Parkinson’s Disease

One of the most common neurodegenerative diseases. Lifetime risk ~1 in 40; mean age of onset 55–65 (peak ~65); more common in men than women, in roughly a 2:1 ratio. Progression is often slow (over 15 years). GP support and education of patients and families is central to care.

Most cases are idiopathic, but around 10-15% have an identifiable genetic cause — LRRK2 is the most commonly implicated gene (autosomal dominant, accounting for 1-2% of all PD but around 40% of familial cases), with GBA1, VPS35, SNCA, PRKN, PINK1 and DJ1 mutations also described; genetic and familial cases tend to present earlier in life.

Diagnosis

Made by history and examination — suspect PD with any of the 4 S’s: slowness, stiffness, shakes (tremor), stumbles (loss of balance). Consider the diagnosis if ≥2 of the following are present:

• Tremor — the most common presenting symptom (50–70%). Resting tremor at 4–6Hz, pill-rolling, worsens with walking/talking/distraction. Most commonly affects the upper limbs but can involve the lower limbs and chin.
• Bradykinesia — slowness/lack of movement, loss of manual dexterity with fine motor tasks, hypophonia and hypomimia (mask facies), slowed velocity/reduced amplitude on repetitive movements (finger tapping, pill rolling).
• Rigidity — increased resistance to passive movement, consistent throughout the movement (“lead pipe”), cogwheeling if tremor is superimposed; complaints of stiffness, aching or cramping.
• Postural instability — loss of postural reflexes, may cause falls.

Features are usually asymmetrical, and a degree of asymmetry typically persists even as the other side becomes affected with progression.

Diagnosis is primarily clinical; dopamine transporter (DAT) single-photon emission computed tomography imaging can help when the clinical picture is uncertain, or to exclude other neurological disorders (e.g. drug-induced or essential tremor) mimicking PD.

Other examination findings: normal power/reflexes/sensation; reduced arm swing; shuffling gait, narrow-based; festination (feet “wanting to rush forward”); freezing/gait ignition failure (usually approaching an obstacle); micrographia; stooped, forward-leaning posture.

Early (often pre-motor) signs

Reduced sense of smell (hyposmia), constipation, orthostatic hypotension — non-motor symptoms such as anxiety, depression, hyposmia and REM sleep behaviour disorder often present in primary care years before the cardinal motor features, by which point at least half of dopaminergic basal ganglia neurons are typically already lost.

Non-motor symptoms

Olfactory loss; dysautonomia (orthostatic hypotension, gastroparesis/ constipation, urinary frequency/urgency, nocturia, erectile dysfunction); depression; anxiety (affects ~1/3 of patients with PD — often overlooked or mistaken for depression, and may predate diagnosis); sleep disturbance (REM behaviour disorder, restless legs syndrome); fatigue; apathy; hallucinations; cognitive decline; excessive salivation.

Differentials

Atypical parkinsonism (Parkinson-plus syndromes, e.g. Lewy body dementia) — warning signs: early postural instability/falls, dysautonomia and dementia; symmetrical presentation; relative lack of tremor; poor L-dopa/dopamine agonist response; other neurological features (cerebellar, pyramidal, cortical signs — aphasia, apraxia, cortical sensory loss).

Drug-induced parkinsonism — antiemetics/dopamine-receptor-blocking drugs (antipsychotics), dopamine-depleting agents (tetrabenazine), sodium valproate.

Other tremor disorders — see essential tremor.

Management overview

Complex — complicated medication regimens, side effects, fluctuating response, slow deterioration, and association with dementia (40%, eventually 80%), anxiety and depression (50%). No cure — the principle is to keep the patient as functional as possible with the minimum medication needed.

• Refer to neurology urgently if atypical parkinsonism warning signs are present.
• Otherwise, seek non-acute neurology assessment to confirm diagnosis and link the patient with a Parkinson’s disease clinical nurse specialist — coordinate via a GPMP/TCA.

GP-initiated levodopa while awaiting specialist confirmation

Diagnostic access delays — especially in rural/regional Australia — can leave probable PD untreated for months to years, worsening quality of life and increasing fall/fracture risk. While UK NICE guidance (the de facto Australian reference, absent a national PD guideline) recommends referral to a movement disorder specialist without initiating treatment (dopaminergic therapy can mask parkinsonian signs and reduce diagnostic accuracy), a 2025 AJGP paper argues this ideal is often impractical, and supports a pragmatic GP-led levodopa trial in probable PD when specialist review will be significantly delayed:

• Levodopa is a safe drug; early dopaminergic treatment is associated with significantly better quality of life over the first 18 months than remaining untreated. Levodopa’s short half-life (1–3h) means it can be withheld overnight before a specialist review without masking signs (the “defined off” method).
• Common levodopa “myths” are unfounded: it is not neurotoxic or progression-hastening, its benefit does not need to be “saved” for later stages (apparent reduced efficacy over time reflects disease progression, not drug tolerance), and delaying treatment does not reduce later motor fluctuations/dyskinesias.
• If the diagnosis turns out to be a different parkinsonism (vascular, drug-induced, atypical degenerative), the risk of a levodopa trial remains low — lack of response can itself help distinguish these from true PD, and some patients (including dementia with Lewy bodies) will still transiently benefit.
• Practical approach (“start low, go slow”): levodopa+benserazide 50+12.5mg (Madopar 62.5) once daily for a week, then twice daily for a week, then three times daily; gradually increase to 100mg levodopa TDS according to response (many patients need at least this to benefit). Warn about nausea and postural lightheadedness (usually settle within 1–2 weeks; slow the titration if problematic). Avoid concurrent dopamine-blocking antiemetics and oral iron (both reduce levodopa absorption).
• Record pre-treatment function (handwriting sample, gait/finger-tapping video) to objectively assess response — useful for both monitoring and for the specialist’s later diagnostic confirmation. Involve a care partner for collateral history, since patients often underestimate their own bradykinesia/postural change.
• Build a multidisciplinary team early: speech pathology, physiotherapy/ exercise physiology, occupational therapy; a Cochrane 2024 review supports exercise for reducing motor symptom severity and improving quality of life. GPMP referral, and NDIS access if aged <65.

Non-motor symptom assessment

Non-motor symptoms are often under-assessed relative to motor symptoms despite being major drivers of quality of life. Screen regularly using a structured tool — the Non-Motor Symptoms Scale (NMSS) covers 30 symptoms across 9 domains (cognitive, autonomic/cardiovascular, sleep, mood, gastrointestinal and more); a shortened self-report version is freely available via Parkinson’s UK. Regular screening lets the team tailor individualised interventions rather than treating non-motor symptoms reactively.

Non-pharmacological interventions are under-recognised — exercise (aerobic, dance, aquatic, yoga, boxing) has evidence for improving both motor and non-motor symptoms (falls risk, gait, strength, cognition, sleep, anxiety) and disease progression/quality of life. Caregiver burden increases through the disease course (Diagnosis → Maintenance → Complex → Palliative phases) — regularly assess the informal carer’s needs and link both patient and carer to Parkinson’s support groups/peak bodies.

Early-stage management

Patient/family education; join a support group; optimise general fitness/core strength/balance. Introduce medication once symptoms affect quality of life. Monitor every 3–6 months for progression and medication side effects — symptoms often stabilise for years in a well-controlled “honeymoon” period.

First-line:

• levodopa+benserazide 50+12.5mg PO TDS, increasing to 100+25mg TDS over 1–2 weeks, OR
• levodopa+carbidopa 50+12.5mg PO TDS, increasing to 100+25mg TDS over 1–2 weeks

Alternatives:

• pramipexole 0.125mg PO TDS, slowly titrating to max 1.5mg TDS, OR
• pramipexole MR 0.375mg PO daily, slowly titrating to max 4.5mg daily, OR
• rotigotine 2mg transdermal patch daily, increasing by 2mg weekly to max 8mg daily

Nausea is common with all anti-Parkinson’s drugs (tolerance builds quickly; taking doses with food helps). Avoid centrally-acting dopamine-blocking antiemetics (they worsen parkinsonism) — use domperidone 10mg TDS for up to 7 days instead.

Long-term/late-stage management

After 3–5 years on levodopa, motor fluctuations and choreiform movements (the on/off phenomenon) commonly develop, with intermittent dose failures. Dosing needs to be frequent and precisely timed; give levodopa separate from meals (protein reduces absorption). Wearing-off may respond to adding entacapone, adjusting dopamine agonists, adjusting dietary protein timing, or smaller/more frequent doses — this is genuinely difficult territory; involve neurology.

Orthostatic hypotension (common in late PD):

• Non-pharmacological: avoid extreme heat/alcohol/large meals/straining/rapid standing; increase sodium/water intake; smaller frequent meals; regular horizontal-position exercise (e.g. swimming); compression stockings; sleep with the head of the bed raised.
• Pharmacological: fludrocortisone 0.1mg daily, increasing to 0.2mg daily. Resistant cases (specialist-guided): pyridostigmine, midodrine, ephedrine, octreotide.

Neuropsychiatric complications:

• Depression/anxiety — treat as usual; both become more common in PD, progressing to psychosis in some.
• Psychosis — first reduce levodopa dose and withdraw dopamine agonists/anticholinergics. If refractory, add low-dose clozapine (effective) — avoid other second-generation antipsychotics (olanzapine, risperidone: less effective, can worsen parkinsonism at higher doses) and all first-generation antipsychotics (e.g. haloperidol). Quetiapine is an option for acute behavioural disturbance if required.
• Dementia can accelerate PD progression and vice versa.
• Sialorrhoea — refractory cases need specialist botulinum toxin injection.
• Nil-by-mouth patients need specialist input for non-oral anti-Parkinson’s medication routes.