Drug treatment for Parkinson's disease

High-Yield Points (Textbook)

Source: Pathy's 6th ed., Chapter 53; Essentials of Clinical Geriatrics 7th ed., Table 10-6.

Principle

Drug Usual dose Mechanism Main side effects

Carbidopa–levodopa (Sinemet) 40/400 to 200/2000 mg/day in Increases dopamine availability; Nausea, vomiting, anorexia; dyskinesias; divided doses decreases peripheral dopamine orthostatic hypotension; behavioural metabolism disturbance; vivid dreams and hallucinations Amantadine (Symmetrel) 100–300 mg/day (200–400 Increases dopamine release Delirium and hallucinations. Renally mg/day for dyskinesia) eliminated — reduce dose in renal impairment Bromocriptine (Parlodel) 1–1.5 mg tid/qid, up to 30–40 Directly activates dopaminergic Behavioural change, hypotension, nausea mg/day receptors Pramipexole (Mirapex) 0.5–1.5 mg tid Dopamine agonist Hallucinations, nausea, somnolence Ropinirole (Requip) 3–8 mg tid Dopamine agonist Orthostatic hypotension, syncope, nausea, somnolence Trihexyphenidyl (Artane) 2–20 mg/day divided Reduces acetylcholine effect; restores Dry mouth, constipation, urinary retention, cholinergic–dopaminergic balance blurred vision, glaucoma exacerbation, tachycardia, confusion, behavioural change Benztropine (Cogentin) 0.5–8.0 mg/day divided As above As above Selegiline (Eldepryl) 10 mg/day single dose MAO-B inhibitor Nausea, confusion, agitation, insomnia, involuntary movements Rasagiline (Azilect) 1 mg/day single dose Selective, irreversible MAO-B inhibitor Balance difficulty, anorexia, vomiting, weight loss, depressive symptoms; no dietary restriction Entacapone (Comtan) 200 mg with each levodopa dose Inhibits catechol-O-methyltransferase Nausea, dyskinesias, orthostatic hypotension, diarrhoea Tolcapone (Tasmar) 100–200 mg tid COMT inhibitor Liver dysfunction Prescribing in the older patient

Latest Updates (2023–Present)

Newly licensed levodopa delivery systems (not in either textbook): Crexont (IPX203 extended-release carbidopa/levodopa capsules, FDA August 2024); Vyalev (foslevodopa/foscarbidopa, first 24-hour subcutaneous infusion, FDA October 2024); Onapgo (subcutaneous apomorphine infusion, FDA February 2025); ND0612 subcutaneous levodopa/carbidopa under review.

Tavapadon — a selective D1/D5 receptor partial agonist, mechanistically distinct from the D2/D3 agonists in the textbook table. Positive Phase 3 TEMPO-1/2/3; NDA filed September 2025, decision expected 2026. If approved it will be the first new oral dopamine agonist for PD in over a decade.

Newer adjuncts absent from the textbooks but now standard in international practice: opicapone (once-daily COMT inhibitor), safinamide (MAO-B inhibitor with glutamate-modulating action) and istradefylline (adenosine A2A antagonist) for off-time reduction. FDA labelling change, March 2026: a warning regarding vitamin B6 deficiency and seizures now applies to all carbidopa/levodopa products, including Sinemet, Rytary, Stalevo, Crexont and Vyalev. Consider periodic B6 assessment in long-treated older patients. Neuroprotection claims withdrawn. No agent has demonstrated disease modification. Exenatide-PD3 (Lancet 2025) was negative, despite positive Phase 2 lixisenatide data (NEJM 2024); the Lancet issued an Expression of Concern on the exenatide paper in June 2026. MAO-B inhibitors are now prescribed for symptomatic benefit only.

Indian practical note: levodopa–carbidopa, levodopa–benserazide, trihexyphenidyl, amantadine, pramipexole, ropinirole, rasagiline, entacapone and the levodopa/carbidopa/entacapone combination are all widely available and inexpensive in India; device-aided therapies (intestinal gel, subcutaneous infusions) and DBS are limited to a few tertiary centres and are largely out-of-pocket.

Current Practice Update

Aspect Textbook position Current evidence-based practice COMT inhibitors Entacapone (with each dose) and tolcapone Opicapone once daily is now preferred where available — (hepatotoxic) better adherence, no hepatotoxicity monitoring MAO-B inhibitors Selegiline and rasagiline "proposed for Used for symptomatic benefit only; safinamide added as neuroprotective effects" an option for wearing-off Off-time adjuncts COMT inhibitors and amantadine Add istradefylline (adenosine A2A antagonist) and the new ER/infusional levodopa formulations Dopamine agonists D2 agonists — avoided in the elderly Position holds for D2/D3 agonists; tavapadon (D1/D5 partial agonist) may change the calculus if approved in 2026 Levodopa safety monitoring Nausea, hypotension, neuropsychiatric effects, Add vitamin B6 deficiency/seizures (FDA March 2026) motor complications and peripheral neuropathy with continuous delivery Examiner's Tip — lines that earn marks Open with the principle: "Treatment aims to restore the dopamine–acetylcholine ratio in the nigrostriatal system." Draw the Essentials table — drug, dose, mechanism, side effect — it converts directly into marks. State both geriatric prohibitions explicitly: "Dopamine agonists are not used and anticholinergics are never used in older people with PD." Quote the two monitoring rules: clozapine — stop if neutrophils <1500/mm3; domperidone — ECG for QT prolongation; and metoclopramide is contraindicated.