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GENERAL MANAGEMENT of
PARKINSON DISEASE
COMMON MANAGEMENT PROBLEMS
“WEARING OFF”
phenomenon
DYSKINESIAS
“ON-OFF” fluctuations
COMMON MANAGEMENT PROBLEMS
• 'Wearing off' phenomenon - several strategies are available:
• Add in or adjust dose of dopamine agonist.
• Smaller, more frequent doses of levodopa.
• Prolonged-release levodopa preparations (ideally taken at
bedtime).
• Severe fluctuations may be helped by a liquid carbidopa.
• Adding selegiline or a dopamine agonist may help.
• Dietary adjustments: take levodopa 30 minutes before food.
• COMT inhibitors (eg, entacapone) can be used to prolong the action
of levodopa and increase the 'on time', reduce the levodopa dose
and modestly improve motor impairment and disability.
• 'On-off' fluctuations (patients may switch from severe
dyskinesia to immobility in a few minutes):
• Combine levodopa with a dopamine agonist.
Cabergoline can be used to reduce the levodopa dose
and modestly improve motor impairment and
disability.
• Fewer doses of levodopa with intermittent injections
or subcutaneous infusion of apomorphine.
• Liquid forms of levodopa (enable more close titration
of the dose).
• Diet: small snacks and one large evening meal
• Dyskinesias (may occur either at the beginning or end
of a dose, or sometimes at its peak):
• At peak dose (usually choreic):
– Reduce each dose of levodopa but make it more frequent
so that the total daily dose remains the same.
– Add a long-acting dopamine agonist.
– Frequent dyskinesias may respond to slow-release or liquid
levodopa.
– Surgery may be indicated.
• At the beginning or end of a dose:
– Try soluble levodopa before meals.
– Add a COMT inhibitor
COMPLICATIONS
• Depression and anxiety
• Depression and anxiety are common in patients with
PD. It is very important to detect and differentiate from
dementia and to treat. Either tricyclics or selective
serotonin reuptake inhibitors (SSRIs) can be used.
• Use tricyclic antidepressants if the sleep pattern is
disturbed. Nortriptyline has the lowest anticholinergic
effects and so may have the fewest side-effects.
• SSRIs can be helpful if apathy is a predominant feature
(but should not be used with selegiline).
• Psychotherapy and support groups are helpful (both for
the patient and carers).
• Dementia
• Cholinesterase inhibitors have been shown to
be effective in patients with PD and dementia,
with a positive impact on global assessment,
cognitive function, behavioural disturbance
and activities of daily living rating scales.
• Compulsive behaviours
• Dopamine agonists have been linked to the development of
compulsive or disinhibited behaviours, including
pathological gambling, hypersexuality, and compulsive
eating and shopping, which can have a major impact on the
lives of those affected. In rare cases, this may also be
observed in some patients on levodopa.
• Patients and their families/carers should be made aware of
this potential side-effect and significant behavioural
changes should be monitored.
• A patient's drug regime should be reviewed by a PD
specialist if compulsive behaviour is observed.
• Hallucinations and psychosis
• May be related to dopaminergic therapy, PD dementia or due to a
confusional state (eg, infection, malnutrition, dehydration or
sudden withdrawal of a dopaminergic drug). Consider gradual
withdrawal of PD drugs - which may have triggered the psychosis.
• Confusion and hallucinations imply a bad prognosis with high
mortality within 1-2 years. Management is very difficult and
admission to a nursing home is often required.
• Always consider other causes; it is not always due to PD or drugs.
• Mild symptoms may not need any treatment but atypical
antipsychotics should be used rather than typical ones.
• Clozapine (selective D4 antagonist) may be used on occasions (only
by specialists). It reduces hallucinations without aggravating the
motor disability of PD
• Acute akinesia (Parkinson's crisis)
• A rare but life-threatening complication of
Parkinson's disease, with a sudden worsening
of motor symptoms and severe akinesia.
• Triggers include infections, surgery,
gastrointestinal disease and changes in
medication.
• Acute akinesia is difficult to treat and often
needs hospital admission

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Management of Parkinsonism

  • 2. COMMON MANAGEMENT PROBLEMS “WEARING OFF” phenomenon DYSKINESIAS “ON-OFF” fluctuations
  • 3. COMMON MANAGEMENT PROBLEMS • 'Wearing off' phenomenon - several strategies are available: • Add in or adjust dose of dopamine agonist. • Smaller, more frequent doses of levodopa. • Prolonged-release levodopa preparations (ideally taken at bedtime). • Severe fluctuations may be helped by a liquid carbidopa. • Adding selegiline or a dopamine agonist may help. • Dietary adjustments: take levodopa 30 minutes before food. • COMT inhibitors (eg, entacapone) can be used to prolong the action of levodopa and increase the 'on time', reduce the levodopa dose and modestly improve motor impairment and disability.
  • 4. • 'On-off' fluctuations (patients may switch from severe dyskinesia to immobility in a few minutes): • Combine levodopa with a dopamine agonist. Cabergoline can be used to reduce the levodopa dose and modestly improve motor impairment and disability. • Fewer doses of levodopa with intermittent injections or subcutaneous infusion of apomorphine. • Liquid forms of levodopa (enable more close titration of the dose). • Diet: small snacks and one large evening meal
  • 5. • Dyskinesias (may occur either at the beginning or end of a dose, or sometimes at its peak): • At peak dose (usually choreic): – Reduce each dose of levodopa but make it more frequent so that the total daily dose remains the same. – Add a long-acting dopamine agonist. – Frequent dyskinesias may respond to slow-release or liquid levodopa. – Surgery may be indicated. • At the beginning or end of a dose: – Try soluble levodopa before meals. – Add a COMT inhibitor
  • 6. COMPLICATIONS • Depression and anxiety • Depression and anxiety are common in patients with PD. It is very important to detect and differentiate from dementia and to treat. Either tricyclics or selective serotonin reuptake inhibitors (SSRIs) can be used. • Use tricyclic antidepressants if the sleep pattern is disturbed. Nortriptyline has the lowest anticholinergic effects and so may have the fewest side-effects. • SSRIs can be helpful if apathy is a predominant feature (but should not be used with selegiline). • Psychotherapy and support groups are helpful (both for the patient and carers).
  • 7. • Dementia • Cholinesterase inhibitors have been shown to be effective in patients with PD and dementia, with a positive impact on global assessment, cognitive function, behavioural disturbance and activities of daily living rating scales.
  • 8. • Compulsive behaviours • Dopamine agonists have been linked to the development of compulsive or disinhibited behaviours, including pathological gambling, hypersexuality, and compulsive eating and shopping, which can have a major impact on the lives of those affected. In rare cases, this may also be observed in some patients on levodopa. • Patients and their families/carers should be made aware of this potential side-effect and significant behavioural changes should be monitored. • A patient's drug regime should be reviewed by a PD specialist if compulsive behaviour is observed.
  • 9.
  • 10. • Hallucinations and psychosis • May be related to dopaminergic therapy, PD dementia or due to a confusional state (eg, infection, malnutrition, dehydration or sudden withdrawal of a dopaminergic drug). Consider gradual withdrawal of PD drugs - which may have triggered the psychosis. • Confusion and hallucinations imply a bad prognosis with high mortality within 1-2 years. Management is very difficult and admission to a nursing home is often required. • Always consider other causes; it is not always due to PD or drugs. • Mild symptoms may not need any treatment but atypical antipsychotics should be used rather than typical ones. • Clozapine (selective D4 antagonist) may be used on occasions (only by specialists). It reduces hallucinations without aggravating the motor disability of PD
  • 11.
  • 12. • Acute akinesia (Parkinson's crisis) • A rare but life-threatening complication of Parkinson's disease, with a sudden worsening of motor symptoms and severe akinesia. • Triggers include infections, surgery, gastrointestinal disease and changes in medication. • Acute akinesia is difficult to treat and often needs hospital admission