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Pramipexole vs levodopa as initial treatment for Parkinson disease: a 4-year randomized controlled trial.
Arch Neurol. 2004 Jul; 61(7):1044-53.AN

Abstract

BACKGROUND

The best way to initiate dopaminergic therapy for early Parkinson disease remains unclear.

OBJECTIVE

To compare initial treatment with pramipexole vs levodopa in early Parkinson disease, followed by levodopa supplementation, with respect to the development of dopaminergic motor complications, other adverse events, and functional and quality-of-life outcomes.

DESIGN

Multicenter, parallel-group, double-blind, randomized controlled trial.

SETTING

Academic movement disorders clinics at 22 sites in the United States and Canada.

PATIENTS

Patients with early Parkinson disease (N = 301) who required dopaminergic therapy to treat emerging disability, enrolled between October 1996 and August 1997 and observed until August 2001.

INTERVENTION

Subjects were randomly assigned to receive 0.5 mg of pramipexole 3 times per day with levodopa placebo (n = 151) or 25/100 mg of carbidopa/levodopa 3 times per day with pramipexole placebo (n = 150). Dosage was escalated during the first 10 weeks for patients with ongoing disability. Thereafter, investigators were permitted to add open-label levodopa or other antiparkinsonian medications to treat ongoing or emerging disability.

MAIN OUTCOME MEASURES

Time to the first occurrence of dopaminergic complications: wearing off, dyskinesias, on-off fluctuations, and freezing; changes in the Unified Parkinson's Disease Rating Scale and quality-of-life scales; and adverse events.

RESULTS

Initial pramipexole treatment resulted in a significant reduction in the risk of developing dyskinesias (24.5% vs 54%; hazard ratio, 0.37; 95% confidence interval [CI], 0.25-0.56; P<.001) and wearing off (47% vs 62.7%; hazard ratio, 0.68; 95% CI, 0.49-0.63; P =.02). Initial levodopa treatment resulted in a significant reduction in the risk of freezing (25.3% vs 37.1%; hazard ratio, 1.7; 95% CI, 1.11-2.59; P =.01). By 48 months, the occurrence of disabling dyskinesias was uncommon and did not significantly differ between the 2 groups. The mean improvement in the total Unified Parkinson's Disease Rating Scale score from baseline to 48 months was greater in the levodopa group than in the pramipexole group (2 +/- 15.4 points vs -3.2 +/- 17.3 points, P =.003). Somnolence (36% vs 21%, P =.005) and edema (42% vs 15%, P<.001) were more common in pramipexole-treated subjects than in levodopa-treated subjects. Mean changes in quality-of-life scores did not differ between the groups.

CONCLUSIONS

Initial treatment with pramipexole resulted in lower incidences of dyskinesias and wearing off compared with initial treatment with levodopa. Initial treatment with levodopa resulted in lower incidences of freezing, somnolence, and edema and provided for better symptomatic control, as measured by the Unified Parkinson's Disease Rating Scale, compared with initial treatment with pramipexole. Both options resulted in similar quality of life. Levodopa and pramipexole both appear to be reasonable options as initial dopaminergic therapy for Parkinson disease, but they are associated with different efficacy and adverse-effect profiles.

Authors+Show Affiliations

Department of Neurology, University of Rochester, 1351 Mt. Hope Avenue, Suite 220, Rochester, NY 14620, USA. robert.holloway@ctcc.rochester.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15262734

Citation

Holloway, Robert G., et al. "Pramipexole Vs Levodopa as Initial Treatment for Parkinson Disease: a 4-year Randomized Controlled Trial." Archives of Neurology, vol. 61, no. 7, 2004, pp. 1044-53.
Holloway RG, Shoulson I, Fahn S, et al. Pramipexole vs levodopa as initial treatment for Parkinson disease: a 4-year randomized controlled trial. Arch Neurol. 2004;61(7):1044-53.
Holloway, R. G., Shoulson, I., Fahn, S., Kieburtz, K., Lang, A., Marek, K., McDermott, M., Seibyl, J., Weiner, W., Musch, B., Kamp, C., Welsh, M., Shinaman, A., Pahwa, R., Barclay, L., Hubble, J., LeWitt, P., Miyasaki, J., Suchowersky, O., ... Watts, A. (2004). Pramipexole vs levodopa as initial treatment for Parkinson disease: a 4-year randomized controlled trial. Archives of Neurology, 61(7), 1044-53.
Holloway RG, et al. Pramipexole Vs Levodopa as Initial Treatment for Parkinson Disease: a 4-year Randomized Controlled Trial. Arch Neurol. 2004;61(7):1044-53. PubMed PMID: 15262734.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pramipexole vs levodopa as initial treatment for Parkinson disease: a 4-year randomized controlled trial. AU - Holloway,Robert G, AU - Shoulson,Ira, AU - Fahn,Stanley, AU - Kieburtz,Karl, AU - Lang,Anthony, AU - Marek,Kenneth, AU - McDermott,Michael, AU - Seibyl,John, AU - Weiner,William, AU - Musch,Bruno, AU - Kamp,Cornelia, AU - Welsh,Mickie, AU - Shinaman,Aileen, AU - Pahwa,Rajesh, AU - Barclay,Lynn, AU - Hubble,Jean, AU - LeWitt,Peter, AU - Miyasaki,Janis, AU - Suchowersky,Oksana, AU - Stacy,Mark, AU - Russell,David S, AU - Ford,Blair, AU - Hammerstad,John, AU - Riley,David, AU - Standaert,David, AU - Wooten,Frederick, AU - Factor,Stewart, AU - Jankovic,Joseph, AU - Atassi,Farah, AU - Kurlan,Roger, AU - Panisset,Michel, AU - Rajput,Ali, AU - Rodnitzky,Robert, AU - Shults,Cliff, AU - Petsinger,Giselle, AU - Waters,Cheryl, AU - Pfeiffer,Ronald, AU - Biglan,Kevin, AU - Borchert,Leona, AU - Montgomery,Amy, AU - Sutherland,Laura, AU - Weeks,Carolyn, AU - DeAngelis,Maryan, AU - Sime,Elspeth, AU - Wood,Susan, AU - Pantella,Carol, AU - Harrigan,Mary, AU - Fussell,Barbara, AU - Dillon,Sandra, AU - Alexander-Brown,Barbara, AU - Rainey,Pamela, AU - Tennis,Marsha, AU - Rost-Ruffner,Elke, AU - Brown,Diane, AU - Evans,Sharon, AU - Berry,Debra, AU - Hall,Jean, AU - Shirley,Theresa, AU - Dobson,Judith, AU - Fontaine,Deborah, AU - Pfeiffer,Brenda, AU - Brocht,Alicia, AU - Bennett,Susan, AU - Daigneault,Susan, AU - Hodgeman,Karen, AU - O'Connell,Carolynn, AU - Ross,Tori, AU - Richard,Karen, AU - Watts,Arthur, AU - ,, PY - 2004/7/21/pubmed PY - 2004/8/11/medline PY - 2004/7/21/entrez SP - 1044 EP - 53 JF - Archives of neurology JO - Arch Neurol VL - 61 IS - 7 N2 - BACKGROUND: The best way to initiate dopaminergic therapy for early Parkinson disease remains unclear. OBJECTIVE: To compare initial treatment with pramipexole vs levodopa in early Parkinson disease, followed by levodopa supplementation, with respect to the development of dopaminergic motor complications, other adverse events, and functional and quality-of-life outcomes. DESIGN: Multicenter, parallel-group, double-blind, randomized controlled trial. SETTING: Academic movement disorders clinics at 22 sites in the United States and Canada. PATIENTS: Patients with early Parkinson disease (N = 301) who required dopaminergic therapy to treat emerging disability, enrolled between October 1996 and August 1997 and observed until August 2001. INTERVENTION: Subjects were randomly assigned to receive 0.5 mg of pramipexole 3 times per day with levodopa placebo (n = 151) or 25/100 mg of carbidopa/levodopa 3 times per day with pramipexole placebo (n = 150). Dosage was escalated during the first 10 weeks for patients with ongoing disability. Thereafter, investigators were permitted to add open-label levodopa or other antiparkinsonian medications to treat ongoing or emerging disability. MAIN OUTCOME MEASURES: Time to the first occurrence of dopaminergic complications: wearing off, dyskinesias, on-off fluctuations, and freezing; changes in the Unified Parkinson's Disease Rating Scale and quality-of-life scales; and adverse events. RESULTS: Initial pramipexole treatment resulted in a significant reduction in the risk of developing dyskinesias (24.5% vs 54%; hazard ratio, 0.37; 95% confidence interval [CI], 0.25-0.56; P<.001) and wearing off (47% vs 62.7%; hazard ratio, 0.68; 95% CI, 0.49-0.63; P =.02). Initial levodopa treatment resulted in a significant reduction in the risk of freezing (25.3% vs 37.1%; hazard ratio, 1.7; 95% CI, 1.11-2.59; P =.01). By 48 months, the occurrence of disabling dyskinesias was uncommon and did not significantly differ between the 2 groups. The mean improvement in the total Unified Parkinson's Disease Rating Scale score from baseline to 48 months was greater in the levodopa group than in the pramipexole group (2 +/- 15.4 points vs -3.2 +/- 17.3 points, P =.003). Somnolence (36% vs 21%, P =.005) and edema (42% vs 15%, P<.001) were more common in pramipexole-treated subjects than in levodopa-treated subjects. Mean changes in quality-of-life scores did not differ between the groups. CONCLUSIONS: Initial treatment with pramipexole resulted in lower incidences of dyskinesias and wearing off compared with initial treatment with levodopa. Initial treatment with levodopa resulted in lower incidences of freezing, somnolence, and edema and provided for better symptomatic control, as measured by the Unified Parkinson's Disease Rating Scale, compared with initial treatment with pramipexole. Both options resulted in similar quality of life. Levodopa and pramipexole both appear to be reasonable options as initial dopaminergic therapy for Parkinson disease, but they are associated with different efficacy and adverse-effect profiles. SN - 0003-9942 UR - https://www.unboundmedicine.com/medline/citation/15262734/Pramipexole_vs_levodopa_as_initial_treatment_for_Parkinson_disease:_a_4_year_randomized_controlled_trial_ L2 - https://jamanetwork.com/journals/jamaneurology/fullarticle/10.1001/archneur.61.7.1044 DB - PRIME DP - Unbound Medicine ER -