Profile and frequency of antiparkinsonian drugs adverse reactions: a systematic review and meta-analysis

Abstract

Objective: to assess the predictors and prevalence of adverse drug reactions (ADRs) associated with antiparkinsonian drugs.Materials and methods. 18 clinical studies and randomized controlled trials were included in the analysis. We combined all registered ADRs for each drug and made direct comparisons with odds ratio (OR) and 95% confidence interval (95% CI) calculation.Results and discussion. Levodopa/benserazide (LB) had the best safety profile among levodopa drugs. Levodopa/carbidopa (LC) compared with LB was associated with more frequent development of nausea (OR=2.8; 95% CI: 1.51–5.21), aggravation of parkinsonism (OR=4.44; 95% CI: 2.12–9.28) and dizziness (OR=3.32; 95% CI: 1.5–7.33; p=0.002). Piribedil had the lowest number of ADRs among dopamine receptor agonists. Dizziness was more common with pramipexole and ropinirole than with levodopa (OR=1.82; 95% CI: 1.21–2.74 and OR=1.65; 95% CI: 1.11–2.44 respectively). Increased daytime sleepiness and peripheral edema have also been associated with pramipexole. Arterial hypertension was present in 9.6% of patients prescribed with piribedil. Amantadine compared with pramipexole was associated with a higher risk of hallucinations (OR=2.27; 95% CI: 1.24–4.12) and constipation (OR=2.40; 95% CI: 1.14–5.05). Patients prescribed with selegeline had higher odds of dizziness (OR=3.40; 95% CI: 1.76–6.55) and hallucinations (OR=4.30; 95% CI: 1.83–10.09) compared to rasagiline.Conclusion. Based on the results, we propose a diagram of the relationship between ADRs and their frequency with antiparkinsonian drugs. We hope that the study will find clinical application and allow neurologists to consider the effectiveness and the expected risks of ADRs in the treatment of PD.

Keywords

• parkinson's disease
• levodopa
• dopamine receptor agonists
• amantadine
• mao-b inhibitors
• personalized medicine
• adverse drug reactions
• meta-analysis
• systematic review