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Parkinson's Disease (PD)

NICE guideline [NG71] Parkinson's disease in adults. Published: Jul 2017.

Background Information

Here are 4 confusing terms, but NOT interchangable.
 
Term Definition
Parkinsonism (Parkinsonian syndrome) Clinical syndrome defined by bradykinesia + resting tremor / rigidity / postural instability
Parkinson's disease Idiopathic (primary) form of parkinsonism.

Caused by degeneration of dopaminergic neurons in the substantia nigra wiht Lewy body pathology.
Pseudoparkinsonism Secondary parkinsonism.

Parkinsonism-like symptoms caused by non-degenerative and often reversible causes
  • Drugs - most common
  • Hydrocephalus
  • Psychogenic disorders
Parkinson-plus syndromes (atypical parkinsonism) A group conditions with parkinsonism and additional features, that are typically poorly responsive to levodopa

4 main ones:
  • Lewy body dementia
  • Multiple system atrophy 
  • Progressive supranuclear palsy
  • Corticobasal degeneration
 

Guidelines

If PD is suspected:
  • Refer to specialist
  • Diagnosis is mostly clinically using the UK Parkinson's Disease Society Brain Bank Clinical Diagnostic Criteria

Imaging:
  • Consider DaT scanDopamine transporter scan (123I‑FP‑CIT SPECT) if essential tremor cannot be clinically differentiated from parkinsonism
  • MRI only to be considered if parkinsonian syndromes suspected (but not Parkinson's disease)
 

This is a simplified, high yield version for Parkinson's disease (PD):
 
Steps Description Criteria
Step 1 Diagnosis of Parkinsonian syndrome
  • Bradykinesia, and
  • At least 1 of the following
    • Muscular rigidity
    • Resting tremor (4-6 Hz)
    • Postural instability (not by other causes)
Step 2 Exclusion criteria
  • Essentially those of parkinson-plus syndrome and pseudoparkinsonism
Step 3 Supportive prospective criteria 3 or more of the following is required:
  • Unilateral onset
  • Asymmetry
  • Resting tremor
  • Progressive
  • Clinical course of ≥10 years
  • Excellent response to levodopa
  • Severe levodopa-induced chorea
  • Levodopa response for ≥5 years

To see the full diagnostic criteria, view here.

1st line:
  • If motor symptoms affect quality of life → levodopa
  • Otherwise consider a choice of levodopa / dopamine agonits / MOA-BMonoamine oxidase B inhibitor
 

To manage mdyskinesia or motor fluctuations
  • First, attempt optimising levodopa therapy
  • If ineffective → consider adding dopamine agonist / MOA-BMonoamine oxidase B inhibitor / COMTCatechol-O-methyltransferase inhibitor as an adjunct to levedopa
  • If still ineffective → consider amantadine

  • 1st line: apomorphine (intermittent injection and/or continuous subcutaneous infusion)
  • 2nd line: deep brain stimulation
  • 3rd line: foslevodopa-foscarbidopa

Non-motor symptom Management
Drooling of saliva (sialorrhoea) Consider:
  • 1st line: glycopyrroniu bromide
  • 2nd line: xeomin (botulinum neurotoxin A)
PD dementia
  • 1st line: rivastigmine capsules (only licensed cholinesterase inhibitor)
  • 2nd line: memantine
Psychotic symptoms (hallucinations and delusions) If pharmacological intervention is deemed necessary:
  • 1st line: quetiapine
  • 2nd line: clozapine

Note that other antipsychotic medications (esp. 1st generation) can worsen motor featurs of PD.
Daytime sleepiness Consider modafinil
Orthostatic hypotension
  • 1st line: medication review and de-prescribe if possible
  • 2nd line: midodrine
  • 3rd line: fludrocortisone
REM sleep behaviour disorder Consider clonazepam or melatonin
 

The following are important precautions regarding PD medicines:
  • DO NOT withdraw abrupty due to risk of neuroleptic malignant syndrome and acute akinesia
    • If unable to take oral medicine (e.g. gastroenteritis, surgery) → use rescue transdermal patches
 
  • Do not offer 'drug holidays' to reduce motor complications (due to risk of neuroleptic malignant syndrome)

PD Pharmacology

Class Examples MoA Important Side Effects
Levodopa* Levodopa Dopamine precursor that is converted into dopamine Motor complications:
  • Dyskinesia
  • Motor fluctuations
  • On–off effect
  • End-of-dose wearing off
Dopamine decarboxylase inhibitors* Benserazide, Carbidopa Inhibit peripheral conversion of levodopa to dopamine (increases delivery ot the CNS) From peripheral dopaminergic effects
  • Nausea and vomiting
  • Hypotension
  • Flushing
Dopamine agonists Ropinirole, Pramipexole, Rotigotine, Apomorphine Dopamine receptor agonist (mainly D2) All dopaminergic therapy can cause the following effects but the risk is greatest with dopamine agonists:
  • Impulse control disorders (gambling, hypersexuality)
  • Psychotic symptoms (hallucinations and delusions)
  • Excessive sleepiness and sudden onset of sleep 
MAO-B inhibitors Selegiline, Rasagiline, Safinamide Inhibit MAO-B → ↓ dopamine breakdown in CNS
  • Insomnia
  • Nausea
  • Postural hypotension
  • Risk of serotonin syndrome
COMT inhibitors Entacapone, Opicapone, Tolcapone Inhibit COMT → ↓ Levodopa breakdown, prolonging its CNS action
  • Diarrhoea
  • Orange urine
  • ↑ Dyskinesia
  • Hepatotoxicity (Tolcapone ++)
NMDA receptor antagonist Amantadine
  •  ↑ Dopamine release
  • ↓ Glutamate-mediated excitotoxicity in the basal ganglia
 Hallucinations, livedo reticularis, leg oedema, confusion
*Levodopa is always combined with a dopamine decarboxylase inhibitor to maximise delivery to the CNS and minimise peripehral side effects.
 

References

Author: Adams Lau
Reviewer:
Last edited: 19/07/25