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Progressive Supranuclear Palsy Medication

  • Author: Eric R Eggenberger, MS, DO, FAAN; Chief Editor: Selim R Benbadis, MD  more...
Updated: Jul 11, 2016

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.


Antiparkinson/dopamine agonists

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)


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)


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.


Tricyclic Antidepressants, TCAs

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

Clomipramine (Anafranil)


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)


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)


Nortriptyline has demonstrated effectiveness in the treatment of chronic pain.

Desipramine (Norpramin)


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.

Contributor Information and Disclosures

Eric R Eggenberger, MS, DO, FAAN Professor, Vice-Chairman, Department of Neurology and Ophthalmology, Colleges of Osteopathic Medicine and Human Medicine, Michigan State University; Director of Michigan State University Ocular Motility Laboratory; Director of National Multiple Sclerosis Society Clinic, Michigan State University College of Human Medicine

Eric R Eggenberger, MS, DO, 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: Serve(d) as a speaker or a member of a speakers bureau for: Biogen; Genzyme; Novartis; Teva <br/>Received research grant from: Biogen; Genzyme; Novartis<br/>Received consulting fee from Biogen for consulting; Received consulting fee from Teva for consulting; Received consulting fee from Acorda for consulting; Received grant/research funds from Novartis for independent contractor; Received honoraria from Genentech for speaking and teaching; Received honoraria from Genzyme for speaking and teaching.


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 College of Medicine

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

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Cyberonics; Eisai; Lundbeck; Sunovion; UCB; Upsher-Smith<br/>Serve(d) as a speaker or a member of a speakers bureau for: Cyberonics; Eisai; Glaxo Smith Kline; Lundbeck; Sunovion; UCB<br/>Received research grant from: Cyberonics; Lundbeck; Sepracor; Sunovion; UCB; Upsher-Smith.


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.

  1. Hauw JJ, Daniel SE, Dickson D, Horoupian DS, Jellinger K, Lantos PL, et al. Preliminary NINDS neuropathologic criteria for Steele-Richardson-Olszewski syndrome (progressive supranuclear palsy). Neurology. 1994 Nov. 44(11):2015-9. [Medline].

  2. Drayer BP, Olanow W, Burger P, et al. Parkinson plus syndrome: diagnosis using high field MR imaging of brain iron. Radiology. 1986 May. 159(2):493-8. [Medline].

  3. Schonfeld SM, Golbe LI, Sage JI, et al. Computed tomographic findings in progressive supranuclear palsy: correlation with clinical grade. Mov Disord. 1987. 2(4):263-78. [Medline].

  4. Stern MB, Braffman BH, Skolnick BE, et al. Magnetic resonance imaging in Parkinson''s disease and parkinsonian syndromes. Neurology. 1989 Nov. 39(11):1524-6. [Medline].

  5. Savoiardo M, Girotti F, Strada L, Ciceri E. Magnetic resonance imaging in progressive supranuclear palsy and other parkinsonian disorders. J Neural Transm Suppl. 1994. 42:93-110. [Medline].

  6. Paviour DC, Price SL, Stevens JM, et al. Quantitative MRI measurement of superior cerebellar peduncle in progressive supranuclear palsy. Neurology. 2005 Feb 22. 64(4):675-9. [Medline].

  7. Aldrich MS, Foster NL, White RF, et al. Sleep abnormalities in progressive supranuclear palsy. Ann Neurol. 1989 Jun. 25(6):577-81. [Medline].

  8. Santamaria J, Iranzo A. Alteraciones del sueno en los trastornos del movimiento. Neurologia. 1997. 12 (Suppl 3):35-47.

  9. Gross RA, Spehlmann R, Daniels JC. Sleep disturbances in progressive supranuclear palsy. Electroencephalogr Clin Neurophysiol. 1978 Jul. 45(1):16-25. [Medline].

  10. Laffont F, Autret A, Minz M, Beillevaire T, Gilbert A, Cathala HP, et al. [Polygraphic sleep recordings in 9 cases of Steele-Richardson's disease (author's transl)]. Rev Neurol (Paris). 1979 Feb. 135(2):127-41. [Medline].

  11. Polo KB, Jabbari B. Botulinum toxin-A improves the rigidity of progressive supranuclear palsy. Ann Neurol. 1994 Feb. 35(2):237-9. [Medline].

  12. Golbe LI. Progressive Supranuclear Palsy. Curr Treat Options Neurol. 2001 Nov. 3(6):473-477. [Medline].

  13. Boeve BF. Progressive supranuclear palsy. Parkinsonism Relat Disord. 2012 Jan. 18 Suppl 1:S192-4. [Medline].

  14. Williams DR, Lees AJ. Progressive supranuclear palsy: clinicopathological concepts and diagnostic challenges. Lancet Neurol. 2009 Mar. 8(3):270-9. [Medline].

  15. Conrad C, Andreadis A, Trojanowski JQ, et al. Genetic evidence for the involvement of tau in progressive supranuclear palsy. Ann Neurol. 1997 Feb. 41(2):277-81. [Medline].

  16. Liao K, Wagner J, Joshi A, Estrovich I, Walker MF, Strupp M, et al. Why do patients with PSP fall? Evidence for abnormal otolith responses. Neurology. 2008 Mar 4. 70(10):802-9. [Medline].

  17. Golbe LI, Rubin RS, Cody RP, et al. Follow-up study of risk factors in progressive supranuclear palsy. Neurology. 1996 Jul. 47(1):148-54. [Medline].

  18. Tetrud JW, Golbe LI, Forno LS, Farmer PM. Autopsy-proven progressive supranuclear palsy in two siblings. Neurology. 1996 Apr. 46(4):931-4. [Medline].

  19. Kaat LD, Boon AJ, Azmani A, Kamphorst W, Breteler MM, Anar B, et al. Familial aggregation of parkinsonism in progressive supranuclear palsy. Neurology. 2009 Jul 14. 73(2):98-105. [Medline].

  20. de Yebenes JG, Sarasa JL, Daniel SE, Lees AJ. Familial progressive supranuclear palsy. Description of a pedigree and review of the literature. Brain. 1995 Oct. 118 ( Pt 5):1095-103. [Medline].

  21. Steele JC, Richardson JC, Olszewski J. Progressive supranuclear palsy. A heterogenous degeneration involving the brain stem, basal ganglia and cerebellum with vertical gaze and pseudobulbar palsy, nuchal dystonia and dementia. Arch Neurol. 1964 Apr. 10:333-59. [Medline].

  22. Golbe LI, Davis PH, Schoenberg BS, Duvoisin RC. Prevalence and natural history of progressive supranuclear palsy. Neurology. 1988 Jul. 38(7):1031-4. [Medline].

  23. Jackson JA, Jankovic J, Ford J. Progressive supranuclear palsy: clinical features and response to treatment in 16 patients. Ann Neurol. 1983 Mar. 13(3):273-8. [Medline].

  24. Mastaglia FL, Grainger K, Kee F, et al. Progressive supranuclear palsy (the Steele-Richardson-Olszewski syndrome) clinical and electrophysiological observations in eleven cases. Proc Aust Assoc Neurol. 1973. 10(0):35-44. [Medline].

  25. Maher ER, Lees AJ. The clinical features and natural history of the Steele-Richardson- Olszewski syndrome (progressive supranuclear palsy). Neurology. 1986 Jul. 36(7):1005-8. [Medline].

  26. Kristensen MO. Progressive supranuclear palsy--20 years later. Acta Neurol Scand. 1985 Mar. 71(3):177-89. [Medline].

  27. Litvan I, Mangone CA, McKee A, et al. Natural history of progressive supranuclear palsy (Steele-Richardson- Olszewski syndrome) and clinical predictors of survival: a clinicopathological study. J Neurol Neurosurg Psychiatry. 1996 Jun. 60(6):615-20. [Medline].

  28. Barclay CL, Lang AE. Dystonia in progressive supranuclear palsy. J Neurol Neurosurg Psychiatry. 1997 Apr. 62(4):352-6. [Medline].

  29. Gibb WR, Luthert PJ, Marsden CD. Corticobasal degeneration. Brain. 1989 Oct. 112 ( Pt 5):1171-92. [Medline].

  30. Sakakibara R, Hattori T, Tojo M, et al. Micturitional disturbance in progressive supranuclear palsy. J Auton Nerv Syst. 1993 Nov. 45(2):101-6. [Medline].

  31. Tolosa E, Espuna M, Valls J. Bladder dysfunction in PSP and other parkinsonian disorders. Mov Disord. 1997. 12:272.

  32. Josephs KA, Duffy JR. Apraxia of speech and nonfluent aphasia: a new clinical marker for corticobasal degeneration and progressive supranuclear palsy. Curr Opin Neurol. 2008 Dec. 21(6):688-92. [Medline].

  33. Cooper AD, Josephs KA. Photophobia, visual hallucinations, and REM sleep behavior disorder in progressive supranuclear palsy and corticobasal degeneration: a prospective study. Parkinsonism Relat Disord. 2009 Jan. 15(1):59-61. [Medline].

  34. Schmidt C, Herting B, Prieur S, Junghanns S, Schweitzer K, Globas C. Pupil diameter in darkness differentiates progressive supranuclear palsy (PSP) from other extrapyramidal syndromes. Mov Disord. 2007 Oct 31. 22(14):2123-6. [Medline].

  35. Litvan I, Mega MS, Cummings JL, Fairbanks L. Neuropsychiatric aspects of progressive supranuclear palsy. Neurology. 1996 Nov. 47(5):1184-9. [Medline].

  36. Litvan I, Agid Y, Jankovic J, et al. Accuracy of clinical criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome). Neurology. 1996 Apr. 46(4):922-30. [Medline].

  37. Litvan I, Agid Y, Calne D, et al. Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome): report of the NINDS-SPSP international workshop. Neurology. 1996 Jul. 47(1):1-9. [Medline].

  38. Borroni B, Malinverno M, Gardoni F, Alberici A, Parnetti L, Premi E, et al. Tau forms in CSF as a reliable biomarker for progressive supranuclear palsy. Neurology. 2008 Nov 25. 71(22):1796-803. [Medline].

  39. Righini A, Antonini A, De Notaris R, et al. MR imaging of the superior profile of the midbrain: differential diagnosis between progressive supranuclear palsy and Parkinson disease. AJNR Am J Neuroradiol. 2004 Jun-Jul. 25(6):927-32. [Medline].

  40. Boelmans K, Holst B, Hackius M, Finsterbusch J, Gerloff C, Fiehler J, et al. Brain iron deposition fingerprints in Parkinson's disease and progressive supranuclear palsy. Mov Disord. 2012 Jan 30. [Medline].

  41. Foster NL, Gilman S, Berent S, et al. Cerebral hypometabolism in progressive supranuclear palsy studied with positron emission tomography. Ann Neurol. 1988 Sep. 24(3):399-406. [Medline].

  42. Foster NL, Gilman S, Berent S, et al. Progressive subcortical gliosis and progressive supranuclear palsy can have similar clinical and PET abnormalities. J Neurol Neurosurg Psychiatry. 1992 Aug. 55(8):707-13. [Medline].

  43. Blin J, Baron JC, Dubois B, et al. Positron emission tomography study in progressive supranuclear palsy. Brain hypometabolic pattern and clinicometabolic correlations. Arch Neurol. 1990 Jul. 47(7):747-52. [Medline].

  44. Mishina M, Ishii K, Mitani K, et al. Midbrain hypometabolism as early diagnostic sign for progressive supranuclear palsy. Acta Neurol Scand. 2004 Aug. 110(2):128-35. [Medline].

  45. Brooks DJ, Ibanez V, Sawle GV, et al. Differing patterns of striatal 18F-dopa uptake in Parkinson''s disease, multiple system atrophy, and progressive supranuclear palsy. Ann Neurol. 1990 Oct. 28(4):547-55. [Medline].

  46. Arnold G, Tatsch K, Oertel WH, et al. Clinical progressive supranuclear palsy: differential diagnosis by IBZM- SPECT and MRI. J Neural Transm Suppl. 1994. 42:111-8. [Medline].

  47. Sixel-Döring F, Schweitzer M, Mollenhauer B, Trenkwalder C. Polysomnographic findings, video-based sleep analysis and sleep perception in progressive supranuclear palsy. Sleep Med. 2009 Apr. 10(4):407-15. [Medline].

  48. Stamelou M, Reuss A, Pilatus U, Magerkurth J, Niklowitz P, Eggert KM. Short-term effects of coenzyme Q10 in progressive supranuclear palsy: a randomized, placebo-controlled trial. Mov Disord. 2008 May 15. 23(7):942-9. [Medline].

  49. Zampieri C, Di Fabio RP. Improvement of gaze control after balance and eye movement training in patients with progressive supranuclear palsy: a quasi-randomized controlled trial. Arch Phys Med Rehabil. 2009 Feb. 90(2):263-70. [Medline].

  50. 23rd Meeting of the European Neurological Society (ENS). Abstract P729. Presented June 10, 2013.

  51. Keller DM. Botulinum Toxin Benefits Many PSP Patients With Dystonia. Medscape Medical News. Available at Accessed: July 7, 2013.

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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