How to treat orthostatic tremor – Cohort study and systematic review

Introduction: Orthostatic tremor (OT) is a highly disabling condition. Effectiveness of treatments is largely unverified and no treatment guideline exists. The objective of this study is to evaluate the efficacy and adverse effects of treatments used for OT. Methods: Patients from our online OT-registry were compared to findings from a systematic search in PUBMED. The search included original articles describing clinical features in human primary OT (electromyography peak frequency ≥ 13 Hz), in English or Dutch, and published after 1985. Outcome measures were prescribed treatments and their efficacy (percentage of patients per treatment with a reduction of tremor symptoms) and adverse effects. Results: A total of 78 primary OT patients in the Netherlands and 613 OT patients from 74 articles, mostly case reports and cohort studies, were included. In the cohort from the Netherlands, perampanel showed both the highest efficacy and adverse effects. In the literature, clonazepam showed the highest efficacy, while data on adverse effects was lacking. Overall, pharmacological treatments were reported often to be insufficient. Bilateral deep brain stimulation (DBS) was reported to be effective in the majority of patients, without a higher prevalence of adverse effects. Conclusion: Pharmacological treatment is sufficient in some patients, although overall efficacy is limited and often accompanied by adverse effects. Perampanel and clonazepam are first choice treatments. Surgical interventions seem suitable alternatives for medication resistant patients, although this is based on small studies. Future studies should use diagnostic criteria, standardized outcome scales and good study designs, to increase reliability of findings and comparability.