| BackgroundParkinson's disease(PD)is a chronic progressive neurological degeneration disease,which is common in the elderly.However,it trends to the young in recent years.According to statistics,China has more than 2.5 million patients with PD.PD clinical manifestations are,on one hand,bradykinesia,tremor,myotonia and other rmotor symptoms,on the other hand,hyposmia,constipation,sleep disorders and other non-motor symptoms.Restless leg syndrome(RLS)is a common movement disorder in the elderly.Epidemiological data show that the prevalence of RLS is 1%-10%,and male to female ratio is about 1:2.The prevalence rate increases year by year with age.The typical clinical features are the lower limb extreme discomfort and the desire to move the limbs.Although the clinical manifestations of these two diseases are significantly different,it is now generally believed that both of them are associated with dopaminergic neuronal damage in the central nervous system.L-dopa and dopamine agonist have a clear effect on these two diseases.The treatment of these two diseases are mainly levodopa(L-dopa)and dopamine agonists(DAs).The earliest receptor agonist is bromocriptine,which is rarely used due to the severe adverse reactions.Nowadays,the non-ergot DAs have become the first choice.For example,pramipexole is a novel selective D3 receptor agonist.However,ropinirole and cabergoline are D2 receptor agonists.These long half-life drugs can maintain a more stable plasma concentration to avoid from pulse-like stimulation to the dopamine receptors on the striatum postsynaptic membranes,postponing the disease progression.Rotigotine was discovered in the early 80s of last century.It was not put into the market until 2007 as the first transdermal dosage form of dopamine receptor agonist.However,it was recalled by the company due to manufacturing problems which results in the crystallization during the application.Soon,rotigotine came back again in the United States in 2012.Rotigotine mainly binds to the Di,D2 and D3 receptors.Once a day administration,mild stimulations,24 hours'efficacy,easy management,no first pass effect and stable blood concentration make rotigotine play a big role in the clinical practice.Nevertheless,its adverse effects,like nausea,vomiting,erythema,rash,pruritus and other symptoms,greatly affects the patients'compliance.ObjectiveTo comprehensively evaluate the adverse events(AEs)significantly associated with Rotigotine transdermal patch(R-TDP)treatment in a large selection of randomized control trials.MethodWe searched the randomized controlled trials(RCTs)for the efficacy and adverse effects of rotigotineon the Pubmed,Embase,Cochrane Online Library and Clinicaltrial.gov,whether the articles published or unpublished.Based on the established inclusion and exclusion criteria to screen studies,we evaluated these eligible studies using Cochrane's recommended "bias risk assessment" tool for biased risk assessment.We extracted the basic information of the study,the type of research,the characteristics of the method,the characteristics of the study object,the intervention measures,the outcome index,the meta-analysis effect index,the sample content and other information from these,studies.The RR was used as the outcomes,and the heterogeneity test was performed with I2.Serious AEs(SAEs),withdrawal,and treatment-emergent adverse effects were then assessed for their association with rotigotine by the method of M-H and random effect modles.Finally,a meta-analysis was performed using Review Manager 5.3 software and the the publication bias was analyzed by Stata 14.0 software using Egger and Harbord method.Results31 RCTs with a total of 7169 patients were included in our study,4753 of which were randomized with respect to rotigotine.Serious AEs,overall withdrawal were not significantly associated with rotigotine treatment.But AE-related withdrawal was related to the treatment of rotigotine.Asians showed better tolerance than Europeans and Americans.Rotigotine was probably associated with a heightened risk of AE-related withdrawal with increasing doses.Of the 29 AEs included in our meta-analysis,13 AEs(nausea,application site reactions,headache,dizziness,somnolence,vomiting,insomnia,dyskinesia,hallucination,anorexia and dyspepsia)were found to be significantly associated with rotigotine treatment.But we found that the risks of orthostatic hypotensionand sinusitis in rogitotine treatment group are lower than the placebo.ConclusionMeta analysis showed that rotigotine rarely induced serious adverse effects compared with placebo,but increased the risk of adverse events as the dose increased.Rotigotine was better tolerated by Asians than Europeans and Americans.Rotigotine mainly causednausea,application site reactions,headache,dizziness,somnolence,vomiting,insomnia,dyskinesia,hallucination,anorexia and dyspepsia.Rotigotine may have a potential protective effect on orthostatic hypotension and sinusitis. |
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