Part 3 · Treatment
The other medicines
Besides levodopa, other medicines copy dopamine, slow its breakdown, or act on other signals in the movement circuit. Press play to climb the treatment ladder as NICE NG71 and the 2018 MDS evidence review describe it, and watch where each class acts at the synapse. This page reports guidelines, labels and trials. It is not advice for any person.
Click a rung to read it. Ladder and synapse are schematic, not to scale.
How big are the effects?
What the trials measured, drug against placebo or against another drug. Choose a measure, then play the bars. Each row is a separate trial with its own design, so compare a drug with its own comparator, not with the row above it.
Drug by drug
Each card gives the class, how it acts, what the trials found, the key harms with their rates, and the first US approval from Drugs@FDA. Filter by a side effect to see which medicines the sources link to it.
The trials behind the first choice
Five trials shaped how the first medicine is chosen and what can be claimed for it. Pick one to see its result.
Kidneys, liver and interactions: label information
What the US prescribing information says, reported as published for study. It is not dosing advice for any person; doses are set with a prescriber.
Never change or stop a Parkinson's medicine without a clinician. NICE says antiparkinsonian medicines "should not be withdrawn abruptly or allowed to fail suddenly due to poor absorption", and advises against drug holidays, because of the risk of acute akinesia or neuroleptic malignant syndrome. Labels describe a neuroleptic malignant syndrome-like reaction after levodopa is cut or stopped, and parkinsonian crisis after amantadine is stopped abruptly; tapering a dopamine agonist produced a withdrawal syndrome in 19% of tapers in one series. 13,189,241,301
| Medicine | Kidneys (as published) | Liver, interactions and other label points |
|---|---|---|
| Pramipexole (immediate release) | Start and maximum by creatinine clearance: above 50 mL/min, 0.125 mg three times daily up to 1.5 mg three times daily; 30 to 50, 0.125 mg twice daily up to 0.75 mg three times daily; 15 to 30, 0.125 mg once daily up to 1.5 mg once daily; below 15 or on haemodialysis, no data. 7 | Titrated no faster than every 5 to 7 days. Somnolence is "common" above 1.5 mg/day, and higher fixed doses added no significant benefit over 1.5 mg/day in early Parkinson's. 7 |
| Ropinirole (immediate release) | Maximum 18 mg/day in end-stage kidney disease on haemodialysis, against 24 mg/day otherwise. 7 | Starts at 0.25 mg three times daily. 7 |
| Amantadine, and amantadine ER (Gocovri) | Half-life about 16 to 17 hours, rising 2- to 3-fold or more below a creatinine clearance of 40 mL/min/1.73 m², and averaging 8 days on haemodialysis. Gocovri: clearance 30 to 59 starts at 68.5 mg with a maximum of 137 mg; 15 to 29 takes 68.5 mg; below 15 is contraindicated. 13 | Gocovri: 137 mg at bedtime for a week, then 274 mg. Abrupt discontinuation has caused parkinsonian crisis and NMS-like reactions. A pregnancy review advises avoiding amantadine in pregnancy or when trying to conceive. 13,327 |
| Rasagiline | No kidney adjustment is given in the sources read for this guide. | Maximum 0.5 mg with ciprofloxacin or other CYP1A2 inhibitors (which can double levels) and in mild hepatic impairment; not for moderate or severe impairment. Contraindicated with meperidine (pethidine), tramadol, methadone, propoxyphene and other MAO inhibitors (serotonin syndrome risk), with at least 14 days between stopping rasagiline and starting them, and with St John's wort, cyclobenzaprine and dextromethorphan. SSRIs, SNRIs and tricyclic, tetracyclic or triazolopyridine antidepressants are "not recommended". Very high-tyramine foods (over 150 mg) are to be avoided. 93,104 |
| Safinamide | Not covered in the sources read. | Contraindicated with other MAO inhibitors (including linezolid), opioids such as meperidine, methadone, propoxyphene and tramadol, SNRIs, tricyclic, tetracyclic and triazolopyridine antidepressants, cyclobenzaprine, methylphenidate, amphetamines and St John's wort. 93 |
| Selegiline | Not covered in the sources read. | With carbidopa-levodopa it may cause severe orthostatic hypotension. Carbidopa-levodopa is contraindicated with non-selective MAO inhibitors, which are stopped at least two weeks beforehand. 189 |
| Opicapone | Not covered in the sources read. | 50 mg once daily at bedtime, with no food for 1 hour before and at least 1 hour after. Moderate hepatic impairment: 25 mg; severe: avoid. 93 |
| Tolcapone | Not covered in the sources read. | Boxed warning for liver failure. ALT and AST at baseline and every 2 to 4 weeks for the first 6 months; stopped above twice the upper limit of normal, or if there is no substantial benefit within 3 weeks. 93 |
| Apomorphine | Not covered in the sources read. | 5-HT3 antagonists such as ondansetron are contraindicated because of profound hypotension and loss of consciousness. The injection is started under medical supervision, with trimethobenzamide from 3 days beforehand. 7 |