Objective: The present meta-analysis aims to find out association between risk of hallucinations and amantadine treatment in levodopa-induced dyskinesia (LID) patients with Parkinson’s disease (PD).

Background: Levodopa is considered as a standard treatment for PD. However long-term levodopa treatment results in motor instabilities and dyskinesia. LID still poses a challenge to effective PD management. The LID treatment in PD is an unmet need as it affects daily living activities and quality of life. Amantadine is the first US FDA approved medication for the treatment of LID in PD patients, however available safety results are inconclusive to justify its effect on hallucinations risk.

Method: Databases such as PubMed, Web of Science, PsychInfo, and clinical trials registries were searched for randomized controlled trials (RCTs) evaluating amantadine treatment in LID patients with PD. Random effects model was used to calculate the pooled estimates of risk ratio (RR) and 95% confidence interval (CI). Pairwise meta-analysis was carried out using Review Manager 5.4 and the risk of bias of included studies were measured by Cochrane’s risk of bias (RoB 2.0) tool.

Results: A total of 6 RCTs, including 452 patients (amantadine=226 and placebo=226) were meta-analysed. Hallucination events were reported by 41 patients.  Patients age were ranged from 62-66 years. Baseline levodopa dose and duration of LID ranged from 435-905 mg and 3.1-8 years, respectively.

Results from the pooled meta-analysis showed that amantadine treatment significantly associated with hallucinations risk (any; visual or audible) [RR 4.01, 95% CI 1.74, 9.25, p=0.001]. In addition, subgroup analysis also suggested significant association between hallucinations risk (visual) and amantadine treatment [RR 6.14, 95% CI 2.01, 18.75, p=0.001] in LID patients with PD when compared to placebo. Overall moderate risk of bias reported from the included studies.

Conclusion: Amantadine significantly associated with hallucinations risk in LID patients with PD. So, patients treated with amantadine should be observed for the hallucination’s incidence during treatment, particularly at initiation and after dose escalation. Due to low number of studies and small sample size, further long-term, multinational and large sample size clinical studies are warranted to justify the current findings.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/risk-of-hallucinations-and-amantadine-treatment-in-levodopa-induced-dyskinesia-patients-with-parkinsons-disease-a-meta-analysis-of-randomized-controlled-trials/