A double-blind placebo-controlled trial of topiramate treatment for essential tremor

Connor, Gregory S.

doi:10.1212/wnl.59.1.132

Cited by 124 publications

(59 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Four relevant studies [50][51][52][53] assessed the effect of topiramate in limb tremor, providing evidence for therapeutic benefit [50][51][52][53]. A placebo-controlled cross-over study in 24 patients using up to 400 mg/d as mono-or adjunct therapy [51] found a significant reduction of tremor subscores. In a subsequent article [53], the same authors report combined results of 3 randomized, double-blind, placebo-controlled, cross-over trials of topiramate for ET (maximum tolerated dose of up to 400 mg/d) in adult patients observed for 10 weeks per treatment arm (active drug then placebo vs placebo then active drug).…”

Section: Topiramatementioning

confidence: 99%

The Treatment of Tremor

Schneider

Deuschl

2014

Neurotherapeutics

View full text Add to dashboard Cite

Tremor is a hyperkinetic movement disorder characterized by rhythmic oscillations of one or more body parts. It can be disabling and may impair quality of life. Various etiological subtypes of tremor are recognized, with essential tremor (ET) and Parkinsonian tremor being the most common. Here we review the current literature on tremor treatment regarding ET and head and voice tremor, as well as dystonic tremor, orthostatic tremor, tremor due to multiple sclerosis (MS) or lesions in the brainstem or thalamus, neuropathic tremor, and functional (psychogenic) tremor, and summarize main findings. Most studies are available for ET and only few studies specifically focused on other tremor forms. Controlled trials outside ET are rare and hence most of the recommendations are based on a low level of evidence. For ET, propranolol and primidone are considered drugs of first choice with a mean effect size of approximately 50 % tremor reduction. The efficacy of topiramate is also supported by a large double-blind placebocontrolled trial, while other drugs have less supporting evidence. With a mean effect size of about 90 % deep brain stimulation in the nucleus ventralis intermedius or the subthalamic nucleus may be the most potent treatment; however, there are no controlled trials and it is reserved for severely affected patients. Dystonic limb tremor may respond to anticholinergics. Botulinum toxin improves head and voice tremor. Gabapentin and clonazepam are often recommended for orthostatic tremor. MS tremor responds only poorly to drug treatment. For patients with severe MS tremor, thalamic deep brain stimulation has been recommended. Patients with functional tremor may benefit from antidepressants and are best be treated in a multidisciplinary setting. Several tremor syndromes can already be treated with success. But new drugs specifically designed for tremor treatment are needed. ET is most likely covering different entities and their delineation may also improve treatment. Modern study designs and long-term studies are needed.

show abstract

Section: Topiramatementioning

confidence: 99%

The Treatment of Tremor

Schneider

Deuschl

2014

Neurotherapeutics

View full text Add to dashboard Cite

show abstract

“…Although its mechanisms of action have not been fully elucidated, TPM is known to enhance the activity of g-aminobutyric acid (GABA) through interaction with GABA A receptors, as well as to block voltage-dependent sodium channels and kainate/ [alpha]-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) glutamate receptors (Schneiderman, 1998). Emerging evidence indicates that TPM might offer promising applications for the therapy of other neurological conditions, such as neuropathic pain and essential tremor (Chong and Libretto, 2003;Connor, 2002), as well as several psychiatric disorders, such as bipolar disorder (Calabrese et al, 2001;Grunze et al, 2001), schizoaffective disorder (Deutsch et al, 2003), posttraumatic disorder (Berlant and Van Kammen, 2002), Tourette's syndrome (Abuzzahab and Brown, 2001) and some clusters of schizophrenia (Drapalski et al, 2001). The therapeutic potential of TPM for these disorders, however, is disputed on account of contrasting findings (Arnone, 2005;Millson et al, 2002) and in view of its numerous cognitive and affective side effects, such as depression, hallucinosis and cognitive deterioration (Matthews and Miller, 2001).…”

Section: Introductionmentioning

confidence: 99%

Effects of Topiramate on the Prepulse Inhibition of the Acoustic Startle in Rats

Frau

Orrù

Fà

et al. 2006

Neuropsychopharmacol

View full text Add to dashboard Cite

The anticonvulsant topiramate (TPM) has been recently proposed as a novel adjuvant therapy for bipolar disorder and schizophrenia, yet its efficacy remains controversial. As both disorders are characterized by gating deficits, we tested the effects of TPM on the behavioral paradigm of prepulse inhibition (PPI) of the acoustic startle response, a validated animal model of sensorimotor gating. TPM (10, 18, 32, 58, 100 mg/kg, intraperitoneal, i.p.) enhanced PPI in rats in a dose-dependent fashion, prevented the PPI reduction mediated by the dopaminergic agonist apomorphine (0.25 mg/kg, subcutaneous, s.c.) and potentiated the effects of the antipsychotic drugs haloperidol (0.05, 0.1 mg/kg, i.p.) and clozapine (2.5, 5 mg/kg, i.p.). Conversely, TPM elicited no significant effect on the PPI disruption mediated by the NMDA receptor antagonist dizocilpine (0.05, 0.1 mg/kg, s.c.) and surprisingly antagonized the attenuation of dizocilpine-induced PPI disruption mediated by clozapine (5 mg/kg, i.p.). Our results suggest that TPM may exert diverse actions on the neural substrates of sensorimotor gating. While the pharmacological mechanisms of such effects are still elusive, our findings might contribute to shed light on some controversies on the therapeutic action of TPM, and point to this drug as a putative novel adjuvant therapy for some clusters of gating disturbances.

show abstract

“…Topiramate is an anticonvulsant that blocks sodium channels and potentiates GABA activity. Three class II studies [25][26][27] and one class IV study 28 found that topiramate in doses up to 400 mg/day reduced tremor. One double-blind, placebo-controlled trial 28 in 62 patients with ET reported an 18% to 23% improvement in clinical rating scales with topiramate use, compared to 0 to 1% in patients taking placebo.…”

mentioning

confidence: 99%

Practice Parameter: Therapies for essential tremor [RETIRED]

et al. 2005

View full text Add to dashboard Cite

Abstract-Background: Essential tremor (ET) is one of the most common tremor disorders in adults and is characterized by kinetic and postural tremor. To develop this practice parameter, the authors reviewed available evidence regarding initiation of pharmacologic and surgical therapies, duration of their effect, their relative benefits and risks, and the strength of evidence supporting their use. Methods: A literature review using MEDLINE, EMBASE, Science Citation Index, and CINAHL was performed to identify clinical trials in patients with ET published between 1966 and August 2004. Articles were classified according to a four-tiered level of evidence scheme and recommendations were based on the level of evidence. Results and Conclusions: Propranolol and primidone reduce limb tremor (Level A). Alprazolam, atenolol, gabapentin (monotherapy), sotalol, and topiramate are probably effective in reducing limb tremor (Level B). Limited studies suggest that propranolol reduces head tremor (Level B). Clonazepam, clozapine, nadolol, and nimodipine possibly reduce limb tremor (Level C). Botulinum toxin A may reduce hand tremor but is associated with dose-dependent hand weakness (Level C). Botulinum toxin A may reduce head tremor (Level C) and voice tremor (Level C), but breathiness, hoarseness, and swallowing difficulties may occur in the treatment of voice tremor. Chronic deep brain stimulation (DBS) (Level C) and thalamotomy (Level C) are highly efficacious in reducing tremor. Each procedure carries a small risk of major complications. Some adverse events from DBS may resolve with time or with adjustment of stimulator settings. There is insufficient evidence regarding the surgical treatment of head and voice tremor and the use of gamma knife thalamotomy (Level U). Additional prospective, double-blind, placebo-controlled trials are needed to better determine the efficacy and side effects of pharmacologic and surgical treatments of ET.

show abstract

A double-blind placebo-controlled trial of topiramate treatment for essential tremor

Cited by 124 publications

References 8 publications

The Treatment of Tremor

The Treatment of Tremor

Effects of Topiramate on the Prepulse Inhibition of the Acoustic Startle in Rats

Practice Parameter: Therapies for essential tremor [RETIRED]

Contact Info

Product

Resources

About