Definitions of the strength of the recommendations (A, B, C, and U) and classification of the evidence (Class I-IV) are provided at the end of the "Major Recommendations" field.
Pharmacologic Treatment of Essential Tremor (ET)
- Propranolol, propranolol LA, or primidone should be offered to patients who desire treatment for limb tremor in essential tremor (ET), depending on concurrent medical conditions and potential side effects (Level A).
- Either primidone or propranolol may be used as initial therapy to treat limb tremor in ET (Level B).
- Atenolol, gabapentin (monotherapy), sotalol, and topiramate should be considered as treatment of limb tremor associated with ET (Level B). Alprazolam is recommended with caution due to its abuse potential (Level B). Propranolol should be considered as treatment of head tremor in patients with ET (Level B).
- Nadolol and nimodipine may be considered when treating limb tremor in patients with ET (Level C). Clonazepam should be used with caution due to its abuse potential and possible withdrawal symptoms (Level C). Clozapine is recommended only for refractory cases of limb tremor in ET due to the risk of agranulocytosis (Level C).
- Trazodone is not recommended for treatment of limb tremor in ET (Level A).
- Acetazolamide, isoniazid, and pindolol are not recommended for treatment of limb tremor in ET (Level B).
- Methazolamide, mirtazapine, nifedipine, and verapamil are not recommended for treatment of limb tremor in ET (Level C).
- There is insufficient evidence to make recommendations regarding the use of amantadine, clonidine, gabapentin (adjunct therapy), glutethimide, L-tryptophan/pyridoxine, metoprolol, nicardipine, olanzapine, phenobarbital, quetiapine, and theophylline in the treatment of limb tremor in ET (Level U).
- Primidone and propranolol may be used in combination to treat limb tremor when monotherapy does not sufficiently reduce tremor (Level B).
- The dosages of propranolol and primidone may need to be increased by 12 months of therapy when treating limb tremor in ET (Level C).
- Botulinum toxin (BTX) A injections for limb, head, and voice tremor associated with ET may be considered in medically refractory cases (Level C for limb, head, and voice tremor).
Surgical Treatment of ET
- Unilateral thalamotomy may be used to treat limb tremor in ET that is refractory to medical management (Level C), but bilateral thalamotomy is not recommended due to adverse side effects (Level C).
- Deep brain stimulation (DBS) of the ventral intermediate (VIM) thalamic nucleus may be used to treat medically refractory limb tremor in ET (Level C).
- There is insufficient evidence to make recommendations regarding the use of thalamic DBS for head or voice tremor (Level U).
- DBS has fewer adverse events than thalamotomy (Level B). However, the decision to use either procedure depends on each patient's circumstances and risk for intraoperative complications compared to feasibility of stimulator monitoring and adjustments.
- Bilateral DBS is necessary to suppress tremor in both upper limbs, but there are insufficient data regarding the risk:benefit ratio of bilateral vs unilateral DBS in the treatment of limb tremor (Level U). Similarly, there are insufficient data to recommend bilateral or unilateral DBS for head and voice tremors. Side effects are more frequent with bilateral DBS, and bilateral thalamotomy is not recommended.
- There is insufficient evidence to make recommendations regarding the use of gamma knife thalamotomy in the treatment of ET (Level U).
Definitions:
Classification of Recommendations
A = Established as effective, ineffective, or harmful for the given condition in the specified population (Level A rating requires at least two consistent Class I studies.)
B = Probably effective, ineffective, or harmful for the given condition in the specified population (Level B rating requires at least one Class I study or at least two consistent Class II studies.)
C = Possibly effective, ineffective, or harmful for the given condition in the specified population (Level C rating requires at least one Class II study or two consistent Class III studies.)
U = Data inadequate or conflicting given current knowledge, treatment is unproven
Classification of Evidence
Class I: Prospective, randomized, controlled clinical trial with masked outcome assessment, in a representative population. The following are required:
- Primary outcome(s) clearly defined
- Exclusion/inclusion criteria clearly defined
- Adequate accounting for drop-outs and cross-overs with numbers sufficiently low to have minimal potential for bias
- Relevant baseline characteristics are presented and substantially equivalent among treatment groups or there is appropriate statistical adjustment for differences.
Class II: Prospective matched group cohort study in a representative population with masked outcome assessment that meets a-d above OR a randomized controlled trial in a representative population that lacks one criteria a-d
Class III: All other controlled trials including well-defined natural history controls or patients serving as own controls in a representative population, where outcome is independently assessed or independently derived by objective outcome measurement*
Class IV: Evidence from uncontrolled studies, case series, case reports, or expert opinion
*Objective outcome measurement: an outcome measure that is unlikely to be affected by an observer's (patient, treating physician, investigator) expectation or bias (e.g., blood tests, administrative outcome data).