant therapies versus or active comparator. No controlled trials were found on electroconvulsive therapy or behavioural therapy for the treatment of depression in people. The included three trials: one trial compared a selective serotonin re- inhibitor (SSRI) with; another study compared a tricyclic antidepressant (TCA) with placebo; and the third trial compared the effectiveness of an SSRI versus a TCA. These trials included small sample sizes (range 22–47). There were several methodological limitations of the included studies: lack of power calculations, lack of characteristics, and no details on methods of.
The duration of the included trials varied from 16 to 52 weeks (with one study not reporting the trial duration). One of the independent RCTs compared the effectiveness of an SSRI with. The methodological limitations of this study included unclear methods of and, small (N=12, six in each arm) and lack of power calculations. The study reported that, because of the low recruitment, the study was terminated after 10 weeks. The second independent compared repetitive transcranial magnetic stimulation (rTMS) versus an SSRI as an effective antidepressant therapy.
The methodological limitations included: short trial duration (8 weeks), small (N=42, 21 in each arm) and lack of power calculation. Confusion and visual hallucination were infrequently reported in people taking fluvoxamine and amitriptyline; otherwise, no other major were reported. (1) One of the independent RCTs reported no significant difference between sertraline (SSRI) and in terms of ‘response’ to treatment (defined as at least 50% reduction of the pre-treatment ), or motor scores.
(1+) One of the independent RCTs reported that the following outcomes were improved in both rTMS and fluoxetine-treated groups: the Hamilton Depression Rating Scale and, scores, and the (MMSE), with no significant differences between groups. However, were found more frequently in the fluoxetine-treated group than the rTMS group (p=0.03). From evidence to recommendation There is insufficient evidence from RCTs of the efficacy or safety of any antidepressant therapy in. This includes cognitive behavioural therapy, all classes of antidepressant medication and electroconvulsive therapy.
Has recently published guidelines for the management of depression which include people with physical disorders. While it is tempting to adopt these guidelines for people with, there are a number of factors that suggest that the management of depression in PD may require different strategies:. Psychotic symptoms Psychotic symptoms indicate a loss of reality testing; that is, the formation of beliefs and sensations without a basis in reason or external sensory stimulus. Delusions (false unshakeable beliefs that cannot be understood from the individual’s sociocultural context) and hallucinations (perceptions in any sensory modality occurring without external sensory stimulus) are the most common symptoms of psychosis.
Psychotic symptoms may occur at any stage in. Up to 50% of people with the condition may develop psychotic symptoms and 30% may experience hallucinations within the first 5 years.
Although visual hallucination is the most frequent psychotic symptom, a degree of auditory hallucination is found in 40%. Delusions may involve themes of persecution, infidelity and jealousy but these are much less common. The aetiology of psychotic symptoms in is complex. They may arise from the neuro-transmitter disturbances of PD but can be caused by any of the drugs used to treat motor symptoms. The appearance of psychotic symptoms requires careful evaluation.
Psychotic symptoms may also occur as part of delirium (caused by other physical illness or drug treatments) or dementia, or may indicate the development of a co-morbid mental illness. Psychotic symptoms are distressing and may be frightening to people with and their carers who may not appreciate that they are symptoms of illness. It is essential to explain the nature of these symptoms to people with PD and their carers.
What is the effectiveness of atypical antipsychotic therapies versus or active comparator in the treatment of psychotic symptoms in? Methodology Five RCTs were found which addressed the effectiveness of atypical antipsychotic therapies versus or active comparator in the treatment of psychosis. Three trials were found that compared two atypical antipsychotic drugs, and these were excluded as within drug class comparisons. The methodological limitations for some of the included studies involved: lack of and methods, lack of multi-centre comparative results analysis, lack of power calculations, small sample sizes (N=31, 160, 30 and 60) short trial duration and no intention-to-treat analysis protocols. From evidence to recommendation Psychosis is a common problem in later and can be difficult to manage. It may be precipitated by intercurrent illnesses (eg infections), addition of new anti-parkinsonian medication or dementia. Correspondingly, the initial treatment of psychosis should include general medical assessment and treatment of any potential causative factor.
Consideration should be given to of any recently added medication that may have triggered a psychotic reaction. Drugs that are particularly prone to trigger psychosis, such as anti-cholinergics, selegiline and amantadine, should be withdrawn first. The patient should be evaluated for a fixed cognitive deficit that might suggest the development of dementia. For psychosis which does not respond to the above measures, no treatment may be required if psychotic features are not troublesome to the patient or their carers. In more severe psychosis, antipsychotic medication should be considered.
Typical antipsychotics (eg phenothiazines and butyrophenones) are well known to exacerbate and should not be used. Various atypical antipsychotics have been evaluated in PD, but only clozapine has a licence for this indication in England and Wales: Several randomised -controlled trials have shown that clozapine can reduce psychotic symptoms in without exacerbating parkinsonian features.
However, the use of clozapine requires intensive monitoring to detect the uncommon but potentially life-threatening complication of agranulocytosis. As a result, it is rarely used in PD. Limited trial evidence suggests that olanzapine is not effective against psychotic features and makes parkinsonian symptoms worse. There are concerns about the safety of olanzapine and risperidone in elderly people with dementia and risk factors for stroke.
There is no evidence from RCTs of the efficacy and safety of quetiapine as an antipsychotic in. However, several trials are ongoing in this area.
Quetiapine is thought to be relatively safe and does not require haematological monitoring. As a result, quetiapine has been widely used in PD psychosis. RECOMMENDATIONS R62. All people with and psychosis should receive a general medical evaluation and treatment for any precipitating condition. D (GPP) R63. Consideration should be given to withdrawing gradually anti-parkinsonian medication that might have triggered psychosis in people with.
D (GPP) R64. Mild psychotic symptoms in people with may not need to be actively treated if they are well tolerated by the patient and carer. D (GPP) R65. Typical antipsychotic drugs (such as phenothiazines and butyrophenones) should not be used in people with because they exacerbate the motor features of the condition.
D (GPP) R66. Atypical antipsychotics may be considered for treatment of psychotic symptoms in people with, although the evidence base for their efficacy and safety is limited. D (GPP) R67. Clozapine may be used in the treatment of psychotic symptoms in, but registration with a mandatory monitoring scheme is required. It is recognised that few specialists caring for people with PD have experience with clozapine. Dementia is associated with impairment of cognitive function.
Compared with people without PD, deficits in visuospatial abilities, category learning, verbal fluency, set switching and executive functions are typically reported. Particular attention has focused on deficits of executive function that may mediate many of the other impairments. Executive functions include working memory, mental flexibility, and the ability to initiate and suppress responses.
Dementia (the progressive loss of global cognitive function) is also common in; 48% to 80% of people may develop dementia at some point in the course of the condition. In addition to cognitive decline, dementia leads to impairment in and disturbance of behaviour and other psychological functions. Dementia in is accompanied by reduced for people with PD and their carers., Other pathologies commonly causing dementia include Alzheimer’s disease, vascular brain disease and dementia with Lewy bodies.
Traditionally, dementia developing more than 1 year after the onset of the motor features of is referred to as PD with dementia (PDD). Dementia developing within 1 year of the onset of motor features is classified as dementia with Lewy bodies. The relationship between PDD and dementia with Lewy bodies is unclear, but many consider them to be a continuum rather than discrete entities. Since people with dementia with Lewy bodies may not develop parkinsonism, we have not considered the treatment of this type of dementia in this guideline. The acknowledges that this decision may need to be revisited in the future if new evidence proves that a continuum exists between PDD and dementia with Lewy bodies. Rarely, dementia may arise due to a treatable illness.
All people with dementia require careful evaluation of their medical condition, treatment and investigations to clarify the diagnosis with attention to potentially treatable conditions. In this context, cognitive decline due to depression, often referred to as depressive ‘pseudodementia’, should be considered. The assessment and management of dementia will require a range of clinical expertise that can be provided only by a multidisciplinary team. Are cholinesterase inhibitors effective cognitive enhancement therapies in? Methodology Seven papers were found which addressed the effectiveness of cholinesterase inhibitors as cognitive enhancement therapies in. All levels of evidence (RCTs and case series) were selected in order to provide a comprehensive body of evidence upon which to analyse the cost-effectiveness of these treatments in people with PDD.
In addition, the literature search cut-off date, for this particular section of the guideline, was August 2005 instead of February 2005. In addition to the seven papers selected, a which included only one on rivastigmine versus was excluded. This paper was excluded as the patient population was defined as people suffering from dementia with Lewy bodies and not PDD. From evidence to recommendation There is evidence from randomised -controlled trials of the effectiveness and safety of cholinesterase inhibitors in the treatment of PDD. They are effective in treating both cognitive decline and psychosis in this context.
However, not all patients respond, so regular review of the need for these agents is required. At the time of writing, only one of the cholinesterase inhibitors has a product licence in the UK. The considers that these are useful agents that are commonly used in clinical practice and that they should be available. Has commissioned the guideline: ‘Dementia: management of dementia, including use of antipsychotic medication in older people’. NICE is developing this guideline in collaboration with the Social Care Institute for Excellence. This guideline will cover all major forms of dementia, including Alzheimer’s disease, vascular dementia, Lewy body dementia, subcortical dementia, frontotemporal dementias, and mixed cortical and subcortical dementia.
Dementia encountered in the course of will be addressed. The guidelines will, where appropriate, address the differences in treatment and care for people with mild, moderate and severe dementia. Questioning whether dreams are acted out, sometimes violently, indicative of RBD, which occurs in up to 15% of people with and may precede the diagnosis of PD. Drug-induced hallucinations and/or vivid dreams may occur, and should be distinguished from RBD.
Many centrally acting drugs may disturb sleep patterns, mainly by inducing sedation, but some may cause nocturnal alertness (eg selegiline). One of the most common sleep disorders seen in is RLS.
The International RLS Study Group criteria for the diagnosis of RLS are:. Symptoms are worse later in the day or at night.
Vivid dreams and nightmares may be provoked by many of the commonly used drugs in. A review of medication and reduction/avoidance of suspected causes is usually effective.
However, RBD may also occur in which dreams are so vivid that they are acted out. When pharmacotherapy is required, a response may be seen to low doses of clonazepam. ‘Sudden onset of sleep’ without warning has recently been described in people, with the potential to cause road traffic accidents.
While certain dopamine agonists were initially incriminated, current opinion is that all PD medications can cause daytime and that all people with PD are liable to hypersomnolence and should be warned of the possibility of falling asleep at the wheel. This may be more likely in people with later PD on multiple medications and also during upwards dose titration, particularly with dopaminergic agonists. Any people so affected should not drive.
A review of all medication and avoidance of any drugs that may affect sleep or alertness, or may interact with other medication (for example, selegiline, antihistamines, H 2 antagonists, antipsychotics and sedatives). D (GPP) R71.
Care should be taken to identify and manage restless leg syndrome (RLS) and rapid eye movement (REM) sleep behaviour disorder in people with and sleep disturbance D (GPP) R72. People with who have sudden onset of sleep should be advised not to drive and to consider any occupational hazards. Attempts should be made to adjust their medication to reduce its occurrence. Methodology Three -controlled, double-blind RCTs, were found which investigated the effectiveness of modafinil treatment for sleep disorders in people with. Two of the studies used a 200 mg/d dose, while the third increased the dose to 400 mg/d after 1 week.
All studies were small (N=15, 21 and 40), and of short duration (between 4 and 8 weeks). The mean age of the people included in these studies was 65 years, with mean disease duration of 7 years. No RCTs were found on the specific treatment of RBD and RLS in. Nocturnal akinesia Turning over in bed (nocturnal ) may become difficult in due to truncal. This can have a major impact on people with PD and can interfere with sleep and thus lead to daytime. Treatment has traditionally been with either small doses of immediate-release levodopa or controlled-release levodopa last thing at night. There is insufficient experience with dopamine agonists and COMT inhibitors in this area.
Are controlled-release levodopa preparations effective in the management of nocturnal in? Methodology A double-blind was found which compared controlled-release levodopa and immediate-release levodopa in the treatment of nocturnal and early-morning disability. The was a multi-centre trial including 103 people from 11 centres in the UK. The mean age of people included in the study was 68 years, with average disease duration of 8 years. Controlled-release co-beneldopa or immediate-release co-beneldopa was given at a dose of 125 mg/day immediately before going to bed. Methodological limitations included: lack of and methods, no or first-arm results, and intention-to-treat analysis was not stated. However, carry-over effects and differences between centres were statistically analysed and produced no significant differences.
Assessment and prevention of falls People with require a multidisciplinary assessment of the specific and non-specific predictors of falls together with the intrinsic and extrinsic factors that contribute to falls. In common with other people with repeated falls the assessment and prevention of falls in PD requires multifactorial assessment and intervention by a professional with understanding of PD. The clinical guideline no. 21 ‘Falls: assessment and prevention of falls in older people’ provides a framework for this process. The ‘Quick Reference Guide’ of this guideline is applicable to all people with PD. Weight loss Unintended weight loss is common in, occurring in over 50% of individuals, with 20% losing over 12 kg in one study. A larger proportion of women than men with PD may experience weight loss.
Moderate or severe is the strongest correlate of under-nutrition in PD, although the reasons for weight loss are likely to be more complex than simply ‘burning off’ more calories. Similarly, the weight gain commonly observed after bilateral has not yet been adequately explained. When significant weight loss occurs, the following general points should be considered:. Dysphagia is an impairment of swallowing. It is a complex process with risks of asphyxiation, aspiration pneumonia, malnutrition and dehydration. Swallowing difficulties in usually relate to disease severity and may affect all phases of the swallow process (oral, pharyngeal and oesophageal).
Abnormalities are often detected on video fluoroscopy (modified barium swallow). One group studied 75 people at different stages of and showed that up to 94% had problems with swallowing. In Hoehn and Yahr stages I–III the problems were often not noticed by the person with PD. However, abnormalities are often detected on modified barium swallow testing.
In advanced PD, swallowing difficulties can be severe and are usually obvious to patients and their carers. There is a high incidence of silent aspiration in PD, putting the person at risk of developing recurrent chest infections if not properly investigated. Infected oral secretions are a prime cause of pneumonia and this may be caused by poor oral hygiene due to reduced motor movement in the mouth. Pneumonia is a leading cause of death in later stages of PD. In results from catecholaminergic degeneration and Lewy body formation in the brainstem and within the pharyngeal muscles.
It does not respond fully to optimisation of dopaminergic medication. Poses a major problem to the taking of medications which are critical in the successful management of. Reduced tongue leads to difficulty manipulating and clearing tablets from the mouth. Pharyngeal pooling and dysmotility may lead to retention of pills in the valleculae and pyriform fossae; consequently, delivery of medications may be erratic. The management of in may involve the following generic issues:.
Constipation Colonic dysmotility and anorectal dysfunction are common in, occurring in up to 30% and 60% of cases, respectively. Lewy body degeneration occurs within the myenteric plexus of the colon in PD, leading to slow transit times and, occasionally, megacolon, intestinal pseudo-obstruction and volvulus. A combination of disordered contraction and relaxation of the muscles of defecation, which may in part be dystonic, leads to excessive straining, pain, and a sense of incomplete evacuation. Faecal incontinence, when it occurs in PD, is usually due to overflow around faecal impaction. The management of constipation due to colonic dysmotility in should follow a staged, or stepladder, approach:. Urinary dysfunction Up to 75% of people with develop bladder problems. Nocturia is the earliest and most common urinary problem, although daytime urgency and frequency may also be troublesome.
Urinary incontinence is common in PD. Detrusor overactivity of neurogenic origin appears to result from disinhibition of the ponto-mesencephalic micturition centre. Where there are refractory or persistent bladder problems, referral to a person with urological expertise should be considered. Other management approaches include:. Orthostatic hypotension Orthostatic hypotension (OH) occurs in 48% of people with in the community but is asymptomatic in up to 60%. It may be defined as a drop in systolic blood pressure after standing greater than or equal to 20 mmHg or to less than 90 mmHg. The aetiology of OH in PD is multifactorial and includes Lewy body degeneration in the hypothalamus, brainstem and peripheral nervous system.
Symptoms of OH include fatigue, pre-syncope and syncope, while OH may also contribute to falling. Persisting or troublesome OH may warrant referral to a unit with expertise in falls and syncope. The management of OH in should follow a stepladder approach:.