Dyskinesias and Treatment with Pramipexole in Patients with Parkinson's Disease

Table 1

Dyskinesia with pramipexole treatment: summary of double-blind randomised-controlled trials of pramipexole in Parkinson’s disease.

Disease stage*	Study	Drug regimen (N): mean daily dose, mg (SD/range)	Incidence of dyskinesia (%), change in UPDRS IV or PDS (%)	Concomitant L-DOPA ( % usage and/or mean dose, mg (SD/range))	Other concomitant APDs	Study duration	PPX group characteristics: H-Y stage, age, disease duration (mean (SD))
Early	Hubble et al. [20]	PPX (28), PL (27): 4.5	None	None	MAOBI	9 wks	1–3, 63.5 (12.3), 2.1 (2.5)
	PSG [21]	PPX (213), PL (151): fixed dose at 1.5, 3.0, 4.5, 6.0	None	PPX: 24.4%, PL: 27.5%	MAOBI	10 wks	1–4 (1.9, 0.6), 62.0 (10.9), 2.0 (1.6)
	Shannon et al. [17]	PPX (164): 3.8, PL (171): 0.375–4.5	PPX: 0%, PL: 0.6% (leading to discontinuation)	None	MAOBI	31 wks	1–3, 62.7, 1.8
	PSG [22]^†	PPX (151): 1.5–4.5, L-DOPA (150): 300–600	PPX: 9.9%, L-DOPA: 30.7% (HR 0.33 (95% CI, 0.18–0.60); 𝑃<.001)-↑66.7% (PPX), ↑82.6% after O/L L-DOPA	Part of study intervention	MAOBI, amantadine, AC	23.5 mos	1–3 (82.8%≤2), 61.5 (10.1), 1.5 (1.4)
	Pogarell et al. [19]	PPX (44), PL (39): 0.375–4.5	None	PPX: 11%, PL: 13%	MAOBI and amantadine	11 wks	1–3 (72.7%≤2), 62.0 (10.1), 6.5 (4.0)
	Navan et al. [23]	PPX, PGL, PL (10): 4.5	PPX: 10.0%, PGL: 10.0%, PL: 0.0%	PPX: 60%, 400 (200–600), PGL: 60%, 383 (300–700), PL: 40%, 550 (300–800)	MAOBI, amantadine, and AC	3 mos	1-2 (1), 66 (55–80), 4 (0.5–10)
	Wong et al. [12]	PPX (73), PL (77): 0.375–4.5	PPX: 12.3%, PL: 5.2%	PPX: 68.5%, PL: 70.1%	None	15 wks	2.2 (0.07), 58.8 (1.28), 4.5 (0.4)
	PSG [24]^†	PPX (83): 2.78 (1.1), L-DOPA (100): 427 (112)	PPX: 24.5.5, L-DOPA: 54.0 (HR 0.37 (95% CI 0.25–0.56); 𝑃<.001)	PPX: 434 (498), L-DOPA: 274 (442)	MAOBI, amantadine, AC	4 yrs	1–3 (79.5%≤2), 61.1 (9.6), 1.4 (1.3)
	Navan et al. [25]	PPX (9): 3.09, PGL (8): 3.0, cross-over	PPX: 33.3%, PGL: 37.5%	52.9%; 544 (300–1000)	AC	12 wks–9 wks cross-over	1-2 (1.4), 68.4 (55–84), 3.9 (0.2–12.0)
	Barone et al. [15]	PPX (139): 2.18 (0.83), PL (148): 2.51 (1.66)	PPX: 7%, PL: 3%	PPX: 76%, PL: 74%	Amantadine, MAOBI, ACI, and ODD	12 wks	1–3 (79%≥2), 67.4 (9.0), 4.0 (4.5)
	Hauser et al. [26]	PPX IR (103), PPX ER (106), PL (50): 0.375–4.5	None	PPX IR: 1.0%, PPX ER: 2.9%, PL: 14.0%	None	18 wks	1–3 (72.3% 2-3), 61.8 (8.9), 1.0 (1.3)
	Rascol et al. [27]	PPX IR (52), PPX ER (104): 1.5–4.5	None	PPX IR: 51.9%, PPX ER: 56.7%	MAOBI, COMTI, AC, and amantadine	4 wks IR + 9 wks IR/ER	1–3 (80.8% 1-2), 63.7 (9.1), 3.3 (2.0)
	PSG [28]	PPX 0.5 bd (81), 0.75 bd (73), 0.5 td (80), PL (77)	None	None	MAOBI, AC, and amantadine	12 wks	1–2.5 (89.7% 1-2), 63.3 (10.0), 2.6 (2.6)
Advanced	Guttman et al. [29]	PPX (79): 3.4, BRC (84): 22.6, PL (83)	PPX: 40%, BRC: 45%, PL: 27%; NS changes in UPDRS IV and PDS	100%	AC, amantadine, and MAOBI	9 mos	2–4, 62.9 (10.0), 0.67–36
	Lieberman et al. [10]	PPX (181), PL (179): 0.375–4.5	PPX: 61.3%, PL: 40.8%; UPDRS IV PPX > PL (𝑃<.0001), PDS PPX > PL (P = NS)	100%; PPX: 843.4 (578.9), PL: 819.2 (466.1)	MAOBI and amantadine	31 wks	2–4 (3.0), 63.4, 9.4
	Wermuth et al. [18]	PPX (36): 4.59 (0.95), PL (33): 4.77	PPX: 5.6%, PL: 6.1%; NS change in PDS; NS change in UPDRS IV	PPX: 100%(61.1%>600), PL: 100%(66.7%>600)	MAOBI, ACI, and amantadine	11 wks	2–4 (91.7% 2-3),63.2 (7.9), 10.1 (5.0)
	Pinter et al. [11]	PPX (34), PL (44): 0.2–5.0	PPX: 14.7%, PL: 4.5%; UPDRS IV PPX > PL (P = .0092); PDS PPX < PL (P = NS)	PPX: 26.5%(11.8%>600), PL: 34.1%(18.2%>600)	MAOBI and amantadine	11 wks	2–4 (79.4%≥3), 59.3 (8.3), 7.8 (4.3)
	Mizuno et al. [30]	PPX (102): 3.24 (1.33), BRC (105): 17.8 (5.8), PL (108)	PPX: 15.7%, BRC: 8.6%, PL: 5.6%; UPDRS IV PPX < PL (P = .006), PPX ≈ BRC (P = NS)	PPX: 404.9 (275.2), BRC: 377.9 (237.8), PL: 422.4 (330.3)	ACI, amantadine, ODD, and MAOBI	12 wks	2.7 (0.7), 65.5 (9.5), 4.8 (4.2)
	Möller et al. [13]	PPX (168): 3.7, PL: 0.375–4.5	PPX: 30.0%, PL: 8.7%; UPDRS IV PPX > PL (P = .0114), PDS (P = NS)	PPX: 637.7, PL: 648.8	MAOBI and AC	31 wks	1–4 (85.0% 2-3), 63.4, 7.6
	Poewe et al. [31]	PPX (200): 3.1 (1.2), RTG (201): 13.0 (3.5), PL (100)	PPX: 15%, RTG: 12%, PL: 3%; hrs “on” without troublesome dyskinesia PPX > PL (P = .0429), PPX < RTG (P = NS)	PPX: 813 (459), RTG: 795 (380), PL: 814 (398)	AC, COMTI, amantadine, and MAOBI	23 wks	2–4, 63.2 (9.7), 8.4 (4.7)
	PSG [14]	PPX (109), PL (35): 0.375–4.5	PPX: 21.1%, PL: 11.4%	100%; PPX: 278.9 (211.6), PL: 272.9 (204.1)	NR	10 wks	2–4 (2.5, 0.5), 64.8 (10.6), 6.1 (5.1)
	Brodsky et al. [32]	PPX/PL cross-over (13): 3.0	PPX ↑ PDS scores compared to baseline (P = .05), ↑ peak scores with L-DOPA infusion	100%, 871.2 (448.6); + infusion at 5+10 wks	Unclear on which APDs	10 wks–5 wks cross-over	NR, 61.9 (8.0), 10.3 (4.3)

*Studies were categorised according to the disease stage (early versus advanced, plus Hoehn and Yahr stage, where available).
Abbreviations: 𝑁: number of patients, SD: standard deviation, PSG: Parkinson Study Group, NR: not reported, HR: hazard ratio (risk ratio of developing dyskinesia per unit of time for patients assigned to PPX compared to risk ratio for L-DOPA), CI: confidence interval, ^†the report by PSG [22] is an extension of the PSG [31] protocol, H-Y stage: Hoehn-Yahr stage (a staging system to describe PD progression from 0 to 5 with stages 1.5 and 2.5 in the modified version, incorporated into the UPDRS), PPX: pramipexole, PL: placebo, BRC: bromocriptine, L-DOPA: levodopa (with or without carbidopa), PGL: pergolide, RTG: rotigotine, APDs: anti-Parkinson’s drugs, MAOBI: monoamine oxidase-B inhibitors (e.g., selegiline), AC: anticholinergics (e.g., orphenadrine, benzhexol), ODD: other dopaminergic drugs (e.g., droxidopa), UPDRS IV: Unified Parkinson’s Disease Rating Scale part IV (complications of therapy, higher scores indicate more severe dyskinesia), which also includes subitems on dyskinesia symptoms [33], PDS: Parkinson’s Dyskinesia Scale (higher scores indicate more severe dyskinesia), which rates the severity of dyskinesia according to body regions [34].