Current and Emerging Therapeutic Targets for Essential Tremor: A Critical Appraisal of Recent Preclinical and Clinical Studies.

Background: Essential tremor (ET) is a common hyperkinetic movement disorder and causes significant disability. However, the response to the commonly used medications is often unsatisfactory. Hence, there is a requirement for improved treatment modalities involving novel therapeutic targets.

Objective: To review the literature on the recent clinical and preclinical studies regarding the treatment of ET, to identify and discuss the emerging therapeutic targets.

Methods: The authors conducted a literature search on PubMed and Scopus on March 25, 2025 using different search terms and included the relevant articles in the review. Ongoing clinical trials in ET were noted by searching https://clinicaltrials.gov/.

Results: Evidence collected from preclinical studies has led to clinical trials on several pharmacological agents such as T-type calcium channel antagonists, GABA_A receptor modulators, SK channel modulators, and agents targeting glutamatergic neurotransmission. However, some promising clinical trials had negative results, and the outcomes of the other phase 2 and 3 studies are still pending. Preclinical studies have identified other pharmacological targets that have yet to be replicated in clinical studies. Regarding deep brain stimulation and magnetic resonance-guided focused ultrasound surgery, in addition to the thalamic ventralis intermedius nucleus, the posterior subthalamic area has also shown efficacy, possibly due to its proximity to the dentato-rubro-thalamic tract. Non-invasive brain, spinal cord, and peripheral stimulation techniques are the other potential treatment modalities investigated in ET.

Conclusions: New therapeutic targets including pharmacological, surgical, and non-invasive stimulation techniques have shown promise in ET. Translating preclinical research into useful treatment strategies requires further clinical trials.