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Medication

Medication Summary

No effective therapy for progressive supranuclear palsy (PSP) is known. A trial of a dopamine agonist is often undertaken to help eliminate Parkinson disease in diagnostically confusing cases or to provide modest symptomatic improvement.

Class Summary

Dopamine agonists directly stimulate postsynaptic dopamine receptors to provide benefit against symptoms of Parkinson disease. In order for a dopamine agonist to offer clinical benefit, it must stimulate D2 receptors. The role of other dopamine receptor subtypes is currently unclear.

Levodopa and carbidopa (Sinemet, Parcopa)

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The combination of carbidopa and levodopa generally produces no dramatic symptomatic improvement in patients with PSP, in sharp contrast with its effect in patients with idiopathic Parkinson disease. Accordingly, administration of carbidopa-levodopa may serve as a diagnostic test to help eliminate the possibility of Parkinson disease.

Carbidopa-levodopa is available in 10/100, 25/100, 25/250 formulations.

Bromocriptine (Parlodel, Cycloset)

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Bromocriptine is a semisynthetic ergot alkaloid derivative that is a strong D2 receptor agonist and a weak D1 receptor antagonist. It is approved by the US Food and Drug Administration (FDA) as an adjunct to carbidopa-levodopa; it is less effective than other dopamine agonists. It may relieve akinesia, rigidity, and tremor in Parkinson disease. The mechanism of the therapeutic effect involves direct stimulation of dopamine receptors in the corpus striatum.

Approximately 28% of a bromocriptine dose is absorbed from the gastrointestinal tract and metabolized in the liver. Elimination half-life is approximately 50 hours, with 85% excreted in feces and 3-6% eliminated in urine.

Initiate the drug at a low dosage and individualize. Slowly increase the daily dose until maximal therapeutic response is achieved. If possible, maintain the dosage of levodopa during this introductory period. Assess dosage titrations every 2 weeks to ensure that the lowest dosage producing optimal therapeutic response is not exceeded. If adverse reactions mandate dose reduction, reduce the daily dose gradually in 2.5-mg increments.

Class Summary

Tricyclic antidepressants are a complex group of drugs that have central and peripheral anticholinergic effects, as well as sedative effects. They have central effects on pain transmission.

Amitriptyline

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Amitriptyline inhibits reuptake of serotonin or norepinephrine at the presynaptic neuronal membrane, thereby increasing the concentration in the central nervous system.

Clomipramine (Anafranil)

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Clomipramine is a dibenzazepine compound belonging to the family of tricyclic antidepressants. The drug inhibits the membrane pump mechanism responsible for the uptake of norepinephrine and serotonin in adrenergic and serotonergic neurons.

Clomipramine affects serotonin uptake while it affects norepinephrine uptake when converted into its metabolite desmethylclomipramine. It is believed that these actions are responsible for its antidepressant activity.

Doxepin (Silenor)

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Doxepin increases the concentration of serotonin and norepinephrine in the CNS by inhibiting their reuptake by the presynaptic neuronal membrane. It inhibits histamine and acetylcholine activity and has proven useful in the treatment of various forms of depression associated with chronic pain.

Nortriptyline (Pamelor)

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Nortriptyline has demonstrated effectiveness in the treatment of chronic pain.

Desipramine (Norpramin)

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This is the original TCA used for depression and has been shown to treat chronic pain. These agents have been suggested to act by inhibiting the reuptake of noradrenaline at synapses in central descending pain modulating pathways located in the brainstem and spinal cord.

Questions

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Media Gallery

Sagittal T1-weighted image shows atrophy of midbrain, preservation of pontine volume, and atrophy of the tectum, suggestive of progressive supranuclear palsy (Steele-Olszewski-Richardson disease).
Characteristic facial appearance of patient with progressive supranuclear palsy.

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Author

Eric R Eggenberger, DO, MS, FAAN Neurologist, Departments of Neurology and Ophthalmology, Mayo Clinic

Eric R Eggenberger, DO, MS, FAAN is a member of the following medical societies: American Academy of Neurology, American Academy of Ophthalmology, American Osteopathic Association, North American Neuro-Ophthalmology Society

Disclosure: Nothing to disclose.

Coauthor(s)

David Clark, DO Clinical Assistant Professor of Neurology, Western University of Health Sciences; Neuro-ophthalmologist, Oregon Neurology Associates

David Clark, DO is a member of the following medical societies: American Academy of Neurology, American Osteopathic Association, North American Neuro-Ophthalmology Society

Disclosure: Received honoraria from Teva for speaking and teaching; Received honoraria from Biogen Idec for speaking and teaching.

Chief Editor

Selim R Benbadis, MD Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, Tampa General Hospital, University of South Florida Morsani College of Medicine

Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, American Medical Association

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Bioserenity, Ceribell, Eisai, Jazz, LivaNova, Neurelis, Neuropace, SK life science, Sunovion, Takeda, UCB<br/>Serve(d) as a speaker or a member of a speakers bureau for: Aquestive, Bioserenity, Eisai, Jazz, LivaNova, Neurelis, SK life science, Stratus, Sunovion, UCB<br/>Received research grant from: Cerevel Therapeutics, Ovid Therapeutics, Neuropace, Greenwich Jazz, SK Life Science, Xenon Pharmaceuticals, UCB, Marinus, Neuroelectrics Corporation, Longboard, Janssen, Equilibre Biopharmaceuticals.

Acknowledgements

Nestor Galvez-Jimenez, MD, MSc, MHA Chairman, Department of Neurology, Program Director, Movement Disorders, Department of Neurology, Division of Medicine, Cleveland Clinic Florida

Nestor Galvez-Jimenez, MD, MSc, MHA is a member of the following medical societies: American Academy of Neurology, American College of Physicians, and Movement Disorders Society

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Reference Salary Employment

Zeba F Vanek, MD, MBBS, DCN Associate Professor of Neurology, David Geffen School of Medicine at UCLA; Director, UCLA Spasticity Clinic

Zeba F Vanek, MD, MBBS, DCN is a member of the following medical societies: Movement Disorders Society

Disclosure: Nothing to disclose.

Progressive Supranuclear Palsy Medication

Medication Summary

Antiparkinson/dopamine agonists

Class Summary

Levodopa and carbidopa (Sinemet, Parcopa)