Parkinson's disease medical therapy: Difference between revisions

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==Overview==
==Overview==
The mainstay of therapy for motor symptoms of Parkinson disease are:  
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.  
* Levodopa: This drug is the most effective in controlling motor symptoms in [[Parkinson's disease|PD]] patients.<ref name="pmid24756517">{{cite journal |vauthors=Connolly BS, Lang AE |title=Pharmacological treatment of Parkinson disease: a review |journal=JAMA |volume=311 |issue=16 |pages=1670–83 |date=2014 |pmid=24756517 |doi=10.1001/jama.2014.3654 |url=}}</ref><ref name="pmid23279439">{{cite journal |vauthors=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 |title=Summary of the recommendations of the EFNS/MDS-ES review on therapeutic management of Parkinson's disease |journal=Eur. J. Neurol. |volume=20 |issue=1 |pages=5–15 |date=January 2013 |pmid=23279439 |doi=10.1111/j.1468-1331.2012.03866.x |url=}}</ref> 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.<ref name="pmid15706700">{{cite journal |vauthors= |title=Parcopa: a rapidly dissolving formulation of carbidopa/levodopa |journal=Med Lett Drugs Ther |volume=47 |issue=1201 |pages=12 |date=January 2005 |pmid=15706700 |doi= |url=}}</ref><ref name="pmid20925074">{{cite journal |vauthors=Ondo WG, Shinawi L, Moore S |title=Comparison of orally dissolving carbidopa/levodopa (Parcopa) to conventional oral carbidopa/levodopa: A single-dose, double-blind, double-dummy, placebo-controlled, crossover trial |journal=Mov. Disord. |volume=25 |issue=16 |pages=2724–7 |date=December 2010 |pmid=20925074 |doi=10.1002/mds.23158 |url=}}</ref> The [[adverse effects]] of this drug includes elevated serum [[homocysteine]], low levels of [[vitamin B12]], elevated [[methylmalonic acid]] and sensorimotor peripheral neuropathy.<ref name="pmid18785232">{{cite journal |vauthors=Toth C, Brown MS, Furtado S, Suchowersky O, Zochodne D |title=Neuropathy as a potential complication of levodopa use in Parkinson's disease |journal=Mov. Disord. |volume=23 |issue=13 |pages=1850–9 |date=October 2008 |pmid=18785232 |doi=10.1002/mds.22137 |url=}}</ref><ref name="pmid20582991">{{cite journal |vauthors=Toth C, Breithaupt K, Ge S, Duan Y, Terris JM, Thiessen A, Wiebe S, Zochodne DW, Suchowersky O |title=Levodopa, methylmalonic acid, and neuropathy in idiopathic Parkinson disease |journal=Ann. Neurol. |volume=68 |issue=1 |pages=28–36 |date=July 2010 |pmid=20582991 |doi=10.1002/ana.22021 |url=}}</ref><ref name="pmid23836370">{{cite journal |vauthors=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 |title=Neuropathy and levodopa in Parkinson's disease: evidence from a multicenter study |journal=Mov. Disord. |volume=28 |issue=10 |pages=1391–7 |date=September 2013 |pmid=23836370 |doi=10.1002/mds.25585 |url=}}</ref><ref name="pmid25168395">{{cite journal |vauthors=Uncini A, Eleopra R, Onofrj M |title=Polyneuropathy associated with duodenal infusion of levodopa in Parkinson's disease: features, pathogenesis and management |journal=J. Neurol. Neurosurg. Psychiatry |volume=86 |issue=5 |pages=490–5 |date=May 2015 |pmid=25168395 |doi=10.1136/jnnp-2014-308586 |url=}}</ref> It can also cause motor fluctuations, [[dyskinesia]], [[cramps]] and [[dystonia]].<ref name="pmid20880751">{{cite journal |vauthors=Calabresi P, Di Filippo M, Ghiglieri V, Tambasco N, Picconi B |title=Levodopa-induced dyskinesias in patients with Parkinson's disease: filling the bench-to-bedside gap |journal=Lancet Neurol |volume=9 |issue=11 |pages=1106–17 |date=November 2010 |pmid=20880751 |doi=10.1016/S1474-4422(10)70218-0 |url=}}</ref><ref name="pmid25488260">{{cite journal |vauthors=Aquino CC, Fox SH |title=Clinical spectrum of levodopa-induced complications |journal=Mov. Disord. |volume=30 |issue=1 |pages=80–9 |date=January 2015 |pmid=25488260 |doi=10.1002/mds.26125 |url=}}</ref> One of the concerns regarding long term use of [[levodopa]] is that it may be increase the rate of [[dopamine]] [[Neuron|neurons]] degeneration<ref name="pmid15372588">{{cite journal |vauthors=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 |title=Levodopa in the treatment of Parkinson's disease: current controversies |journal=Mov. Disord. |volume=19 |issue=9 |pages=997–1005 |date=September 2004 |pmid=15372588 |doi=10.1002/mds.20243 |url=}}</ref> but other studies demonstrated  that it does not damage [[Neuron|neurons]].<ref name="pmid11553992">{{cite journal |vauthors=Rajput AH |title=The protective role of levodopa in the human substantia nigra |journal=Adv Neurol |volume=86 |issue= |pages=327–36 |date=2001 |pmid=11553992 |doi= |url=}}</ref><ref name="pmid21917769">{{cite journal |vauthors=Parkkinen L, O'Sullivan SS, Kuoppamäki M, Collins C, Kallis C, Holton JL, Williams DR, Revesz T, Lees AJ |title=Does levodopa accelerate the pathologic process in Parkinson disease brain? |journal=Neurology |volume=77 |issue=15 |pages=1420–6 |date=October 2011 |pmid=21917769 |doi=10.1212/WNL.0b013e318232ab4c |url=}}</ref>
 
* Dopamine agonists: [[Dopamine agonist]] such as [[bromocriptine]], [[pramipexole]] and [[ropinirole]] are proved to be effective in managing motor symptoms of [[Parkinson's disease|PD]] patients.<ref name="pmid11402154">{{cite journal |vauthors=Olanow CW, Watts RL, Koller WC |title=An algorithm (decision tree) for the management of Parkinson's disease (2001): treatment guidelines |journal=Neurology |volume=56 |issue=11 Suppl 5 |pages=S1–S88 |date=June 2001 |pmid=11402154 |doi= |url=}}</ref> 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]]<ref name="pmid8959987">{{cite journal |vauthors=Fahn S |title=Is levodopa toxic? |journal=Neurology |volume=47 |issue=6 Suppl 3 |pages=S184–95 |date=December 1996 |pmid=8959987 |doi= |url=}}</ref><ref name="pmid3341935">{{cite journal |vauthors= |title=International symposium on early dopamine agonist therapy of Parkinson's disease |journal=Arch. Neurol. |volume=45 |issue=2 |pages=204–8 |date=February 1988 |pmid=3341935 |doi= |url=}}</ref> but since [[dopamine agonist]]<nowiki/>s have fewer [[Side effects|side effects,]] some experts suggest using these drugs as the first line therapy especially for [[Parkinson's disease|PD]] patients under 60 years old.<ref name="pmid18490620">{{cite journal |vauthors=Marras C, Lang A |title=Invited article: changing concepts in Parkinson disease: moving beyond the decade of the brain |journal=Neurology |volume=70 |issue=21 |pages=1996–2003 |date=May 2008 |pmid=18490620 |doi=10.1212/01.wnl.0000312515.52545.51 |url=}}</ref> The [[adverse effects]] of [[dopamine agonist]] are [[nausea]], [[vomiting]], sleep disorders, [[confusion]], [[peripheral edema]] and [[valvular heart disease]].<ref name="pmid18425954">{{cite journal |vauthors=Stowe RL, Ives NJ, Clarke C, van Hilten J, Ferreira J, Hawker RJ, Shah L, Wheatley K, Gray R |title=Dopamine agonist therapy in early Parkinson's disease |journal=Cochrane Database Syst Rev |volume= |issue=2 |pages=CD006564 |date=April 2008 |pmid=18425954 |doi=10.1002/14651858.CD006564.pub2 |url=}}</ref><ref name="pmid17202450">{{cite journal |vauthors=Roth BL |title=Drugs and valvular heart disease |journal=N. Engl. J. Med. |volume=356 |issue=1 |pages=6–9 |date=January 2007 |pmid=17202450 |doi=10.1056/NEJMp068265 |url=}}</ref>
* Monoamine oxidase (MAO) B inhibitors: [[MAO inhibitors|MAO B inhibitors]] such as [[selegiline]], [[rasagiline]] and safinamide are proved to be helpful in managing motor symptoms of [[Parkinson's disease|PD]] patients.<ref name="pmid8959990">{{cite journal |vauthors=Olanow CW |title=Selegiline: current perspectives on issues related to neuroprotection and mortality |journal=Neurology |volume=47 |issue=6 Suppl 3 |pages=S210–6 |date=December 1996 |pmid=8959990 |doi= |url=}}</ref><ref name="pmid15477585">{{cite journal |vauthors=Horn S, Stern MB |title=The comparative effects of medical therapies for Parkinson's disease |journal=Neurology |volume=63 |issue=7 Suppl 2 |pages=S7–12 |date=October 2004 |pmid=15477585 |doi= |url=}}</ref><ref name="pmid12470183">{{cite journal |vauthors= |title=A controlled trial of rasagiline in early Parkinson disease: the TEMPO Study |journal=Arch. Neurol. |volume=59 |issue=12 |pages=1937–43 |date=December 2002 |pmid=12470183 |doi= |url=}}</ref><ref name="pmid15096406">{{cite journal |vauthors= |title=A controlled, randomized, delayed-start study of rasagiline in early Parkinson disease |journal=Arch. Neurol. |volume=61 |issue=4 |pages=561–6 |date=April 2004 |pmid=15096406 |doi=10.1001/archneur.61.4.561 |url=}}</ref> these drugs can cause [[nausea]] and [[headaches]].<ref name="pmid15477585">{{cite journal |vauthors=Horn S, Stern MB |title=The comparative effects of medical therapies for Parkinson's disease |journal=Neurology |volume=63 |issue=7 Suppl 2 |pages=S7–12 |date=October 2004 |pmid=15477585 |doi= |url=}}</ref> [[Rasagiline]] can also cause impulse control disorders.<ref name="pmid23305965">{{cite journal |vauthors=Vitale C, Santangelo G, Erro R, Errico D, Manganelli F, Improta I, Moccia M, Barone P |title=Impulse control disorders induced by rasagiline as adjunctive therapy for Parkinson's disease: report of 2 cases |journal=Parkinsonism Relat. Disord. |volume=19 |issue=4 |pages=483–4 |date=April 2013 |pmid=23305965 |doi=10.1016/j.parkreldis.2012.11.008 |url=}}</ref>
* Anticholinergic agents: In [[Parkinson's disease|PD]] we have reduced amount of [[dopamine]] and excess amount of [[Cholinergic|cholinergic effects]], so [[anticholinergic]] drugs such as [[trihexyphenidyl]] and [[benztropine]] can reduce the [[Symptom|symptoms]] of [[Parkinson's disease|PD]].<ref name="pmid4382112">{{cite journal |vauthors=Duvoisin RC |title=Cholinergic-anticholinergic antagonism in parkinsonism |journal=Arch. Neurol. |volume=17 |issue=2 |pages=124–36 |date=August 1967 |pmid=4382112 |doi= |url=}}</ref><ref name="pmid12804486">{{cite journal |vauthors=Katzenschlager R, Sampaio C, Costa J, Lees A |title=Anticholinergics for symptomatic management of Parkinson's disease |journal=Cochrane Database Syst Rev |volume= |issue=2 |pages=CD003735 |date=2003 |pmid=12804486 |doi=10.1002/14651858.CD003735 |url=}}</ref><ref name="pmid6143611">{{cite journal |vauthors=Lang AE |title=Treatment of Parkinson's disease with agents other than levodopa and dopamine agonists: controversies and new approaches |journal=Can J Neurol Sci |volume=11 |issue=1 Suppl |pages=210–20 |date=February 1984 |pmid=6143611 |doi= |url=}}</ref>
* Amantadine: [[Amantadine]], an [[Antiviral drugs|antiviral drug]] can improve [[Parkinson's disease|PD]] [[Symptom|symptoms]] by increasing [[dopamine]] release, inhibition of [[dopamine]] reuptake, stimulation of [[Dopamine receptor|dopamine receptors]] and [[anticholinergic]] effect.<ref name="pmid4677928">{{cite journal |vauthors=Schwab RS, Poskanzer DC, England AC, Young RR |title=Amantadine in Parkinson's disease. Review of more than two years' experience |journal=JAMA |volume=222 |issue=7 |pages=792–5 |date=November 1972 |pmid=4677928 |doi= |url=}}</ref><ref name="pmid12211136">{{cite journal |vauthors= |title=Amantadine and other antiglutamate agents: management of Parkinson's disease |journal=Mov. Disord. |volume=17 Suppl 4 |issue= |pages=S13–22 |date=2002 |pmid=12211136 |doi=10.1002/mds.5557 |url=}}</ref> Some studies showed that in controlling bardykinesia, this drug can be more effective than [[anticholinergic]] drugs.<ref name="pmid4838913">{{cite journal |vauthors=Parkes JD, Baxter RC, Marsden CD, Rees JE |title=Comparative trial of benzhexol, amantadine, and levodopa in the treatment of Parkinson's disease |journal=J. Neurol. Neurosurg. Psychiatry |volume=37 |issue=4 |pages=422–6 |date=April 1974 |pmid=4838913 |pmc=494673 |doi= |url=}}</ref>
* Catechol-O-methyl transferase (COMT) inhibitors: The [[Catechol-O-methyl transferase|catechol-o-methyl transferase]] ([[Catechol-O-methyl transferase|COMT]]) inhibitors such as [[entacapone]] and [[tolcapone]] can potentiate the effect of [[levodopa]] in reducing [[Parkinson's disease|PD]] motor symptoms.<ref name="pmid9643737">{{cite journal |vauthors=Nutt JG |title=Catechol-O-methyltransferase inhibitors for treatment of Parkinson's disease |journal=Lancet |volume=351 |issue=9111 |pages=1221–2 |date=April 1998 |pmid=9643737 |doi=10.1016/S0140-6736(05)79311-9 |url=}}</ref><ref name="pmid12876237">{{cite journal |vauthors=Brooks DJ, Sagar H |title=Entacapone is beneficial in both fluctuating and non-fluctuating patients with Parkinson's disease: a randomised, placebo controlled, double blind, six month study |journal=J. Neurol. Neurosurg. Psychiatry |volume=74 |issue=8 |pages=1071–9 |date=August 2003 |pmid=12876237 |pmc=1738605 |doi= |url=}}</ref>
* Estrogen: In [[postmenopausal]] women who are experiencing motor fluctuation on antiparkinsonism drugs we can use low dose [[estrogen]] to improve their condition.<ref name="pmid10881255">{{cite journal |vauthors=Tsang KL, Ho SL, Lo SK |title=Estrogen improves motor disability in parkinsonian postmenopausal women with motor fluctuations |journal=Neurology |volume=54 |issue=12 |pages=2292–8 |date=June 2000 |pmid=10881255 |doi= |url=}}</ref><ref name="pmid10227628">{{cite journal |vauthors=Saunders-Pullman R, Gordon-Elliott J, Parides M, Fahn S, Saunders HR, Bressman S |title=The effect of estrogen replacement on early Parkinson's disease |journal=Neurology |volume=52 |issue=7 |pages=1417–21 |date=April 1999 |pmid=10227628 |doi= |url=}}</ref>
* Other agents: Other drugs such as [[Exenatide]]<ref name="pmid18492290">{{cite journal |vauthors=Harkavyi A, Abuirmeileh A, Lever R, Kingsbury AE, Biggs CS, Whitton PS |title=Glucagon-like peptide 1 receptor stimulation reverses key deficits in distinct rodent models of Parkinson's disease |journal=J Neuroinflammation |volume=5 |issue= |pages=19 |date=May 2008 |pmid=18492290 |pmc=2426681 |doi=10.1186/1742-2094-5-19 |url=}}</ref>, [[uric acid]]<ref name="pmid19822770">{{cite journal |vauthors=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 |title=Urate as a predictor of the rate of clinical decline in Parkinson disease |journal=Arch. Neurol. |volume=66 |issue=12 |pages=1460–8 |date=December 2009 |pmid=19822770 |pmc=2795011 |doi=10.1001/archneurol.2009.247 |url=}}</ref>, [[isradipine]]<ref name="pmid21515375">{{cite journal |vauthors=Ilijic E, Guzman JN, Surmeier DJ |title=The L-type channel antagonist isradipine is neuroprotective in a mouse model of Parkinson's disease |journal=Neurobiol. Dis. |volume=43 |issue=2 |pages=364–71 |date=August 2011 |pmid=21515375 |pmc=3235730 |doi=10.1016/j.nbd.2011.04.007 |url=}}</ref>, [[nilotinib]]<ref name="pmid27434298">{{cite journal |vauthors=Wyse RK, Brundin P, Sherer TB |title=Nilotinib - Differentiating the Hope from the Hype |journal=J Parkinsons Dis |volume=6 |issue=3 |pages=519–22 |date=July 2016 |pmid=27434298 |pmc=5044778 |doi=10.3233/JPD-160904 |url=}}</ref> and [[GDNF]] infusion<ref name="pmid12669033">{{cite journal |vauthors=Gill SS, Patel NK, Hotton GR, O'Sullivan K, McCarter R, Bunnage M, Brooks DJ, Svendsen CN, Heywood P |title=Direct brain infusion of glial cell line-derived neurotrophic factor in Parkinson disease |journal=Nat. Med. |volume=9 |issue=5 |pages=589–95 |date=May 2003 |pmid=12669033 |doi=10.1038/nm850 |url=}}</ref> can be effective in controlling [[Parkinson's disease|PD]] patients [[Symptom|symptoms]].
Treatment choices for some of the nonmotor symptoms of PD are:
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 [[Parkinson's disease|PD]].<ref name="pmid21179595">{{cite journal |vauthors=Shotbolt P, Samuel M, David A |title=Quetiapine in the treatment of psychosis in Parkinson's disease |journal=Ther Adv Neurol Disord |volume=3 |issue=6 |pages=339–50 |date=November 2010 |pmid=21179595 |pmc=3002640 |doi=10.1177/1756285610389656 |url=}}</ref><ref name="pmid24183563">{{cite journal |vauthors=Cummings J, Isaacson S, Mills R, Williams H, Chi-Burris K, Corbett A, Dhall R, Ballard C |title=Pimavanserin for patients with Parkinson's disease psychosis: a randomised, placebo-controlled phase 3 trial |journal=Lancet |volume=383 |issue=9916 |pages=533–40 |date=February 2014 |pmid=24183563 |doi=10.1016/S0140-6736(13)62106-6 |url=}}</ref> one of the [[side effects]] of [[clozapine]] is [[leukopenia]] and [[agranulocytosis]].<ref name="pmid16595571">{{cite journal |vauthors=Schulte P |title=Risk of clozapine-associated agranulocytosis and mandatory white blood cell monitoring |journal=Ann Pharmacother |volume=40 |issue=4 |pages=683–8 |date=April 2006 |pmid=16595571 |doi=10.1345/aph.1G396 |url=}}</ref>
 
* Dementia: [[Cholinesterase inhibitors]] such as [[rivastigmine]] and [[donepezil]] are the main treatment of [[dementia]] in [[Parkinson's disease|PD]].<ref name="pmid22419314">{{cite journal |vauthors=Rolinski M, Fox C, Maidment I, McShane R |title=Cholinesterase inhibitors for dementia with Lewy bodies, Parkinson's disease dementia and cognitive impairment in Parkinson's disease |journal=Cochrane Database Syst Rev |volume= |issue=3 |pages=CD006504 |date=March 2012 |pmid=22419314 |doi=10.1002/14651858.CD006504.pub2 |url=}}</ref><ref name="pmid15590953">{{cite journal |vauthors=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 |title=Rivastigmine for dementia associated with Parkinson's disease |journal=N. Engl. J. Med. |volume=351 |issue=24 |pages=2509–18 |date=December 2004 |pmid=15590953 |doi=10.1056/NEJMoa041470 |url=}}</ref><ref name="pmid22915447">{{cite journal |vauthors=Dubois B, Tolosa E, Katzenschlager R, Emre M, Lees AJ, Schumann G, Pourcher E, Gray J, Thomas G, Swartz J, Hsu T, Moline ML |title=Donepezil in Parkinson's disease dementia: a randomized, double-blind efficacy and safety study |journal=Mov. Disord. |volume=27 |issue=10 |pages=1230–8 |date=September 2012 |pmid=22915447 |doi=10.1002/mds.25098 |url=}}</ref>
psychosi<nowiki/>s: [[quetiapine|quet]][[quetiapine|iapine]], [[clozapine|clozap]]<nowiki/>[[clozapine|ine]] and [[pimavanserin]].
* Fatigue: [[Amantadine]], [[methylphenidate]] and [[pemoline]] can improve [[fatigue]] in [[Parkinson's disease|PD]] patients.<ref name="pmid26447539">{{cite journal |vauthors=Elbers RG, Verhoef J, van Wegen EE, Berendse HW, Kwakkel G |title=Interventions for fatigue in Parkinson's disease |journal=Cochrane Database Syst Rev |volume= |issue=10 |pages=CD010925 |date=October 2015 |pmid=26447539 |doi=10.1002/14651858.CD010925.pub2 |url=}}</ref><ref name="pmid17674415">{{cite journal |vauthors=Mendonça DA, Menezes K, Jog MS |title=Methylphenidate improves fatigue scores in Parkinson disease: a randomized controlled trial |journal=Mov. Disord. |volume=22 |issue=14 |pages=2070–6 |date=October 2007 |pmid=17674415 |doi=10.1002/mds.21656 |url=}}</ref><ref name="pmid20231670">{{cite journal |vauthors=Zesiewicz TA, Sullivan KL, Arnulf I, Chaudhuri KR, Morgan JC, Gronseth GS, Miyasaki J, Iverson DJ, Weiner WJ |title=Practice Parameter: treatment of nonmotor symptoms of Parkinson disease: report of the Quality Standards Subcommittee of the American Academy of Neurology |journal=Neurology |volume=74 |issue=11 |pages=924–31 |date=March 2010 |pmid=20231670 |doi=10.1212/WNL.0b013e3181d55f24 |url=}}</ref>
 
* Depression: [[Amitriptyline]]<ref name="pmid12497304">{{cite journal |vauthors=Serrano-Dueñas M |title=[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] |language=Spanish; Castilian |journal=Rev Neurol |volume=35 |issue=11 |pages=1010–4 |date=2002 |pmid=12497304 |doi= |url=}}</ref>, [[desipramine]], [[citalopram]]<ref name="pmid18311826">{{cite journal |vauthors=Devos D, Dujardin K, Poirot I, Moreau C, Cottencin O, Thomas P, Destée A, Bordet R, Defebvre L |title=Comparison of desipramine and citalopram treatments for depression in Parkinson's disease: a double-blind, randomized, placebo-controlled study |journal=Mov. Disord. |volume=23 |issue=6 |pages=850–7 |date=April 2008 |pmid=18311826 |doi=10.1002/mds.21966 |url=}}</ref>,[[paroxetine]], [[venlafaxine]]<ref name="pmid22496199">{{cite journal |vauthors=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 |title=A randomized, double-blind, placebo-controlled trial of antidepressants in Parkinson disease |journal=Neurology |volume=78 |issue=16 |pages=1229–36 |date=April 2012 |pmid=22496199 |pmc=3324323 |doi=10.1212/WNL.0b013e3182516244 |url=}}</ref>, [[ropinirole]] and [[pramipexole]]<ref name="pmid22021174">{{cite journal |vauthors=Seppi K, Weintraub D, Coelho M, Perez-Lloret S, Fox SH, Katzenschlager R, Hametner EM, Poewe W, Rascol O, Goetz CG, Sampaio C |title=The Movement Disorder Society Evidence-Based Medicine Review Update: Treatments for the non-motor symptoms of Parkinson's disease |journal=Mov. Disord. |volume=26 Suppl 3 |issue= |pages=S42–80 |date=October 2011 |pmid=22021174 |pmc=4020145 |doi=10.1002/mds.23884 |url=}}</ref><ref name="pmid17404192">{{cite journal |vauthors=Pahwa R, Stacy MA, Factor SA, Lyons KE, Stocchi F, Hersh BP, Elmer LW, Truong DD, Earl NL |title=Ropinirole 24-hour prolonged release: randomized, controlled study in advanced Parkinson disease |journal=Neurology |volume=68 |issue=14 |pages=1108–15 |date=April 2007 |pmid=17404192 |doi=10.1212/01.wnl.0000258660.74391.c1 |url=}}</ref><ref name="pmid20452823">{{cite journal |vauthors=Barone P, Poewe W, Albrecht S, Debieuvre C, Massey D, Rascol O, Tolosa E, Weintraub D |title=Pramipexole for the treatment of depressive symptoms in patients with Parkinson's disease: a randomised, double-blind, placebo-controlled trial |journal=Lancet Neurol |volume=9 |issue=6 |pages=573–80 |date=June 2010 |pmid=20452823 |doi=10.1016/S1474-4422(10)70106-X |url=}}</ref> are useful in managing [[depression]] in [[Parkinson's disease|PD]] patients. If we intent to use tricyclics we should be aware that their [[anticholinergic]] effect can increase [[orthostatic hypotension]] and [[cognitive impairment]]<ref name="pmid16606910">{{cite journal |vauthors=Miyasaki JM, Shannon K, Voon V, Ravina B, Kleiner-Fisman G, Anderson K, Shulman LM, Gronseth G, Weiner WJ |title=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 |journal=Neurology |volume=66 |issue=7 |pages=996–1002 |date=April 2006 |pmid=16606910 |doi=10.1212/01.wnl.0000215428.46057.3d |url=}}</ref> and for [[SSRI]] we should know that they can cause [[dystonia]], [[tremor]] and [[parkinsonism]].<ref name="pmid8723152">{{cite journal |vauthors=Bharucha KJ, Sethi KD |title=Complex movement disorders induced by fluoxetine |journal=Mov. Disord. |volume=11 |issue=3 |pages=324–6 |date=May 1996 |pmid=8723152 |doi=10.1002/mds.870110318 |url=}}</ref> the combination of [[MAO inhibitors|MAO B inhibitors]] with [[SSRIs]] or tricyclics can cause [[serotonin syndrome]]<nowiki/>s<ref name="pmid9109902">{{cite journal |vauthors=Richard IH, Kurlan R, Tanner C, Factor S, Hubble J, Suchowersky O, Waters C |title=Serotonin syndrome and the combined use of deprenyl and an antidepressant in Parkinson's disease. Parkinson Study Group |journal=Neurology |volume=48 |issue=4 |pages=1070–7 |date=April 1997 |pmid=9109902 |doi= |url=}}</ref>
Dementia: [[Cholinesterase inhibitors|C]]<nowiki/>[[Cholinesterase inhibitors|holinesterase inhibitors]] such as [[rivastigmine]] and [[donepezil]].
* Constipation: Increasing [[Probiotic|probiotics]] and fibers, [[lubiprostone]] and [[polyethylene glycol]] are effective in treatment of [[constipation]].<ref name="pmid22573627">{{cite journal |vauthors=Ondo WG, Kenney C, Sullivan K, Davidson A, Hunter C, Jahan I, McCombs A, Miller A, Zesiewicz TA |title=Placebo-controlled trial of lubiprostone for constipation associated with Parkinson disease |journal=Neurology |volume=78 |issue=21 |pages=1650–4 |date=May 2012 |pmid=22573627 |doi=10.1212/WNL.0b013e3182574f28 |url=}}</ref><ref name="pmid17566120">{{cite journal |vauthors=Zangaglia R, Martignoni E, Glorioso M, Ossola M, Riboldazzi G, Calandrella D, Brunetti G, Pacchetti C |title=Macrogol for the treatment of constipation in Parkinson's disease. A randomized placebo-controlled study |journal=Mov. Disord. |volume=22 |issue=9 |pages=1239–44 |date=July 2007 |pmid=17566120 |doi=10.1002/mds.21243 |url=}}</ref><ref name="pmid27543643">{{cite journal |vauthors=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 |title=Probiotics and prebiotic fiber for constipation associated with Parkinson disease: An RCT |journal=Neurology |volume=87 |issue=12 |pages=1274–80 |date=September 2016 |pmid=27543643 |doi=10.1212/WNL.0000000000003127 |url=}}</ref>
 
* Sialorrhea: If the [[sialorrhea]] is mild we can treat it with chewing gum and hard candy<ref name="pmid20829091">{{cite journal |vauthors=Pfeiffer RF |title=Gastrointestinal dysfunction in Parkinson's disease |journal=Parkinsonism Relat. Disord. |volume=17 |issue=1 |pages=10–5 |date=January 2011 |pmid=20829091 |doi=10.1016/j.parkreldis.2010.08.003 |url=}}</ref><ref name="pmid21499704">{{cite journal |vauthors=Cloud LJ, Greene JG |title=Gastrointestinal features of Parkinson's disease |journal=Curr Neurol Neurosci Rep |volume=11 |issue=4 |pages=379–84 |date=August 2011 |pmid=21499704 |doi=10.1007/s11910-011-0204-0 |url=}}</ref> but in severe cases, [[botulinum toxin]] injection into [[Salivary gland|salivary glands]] is helpful.<ref name="pmid22021174">{{cite journal |vauthors=Seppi K, Weintraub D, Coelho M, Perez-Lloret S, Fox SH, Katzenschlager R, Hametner EM, Poewe W, Rascol O, Goetz CG, Sampaio C |title=The Movement Disorder Society Evidence-Based Medicine Review Update: Treatments for the non-motor symptoms of Parkinson's disease |journal=Mov. Disord. |volume=26 Suppl 3 |issue= |pages=S42–80 |date=October 2011 |pmid=22021174 |pmc=4020145 |doi=10.1002/mds.23884 |url=}}</ref><ref name="pmid21887710">{{cite journal |vauthors=Chinnapongse R, Gullo K, Nemeth P, Zhang Y, Griggs L |title=Safety and efficacy of botulinum toxin type B for treatment of sialorrhea in Parkinson's disease: a prospective double-blind trial |journal=Mov. Disord. |volume=27 |issue=2 |pages=219–26 |date=February 2012 |pmid=21887710 |doi=10.1002/mds.23929 |url=}}</ref>
Fatigue: [[Amantadine]], [[methylphenidate]] and [[pemoline]].
* Sexual dysfunction: Male [[sexual dysfunction]] can be treated with [[sildenafil]].<ref name="pmid12074807">{{cite journal |vauthors=Raffaele R, Vecchio I, Giammusso B, Morgia G, Brunetto MB, Rampello L |title=Efficacy and safety of fixed-dose oral sildenafil in the treatment of sexual dysfunction in depressed patients with idiopathic Parkinson's disease |journal=Eur. Urol. |volume=41 |issue=4 |pages=382–6 |date=April 2002 |pmid=12074807 |doi= |url=}}</ref>
 
* Ortostatic hypotention: [[Fludrocortisone]]<ref name="pmid1094320">{{cite journal |vauthors=Campbell IW, Ewing DJ, Clarke BF |title=9-Alpha-fluorohydrocortisone in the treatment of postural hypotension in diabetic autonomic neuropathy |journal=Diabetes |volume=24 |issue=4 |pages=381–4 |date=April 1975 |pmid=1094320 |doi= |url=}}</ref>, [[Sympathomimetic agents]] such as [[ephedrine]], [[pseudoephedrine]], [[methylphenidate]] and [[dextroamphetamine]] are used to treat [[orthostatic hypotension]].<ref name="pmid74603">{{cite journal |vauthors=Davies B, Bannister R, Sever P |title=Pressor amines and monoamine-oxidase inhibitors for treatment of postural hypotension in autonomic failure. Limitations and hazards |journal=Lancet |volume=1 |issue=8057 |pages=172–5 |date=January 1978 |pmid=74603 |doi= |url=}}</ref><ref name="pmid3599310">{{cite journal |vauthors=Biaggioni I, Onrot J, Stewart CK, Robertson D |title=The potent pressor effect of phenylpropanolamine in patients with autonomic impairment |journal=JAMA |volume=258 |issue=2 |pages=236–9 |date=July 1987 |pmid=3599310 |doi= |url=}}</ref>
<nowiki/>Depression: [[Amitriptyline]], [[desipramine]], [[citalopram]] ,[[paroxetine]], [[venlafaxine]], [[ropinirole]] and [[pramipexole]].
 
Constipati<nowiki/>on: Increasing [[Probiotic|probiotics]] and fibers, [[lubiprostone]] and [[polyethylene glycol]].
 
Sialorrhea: chewing gum and hard candy but in severe cases, [[botulinum toxin]] injection into [[Salivary gland|salivary glands]] .  
 
Sexual dysfunction: [[sildenafil]] (for male)
 
Ortostatic hypotention: [[Fludrocortisone]], [[Sympathomimetic agents]] such as [[ephedrine]], [[pseudoephedrine]], [[methylphenidate|methylp]]<nowiki/>[[methylphenidate|henidate]] and<nowiki/> [[dextroamphetamine]].


==Medical Therapy==
==Medical Therapy==

Latest revision as of 19:15, 28 November 2018

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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:

Treatment choices for some of the nonmotor symptoms of PD are:

References

  1. ↑ 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.
  2. ↑ 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.
  3. ↑ "Parcopa: a rapidly dissolving formulation of carbidopa/levodopa". Med Lett Drugs Ther. 47 (1201): 12. January 2005. PMID 15706700.
  4. ↑ 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.
  5. ↑ 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.
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ 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.
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  11. ↑ 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.
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  13. ↑ 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.
  14. ↑ 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.
  15. ↑ Fahn S (December 1996). "Is levodopa toxic?". Neurology. 47 (6 Suppl 3): S184–95. PMID 8959987.
  16. ↑ "International symposium on early dopamine agonist therapy of Parkinson's disease". Arch. Neurol. 45 (2): 204–8. February 1988. PMID 3341935.
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  18. ↑ 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.
  19. ↑ Roth BL (January 2007). "Drugs and valvular heart disease". N. Engl. J. Med. 356 (1): 6–9. doi:10.1056/NEJMp068265. PMID 17202450.
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  21. ↑ 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.
  22. ↑ "A controlled trial of rasagiline in early Parkinson disease: the TEMPO Study". Arch. Neurol. 59 (12): 1937–43. December 2002. PMID 12470183.
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  24. ↑ 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.
  25. ↑ Duvoisin RC (August 1967). "Cholinergic-anticholinergic antagonism in parkinsonism". Arch. Neurol. 17 (2): 124–36. PMID 4382112.
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  27. ↑ 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.
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  31. ↑ 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.
  32. ↑ 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.
  33. ↑ 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.
  34. ↑ 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.
  35. ↑ 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.
  36. ↑ 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.
  37. ↑ 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.
  38. ↑ 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.
  39. ↑ 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.
  40. ↑ 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.
  41. ↑ 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.
  42. ↑ 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.
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  44. ↑ 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.
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