Parkinson's disease medical therapy
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
The mainstay of therapy for motor symptoms of Parkinson disease are: Levodopa, dopamine agonists, monoamine oxidase (MAO) B inhibitors, anticholinergic agents, amantadine, catechol-O-methyl transferase (COMT) inhibitors, estrogen and other drugs such as Exenatide, uric acid, isradipine, nilotinib and GDNF infusion.
Treatment choices for some of the nonmotor symptoms of PD are:
psychosis: quetiapine, clozapine and pimavanserin.
Dementia: Cholinesterase inhibitors such as rivastigmine and donepezil.
Fatigue: Amantadine, methylphenidate and pemoline.
Depression: Amitriptyline, desipramine, citalopram ,paroxetine, venlafaxine, ropinirole and pramipexole.
Constipation: Increasing probiotics and fibers, lubiprostone and polyethylene glycol.
Sialorrhea: chewing gum and hard candy but in severe cases, botulinum toxin injection into salivary glands .
Sexual dysfunction: sildenafil (for male)
Ortostatic hypotention: Fludrocortisone, Sympathomimetic agents such as ephedrine, pseudoephedrine, methylphenidate and dextroamphetamine.
Medical Therapy
The mainstay of therapy for motor symptoms of Parkinson disease are:
- Levodopa: This drug is the most effective in controlling motor symptoms in PD patients.[1][2] If we use levodopa alone, it will convert to dopamine in the peripheral circulation, so we combine it with a decarboxylase inhibitor like carbidopa to prevent this. The ratio of carbidopa_levodopa in tablets are 10/100, 25/100 or 25/250.[3][4] The adverse effects of this drug includes elevated serum homocysteine, low levels of vitamin B12, elevated methylmalonic acid and sensorimotor peripheral neuropathy.[5][6][7][8] It can also cause motor fluctuations, dyskinesia, cramps and dystonia.[9][10] One of the concerns regarding long term use of levodopa is that it may be increase the rate of dopamine neurons degeneration[11] but other studies demonstrated that it does not damage neurons.[12][13]
- Dopamine agonists: Dopamine agonist such as bromocriptine, pramipexole and ropinirole are proved to be effective in managing motor symptoms of PD patients.[14] At first, the use of dopamine agonist were limited t the condition where there is reduced levodopa response or when we had disturbing levodopa complications[15][16] but since dopamine agonists have fewer side effects, some experts suggest using these drugs as the first line therapy especially for PD patients under 60 years old.[17] The adverse effects of dopamine agonist are nausea, vomiting, sleep disorders, confusion, peripheral edema and valvular heart disease.[18][19]
- Monoamine oxidase (MAO) B inhibitors: MAO B inhibitors such as selegiline, rasagiline and safinamide are proved to be helpful in managing motor symptoms of PD patients.[20][21][22][23] these drugs can cause nausea and headaches.[21] Rasagiline can also cause impulse control disorders.[24]
- Anticholinergic agents: In PD we have reduced amount of dopamine and excess amount of cholinergic effects, so anticholinergic drugs such as trihexyphenidyl and benztropine can reduce the symptoms of PD.[25][26][27]
- Amantadine: Amantadine, an antiviral drug can improve PD symptoms by increasing dopamine release, inhibition of dopamine reuptake, stimulation of dopamine receptors and anticholinergic effect.[28][29] Some studies showed that in controlling bardykinesia, this drug can be more effective than anticholinergic drugs.[30]
- Catechol-O-methyl transferase (COMT) inhibitors: The catechol-o-methyl transferase (COMT) inhibitors such as entacapone and tolcapone can potentiate the effect of levodopa in reducing PD motor symptoms.[31][32]
- Estrogen: In postmenopausal women who are experiencing motor fluctuation on antiparkinsonism drugs we can use low dose estrogen to improve their condition.[33][34]
- Other agents: Other drugs such as Exenatide[35], uric acid[36], isradipine[37], nilotinib[38] and GDNF infusion[39] can be effective in controlling PD patients symptoms.
Treatment choices for some of the nonmotor symptoms of PD are:
- Psychosis: Drugs such as quetiapine, clozapine and pimavanserin are used in managing psychosis in PD.[40][41] one of the side effects of clozapine is leukopenia and agranulocytosis.[42]
- Dementia: Cholinesterase inhibitors such as rivastigmine and donepezil are the main treatment of dementia in PD.[43][44][45]
- Fatigue: Amantadine, methylphenidate and pemoline can improve fatigue in PD patients.[46][47][48]
- Depression: Amitriptyline[49], desipramine, citalopram[50],paroxetine, venlafaxine[51], ropinirole and pramipexole[52][53][54] are useful in managing depression in PD patients. If we intent to use tricyclics we should be aware that their anticholinergic effect can increase orthostatic hypotension and cognitive impairment[55] and for SSRI we should know that they can cause dystonia, tremor and parkinsonism.[56] the combination of MAO B inhibitors with SSRIs or tricyclics can cause serotonin syndromes[57]
- Constipation: Increasing probiotics and fibers, lubiprostone and polyethylene glycol are effective in treatment of constipation.[58][59][60]
- Sialorrhea: If the sialorrhea is mild we can treat it with chewing gum and hard candy[61][62] but in severe cases, botulinum toxin injection into salivary glands is helpful.[52][63]
- Sexual dysfunction: Male sexual dysfunction can be treated with sildenafil.[64]
- Ortostatic hypotention: Fludrocortisone[65], Sympathomimetic agents such as ephedrine, pseudoephedrine, methylphenidate and dextroamphetamine are used to treat orthostatic hypotension.[66][67]
References
- ↑ Connolly BS, Lang AE (2014). "Pharmacological treatment of Parkinson disease: a review". JAMA. 311 (16): 1670–83. doi:10.1001/jama.2014.3654. PMID 24756517.
- ↑ Ferreira JJ, Katzenschlager R, Bloem BR, Bonuccelli U, Burn D, Deuschl G, Dietrichs E, Fabbrini G, Friedman A, Kanovsky P, Kostic V, Nieuwboer A, Odin P, Poewe W, Rascol O, Sampaio C, Schüpbach M, Tolosa E, Trenkwalder C, Schapira A, Berardelli A, Oertel WH (January 2013). "Summary of the recommendations of the EFNS/MDS-ES review on therapeutic management of Parkinson's disease". Eur. J. Neurol. 20 (1): 5–15. doi:10.1111/j.1468-1331.2012.03866.x. PMID 23279439.
- ↑ "Parcopa: a rapidly dissolving formulation of carbidopa/levodopa". Med Lett Drugs Ther. 47 (1201): 12. January 2005. PMID 15706700.
- ↑ Ondo WG, Shinawi L, Moore S (December 2010). "Comparison of orally dissolving carbidopa/levodopa (Parcopa) to conventional oral carbidopa/levodopa: A single-dose, double-blind, double-dummy, placebo-controlled, crossover trial". Mov. Disord. 25 (16): 2724–7. doi:10.1002/mds.23158. PMID 20925074.
- ↑ Toth C, Brown MS, Furtado S, Suchowersky O, Zochodne D (October 2008). "Neuropathy as a potential complication of levodopa use in Parkinson's disease". Mov. Disord. 23 (13): 1850–9. doi:10.1002/mds.22137. PMID 18785232.
- ↑ Toth C, Breithaupt K, Ge S, Duan Y, Terris JM, Thiessen A, Wiebe S, Zochodne DW, Suchowersky O (July 2010). "Levodopa, methylmalonic acid, and neuropathy in idiopathic Parkinson disease". Ann. Neurol. 68 (1): 28–36. doi:10.1002/ana.22021. PMID 20582991.
- ↑ Ceravolo R, Cossu G, Bandettini di Poggio M, Santoro L, Barone P, Zibetti M, Frosini D, Nicoletti V, Manganelli F, Iodice R, Picillo M, Merola A, Lopiano L, Paribello A, Manca D, Melis M, Marchese R, Borelli P, Mereu A, Contu P, Abbruzzese G, Bonuccelli U (September 2013). "Neuropathy and levodopa in Parkinson's disease: evidence from a multicenter study". Mov. Disord. 28 (10): 1391–7. doi:10.1002/mds.25585. PMID 23836370.
- ↑ Uncini A, Eleopra R, Onofrj M (May 2015). "Polyneuropathy associated with duodenal infusion of levodopa in Parkinson's disease: features, pathogenesis and management". J. Neurol. Neurosurg. Psychiatry. 86 (5): 490–5. doi:10.1136/jnnp-2014-308586. PMID 25168395.
- ↑ Calabresi P, Di Filippo M, Ghiglieri V, Tambasco N, Picconi B (November 2010). "Levodopa-induced dyskinesias in patients with Parkinson's disease: filling the bench-to-bedside gap". Lancet Neurol. 9 (11): 1106–17. doi:10.1016/S1474-4422(10)70218-0. PMID 20880751.
- ↑ Aquino CC, Fox SH (January 2015). "Clinical spectrum of levodopa-induced complications". Mov. Disord. 30 (1): 80–9. doi:10.1002/mds.26125. PMID 25488260.
- ↑ Olanow CW, Agid Y, Mizuno Y, Albanese A, Bonuccelli U, Bonucelli U, Damier P, De Yebenes J, Gershanik O, Guttman M, Grandas F, Hallett M, Hornykiewicz O, Jenner P, Katzenschlager R, Langston WJ, LeWitt P, Melamed E, Mena MA, Michel PP, Mytilineou C, Obeso JA, Poewe W, Quinn N, Raisman-Vozari R, Rajput AH, Rascol O, Sampaio C, Stocchi F (September 2004). "Levodopa in the treatment of Parkinson's disease: current controversies". Mov. Disord. 19 (9): 997–1005. doi:10.1002/mds.20243. PMID 15372588.
- ↑ Rajput AH (2001). "The protective role of levodopa in the human substantia nigra". Adv Neurol. 86: 327–36. PMID 11553992.
- ↑ Parkkinen L, O'Sullivan SS, Kuoppamäki M, Collins C, Kallis C, Holton JL, Williams DR, Revesz T, Lees AJ (October 2011). "Does levodopa accelerate the pathologic process in Parkinson disease brain?". Neurology. 77 (15): 1420–6. doi:10.1212/WNL.0b013e318232ab4c. PMID 21917769.
- ↑ Olanow CW, Watts RL, Koller WC (June 2001). "An algorithm (decision tree) for the management of Parkinson's disease (2001): treatment guidelines". Neurology. 56 (11 Suppl 5): S1–S88. PMID 11402154.
- ↑ Fahn S (December 1996). "Is levodopa toxic?". Neurology. 47 (6 Suppl 3): S184–95. PMID 8959987.
- ↑ "International symposium on early dopamine agonist therapy of Parkinson's disease". Arch. Neurol. 45 (2): 204–8. February 1988. PMID 3341935.
- ↑ Marras C, Lang A (May 2008). "Invited article: changing concepts in Parkinson disease: moving beyond the decade of the brain". Neurology. 70 (21): 1996–2003. doi:10.1212/01.wnl.0000312515.52545.51. PMID 18490620.
- ↑ Stowe RL, Ives NJ, Clarke C, van Hilten J, Ferreira J, Hawker RJ, Shah L, Wheatley K, Gray R (April 2008). "Dopamine agonist therapy in early Parkinson's disease". Cochrane Database Syst Rev (2): CD006564. doi:10.1002/14651858.CD006564.pub2. PMID 18425954.
- ↑ Roth BL (January 2007). "Drugs and valvular heart disease". N. Engl. J. Med. 356 (1): 6–9. doi:10.1056/NEJMp068265. PMID 17202450.
- ↑ Olanow CW (December 1996). "Selegiline: current perspectives on issues related to neuroprotection and mortality". Neurology. 47 (6 Suppl 3): S210–6. PMID 8959990.
- ↑ 21.0 21.1 Horn S, Stern MB (October 2004). "The comparative effects of medical therapies for Parkinson's disease". Neurology. 63 (7 Suppl 2): S7–12. PMID 15477585.
- ↑ "A controlled trial of rasagiline in early Parkinson disease: the TEMPO Study". Arch. Neurol. 59 (12): 1937–43. December 2002. PMID 12470183.
- ↑ "A controlled, randomized, delayed-start study of rasagiline in early Parkinson disease". Arch. Neurol. 61 (4): 561–6. April 2004. doi:10.1001/archneur.61.4.561. PMID 15096406.
- ↑ Vitale C, Santangelo G, Erro R, Errico D, Manganelli F, Improta I, Moccia M, Barone P (April 2013). "Impulse control disorders induced by rasagiline as adjunctive therapy for Parkinson's disease: report of 2 cases". Parkinsonism Relat. Disord. 19 (4): 483–4. doi:10.1016/j.parkreldis.2012.11.008. PMID 23305965.
- ↑ Duvoisin RC (August 1967). "Cholinergic-anticholinergic antagonism in parkinsonism". Arch. Neurol. 17 (2): 124–36. PMID 4382112.
- ↑ Katzenschlager R, Sampaio C, Costa J, Lees A (2003). "Anticholinergics for symptomatic management of Parkinson's disease". Cochrane Database Syst Rev (2): CD003735. doi:10.1002/14651858.CD003735. PMID 12804486.
- ↑ Lang AE (February 1984). "Treatment of Parkinson's disease with agents other than levodopa and dopamine agonists: controversies and new approaches". Can J Neurol Sci. 11 (1 Suppl): 210–20. PMID 6143611.
- ↑ Schwab RS, Poskanzer DC, England AC, Young RR (November 1972). "Amantadine in Parkinson's disease. Review of more than two years' experience". JAMA. 222 (7): 792–5. PMID 4677928.
- ↑ "Amantadine and other antiglutamate agents: management of Parkinson's disease". Mov. Disord. 17 Suppl 4: S13–22. 2002. doi:10.1002/mds.5557. PMID 12211136.
- ↑ Parkes JD, Baxter RC, Marsden CD, Rees JE (April 1974). "Comparative trial of benzhexol, amantadine, and levodopa in the treatment of Parkinson's disease". J. Neurol. Neurosurg. Psychiatry. 37 (4): 422–6. PMC 494673. PMID 4838913.
- ↑ Nutt JG (April 1998). "Catechol-O-methyltransferase inhibitors for treatment of Parkinson's disease". Lancet. 351 (9111): 1221–2. doi:10.1016/S0140-6736(05)79311-9. PMID 9643737.
- ↑ Brooks DJ, Sagar H (August 2003). "Entacapone is beneficial in both fluctuating and non-fluctuating patients with Parkinson's disease: a randomised, placebo controlled, double blind, six month study". J. Neurol. Neurosurg. Psychiatry. 74 (8): 1071–9. PMC 1738605. PMID 12876237.
- ↑ Tsang KL, Ho SL, Lo SK (June 2000). "Estrogen improves motor disability in parkinsonian postmenopausal women with motor fluctuations". Neurology. 54 (12): 2292–8. PMID 10881255.
- ↑ Saunders-Pullman R, Gordon-Elliott J, Parides M, Fahn S, Saunders HR, Bressman S (April 1999). "The effect of estrogen replacement on early Parkinson's disease". Neurology. 52 (7): 1417–21. PMID 10227628.
- ↑ Harkavyi A, Abuirmeileh A, Lever R, Kingsbury AE, Biggs CS, Whitton PS (May 2008). "Glucagon-like peptide 1 receptor stimulation reverses key deficits in distinct rodent models of Parkinson's disease". J Neuroinflammation. 5: 19. doi:10.1186/1742-2094-5-19. PMC 2426681. PMID 18492290.
- ↑ Ascherio A, LeWitt PA, Xu K, Eberly S, Watts A, Matson WR, Marras C, Kieburtz K, Rudolph A, Bogdanov MB, Schwid SR, Tennis M, Tanner CM, Beal MF, Lang AE, Oakes D, Fahn S, Shoulson I, Schwarzschild MA (December 2009). "Urate as a predictor of the rate of clinical decline in Parkinson disease". Arch. Neurol. 66 (12): 1460–8. doi:10.1001/archneurol.2009.247. PMC 2795011. PMID 19822770.
- ↑ Ilijic E, Guzman JN, Surmeier DJ (August 2011). "The L-type channel antagonist isradipine is neuroprotective in a mouse model of Parkinson's disease". Neurobiol. Dis. 43 (2): 364–71. doi:10.1016/j.nbd.2011.04.007. PMC 3235730. PMID 21515375.
- ↑ Wyse RK, Brundin P, Sherer TB (July 2016). "Nilotinib - Differentiating the Hope from the Hype". J Parkinsons Dis. 6 (3): 519–22. doi:10.3233/JPD-160904. PMC 5044778. PMID 27434298.
- ↑ Gill SS, Patel NK, Hotton GR, O'Sullivan K, McCarter R, Bunnage M, Brooks DJ, Svendsen CN, Heywood P (May 2003). "Direct brain infusion of glial cell line-derived neurotrophic factor in Parkinson disease". Nat. Med. 9 (5): 589–95. doi:10.1038/nm850. PMID 12669033.
- ↑ Shotbolt P, Samuel M, David A (November 2010). "Quetiapine in the treatment of psychosis in Parkinson's disease". Ther Adv Neurol Disord. 3 (6): 339–50. doi:10.1177/1756285610389656. PMC 3002640. PMID 21179595.
- ↑ Cummings J, Isaacson S, Mills R, Williams H, Chi-Burris K, Corbett A, Dhall R, Ballard C (February 2014). "Pimavanserin for patients with Parkinson's disease psychosis: a randomised, placebo-controlled phase 3 trial". Lancet. 383 (9916): 533–40. doi:10.1016/S0140-6736(13)62106-6. PMID 24183563.
- ↑ Schulte P (April 2006). "Risk of clozapine-associated agranulocytosis and mandatory white blood cell monitoring". Ann Pharmacother. 40 (4): 683–8. doi:10.1345/aph.1G396. PMID 16595571.
- ↑ Rolinski M, Fox C, Maidment I, McShane R (March 2012). "Cholinesterase inhibitors for dementia with Lewy bodies, Parkinson's disease dementia and cognitive impairment in Parkinson's disease". Cochrane Database Syst Rev (3): CD006504. doi:10.1002/14651858.CD006504.pub2. PMID 22419314.
- ↑ Emre M, Aarsland D, Albanese A, Byrne EJ, Deuschl G, De Deyn PP, Durif F, Kulisevsky J, van Laar T, Lees A, Poewe W, Robillard A, Rosa MM, Wolters E, Quarg P, Tekin S, Lane R (December 2004). "Rivastigmine for dementia associated with Parkinson's disease". N. Engl. J. Med. 351 (24): 2509–18. doi:10.1056/NEJMoa041470. PMID 15590953.
- ↑ Dubois B, Tolosa E, Katzenschlager R, Emre M, Lees AJ, Schumann G, Pourcher E, Gray J, Thomas G, Swartz J, Hsu T, Moline ML (September 2012). "Donepezil in Parkinson's disease dementia: a randomized, double-blind efficacy and safety study". Mov. Disord. 27 (10): 1230–8. doi:10.1002/mds.25098. PMID 22915447.
- ↑ Elbers RG, Verhoef J, van Wegen EE, Berendse HW, Kwakkel G (October 2015). "Interventions for fatigue in Parkinson's disease". Cochrane Database Syst Rev (10): CD010925. doi:10.1002/14651858.CD010925.pub2. PMID 26447539.
- ↑ Mendonça DA, Menezes K, Jog MS (October 2007). "Methylphenidate improves fatigue scores in Parkinson disease: a randomized controlled trial". Mov. Disord. 22 (14): 2070–6. doi:10.1002/mds.21656. PMID 17674415.
- ↑ Zesiewicz TA, Sullivan KL, Arnulf I, Chaudhuri KR, Morgan JC, Gronseth GS, Miyasaki J, Iverson DJ, Weiner WJ (March 2010). "Practice Parameter: treatment of nonmotor symptoms of Parkinson disease: report of the Quality Standards Subcommittee of the American Academy of Neurology". Neurology. 74 (11): 924–31. doi:10.1212/WNL.0b013e3181d55f24. PMID 20231670.
- ↑ Serrano-Dueñas M (2002). "[A comparison between low doses of amitriptyline and low doses of fluoxetin used in the control of depression in patients suffering from Parkinson's disease]". Rev Neurol (in Spanish; Castilian). 35 (11): 1010–4. PMID 12497304.
- ↑ Devos D, Dujardin K, Poirot I, Moreau C, Cottencin O, Thomas P, Destée A, Bordet R, Defebvre L (April 2008). "Comparison of desipramine and citalopram treatments for depression in Parkinson's disease: a double-blind, randomized, placebo-controlled study". Mov. Disord. 23 (6): 850–7. doi:10.1002/mds.21966. PMID 18311826.
- ↑ Richard IH, McDermott MP, Kurlan R, Lyness JM, Como PG, Pearson N, Factor SA, Juncos J, Serrano Ramos C, Brodsky M, Manning C, Marsh L, Shulman L, Fernandez HH, Black KJ, Panisset M, Christine CW, Jiang W, Singer C, Horn S, Pfeiffer R, Rottenberg D, Slevin J, Elmer L, Press D, Hyson HC, McDonald W (April 2012). "A randomized, double-blind, placebo-controlled trial of antidepressants in Parkinson disease". Neurology. 78 (16): 1229–36. doi:10.1212/WNL.0b013e3182516244. PMC 3324323. PMID 22496199.
- ↑ 52.0 52.1 Seppi K, Weintraub D, Coelho M, Perez-Lloret S, Fox SH, Katzenschlager R, Hametner EM, Poewe W, Rascol O, Goetz CG, Sampaio C (October 2011). "The Movement Disorder Society Evidence-Based Medicine Review Update: Treatments for the non-motor symptoms of Parkinson's disease". Mov. Disord. 26 Suppl 3: S42–80. doi:10.1002/mds.23884. PMC 4020145. PMID 22021174.
- ↑ Pahwa R, Stacy MA, Factor SA, Lyons KE, Stocchi F, Hersh BP, Elmer LW, Truong DD, Earl NL (April 2007). "Ropinirole 24-hour prolonged release: randomized, controlled study in advanced Parkinson disease". Neurology. 68 (14): 1108–15. doi:10.1212/01.wnl.0000258660.74391.c1. PMID 17404192.
- ↑ Barone P, Poewe W, Albrecht S, Debieuvre C, Massey D, Rascol O, Tolosa E, Weintraub D (June 2010). "Pramipexole for the treatment of depressive symptoms in patients with Parkinson's disease: a randomised, double-blind, placebo-controlled trial". Lancet Neurol. 9 (6): 573–80. doi:10.1016/S1474-4422(10)70106-X. PMID 20452823.
- ↑ Miyasaki JM, Shannon K, Voon V, Ravina B, Kleiner-Fisman G, Anderson K, Shulman LM, Gronseth G, Weiner WJ (April 2006). "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. 66 (7): 996–1002. doi:10.1212/01.wnl.0000215428.46057.3d. PMID 16606910.
- ↑ Bharucha KJ, Sethi KD (May 1996). "Complex movement disorders induced by fluoxetine". Mov. Disord. 11 (3): 324–6. doi:10.1002/mds.870110318. PMID 8723152.
- ↑ Richard IH, Kurlan R, Tanner C, Factor S, Hubble J, Suchowersky O, Waters C (April 1997). "Serotonin syndrome and the combined use of deprenyl and an antidepressant in Parkinson's disease. Parkinson Study Group". Neurology. 48 (4): 1070–7. PMID 9109902.
- ↑ Ondo WG, Kenney C, Sullivan K, Davidson A, Hunter C, Jahan I, McCombs A, Miller A, Zesiewicz TA (May 2012). "Placebo-controlled trial of lubiprostone for constipation associated with Parkinson disease". Neurology. 78 (21): 1650–4. doi:10.1212/WNL.0b013e3182574f28. PMID 22573627.
- ↑ Zangaglia R, Martignoni E, Glorioso M, Ossola M, Riboldazzi G, Calandrella D, Brunetti G, Pacchetti C (July 2007). "Macrogol for the treatment of constipation in Parkinson's disease. A randomized placebo-controlled study". Mov. Disord. 22 (9): 1239–44. doi:10.1002/mds.21243. PMID 17566120.
- ↑ Barichella M, Pacchetti C, Bolliri C, Cassani E, Iorio L, Pusani C, Pinelli G, Privitera G, Cesari I, Faierman SA, Caccialanza R, Pezzoli G, Cereda E (September 2016). "Probiotics and prebiotic fiber for constipation associated with Parkinson disease: An RCT". Neurology. 87 (12): 1274–80. doi:10.1212/WNL.0000000000003127. PMID 27543643.
- ↑ Pfeiffer RF (January 2011). "Gastrointestinal dysfunction in Parkinson's disease". Parkinsonism Relat. Disord. 17 (1): 10–5. doi:10.1016/j.parkreldis.2010.08.003. PMID 20829091.
- ↑ Cloud LJ, Greene JG (August 2011). "Gastrointestinal features of Parkinson's disease". Curr Neurol Neurosci Rep. 11 (4): 379–84. doi:10.1007/s11910-011-0204-0. PMID 21499704.
- ↑ Chinnapongse R, Gullo K, Nemeth P, Zhang Y, Griggs L (February 2012). "Safety and efficacy of botulinum toxin type B for treatment of sialorrhea in Parkinson's disease: a prospective double-blind trial". Mov. Disord. 27 (2): 219–26. doi:10.1002/mds.23929. PMID 21887710.
- ↑ Raffaele R, Vecchio I, Giammusso B, Morgia G, Brunetto MB, Rampello L (April 2002). "Efficacy and safety of fixed-dose oral sildenafil in the treatment of sexual dysfunction in depressed patients with idiopathic Parkinson's disease". Eur. Urol. 41 (4): 382–6. PMID 12074807.
- ↑ Campbell IW, Ewing DJ, Clarke BF (April 1975). "9-Alpha-fluorohydrocortisone in the treatment of postural hypotension in diabetic autonomic neuropathy". Diabetes. 24 (4): 381–4. PMID 1094320.
- ↑ Davies B, Bannister R, Sever P (January 1978). "Pressor amines and monoamine-oxidase inhibitors for treatment of postural hypotension in autonomic failure. Limitations and hazards". Lancet. 1 (8057): 172–5. PMID 74603.
- ↑ Biaggioni I, Onrot J, Stewart CK, Robertson D (July 1987). "The potent pressor effect of phenylpropanolamine in patients with autonomic impairment". JAMA. 258 (2): 236–9. PMID 3599310.