The patient with essential tremor, what therapy is possible?

The patient with essential tremor is the subject for whom the diagnosis of Parkinson's disease has not been established. It represents the "grave" of the neurologist who does not know which treatment to prescribe. And it is not easy to control a patient with essential tremor: if he is nervous he starts to tremble more, sweats, has vertigo, difficulty in maintaining posture, constipation, difficulty in swallowing and breathing. What to do? What drugs to use?

Drugs for essential tremor
The drugs that are used are:
Beta blockers
Barbiturates
Calcium antagonists
Flunarizine
Clonidine
gabapentin

Propranolol

Several small randomized trials have found that compared to placebo, propranolol (60-240 mg), administered for one month, improves short-term clinical parameters such as tremor amplitude and subjectively assessed gravity. There are no long-term randomized studies on the efficacy of propranolol in essential tremor. Side effects of asthenia and bradycardia (for example, 1/10 in a randomized trial). At other times, depression, diarrhea, dyspnoea, sedation, blurred vision and sexual disorders were reported by less than 5% of subjects receiving propranolol therapy. Individuals with congestive heart failure, second-degree block, asthma, severe allergies and type 1 diabetes were usually excluded from studies. All studies were small. Finally, the possibility of publication bias can not be excluded.

Beta-blockers other than propranolol

Four small, randomized, short-term studies found only weak evidence that sotalol and atenolol are effective in the treatment of essential hand tremor. We found no adequate evidence of direct comparison between propranolol and other beta-blockers. However, several small randomized trials have found that compared to placebo, propranolol (60-240 mg) given for one month improves clinical parameters such as tremor amplitude and subjectively assessed gravity in the short term. We did not find long-term randomized studies on the efficacy of propranolol in essential tremor but clinical experience encourages us to say that it controls tremor in dysphoric subjects. Attention to administer it in cardiac patients with hypokinetic arrhythmias because of the side effects.

Barbiturates

Two small randomized trials with short follow-up found that primidone improved clinical parameters compared to placebo. A small randomized study with a short follow-up found that phenobarbital improved clinical parameters compared to placebo. We have not found long-term studies of this type. Primidone compared to placebo significantly improved clinical parameters and subjective assessment of tremor severity (P <0.05). In another study (22 subjects) primidone (maximum dose 750 mg) compared to placebo significantly improved clinical parameters (P <0.02), functionality test (P <0.01) and subjective evaluation (P <0.01 ). However, some patients taking primidone had to discontinue therapy due to side effects (acute first dose toxic reaction, sedation, daytime sleepiness, asthenia and depression). Other barbiturates: Both primidone (metabolised to phenobarbital) and phenobarbital are associated with depression and negative effects on cognition and behavior (in particular, in children, the elderly and in subjects with neuropsychiatric disorders

Benzodiazepines

Two randomized trials with a short follow-up provided limited evidence of the low efficacy of benzodiazepines in essential hand tremor. Clonazepam vs placebo: A randomized study (15 subjects) found no significant difference in the various outcomes. Alprazolam vs placebo: A randomized double-blind study (24 subjects) found that alprazolam (up to 3 mg daily) compared to placebo improved the overall impression of the physician, but did not produce significant differences in clinical parameters, in tests of functionality or in the self-assessment of tremor.

Cannabinoids

Refer to the page on cannabis.

Methazolamide

A randomized trial did not provide evidence of the efficacy of metazolamide compared to placebo. POSITIVE EFFECTS We did not find systematic reviews. Metazolamide vs placebo: We have identified a randomized study with a double-blind crossover design (25 subjects with essential tremor). The study found no significant differences between metazolamide (up to 300 mg per day) and placebo in terms of clinical parameters, functional tasks and self-assessment (7/18 improved with metazolamide, 39%, vs 4/18 with placebo, 22%; reduction of absolute risk 16%, 95% confidence limits from 15 to 45).

Dihydropyridine calcium antagonists

Three randomized trials of poor methodological quality that compared calcium antagonists and placebo have reported inconsistent results. Nicardipine vs placebo: We have identified 2 randomized trials. A double-blind crossover design study (11 subjects) found no significant differences between nicardipine and placebo in accelerometric recordings. Clinical outcomes were not taken into consideration. The second study with crossover design (14 subjects) compared for one month nicardipine (1 mg / kg per day), propranolol (160 mg daily) and placebo. Both nicardipine and propranolol improved symptom scores compared to placebo. Nimodipine vs placebo: We identified a randomized study with a double-blind crossover design (15 subjects), which found no significant difference between nimodipine (90 mg daily) and placebo in the clinical score after 2 weeks of treatment (absolute risk reduction) 20%, 95% confidence limits from -15% to + 55%). With regard to the side effects, both nicardipine and nimodipine may exacerbate or cause heart failure. They are associated with vertigo, flushing, peripheral edema, somnolence, headache and asthenia. Adverse gastrointestinal effects (nausea, vomiting, dyspepsia, constipation, weight gain, thirst, indigestion or taste alteration) are reported in 1-3% of the population. Changes in laboratory values (hepatic function) were generally observed 1 to 8 weeks after initiation of treatment.

Flunarizine

A small randomized trial found evidence that flunarizine could reduce the symptoms of essential hand tremor. We did not find systematic reviews.Flunarizine vs placebo: We identified a randomized study with a double-blind crossover design (17 subjects). The study found that flunarizine (10 mg daily) compared to placebo significantly improved clinical parameters and tremor severity after one month of treatment (P = 0.0006). The majority of subjects who completed the study had improved with flunarizine (13/15), while the number of those who improved with placebo was not reported. Flunarizine, however, is associated with neuropsychiatric side effects and the development of parkinsonism and other movement disorders.

Clonidine

A randomized study has not documented any improvement in essential hand tremor after clonidine treatment. POSITIVE EFFECTS Clonidine vs placebo: We did not find systematic reviews. We identified a small randomized trial (10 subjects), with short-term follow-up and crossover design, which compared clonidine (maximum 0.6 mg per day) and placebo. The study found no significant difference in the number of subjects improved (1/10 with clonidine, 10%, vs 1/10 with placebo,

Gabapentin

Three small randomized trials with short follow-up found contradictory evidence on the efficacy of gabapentin in the essential tremor of the hand. We did not find systematic reviews. Gabapentin vs placebo: We have identified 3 randomized studies with crossover and small design (16-25 subjects). The first study found no differences between gabapentin and placebo in terms of clinical parameters, daily activities or self-assessment. The second study compared gabapentin (up to 1,200 mg per day), propranolol (up to 120 mg per day) and placebo. With respect to placebo, gabapentin improved the number of positive responses to treatment (10/16 with gabapentin, 63% vs 5/16 with placebo, 31%, reduction of absolute risk 32%, 95% confidence limits from 17% to 47%). %, number of cases to be treated 4, 95% confidence limits from 2 to 6), clinical score (P <0.05), disability (P <0.01), self-assessment (P <0, 06) and accelerometric registration The third study (25 subjects) compared 2 doses of gabapentin (1,800 mg or 3,600 mg daily) with placebo. The study found no significant differences with the different dosages of gabapentin in the 20 subjects who completed the study. Gabapentin (at both doses) significantly improved the overall assessment of the participants (P <0.05), the ability to pour water (P <0.05) and the scores in the activities of daily life (P <0.05) compared to placebo. 0.005). The study did not report any specific hand tremor scores; no significant differences were found between gabapentin and placebo in the scores on accelerometry, spirography or overall impression of the physician.

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