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Cabergoline versus bromocriptine for levodopa-induced complications in Parkinson's disease

  • Review
  • Intervention

Authors

  • Carl E Clarke,

    Corresponding author
    1. College of Medical and Dental Sciences, School of Clinical and Experimental Medicine, Birmingham, West Midlands, UK
    • Carl E Clarke, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, West Midlands, B18 7QH, UK. c.e.clarke@bham.ac.uk.

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  • Katherine HO Deane

    1. University of East Anglia, Edith Cavell Building, Norwich, UK
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Abstract

Background

Long term levodopa therapy in Parkinson's disease is associated with the development of motor complications including abnormal involuntary movements and a shortening response to each dose (wearing off phenomenon). It is thought that dopamine agonists can reduce the duration of immobile off periods and the need for levodopa therapy whilst maintaining or improving motor impairments and only minimally increasing dopaminergic adverse events.

Objectives

To compare the efficacy and safety of adjuvant cabergoline therapy versus bromocriptine in patients with Parkinson's disease, already established on levodopa and suffering from motor complications.

Search methods

Electronic searches of MEDLINE, EMBASE and the Cochrane Controlled Trials Register. Handsearching of the neurology literature as part of the Cochrane Movement Disorders Group's strategy. Examination of the reference lists of identified studies and other reviews. Contact with Pharmacia Upjohn Limited.

Selection criteria

Randomised controlled trials of cabergoline versus bromocriptine in patients with a clinical diagnosis of idiopathic Parkinson's disease and long-term complications of levodopa therapy.

Data collection and analysis

Data were abstracted independently by the authors and differences settled by discussion. The outcome measures used included Parkinson's disease rating scales, levodopa dosage, off time measurements and the frequency of withdrawals and adverse events.

Main results

Cabergoline has been compared with bromocriptine in five randomised, double-blind, parallel group studies including 1071 patients. Only one of the phase II studies was medium term (36 weeks), the others all being short term (12 -15 weeks). The non-significant difference in off time reduction produced by cabergoline compared with bromocriptine was 0.29 hours/day in favour of the former (weighted mean difference; 95% CI -0.10, 0.68; p = 0.15). Dyskinesia reported as an adverse event was significantly increased with cabergoline compared with bromocriptine (Peto odds ratio 1.57; 95% CI 1.05, 2.35; p = 0.03). Motor impairment and disability were measured in four of the studies using the UPDRS rating scale but the small differences in UPDRS ADL (part II) and motor (part III) scores were not statistically significant in any study. Similarly, no significant difference in Schwab and England score was seen. The number of patients rated as much or very much improved on a clinician's global impression scale was similar with both agonists. Levodopa dose reduction was no different between cabergoline and bromocriptine. There was more confusion with cabergoline (Peto odds ratio 2.02; 95% CI 1.09, 3.76; p = 0.03). Otherwise, dopaminergic adverse events were comparable with these agonists and no significant difference in all cause withdrawal rate was found.

Authors' conclusions

Cabergoline produces similar benefits to bromocriptine in off time reduction, motor impairment and disability ratings, and levodopa dose reduction over the first three months of therapy. Dyskinesia and confusion were increased with cabergoline but otherwise the frequency of adverse events and withdrawals from treatment were similar with the two agonists.

Plain language summary

Cabergoline versus bromocriptine for levodopa-induced complications in Parkinson's disease

In the later stages of Parkinson's disease, side effects occur because of the use of levodopa treatment. These consist of involuntary writhing movements (dyskinesia), painful cramps in the legs (dystonia) and a shortened response to each dose referred to as 'end-of-dose deterioration' or the 'wearing-off effect'. Dopamine agonist drugs act by mimicking levodopa in the brain, but they do not cause these long-term treatment complications when used as initial therapy. For this reason, dopamine agonists have for some years been added once these problems develop in the hope of improving them. Cabergoline is a new dopamine agonist recently licensed in the UK for the treatment of later Parkinson's disease. In this review, we will examine the trials performed with this drug to see how effective it is compared with the older drug bromocriptine and what side effects it causes.

Cabergoline has been compared with the older agonist bromocriptine in five studies including 1071 patients. Only one of the smaller studies was medium term (36 weeks), the others all being short term (12 -15 weeks). The time patients spent in the immobile off state was reduced with both agonists but slightly more by cabergoline compared with bromocriptine. This small advantage of cabergoline did not reach statistical significance. Dyskinesia reported as a side effect was significantly increased with cabergoline compared with bromocriptine. Physical impairment and disability were measured in four of the studies but no statistically significant advantage for cabergoline was found. The number of patients rated as much or very much improved on a clinician's global impression scale was similar with both agonists. Levodopa dose reduction was no different between cabergoline and bromocriptine. There was significantly more confusion with cabergoline. Otherwise, dopaminergic side effects were comparable with these agonists and no significant difference in the withdrawal rate from the trials was found.

Cabergoline produces similar benefits to bromocriptine in off time reduction, physical impairment and disability ratings, and levodopa dose reduction over the first three months of therapy. The frequency of side effects and withdrawals from treatment were similar with the two agonists apart from increased dyskinesia and confusion with cabergoline.

Laički sažetak

Kabergolin u odnosu na bromokriptin za komplikacije izazvane levodopom kod Parkinsonove bolesti

U kasnijim fazama Parkinsonove bolesti javljaju se nuspojave zbog uporabe levodope u liječenju. Radi se o od nehotičnim pokretima istezanja (diskinezija), bolnim grčevima u nogama (distonija) i skraćenom odgovoru na svaku dozu (engl. end-of-dose deterioration) ili skraćivanje djelovanja doze (engl. wearing-off efect). Agonisti dopamina oponašaju levodopu u mozgu, ali oni ne uzrokuju ove dugoročne komplikacije liječenja kad se koriste u inicijalnoj terapiji. Iz tog razloga, agonisti dopamina se dodaju zadnjih godina kada se razviju spomenuti problemi u očekivanju da će dovesti do njihovog poboljšanja. Kabergolin je agonist dopamina licenciran za liječenje kasne Parkinsonove bolesti. U ovom Cochrane sustavnom pregledu analizirana su istraživanja provedena nad tim lijekom kako bi vidjeli koliko je učinkovit u usporedbi sa starijim lijekom bromokriptinom te koje nuspojave uzrokuje.

Kabergolin je uspoređivan sa starijim agonistom bromokriptinom u pet istraživanja koja su uključila 1071 pacijenta. Samo jedan od manjih istraživanja je bio srednjoročnog trajanja (36 tjedana), svi ostali bili su kratkoročni (12 -15 tjedna). Vrijeme koje su bolesnici proveli u nepokretnom "off" stanju smanjeno je s oba agonista, ali nešto više kod kabergolina u usporedbi s bromokriptinom. Ta mala prednost kabergolina nije dosegla statističku značajnost. Diskinezija prijavljena kao nuspojava je bila značajno povećana kod kabergolina u usporedbi s bromokriptinom. Tjelesna oštećenja i invalidnost mjerena su u četiri istraživanja, ali nije pronađena statistički značajna prednost za kabergolin. Broj bolesnika čija je razina kliničkog globalnog dojma ocijenjen kao mnogo ili vrlo mnogo poboljšana je slična kod oba agonista. Smanjenje doze levodope se ne razlikuje između kabergolina i bromokriptina. Znatno veće dvobje tiču se kabergolina. Inače, dopaminske nuspojave su bile usporedive s ovim agonistima i nije pronađena značajna razlika u učestalosti odustajanja od sudjelovanja u ispitivanju.

Kabergolin proizvodi slične pogodnosti kao bromokriptin u smanjenju "off" vremena, ocjene tjelesnog oštećenja i invalidnosti i smanjenju doze levodope tijekom prva tri mjeseca liječenja. Učestalost nuspojava i povlačenja iz liječenja bila su slična kod ova dva agonista osim povećane diskinezije i zbrke kod kabergolina.

Bilješke prijevoda

Hrvatski Cochrane
Prevela. Diana Rubić
Ovaj sažetak preveden je u okviru volonterskog projekta prevođenja Cochrane sažetaka. Uključite se u projekt i pomozite nam u prevođenju brojnih preostalih Cochrane sažetaka koji su još uvijek dostupni samo na engleskom jeziku. Kontakt: cochrane_croatia@mefst.hr

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