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.

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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.

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.

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

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.

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.

Deep brain stimulation (DBS) is increasingly used to treat advanced Parkinson's disease (PD), but few controlled clinical trials have been published. New evidence from a large controlled study has recently become available.

Many drugs can cause psychiatric symptoms, but a causal connection is often difficult to establish. Psychiatric symptoms that emerge during drug treatment could also be due to the underlying illness, previously unrecognized psychopathology, or psychosocial factors. The withdrawal of some drugs can cause symptoms such as anxiety, psychosis, delirium, agitation or depression.

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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.

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.

Ropinirole (Requip - GlaxoSmithKline), a dopamine agonist already available for treatment of Parkinson's disease, is now the first drug approved by the FDA for treatment of moderate to severe restless legs syndrome (RLS).

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.

Many drugs can cause psychiatric symptoms, but a causal connection is often difficult to establish. Psychiatric symptoms that emerge during drug treatment may also be due to the underlying illness, previously unrecognized psychopathology, or psychosocial factors. The withdrawal of some drugs can cause symptoms such as anxiety, psychosis, delirium, agitation or depression.

Recent articles in the press have trumpeted a new era in the management of Parkinson's disease: dopamine agonists have now replaced levodopa for initial treatment.

Entacapone (Comtan), a catechol-O-methyltransferase (COMT) inhibitor, has been approved by the FDA for adjunctive use with levodopa/carbidopa in patients with Parkinson's disease who have end-of-dose "wearing off"symptoms.

Tolcapone (Tasmar - Roche), a dihydroxy-methyl-nitrobenophenone, has been marketed as an adjunct to levodopa/carbidopa (Sinemet, and others) for treatment of Parkinson's disease in both stable patients and those with end-of-dose "wearing off"of levodopa.

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).

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.

Bupropion (Wellbutrin - Burroughs Wellcome) was recently marketed in the USA for treatment of depression. First approved by the Food and Drug Administration in late 1985, the drug was withdrawn from the market in early 1986 because of a high incidence of seizures in one study.

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).