Current and Future Neuropharmacological Options for the Treatment of Essential Tremor

Alonso‐Navarro, Hortensia; García‐Martín, Elena; Agúndez, José A. G.; Jiménez‐Jiménez, Félix Javier

doi:10.2174/1570159x18666200124145743

Cited by 28 publications

(25 citation statements)

References 224 publications

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“…Among the drugs of first choice for ET is propranolol [32,64], a nonselective β-adrenergic receptor antagonist. The effect is likely exerted on central β2 receptors [65] but peripheral effects on the muscle spindle are also present [66]. As propranolol also has major cardiovascular effects, an electrocardiogram should be carried out before starting the treatment.…”

Section: Propranololmentioning

confidence: 99%

Managing Essential Tremor

Hopfner

Deuschl

2020

Neurotherapeutics

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Essential tremor is one of the most common tremor syndromes. According to the recent tremor classification, tremor as a symptom is defined as an involuntary, rhythmic, oscillatory movement of a body part and is classified along two axes: axis 1-defining syndromes based on the clinical features such as historical features, tremor characteristics, associated signs, and laboratory tests; and axis 2-classifying the etiology (Bhatia et al., Mov Disord 33:75-87, 2018). The management of this condition has two major approaches. The first is to exclude treatable etiologies, as particularly during the onset of this condition the presentation of a variety of etiologies can be with monosymptomatic tremor. Once the few etiologies with causal treatments are excluded, all further treatment is symptomatic. Shared decision-making with enabling the patient to knowledgeably choose treatment options is needed to customize the management. Mild to moderate tremor severity can sometimes be controlled with occupational treatment, speech therapy of psychotherapy, or adaptation of coping strategy. First-line pharmacological treatments include symptomatic treatment with propranolol, primidone, and topiramate. Botulinum toxin is for selected cases. Invasive treatments for essential tremor should be considered for severe tremors. They are generally accepted as the most powerful interventions and provide not only improvement of tremor but also a significant improvement of life quality. The current standard is deep brain stimulation (DBS) of the thalamic and subthalamic region. Focused ultrasound thalamotomy is a new therapy attracting increasing interest. Radiofrequency lesioning is only rarely done if DBS or focused ultrasound is not possible. Radiosurgery is not well established. We present our treatment algorithm.

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Section: Propranololmentioning

confidence: 99%

Managing Essential Tremor

Hopfner

Deuschl

2020

Neurotherapeutics

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“…Kralic et al [ 135 ] also observed that MK-801 (a noncompetitive NMDA receptor antagonist) and CCPA (an adenosine A1 receptor agonist) inhibited tremor in GABA-A α1−/− KO mice, while compounds that enhance GABA-A receptor activity by increasing GABA affinity, such as diazepam and allopregnanolone, intensified tremor. This observation is somewhat inconsistent with clinical data which shows that diazepam, like other drugs in the benzodiazepine group, reduces the symptoms of ET in some patients [ 83 , 84 ].…”

Section: Essential Tremor (Et)mentioning

confidence: 60%

“…Third-line drugs, that is, drugs with a possible but not proven efficacy, include nimodipine (a dihydropyridine-sensitive calcium channel blocker) and clozapine (an atypical neuroleptic) [ 79 ]. According to the MDS Task Force on Tremor and the American Academy of Neurology, there is insufficient evidence to support or deny the use of clozapine in ET [ 84 ]. Several novel T-type calcium channel (Ca v 3) blockers are currently being investigated, such as CX-8998 (Jazz Pharmaceutical, Dublin, Ireland) and PRAX-944 (Praxis Precision Medicines, Boston, MA, USA), which are at the stage of clinical trials [ 83 ].…”

Section: Essential Tremor (Et)mentioning

confidence: 99%

“…The utility of BTX-A therapy for ET and PD tremor has been questioned based on the high incidence of finger and hand weaknesses after the treatment due to the injection method. However, this side effect has been overcome after the introduction of new methods, like the Yale protocol and the computerized kinematic tremor assessment, which produced significantly less weakness compared to previously reported methods [ 83 , 84 , 87 ].…”

Section: Essential Tremor (Et)mentioning

confidence: 99%

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The Pathophysiology and Treatment of Essential Tremor: The Role of Adenosine and Dopamine Receptors in Animal Models

Kosmowska

Wardas

2021

Biomolecules

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Essential tremor (ET) is one of the most common neurological disorders that often affects people in the prime of their lives, leading to a significant reduction in their quality of life, gradually making them unable to independently perform the simplest activities. Here we show that current ET pharmacotherapy often does not sufficiently alleviate disease symptoms and is completely ineffective in more than 30% of patients. At present, deep brain stimulation of the motor thalamus is the most effective ET treatment. However, like any brain surgery, it can cause many undesirable side effects; thus, it is only performed in patients with an advanced disease who are not responsive to drugs. Therefore, it seems extremely important to look for new strategies for treating ET. The purpose of this review is to summarize the current knowledge on the pathomechanism of ET based on studies in animal models of the disease, as well as to present and discuss the results of research available to date on various substances affecting dopamine (mainly D3) or adenosine A1 receptors, which, due to their ability to modulate harmaline-induced tremor, may provide the basis for the development of new potential therapies for ET in the future.

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“…The first-line treatment of ET usually consists of pharmacotherapy: Propranolol and Primidone (First-line treatments); Topiramate and Gabapentin (Second-line treatments); Clonazepam and Mirtazapine (Third-line treatments). To date, the beta-blocker propranolol and the antiepileptic drug primidone are the drugs with the highest efficacy in the treatment of ET [ 2 ]. However, the benefits of pharmacotherapy are limited.…”

Section: Introductionmentioning

confidence: 99%

Local Vibrational Therapy for Essential Tremor Reduction: A Clinical Study

et al. 2020

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Background and objectives: tremor is an unintentional and rhythmic movement of any part of the body that is a typical symptom of Essential Tremor (ET). ET impairs the quality of life of patients and is treated with pharmacotherapy. We investigated the tremor reduction efficacy of an innovative vibrational medical device (IMD) in ET patients. Materials and Methods: we conducted a prospective, single-center, single-arm, pragmatic study in ET patients with an extended safety study to evaluate the efficacy and safety of the Vilim Ball—a local hand-arm vibration device that produces vibrations in the frequency range of 8–18 Hz and amplitude from 0 to 2 mm. The primary endpoint was the decrease in the power spectrum after device use. The secondary endpoints were safety outcomes. Results: In total, 17 patients with ET were included in the main study, and no patients withdrew from the main study. The tremor power spectrum (m2/s3 Hz) was lower after the device use, represented as the mean (standard deviation): 0.106 (0.221); median (Md) 0.009 with the interquartile range; IQR, 0.087 vs. 0.042 (0.078); Md = 0.009 with the IQR 0.012; Wilcoxon signed-rank test V = 123; and p = 0.027. Seven patients reported that vibrational therapy was not effective. Two patients reported an increase in tremor after using the device. In the extended safety study, we included 51 patients: 31 patients with ET and 20 with Parkinsonian tremor, where 48 patients reported an improvement in tremor symptoms and 49 in function. No serious adverse events were reported, while two patients in the Parkinsonian tremor group reported a lack of efficacy of the proposed medical device. Conclusions: the device reduces essential tremor in some patients and is safe to use in ET.

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Current and Future Neuropharmacological Options for the Treatment of Essential Tremor

Cited by 28 publications

References 224 publications

Managing Essential Tremor

Managing Essential Tremor

The Pathophysiology and Treatment of Essential Tremor: The Role of Adenosine and Dopamine Receptors in Animal Models

Local Vibrational Therapy for Essential Tremor Reduction: A Clinical Study

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