Parkinson’s Disease (PD)
NICE guideline [NG71] Parkinson’s disease in adults. Published: Jul 2017.
Background Information
Definition
Four commonly confused terms that are related but not interchangeable:
| 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 with Lewy body pathology. |
| Pseudoparkinsonism | Secondary parkinsonism
Parkinsonism-like symptoms caused by non-degenerative and often reversible causes
|
| Parkinson-plus syndromes (atypical parkinsonism) | A group of conditions with parkinsonism and additional features that are typically poorly responsive to levodopa
4 main ones:
|
Guidelines
Investigation and Diagnosis
If PD is suspected:
- Refer to specialist
- Diagnosis is mostly clinical, using the UK Parkinson’s Disease Society Brain Bank Clinical Diagnostic Criteria
Imaging:
- Consider DaT 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)
UK Parkinson’s Disease Society Brain Bank Clinical Diagnostic Criteria
This is a simplified, high-yield version for PD:
| Steps | Description | Criteria |
|---|---|---|
| Step 1 | Diagnosis of Parkinsonian syndrome |
|
| Step 2 | Exclusion criteria |
|
| Step 3 | Supportive prospective criteria | 3 or more of the following is required:
|
To see the full diagnostic criteria, view here.
Management
Pharmacological Management
Motor Symptoms
1st line:
- If motor symptoms affect quality of life → levodopa
- Otherwise consider a choice of levodopa / dopamine agonists / MOA-B inhibitor
Further Treatment
To manage dyskinesia or motor fluctuations
- First, attempt to optimise levodopa therapy
- If ineffective → consider adding dopamine agonist / MOA-B inhibitor / COMT inhibitor as an adjunct to levodopa
- If still ineffective → consider amantadine
Advanced PD
- 1st line: apomorphine (intermittent injection and/or continuous subcutaneous infusion)
- 2nd line: deep brain stimulation
- 3rd line: foslevodopa-foscarbidopa
Non-Motor Symptoms
| Non-motor symptom | Management |
|---|---|
| Drooling of saliva (sialorrhoea) | Consider:
|
| PD dementia |
|
| Psychotic symptoms (hallucinations and delusions) | If pharmacological intervention is deemed necessary:
Note that other antipsychotic medications (esp. 1st generation) can worsen motor features of PD. |
| Daytime sleepiness | Consider modafinil |
| Orthostatic hypotension |
|
| REM sleep behaviour disorder | Consider clonazepam or melatonin |
Precautions
The following are important precautions regarding PD medicines:
- DO NOT withdraw abruptly 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
Overview of PD Medications
Shared drug adverse effects (across all classes):
| Category | Adverse effects |
|---|---|
| Neuropsychiatric | Confusion, Somnolence, Psychosis (inc. hallucinations, delusions) |
| Impulse control / compulsive disorders | Gambling, Hypersexuality, Compulsive eating/shopping |
| Autonomic | Orthostatic hypotension |
| Gastrointestinal | Nausea & Vomiting |
| Other | Peripheral oedema
Sleep attacks (dopamine agonists + levodopa) |
Class-specific adverse effects:
| Class | Examples | MoA | Unique / distinctive adverse effects |
|---|---|---|---|
| Levodopa* | Levodopa | Dopamine precursor that is converted into dopamine | Motor complications (esp. with long-term use & higher doses)
|
| Dopamine decarboxylase inhibitors* | Benserazide, Carbidopa | Inhibit peripheral conversion of levodopa to dopamine (increases delivery to the CNS) | Reduce peripheral side effects of levodopa (e.g. nausea, vomiting, hypotension) by limiting peripheral dopamine conversion |
| Dopamine agonists | Ropinirole, Pramipexole, Rotigotine, Apomorphine | Dopamine receptor agonist (mainly D2) | Highest risk of:
Ergot-derived dopamine agonists
|
| MAO-B inhibitors | Selegiline, Rasagiline, Safinamide | Inhibit MAO-B → ↓ dopamine breakdown in CNS | Serotonin syndrome (rare)
NB – at standard doses there isn’t a clinically significant increased risk of tyramine reaction with selective MOA-B inhibitors (risk present with non-selective MOA inhibitors) [ref] |
| COMT inhibitors | Entacapone, Opicapone, Tolcapone | Inhibit COMT → ↓ Levodopa breakdown, prolonging its CNS action |
|
| NMDA receptor antagonist | Amantadine |
|
|
*Levodopa is always combined with a dopamine decarboxylase inhibitor to maximise delivery to the CNS and minimise peripheral side effects.