Acute and chronic effects of clozapine in essential tremor

Abstract

Patients with essential tremor (ET) may not respond to commonly used drugs. Clozapine, an atypical neuroleptic drug, has been reported to improve postural Parkinson's disease tremor clinically resembling ET. The effects of a single dose of 12.5 mg clozapine and placebo were evaluated in a randomized, double‐blind, crossover study in 15 drug‐resistant patients with ET. Patient responders with more than 50% improvement after a single dose of clozapine subsequently received the drug (39 ± 9 mg up to 50 mg) unblinded for a period of 15.8 ± 7.7 months. Tremor was effectively reduced by a single dose of clozapine in 13 of 15 patients (p <0.01). Sedation was the only side effect reported during the clozapine test; however, the time course of sedation and of the antitremor effect were not coincident. A significant reduction of tremor was reported with chronic clozapine treatment (p <0.01) with no tolerance to drug antitremor effect, whereas sedation markedly decreased after 6–7 weeks of therapy. No clozapine‐induced hematologic side effects were observed in our cohort of patients during long‐term treatment. Our results suggest that in selected drug‐resistant ET cases, clozapine should be considered before resorting to neurosurgical options.

The Treatment of Tremor

“…Overall, primidone is considered likely efficacious with a benefit of around 60 % reduction in tremor amplitude [25], which correlates with accelerometry findings (59 %; range, 42-76 %) [25,38,[44][45][46]. At least 50 % of patients experienced some benefit, and occasional "dramatic responders" have been [27] Acetazolamide/methazolamide Olanzapine Clozapine (18-75 mg) [28] Amantadine Pregabalin Flunarizine (10 mg) [29] Carisbamate Tiagabine Nadolol (120-240 mg) [30] Isoniazid Sodium oxybate Nimodipine (120 mg) [31] Levetiracetam Zonisamide Botulinum toxin (depending on injected muscles) Patients in the surgical studies usually have much higher tremor amplitudes. Tremor amplitude estimation is based on standard algorithms computed as change in tremor rating scale and change in tremor amplitude on accelerometry [9,15] described.…”

A functional variant of the dopamine D 3 receptor is associated with risk and age-at-onset of essential tremor

“…Although DRD3 receptor overexpression in the basal ganglia has been implicated in levodopa-induced dyskinesia, abnormalities in the cerebellar DRD3 receptors could be responsible for ET. Although dopaminergic drugs are ineffective in ET, olanzapine and clozapine, which are nonselective dopamine D2-like receptor blockers (acting at both DRD2 and DRD3 receptors), have been found to improve ET (32,33). Therefore, we propose DRD3-selective partial agonists or antagonists (14,34) as a possible pharmacotherapy of ET.…”

Clozapine and prazosin slow the rhythm of head movements during focused stereotypy induced by d-amphetamine in rats

“…Brackets indicate ±1 SEM; some brackets are not visible because the SEM was smaller than the data point impaired in schizophrenia, become normalized after clozapine treatment. Antitremor effects of clozapine have been documented in laboratory rats (Fowler et al 2005a), in Parkinson's disease patients (Bonuccelli et al 1997), and in essential tremor patients (Ceravolo et al 1999). The foregoing considerations show that clozapine modulates several rhythmic processes besides the rhythmic head movements of d-amphetamine-induced FS and raises the possibility that the antipsychotic potential of clozapine may be embodied in the drug's effects on rhythms generated by several brain circuits.…”