The motor symptoms of Parkinson's disease (PD) are caused primarily by degeneration of dopaminergic neurons in the substantia nigra. The nonmotor symptoms of the disease are thought to be caused by degeneration of other neurotransmitter systems. No disease-modifying drugs are available for treatment of PD.

The FDA has approved opicapone (Ongentys – Neurocrine), a peripherally-acting reversible catechol-O-methyltransferase (COMT) inhibitor, for oral use as an adjunct to carbidopa/levodopa in adults with Parkinson’s disease (PD) who experience "off" episodes. It is the third COMT inhibitor to be approved for this indication; tolcapone (Tasmar, and generics) and entacapone (Comtan, and generics) were approved earlier. Opicapone has been available in Europe since 2016.

The FDA has approved a sublingual fi lm formulation of the nonergot dopamine agonist apomorphine (Kynmobi – Sunovion) for acute, intermittent treatment of "off" episodes in patients with Parkinson's disease (PD). A subcutaneous formulation of apomorphine (Apokyn) has been available for years for the same indication in patients with advanced PD.

The FDA has approved istradefylline (Nourianz — Kyowa Kirin), an oral adenosine A_2A receptor antagonist, for use as an adjunct to carbidopa/levodopa in adults with Parkinson's disease (PD) who experience "off" episodes. Istradefylline is the first adenosine A_2A receptor antagonist to be approved in the US; it has been available in Japan since 2013.

Cannabis (marijuana) contains more than 60 pharmacologically active cannabinoids; delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are the best known. THC is the main psychoactive constituent of cannabis. CBD, unlike THC, does not produce intoxication or euphoria.

The FDA has approved Inbrija (Acorda), an orally inhaled dry-powder formulation of levodopa, for intermittent treatment of "off" episodes in patients with Parkinson's disease (PD) being treated with carbidopa/levodopa (Sinemet, and others).

The FDA has approved an extended-release tablet formulation of amantadine (Osmolex ER – Vertical/Osmotica) for once-daily treatment of Parkinson's disease (PD) and drug-induced extrapyramidal symptoms (EPS) in adults. An extended-release capsule formulation of amantadine (Gocovri) was approved in 2017 for treatment of levodopa-induced dyskinesia in patients with PD.

The FDA has approved an extended-release (ER) capsule formulation of amantadine (Gocovri – Adamas) for once-daily treatment of levodopa-induced dyskinesia in patients with Parkinson's disease (PD). It is the first product to be approved in the US for this indication. Immediate-release (IR) amantadine has been used off-label for years to manage levodopa-induced dyskinesia.

The motor symptoms of Parkinson's disease (PD) are caused primarily by degeneration of dopaminergic neurons in the substantia nigra. The nonmotor symptoms of the disease are thought to be caused by degeneration of other neurotransmitter systems.

Alzheimer's disease (AD) is the most common cause of dementia, but cognitive loss is also associated with other neurological conditions such as Parkinson's disease, dementia with Lewy bodies, vascular dementia, and frontotemporal dementia.

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The FDA has approved the monoamine oxidase type B (MAO-B) inhibitor safinamide (Xadago – US Worldmeds) as an adjunct to levodopa/carbidopa for management of "off" episodes in patients with Parkinson’s disease (PD). It is the first reversible MAO-B inhibitor to be approved for this indication. Selegiline (Eldepryl, and others) and rasagiline (Azilect, and generics), two irreversible MAO-B inhibitors, have been used alone and as adjuncts to levodopa/carbidopa for many years. Safinamide is not approved for use as monotherapy.

The FDA has approved the atypical antipsychotic pimavanserin (Nuplazid – Acadia) for treatment of hallucinations and delusions associated with Parkinson's disease. It is the first drug to be approved in the US for this indication.

The FDA has approved Duopa (Abbvie), a carbidopa/levodopa enteral suspension, for treatment of motor fluctuations in patients with advanced Parkinson's disease (PD). It has been available in Europe since 2001.

In patients with advanced PD, emptying of the stomach may be delayed and unpredictable, which can affect the rate and amount of absorption of carbidopa/levodopa and its efficacy. To bypass the stomach, the new formulation is delivered through a nasojejunal (NJ) tube or percutaneous endoscopic gastrostomy with jejunal (PEG-J) tube.

A randomized, double-blind, active-controlled, 12-week trial in 66 levodopa-responsive patients with advanced PD and motor complications found that Duopa reduced daily mean "off" time from baseline significantly more than oral immediate-release carbidopa/levodopa (by 4.04 hours vs 2.14 hours). Mean "on" time without troublesome dyskinesia increased by 4.11 hours with the new formulation and by 2.24 hours with immediate-release tablets.1

Duopa is available in a 100-mL single-use cassette containing 4.63 mg of carbidopa and 20 mg of levodopa per mL. It should be administered over 16 hours through a NJ or PEG-J tube with the CADD-Legacy 1400 portable infusion pump. Patients should be switched to oral immediate-release carbidopa/levodopa before starting Duopa; the labeling has instructions for conversion from immediate-release tablets to Duopa. The maximum recommended daily dose of levodopa is 2000 mg (1 cassette/day). Patients must also take oral immediate-release carbidopa/levodopa in the evening after disconnecting the pump. The medication cassette should be stored in the refrigerator and removed 20 minutes before administration.

One month's supply of Duopa costs $6054;2 PEG-J tube insertion and administration-related expenses will significantly increase the cost of treatment.3

1. CW Olanow et al. Continuous intrajejunal infusion of levodopa-carbidopa intestinal gel for patients with advanced Parkinson's disease: a randomised, controlled, double-blind, double-dummy study. Lancet Neurol 2014; 13:141.
2. Approximate WAC. WAC = wholesaler acquisition cost or manufacturer's published price to wholesalers; WAC represents a published catalogue or list price and may not represent an actual transactional price. Source: AnalySource® Monthly. July 5, 2015. Reprinted with permission by First Databank, Inc. All rights reserved. ©2015. www.fdbhealth.com/policies/drug-pricing-policy.
3. F Valldeoriola et al. Cost analysis of the treatments for patients with advanced Parkinson's disease: SCOPE study. J Med Econ 2013; 16:191.

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The FDA has approved droxidopa (Northera – Lundbeck) for oral treatment of adults with symptomatic neurogenic orthostatic hypotension (NOH) caused by primary autonomic failure (Parkinson's disease, multiple system atrophy, or pure autonomic failure), dopamine beta-hydroxylase deficiency, or nondiabetic autonomic neuropathy. This is the first approval for droxidopa in the US. It has been available in Japan for use in NOH since 1989.

The FDA has approved a new formulation of carbidopa/levodopa (Rytary – Impax) in extended-release capsules for treatment of Parkinson’s disease (PD).

The motor symptoms of Parkinson's disease (PD) are caused primarily by progressive degeneration of dopaminergic neurons in the substantia nigra. The non-motor symptoms of the disease are thought to be caused by degeneration of other neurotransmitter systems.

Deep brain stimulation is FDA-approved and has been used for years to treat patients with advanced Parkinson's disease (PD) who have severe levodopa-induced motor complications. New evidence from a controlled trial suggests that it may also be effective for patients with PD and early motor complications.

A patch formulation of the non-ergot dopamine agonist rotigotine (Neupro – UCB) has returned to the US market after a 4-year absence. Originally approved by the FDA in 2007 for treatment of early Parkinson’s disease,1 it was withdrawn in 2008 because of crystallization of the drug in the patch, which could have led to under-dosing. The new patch has somewhat broader indications than the old one; it is approved for use in any stage of Parkinson’s disease (PD) and also for moderate-to-severe restless legs syndrome (RLS).

1. Transdermal rotigotine (Neupro) for Parkinson’s disease. Med Lett Drugs Ther 2007; 49:69.

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Glycopyrrolate (Robinul, and others), a synthetic muscarinic receptor antagonist, has been used off-label for many years for treatment of excessive drooling in patients with Parkinson’s disease, in patients taking clozapine for schizophrenia, and in developmentally disabled children.1-3 It has now been approved by the FDA as Cuvposa (Shionogi) for use specifically in children 3-16 years old with severe chronic drooling due to a neurologic condition, such as cerebral palsy. It is being marketed as an oral solution, which will permit more precise weight-based dosing than was possible with the oral tablets used in the past. As with other anticholinergic drugs, dry mouth, constipation, flushing and nasal congestion can occur. Since glycopyrrolate decreases secretion not only of saliva, but also of sweat, overheating due to high ambient temperatures or excessive exercise could be dangerous for patients who take it.

1. ME Arbouw et al. Glycopyrrolate for sialorrhea in Parkinson disease: a randomized, double-blind, crossover trial. Neurology 2010; 74:1203.

2. CS Liang et al. Comparison of the efficacy and impact on cognition of glycopyrrolate and biperiden for clozapine-induced sialorrhea in schizophrenic patients: a randomized, double-blind, crossover study. Schizophren Res 2010; 119:138.

3. RJ Mier et al. Treatment of sialorrhea with glycopyrrolate: a double-blind, dose-ranging study. Arch Pediatr Adolesc Med 2000; 154:1214.

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Parkinson’s disease (PD) is caused primarily by progressive degeneration of dopamine-containing neurons in the substantia nigra. Dopamine itself cannot be used to treat PD because it does not cross the blood-brain barrier.

Cholinesterase inhibitors are now used routinely in patients with dementia. Rivastigmine transdermal system (Exelon Patch - Novartis), a patch formulation of the cholinesterase inhibitor rivastigmine tartrate, has been approved by the FDA for treatment of mild to moderate dementia associated with Alzheimer's or Parkinson's disease. An oral formulation of rivastigmine tartrate has been available in the US since 2000,2 but gastrointestinal adverse effects possibly related to rapidly rising serum concentrations have limited its use.

ParkinsonÆs disease (PD) is caused primarily by progressive degeneration of dopamine-containing neurons in the substantia nigra. Dopamine itself cannot be used to treat PD because it does not cross the bloodbrain barrier.

Rotigotine (Neupro - Schwarz Pharma), a nonergot dopamine agonist in a transdermal patch formulation, was recently approved by the FDA for treatment of early Parkinson's disease (PD).

Rasagiline (Azilect - Teva), a monoamine oxidase-type B (MAO-B) inhibitor, was recently approved by the FDA for once-daily oral treatment of Parkinson's disease (PD). It can be taken alone for treatment of early disease or with levodopa/carbidopa (Sinemet, and others) for advanced disease. Selegiline (Eldepryl, and others), the first MAO-B inhibitor marketed in the US, has been available since 1988; a new lower-dose disintegrating tablet (Zelapar) was recently approved.

Coenzyme Q10, a fat-soluble antioxidant also known as ubidecarenone, ubiquinone and CoQ10, is marketed as a dietary supplement in the US, both as a single ingredient and in various combination products.

An orally dissolving, immediate-release tablet formulation of carbidopa/levodopa (Parcopa - Schwarz) that can be taken without water is now available for treatment of Parkinson's disease.

Apomorphine (Apokyn - Mylan/Bertek), an injected non-ergot dopamine agonist, was recently approved by the FDA for intermittent subcutaneous (SC) treatment of hypomobility ("off" episodes) in patients with advanced Parkinson's disease. It has been available in Europe for many years.

Parkinson's disease is caused by progressive degeneration of dopamine-containing neurons in the substantia nigra. Dopamine itself cannot be used to treat Parkinson's disease because it does not cross the blood-brain barrier.

Levodopa combined with carbidopa (Sinemet, and others) is the most widely used treatment for patients with Parkinson's disease, but after 2 to 5 years most patients develop troublesome complications (Treatment Guidelines from The Medical Letter 2004; 2:41). The newest treatment for Parkinson's disease patients with end-of-dose "wearing-off" is Stalevo (Novartis), a combination of the catechol-O-methyltransferase (COMT) inhibitor entacapone (Comtan) with 3 different doses of levodopa/carbidopa. The rationale for Stalevo is that it permits some patients to take only one pill rather than two.

Ablation of the globus pallidus, an old treatment for Parkinsons disease, is being tried again, using more refined stereotactic techniques, improved brain imaging and new methods for recording neuronal activity (CW Olanow, Ann Neurol, 40:341, September 1996).

Interest in surgical treatment of Parkinson's disease has increased as the limitations of medical treatment have become apparent (Medical Letter, 35:31, 1993). Two approaches have been used. The first is transplantation of dopamine-producing cells into the patient's brain. The second is stereotactic surgery in areas of the brain that modify movement.

Approaches to treatment of Parkinson's disease have changed in recent years. Previously, the only goal was to treat symptoms with levodopa or other drugs. A new approach is to try to slow progression of the disease. (This issue is superseded by 1999 Drugs of Choice.)

Controlled-release carbidopa/levodopa (Sinemet CR - Dupont Pharma) was recently approved by the US Food and Drug Administration for treatment of Parkinson's disease. The new formulation of this old combination (Sinemet) has the drugs suspended in a polymeric matrix that erodes slowly in the gastrointestinal tract.

Levodopa combined with carbidopa (Sinemet) is the treatment of choice for Parkinson's disease (Medical Letter, 30:113, 1988). After prolonged treatment, however, the symptoms of the disease often become difficult to manage. The benefit from each dose becomes shorter (the 'wearing-off' effect), sudden fluctuations occur between mobility and immobility (the 'on-off' phenomenon), and abnormal involuntary movements (dyskinesias) may become frequent. The dopamine agonist bromocriptine (Parlodel) can ameliorate some of these effects. Two new drugs, pergolide (Permax - Lilly), another dopamine agonist, and selegiline (Eldepryl - Somerset), a selective type B monoamine oxidase (MAO) inhibitor previously known as deprenyl, were recently approved by the US Food and Drug Administration for use with levodopa-carbidopa in patients with difficult-to-manage Parkinson's disease.

Patients with Parkinson's disease have a deficiency of the neurotransmitter dopamine, a catecholamine. Dpamine itself cannot be used to treat the disease because it does not cross the blood-brain barrier, but its metabolic precursor, levodopa, does cross into the brain and is converted to dopamine by a decarboxylase present both in the brain and in the intestinal tract (JM Cedarbaum, Clin Pharmacokinet, 13:141, 1987).