“Best Practice” Review Finds Low Quality Studies on ET Medications

The BMJ (formerly British Medical Journal) is one of the oldest and most highly ranked medical journals in the world. Its editorial policy strongly favors evidence-based original research. Due to its rigorous process of external review and recommendation followed by internal review, only about 7% of submitted manuscripts are accepted.i It has earned a reputation for authoritative publication.

In 2009, the journal launched a series of topical literature reviews called BMJ Best Practice. Topics range from dementia to smoking cessation guidelines in China and everything in between. The purpose is to present the best available clinical evidence in a given area. In 2015, the journal issued a review of drug treatments for people with essential tremor (ET) of the hand.ii This review of published studies was an update of a 2006 review; the new review covered the original databases (going back to 1966) plus the addition of the years from 2006 to 2014.

The studies were evaluated on several factors: the outcome of the drug on trial, what the comparison was (if any), type of evidence, quality of the study, consistency, directness, size of the drug’s effect, and a GRADE in terms of the overall caliber of the evidence.

Results of the review

Here is a summary of the 41 studies and the overall GRADE awarded by the BMJ Best Practice team:

Trial Total Patients GRADE
Alprazolam versus placebo (2 studies) 46 Very low
Beta-blockers other than propranolol vs. placebo (6 studies) 107 Very low
Beta-blockers other than propranolol vs. propranolol (5 studies) 247 Very low
Botulinum A toxin-haemagglutinin complex vs. placebo (2 studies) 158 Very low
Clonazepam vs. placebo (1 study) 7 Very low
Gabapentin vs. placebo (3 studies) 61 (unclear) Very low
Levetiracetam vs. placebo (2 studies) 25 Very low
Phenobarbital vs. placebo (3 studies) 45 Very low
Primidone vs. placebo (3 studies) 60 Very low
Propranolol vs. placebo (11 studies) < 180 Very low
Topiramate vs. placebo (3 studies) 263 Low

Since medication is the first line of defense when a person is diagnosed with ET, it may seem concerning that BMJ Best Practice gave low ratings to the 41 papers included in this review. However, many variables—including lack of study funds or low recruitment—affect the ultimate reliability and validity of the findings.

What is more problematic is the growing conviction that ET is not a single, universal condition, but rather a “family” of neurologic dysfunctions that have the same symptom (tremors) yet unique individual variations. This may help account for two observations about ET drug treatments:

  1. Drugs have little to no effect for about half of the ET patients who try them
  2. What works for one patient may not for another

This situation makes any research challenging. If a study group is diverse, it is to be expected that the medication being tested will have mixed results. No one knows why a drug that works for one person will not for another. Perhaps even a high quality study will produce disappointing results based on inconsistent participant response.

MRgFUS has promising consistency

Sperling Neurosurgery Associates offers a noninvasive, non-pharmaceutical, non-radiation ET treatment called MRI-guided Focused Ultrasound (MRgFUS). The success of the treatment has been demonstrated with the highest level of research, prompting the FDA to approve it for ET. There are no incisions or holes drilled in the skull that can risk infection, and no implants that can become dislodged. Instead, MRgFUS uses over a thousand “beams” of ultrasound to destroy a very small area in the brain that passes along dysfunctional tremor signals. This outpatient treatment has few-to-no side effect risks, and the results allow a person to throw away his/her pills.

For more information, contact Sperling Neurosurgery Associates.


iZesiewicz TA, Kuo S-H. Essential tremor. BMJ Clin Evid. 2015; 2015: 1206.


About Dr. Dan Sperling

Dan Sperling, MD, DABR, is a board certified radiologist who is globally recognized as a leader in multiparametric MRI for the detection and diagnosis of a range of disease conditions. As Medical Director of the Sperling Prostate Center, Sperling Medical Group and Sperling Neurosurgery Associates, he and his team are on the leading edge of significant change in medical practice. He is the co-author of the new patient book Redefining Prostate Cancer, and is a contributing author on over 25 published studies. For more information, contact the Sperling Neurosurgery Associates.

An update on COVID-19: Your health and safety are our top priority.
 Learn More