Selegiline (Eldepryl, Movergan, Zelepar), also known as deprenyl, is an antioxidant drug that blocks monoamine oxidase B (MAO-B), an enzyme that degrades dopamine. Until recently, selegiline was commonly used in early-onset disease and in combination with levodopa for maintenance. Concerns over significant side effects have been raised, however.
A newer MAO-B inhibitor, rasagiline (Azilect), is used alone during early-stage PD and in combination with L-dopa for moderate-to-advanced PD. Unlike selegiline, which is taken twice a day, rasagiline is taken once a day.
Side Effects. MAO-B inhibitors may have severe side effects:
Debate over Mortality Rates. Some major studies have reported higher mortality rates in patients with advanced PD. Such findings may be due to adverse effects on the heart and blood vessels. Although other studies have not reported lower survival rates, some doctors believe that, given its modest effects, selegiline may be a poorer drug choice than others, particularly in patients with risk factors for heart disease.
Dopamine agonists stimulate dopamine receptors in the substantia nigra, the part of the brain in which Parkinson's is thought to originate. Dopamine agonists are effective in delaying motor complications during the first 1 or 2 years of treatment.
Newer Dopamine Agonists. The most commonly prescribed dopamine agonists are pramipexole (Mirapex) and ropinirole (Requip). They are used either alone or in combination with L-dopa. Pramipexole appears to work better and have fewer side effects than ropinirole.
Recent research suggests that L-dopa is better at improving motor disability and dopamine agonists are better at reducing motor complications. L-dopa has a higher risk for dyskinesia side effects than dopamine agonists, but dyskinesia (difficulty controlling muscle movements) can also occur with dopamine agonists. There is debate about the value of dopamine agonists as initial therapy for Parkinson‚ ' s disease. Recent research suggests that early treatment with dopamine agonists may not provide any long-term advantages compared with starting treatment with L-dopa.
Side Effects. Side effects of pramipexole and ropinirole vary but can be severe and include:
Other Dopamine Agonists.
Catechol-O-methyl transferase (COMT) inhibitors increase concentrations of existing dopamine in the brain. Entacapone (Comtan, Stalevo) is the current standard COMT inhibitor. (Stalevo combines entacapone and levodopa into a single pill.) It improves motor fluctuations related to the wearing-off effect and has shown good results in improving on time and reducing the requirements for L-dopa. If the patient does not respond to the drug within 3 weeks, it should be withdrawn. No one should withdraw abruptly from these drugs.
Side Effects. Side effects include:
Of major concern are reports of a few deaths from liver damage in patients taking the COMT inhibitor tolcapone (Tasmar). The drug has been taken off the market in many countries and is recommended in the U.S. only for patients who cannot tolerate other drugs. Entacapone does not appear to have the same effects on the liver and does not require monitoring. Still, patients should watch out for symptoms of liver damage, including jaundice (yellowish skin), fatigue, and loss of appetite.
Anticholinergics were the first drugs used for PD, but have largely been replaced by dopamine drugs. They are generally used only to control tremor in the early stages. They are not as effective against bradykinesia and posture problems and may increase the risk for dementia in late stages. Among the many anticholinergics are trihexyphenidyl (Artane, Trihexy), benztropine (Cogentin), biperiden (Akineton), procyclidine (Kemadrin), and ethopropazine (Parisdol). Orphenadrine (Norflex) is a drug with anticholinergic properties, but is also a muscle relaxant and does not cause urinary retention.
Side Effects. Anticholinergics commonly cause dryness of the mouth (which can actually be an advantage in some people who experience drooling). Other side effects are nausea, urinary retention, blurred vision, and constipation. These drugs can also increase heart rate and worsen constipation. Anticholinergics can sometimes cause significant mental problems, including memory loss, confusion, and even hallucinations. People with glaucoma should use these drugs cautiously.
Amantadine (Symadine, Symmetrel) stimulates the release of dopamine and may be used for patients with early mild symptoms. It has some benefit against muscle rigidity and slowness and may help some patients in advanced stages who are unresponsive to other drugs. It is less powerful than levodopa and may lose its effectiveness after 6 months. It may also reduce motor fluctuations brought on by levodopa, however, and these benefits appear to persist for at least a year. Large, well-conducted studies are still needed to determine its true benefits and safety.
Side Effects. Side effects are similar to those of anticholinergic drugs and also may include swollen ankles and mottled skin. It can also cause visual hallucinations. Overdose can cause serious and even life-threatening toxicity. Patients with Parkinson's should not withdraw from this drug abruptly. In rare instances, it can cause acute delirium or a life-threatening condition called neuroleptic malignant syndrome.
Benabid AL, Chabardes S, Mitrofanis J, Pollak P. Deep brain stimulation of the subthalamic nucleus for the treatment of Parkinson's disease. Lancet Neurol. 2009 Jan;8(1):67-81.
Deuschl G, Schade-Brittinger C, Krack P, Volkmann J, Schafer H, Botzel K, et al. A randomized trial of deep-brain stimulation for Parkinson's disease. N Engl J Med. 2006 Aug 31;355(9):896-908.
Goodwin VA, Richards SH, Taylor RS, Taylor AH, Campbell JL. The effectiveness of exercise interventions for people with Parkinson's disease: a systematic review and meta-analysis. Mov Disord. 2008 Apr 15;23(5):631-40.
Katzenschlager R, Head J, Schrag A, Ben-Shlomo Y, Evans A, Lees AJ; Parkinson's Disease Research Group of the United Kingdom. Fourteen-year final report of the randomized PDRG-UK trial comparing three initial treatments in PD. Neurology. 2008 Aug 12;71(7):474-80. Epub 2008 Jun 25.
Lang A. Parkinsonism. In: Goldman L, Ausiello D, eds. Cecil Textbook of Medicine. 23rd ed. Philadelphia, Pa: Saunders Elsevier; 2007:chap 433.
Lang AE. When and how should treatment be started in Parkinson disease? Neurology. 2009 Feb 17;72(7 Suppl):S39-43.
Lewitt PA. Levodopa for the treatment of Parkinson's disease. N Engl J Med. 2008 Dec 4;359(23):2468-76.
Miyasaki JM, Shannon K, Voon V, Ravina B, Kleiner-Fisman G, Anderson K, et al. Practice Parameter: evaluation and treatment of depression, psychosis, and dementia in Parkinson disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2006 Apr 11;66(7):996-1002.
Olanow CW, Stern MB, Sethi K. The scientific and clinical basis for the treatment of Parkinson disease (2009). Neurology. 2009 May 26;72(21 Suppl 4):S1-136.
Pahwa R, Factor SA, Lyons KE, Ondo WG, Gronseth G, Bronte-Stewart H, et al. Practice Parameter: treatment of Parkinson disease with motor fluctuations and dyskinesia (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2006 Apr 11;66(7):983-95.
Poewe W. Treatments for Parkinson disease--past achievements and current clinical needs. Neurology. 2009 Feb 17;72(7 Suppl):S65-73.
Schade R, Andersohn F, Suissa S, Haverkamp W, Garbe E. Dopamine agonists and the risk of cardiac-valve regurgitation. N Engl J Med. 2007 Jan 4;356(1):29-38.
Storch A, Jost WH, Vieregge P, Spiegel J, Grelich W, Durner J, et al. Randomized, double-blind, placebo-controlled trial on symptomatic effects of coenzyme Q10 in Parkinson disease. Arch Neurol. 2007 July;64(7):938-944. Epub 2007 May 14.
Suchowersky O, Reich S, Perlmutter J, Zesiewicz T, Gronseth G, Weiner WJ; Quality Standards Subcommittee of the American Academy of Neurology. Practice Parameter: diagnosis and prognosis of new onset Parkinson disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2006 Apr 11;66(7):968-75.
Thurman DJ, Stevens JA, Rao JK; Quality Standards Subcommittee of the American Academy of Neurology. Practice parameter: Assessing patients in a neurology practice for risk of falls (an evidence-based review): report of the Quality Standards Subcommittee of theAmerican Academy of Neurology. Neurology. 2008 Feb 5;70(6):473-9.
Weaver FM, Follett K, Stern M, Hur K, Harris C, Marks WJ Jr, et al. Bilateral deep brain stimulation vs best medical therapy for patients with advanced Parkinson disease: a randomized controlled trial. JAMA. 2009 Jan 7;301(1):63-73.
Zanettini R, Antonini A, Gatto G, Gentile R, Tesei S, Pezzoli G. Valvular heart disease and the use of dopamine agonists for Parkinson's disease. N Engl J Med. 2007 Jan 4;356(1):39-46.
UMMC is a member of the University of Maryland Medical System,
22 S. Greene Street, Baltimore, MD 21201. TDD: 1-800-735-2258 or 1.866.408.6885