Table 4:

Summary of recommendations on treatment of nonmotor features of PD

Recommendation numberRecommendationSourceGrade
Autonomic dysfunction
C67Botulinum toxin A is efficacious for the symptomatic control of sialorrhea in PD.MDS16A
C68General measures for treating urinary urgency and incontinence include before bedtime, avoiding coffee and limiting water ingestion. When symptoms appear suddenly, exclude urinary tract infection.EFNS15GPP
• Nocturia: reduce intake of fluid after 6 pm. Sleep with head-up tilt of bed to reduce urine production.
• Nighttime dopaminergic therapy should be optimized.
• For urinary urgency (overactive bladder), anticholinergic or antispasmodic drugs may be useful, but care must be taken regarding central adverse effects.
• Botulinum toxin type A injected in the detrusor muscle.
C69For orthostatic hypotension, general measures would include the following:EFNS15GPP
• Avoid aggravating factors such as large meals, alcohol, exposure to a warm environment and drugs known to cause orthostatic hypotension, such as diuretics or antihypertensive drugs. Levodopa and dopamine agonists may also worsen orthostatic hypotension.
• Increase salt intake in symptomatic orthostatic hypotension.
• Ensure head-up tilt of the bed at night.
• Wear elastic stockings.
• Highlight postprandial effects. In some patients, hypotension occurs only postprandially. Warning the patient about this effect and taking frequent small meals may be helpful.
C70For orthostatic hypotension, drug therapy includes the addition of:
• MidodrineEFNS14A
• FludrocortisoneEFNS14GPP
• Domperidone.CANGPP
C71For gastrointestinal motility problems in PD, general measures for treating constipation should be applied:EFNS14Varied
• Increased intake of fluid and fibre is recommended (grade: GPP).
• Increased physical activity can be beneficial (grade: GPP).
• Polyethylene glycol solution (macrogol) is recommended (grade: A).
• Fibre supplements such as psyllium (grade: B) or methylcellulose and osmotic laxatives (e.g., lactulose) are recommended (grade: GPP).
• Short-term irritant laxatives for selected patients are recommended (grade: GPP).
• The use of drugs with anticholinergics activity should be reduced or discontinued (grade: GPP).
• Domperidone should be added (grade: B).
C72For individuals with PD and erectile dysfunction:EFNS15Varied
• Drugs associated with erectile dysfunction (e.g., α-blockers) or anorgasmia (e.g., selective serotonin reuptake inhibitors) should be discontinued. Dopaminergic therapy can have both negative and positive effects on this symptom (grade: GPP).
• Sildenafil 50–100 mg, 1 h before sex, can be tried in patients with PD with these problems (grade: B).
• Other drugs of this class, such as tadalafil (10 mg, 30 min–12 h before sex) or vardenafil (10 mg, 1 h before sex) can be alternative choices (grade: GPP).
• In some patients, apomorphine injections (5–10 min before sex) can also be an alternative treatment (grade: GPP).
• Intracavernous injections of papaverine or alprostadil can be considered in selected patients (grade: GPP).
Cognitive impairment
C73The diagnoses of dementia associated with PD and of mild cognitive impairment in PD can be made using the Movement Disorder Society Clinical Diagnostic Criteria. These require reports of subjective cognitive decline and difficulties on psychometric testing.CANGPP
C74For PD dementia, cholinesterase inhibitors could be added: rivastigmine (grade: A), donepezil (grade: A), or galantamine (grade: C). There may be idiosyncrasy in clinical response and adverse effects, so it is worth trying an alternative agent (grade: GPP). Memantine can be added or substituted if cholinesterase inhibitors are not tolerated or lack efficacy (grade: C).EFNS14Varied
C75No interventions have been proven to reduce the risk of progression of PD from mild cognitive impairment to dementia but lifestyle modifications, such as engaging in cognitive and social activities and physical exercise, are encouraged.CANGPP
Sleep disorders
C76A full sleep history should be taken from people with PD who report sleep disturbance.NICE7D
GPP
C77Good sleep hygiene should be advised in people with PD with any sleep disturbance and includes:NICE7D
GPP
• Avoidance of stimulants (e.g., coffee, tea, caffeine) in the evening
• Establishment of a regular pattern of sleep
• Comfortable bedding and temperature
• Provision of assistive devices, such as a bed lever or rails to aid with moving and turning, allowing the person to get more comfortable
• Restriction of napping in the late afternoon and early evening
• Advice about taking regular and appropriate exercise to induce better sleep
• Advice to avoid remaining in bed for long periods of time if unable to sleep
• A review of all medication and avoidance of any drugs that may affect sleep or alertness, or may interact with other medication (e.g., selegiline, antihistamines, H2 antagonists, antipsychotics and sedatives).
C78Optimization of nighttime dopaminergic treatment (grade: B), melatonin (grade: B) and low doses of sedating antidepressants such as doxepin or trazodone (grade: GPP) may be beneficial for subjective symptoms of insomnia in patients with PD.EFNS14Varied
C79Care should be taken to identify REM sleep behaviour disorder in people with PD. Melatonin or clonazepam may be useful, if pharmacologic treatment is required.NICE8GPP
C80Care should be taken to identify and manage restless legs syndrome in people with PD and sleep disturbance.NICE8GPP
Patients with bothersome restless legs syndrome should be screened for iron deficiency.CANGPP
Potential treatments include optimization of dopaminergic therapy or GABAergic agents such as pregabalin.
C81People with PD who have daytime sleepiness or sudden onset of sleep should be advised not to drive, and to consider any occupational hazards. Their medicines should be adjusted to reduce its occurrence.NICE8GPP
C82Modafinil should be considered for the treatment of excessive daytime sleepiness in people with PD, only if a detailed sleep history has excluded reversible pharmacologic and physical causes.NICE8B
GPP
Depression
C83Clinicians should have a low threshold for diagnosing depression in PD.NICE7D
GPP
C84Clinicians should be aware that there are difficulties in diagnosing mild depression in people with PD because the clinical features of depression overlap with the motor features of PD.NICE7D
GPP
C85Self-rating or clinician-rated scales may be used to screen for depression in patients with PD.SIGN13C
• Diagnosis of depression should not be made on the basis of rating scale score alone.SIGN13GPP
• Assessment or formulation of depression should be carried out via clinical interview, with a focus on low mood, and with due caution in relation to interpretation of cognitive or somatic symptoms that may be symptoms of PD rather than depression.SIGN13GPP
• Relatives or caregivers who know the patient well should be invited to provide supplementary information to assist the diagnosis, particularly in the context of cognitive impairment.SIGN13GPP
C86The management of depression in people with PD should be tailored to the individual — in particular, to their co-existing therapy.NICE7D
GPP
Psychosis
C87All people with PD and psychosis should receive a general medical evaluation and treatment for any precipitating condition.NICE7D
GPP
C88For patients with PD and psychosis, polypharmacy should be reduced.EFNS14GPP
• Anticholinergic antidepressants should be reduced or stopped; anxiolytics or sedatives should be reduced or stopped.
• Antiparkinsonian drugs should be reduced. Anticholinergics should be stopped, amantadine should be stopped, dopamine agonists should be reduced or stopped, MAO-B and COMT inhibitors should be reduced or stopped and, lastly, levodopa should be reduced.
C89Hallucinations and delusions should not be treated if they are well tolerated by the person with PD and their family members and caregivers (as appropriate). Even minor hallucinations or delusions should be considered a marker of disease progression, and should warrant a general medical evaluation and treatment for any precipitating factors.NICE8GPP
C90For patients with PD and psychosis needing treatment:
• Quetiapine is possibly useful.EFNS14GPP
• Clozapine is useful but requires monitoring.EFNS14A
C91With the exception of quetiapine and clozapine as described in recommendation C90, all other antipsychotics should be avoided in PD psychosis (grade: GPP). Olanzapine (grade: A), risperidone (grade: C) and aripiprazole (grade: GPP) can worsen parkinsonism (harmful).EFNS14Varied
C92Pimavanserin could be considered as a treatment for PD psychosis.CANB
  • Note: CAN = new Canadian Guideline recommendation, COMT = catechol-O-methyltransferase, EFNS14 = European Federation of Neurological Societies — Motor Guidelines,14 EFNS15 = European Federation of Neurological Societies — late Guidelines,15 GABA = γ-aminobutyric acid, GPP = good practice point, MAO-B = monoamine oxidase B, MDS = Movement Disorder Society Evidence-Based Medicine Review,16 NICE7 = National Institute for Health and Clinical Excellence 2006 PD Guidelines,7 NICE8 = National Institute for Health and Clinical Excellence — 2017 PD Guidelines,8 PD = Parkinson disease, REM = rapid eye movement, SIGN13 = Scottish Intercollegiate Guidelines Network.13