Abstract
Background
The pharmacological treatment of essential tremor (ET) is not optimal. There are only two first-line medications and troublesome side effects are common. It is not uncommon for patients to simply stop taking medication. Yet no published data substantiate or quantify this anecdotal impression.
Objectives
To determine, among ET patients who were prescribed medication for tremor, what proportion are still taking medication and what proportion have stopped?
Methods
528 ET patients from three distinct study settings (clinical, brain donors, population) were interviewed.
Results
A clear pattern that emerged across settings was that the proportion of ET patients who had stopped medication was sizable and consistently similar (nearly one-third): 31.4% (clinical), 24.3% (brain donors), 30.0% (population), 29.8% (overall). A similarly high proportion of cases with severe tremor had stopped their medication: 31.9% (clinical), 36.4% (brain donors). For the four most commonly-used medications (propranolol, primidone, diazepam, topiramate), one-half or more of the treated patients had stopped the medication; among the less commonly used medications, the proportion who stopped was even higher.
Conclusions
Nearly one of every three ET patients who had been prescribed medication for tremor had discontinued pharmacotherapy. Even more revealing was that a similar proportion of cases with severe tremor had stopped medication. These data make tangibly evident that there is a sizable population of ET patients who are untreated and disabled, and underscore the inadequacy of current pharmacotherapeutic options for this common neurological disease.
Keywords: Essential tremor, clinical, treatment, medication
Introduction
Pharmacological treatment of essential tremor (ET) is not optimal. There remain simply two first-line medications [1], a situation that has not changed in nearly 30 years. Medications are generally considered to be effective in only 50% of patients [2], rarely reduce tremor to asymptomatic levels, and are associated with unwanted side effects. Our impression is that there may be a sizable population of patients untreated, with impaired quality of life and disability. However, there are no published data to substantiate or begin to put a figure on this anecdotal clinical impression. To address this gap in the literature, we asked what proportion of ET patients who were prescribed medication for their tremor are still taking medication and what proportion have stopped? We addressed this question utilizing data available on ET patients from three distinct settings, a clinical sample, a population, and a brain repository, in order to sample a broad spectrum of cases across a variety of settings.
Methods
528 ET cases from three studies were used, a clinical study in New York, a brain donor study, and a population-based study in northern Manhattan, New York; each study has been described in detail [3]. Cases were asked whether they had ever been prescribed any medication to treat their tremor and whether they were currently taking any medication to treat their tremor. Tremor severity was rated with a total tremor score (range 0 – 36) based on a videotaped neurological examination [3]. All cases signed written informed consent upon enrollment.
Results
Clinical sample in New York
82/261 (31.4%) 261 cases who had ever been prescribed medication for their tremor had had stopped medication (Table 1); these did not differ by age, gender, education, tremor duration, or tremor severity from the 179 who had continued medication. Among 69 patients with severe tremor (upper quartile of total tremor score [>24]), 22 (31.9%) had stopped medication.
Table 1.
Data from three studies of essential tremor
| Clinical sample in New York |
Future Brain Donors |
Population- based study in New York |
|
|---|---|---|---|
| Number of ET cases | 328 | 94 | 106 |
| Age (years) | 67.8 ± 15.0 | 74.1 ± 10.1 | 69.8 ± 18.4 |
| Women | 174 (53.0%) | 57 (60.6%) | 63 (59.4%) |
| Education (years) | 15.0 ± 3.8 | NA | NA |
| Education | NA | NA | |
| High school graduate | 92 (97.9%) | ||
| Bachelor’s degree | 49 (52.1%) | ||
| Total tremor score | 19.8 ± 7.0 | 19.7 ± 6.6 | 16.4 ± 6.7 |
| Tremor duration (years) | 23.8 ± 18.9 | 40.0 ± 20.3 | 15.4 ± 18.8 |
| Family history of ET or tremor** |
213 (64.9%) | 76 (88.3%)* | 34 (32.1%) |
| Ever prescribed medication for tremor |
261/328 (79.6%) |
82/94 (87.2%) |
10/106 (9.4%) |
| Currently taking medication for tremor |
179/328 (54.6%) |
62/94 (66.0%) |
7/106 (6.6%) |
| Proportion of those ever prescribed medication who are currently taking medication for tremor |
179/261 (68.6%) |
62/82 (75.7%) |
7/10 (70.0%) |
| Proportion of those ever prescribed medication who are no longer taking medication for tremor |
82/261 (31.4%) |
20/82 (24.3%) |
3/10 (30.0%) |
86 of 94 cases knew their family history.
NA = data not available.
Values are mean ± SD or proportion (percentage).
≥1 first-degree relative with ET or tremor.
Future brain bank donors
20/82 (24.3%) cases who had been prescribed tremor medication had stopped medication (Table 1); these did not differ from the 62 who had continued medication. Among 11 patients with severe tremor (upper quartile of total tremor score [>27]), 22 (31.9%) had stopped medication. In this sample, data were available on the use of specific medications (Table 2). For the four most commonly-used medications (propranolol, primidone, diazepam, topiramate), one-half or more of the treated patients had stopped the medication; among the less commonly used medications, the proportion who stopped was even higher. Even among patients on newer medications, the proportion who had stopped was approximately 50% or higher.
Table 2.
Use of specific medications among 82 future brain donors
| Medication | Proportion of cases who had been prescribed the medication and remained on it |
Proportion of cases who had been prescribed the medication and had stopped it |
|---|---|---|
| Propranolol | 34/66 (51.5%) | 32/66 (48.5%) |
| Primidone | 19/45 (42.2%) | 26/45 (57.8%) |
| Diazepam | 3/30 (10.0%) | 27/30 (90.0%) |
| Topiramate | 7/13 (53.9%) | 6/13 (46.1%) |
| Phenobarbital | 0/8 (0%) | 8/8 (100%) |
| Gabapentin | 1/7 (14.3%) | 6/7 (85.7%) |
| Clozapine | 0/6 (0%) | 6/6 (100%) |
| Mirtazapine | 1/4 (25.0%) | 3/4 (75.0%) |
| Acetazolamide | 0/1 (0%) | 1/1 (100%) |
Some patients had used >1 medication.
Population-based study
Three (30.0%) of 10 cases who had ever been prescribed medication for their tremor had had stopped medication (Table 1).
Discussion
We examined data on more than 500 ET patients and a clear pattern that emerged across settings was that the proportion of ET patients who had stopped their medication was sizable; nearly one out of every three treatment-eligible ET patient is unmedicated, an indication of the limitations of our current pharmacotherapeutic options. Perhaps more revealing is that a similarly high proportion of ET cases with severe tremor had stopped their medication, a further indictment of the inadequacy of current medical options. Combining the three samples (n = 528), nearly one-third of the 353 ET cases who had been prescribed medication for their tremor had stopped taking ET medication (105/353 = 29.8%).
In one of our samples, data were available on the use of specific medications. For the four most commonly-used medications (propranolol, primidone, diazepam, topiramate), one-half or more of the treated patients had stopped the medication; among the less commonly used medications, the proportion who stopped was even higher. Even among patients on newer medications, the proportion who had stopped was high.
How do these results compare to patients with other chronic conditions? Studies of other chronic conditions indicate that a sizable proportion of patients stop taking medication. A study of persistence on lipid lowering therapies after stroke found that 39% of patients had discontinued therapy one year after discharge [4]. Mild side effects were the most commonly supplied reason for discontinuation; lack of efficacy was not a reason [4]. In a study of patients with Type II diabetes mellitus, nonpersistence on medications was 37.0% at one year [5]. In a study of patients with hypertension [6], 14% reported that they had stopped taking their medication. Among this 14%, 46% has stopped medication because they believed that their blood pressure had normalized and that they were cured; however, none reported doing so due to lack of efficacy.
A limitation of this study is that we did not collect data on the reason for stopping medications; hence we are unable to elaborate on the reasons for discontinuing drugs. In general, the most likely reason for stopping medications is intolerable side effects; however, limited therapeutic efficacy is another likely reason in ET. Studies of medical adherence in patients with other conditions (e.g., hypertension), indicate that among the most common reasons for non-adherence are side effects ascribed to medication and general dislike of drugs [7] as well as perceived low medication efficacy [8].
This study had limitations. As noted above, we did not collect data on reason for medication discontinuation and hope that this study will stimulate future collection of such data. Also, our data were cross-sectional. Collection of prospective, longitudinal data would be of additional value as it would avoid problems with retrospective recall.
Nearly one out of every three treatment-eligible ET patient is unmedicated and one-third of cases with severe tremor were unmedicated. These data both make evident that current pharmacotherapeutic options for ET are severely limited, and they provide further impetus to advance the current state of treatment.
Acknowledgments
Funding Source: R01 NS039422 (NIH).
References
- 1.Zesiewicz TA, Elble R, Louis ED, et al. Practice parameter: therapies for essential tremor: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2005;64:2008–2020. doi: 10.1212/01.WNL.0000163769.28552.CD. [DOI] [PubMed] [Google Scholar]
- 2.Thanvi B, Lo N, Robinson T. Essential tremor-the most common movement disorder in older people. Age Ageing. 2006;35:344q–349. doi: 10.1093/ageing/afj072. [DOI] [PubMed] [Google Scholar]
- 3.Louis ED, Rios E, Applegate LM, Hernandez NC, Andrews HF. Jaw tremor: prevalence and clinical correlates in three essential tremor case samples. Mov Disord. 2006;21:1872–1878. doi: 10.1002/mds.21069. [DOI] [PubMed] [Google Scholar]
- 4.Colivicchi F, Bassi A, Santini M, Caltagirone C. Discontinuation of statin therapy and clinical outcome after ischemic stroke. Stroke. 2007;38:2652–2657. doi: 10.1161/STROKEAHA.107.487017. [DOI] [PubMed] [Google Scholar]
- 5.Hertz RP, Unger AN, Lustik MB. Adherence with pharmacotherapy for type 2 diabetes: a retrospective cohort study of adults with employer-sponsored health insurance. Clin Ther. 2005;27:1064–1073. doi: 10.1016/j.clinthera.2005.07.009. [DOI] [PubMed] [Google Scholar]
- 6.Gallup G, Jr, Cotugno HE. Preferences and practices of Americans and their physicians in antihypertensive therapy. Am J Med. 1986;81:20–24. doi: 10.1016/0002-9343(86)90524-3. [DOI] [PubMed] [Google Scholar]
- 7.Svensson S, Kjellgren KI, Ahlner J, Saljo R. Reasons for adherence with antihypertensive medication. Int J Cardiol. 2000;76:157–163. doi: 10.1016/s0167-5273(00)00374-0. [DOI] [PubMed] [Google Scholar]
- 8.Gatti ME, Jacobson KL, Gazmararian JA, Schmotzer B, Kripalani S. Relationships between beliefs about medications and adherence. Am J Health Syst Pharm. 2009;66:657–664. doi: 10.2146/ajhp080064. [DOI] [PubMed] [Google Scholar]