Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 Dec 6;2015(12):CD009681.
doi: 10.1002/14651858.CD009681.pub2.

Alprazolam for essential tremor

Elisa Bruno  1 , Alessandra Nicoletti, Graziella Quattrocchi, Graziella Filippini, Mario Zappia, Carlo Colosimo
Affiliations

Alprazolam for essential tremor

Elisa Bruno et al. Cochrane Database Syst Rev. .

Abstract

Background: Essential tremor (ET) is one of the most common movement disorders. Treatment is based primarily on pharmacological agents. On this basis, although primidone and propranolol are well-established treatments in clinical practice, they could be ineffective in 25% to 55% of patients and can produce serious adverse events (AEs) in a large percentage of individuals. For these reasons, evaluating treatment alternatives for ET may be a worthwhile pursuit. Alprazolam has been suggested as a potentially useful agent for treatment of individuals with ET, but its efficacy and safety are uncertain.

Objectives: PrimaryTo assess the efficacy and safety of alprazolam in the treatment of individuals with ET. SecondaryTo examine effects of alprazolam treatment on the quality of life of people with ET.

Search methods: We carried out a systematic search without language restrictions to identify all relevant trials. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (January 1966 to September 2015), EMBASE (January 1988 to September 2015), the National Institute for Health and Care Excellence (NICE) (1999 to September 2015), ClinicalTrials.gov (1997 to September 2015) and the World Health Organiza tion (WHO) International Clinical Trials Registry Platform (ICTRP) (2004 to September 2015). We handsearched grey literature and examined the reference lists of identified studies and reviews.

Selection criteria: We included all randomised controlled trials (RCTs) of alprazolam versus placebo or any other treatment. We included studies in which ET was diagnosed according to accepted and validated diagnostic criteria. We excluded studies that included patients presenting with secondary forms of tremor or reporting only neurophysiological parameters for the pur p ose of assessing outcomes.

Data collection and analysis: Two review authors independently collected and extracted data using a data collection form. We assessed risk of bias and the body of evidence. We used inverse variance methods for continuous outcomes and measurement scales. We compared differences between treatment groups as mean differences. We used Review Manager software for management and analysis of data.

Main results: We included in this review one trial that compared alprazolam versus placebo (24 participants). It was judged to have high overall risk of bias. We graded the overall quality of evidence as very low. Compared with those given placebo, participants treated with alprazolam showed a significant reduction in tremor severity (mean difference (MD) -0.75, 95% confidence interval (CI) -0.83 to -0.67). Nine alprazolam-treated participants (75%) developed AEs, mainly represented by sedation (50%), constipation (17%) and dry mouth (9%). No participants in the alprazolam group and no p articipants in the placebo group discontinued treatment and dropped out of the study.

Authors' conclusions: Currently available data reveal evidence insufficient for assessment of the efficacy and safety of alprazolam treatment for individuals with ET.

PubMed Disclaimer

Conflict of interest statement

The original review was not compliant with Cochrane Commercial Sponsorship policy for the following reasons:

CC received financial support from Merz (manufacturer of Botulinum toxin), Teva (manufacturer of propranolol) and other pharma companies. AN received financial support from Lundbeck (manufacturer of benzodiazepine clobazam) and UCB (manufacturer of levetiracetam). MZ received financial support from Novartis (manufacturer of propranolol [Sandoz]), UCB, Lundbeck and other pharma companies.

Conversely, the current update have a majority of authors and lead author free of conflicts as the lead author and all the other authors have not received payments from manufacturers or marketers of the interventions of interest or potential comparators within the 3 years of the decision to update and none of the authors are/were employed by a company who has a real or potential financial interest in the findings of the review and/or have a relevant patent.

Figures

1
1
Flowchart of the literature search on alprazolam and essential tremor.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1: Comparison for efficacy, Outcome 1: Clinical rating scale
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Huber 1988 {published data only}
    1. Huber SJ, Paulson GE. Efficacy of alprazolam for essential tremor. Neurology 1988;38:241-3. - PubMed

References to studies excluded from this review

Ibanez 2014 {published data only}
    1. Ibanez J, la Aleja JG, Gallego JA, Romero JP, Saiz-Diaz RA, Benito-Leon J, et al. Effects of alprazolam on cortical activity and tremors in patients with essential tremor. PLoS One 2014;9(3):e93159. - PMC - PubMed

References to studies awaiting assessment

Gunal 2000 {published data only}
    1. Gunal DI, Afsar N, Nekiroglu N, Aktan S. New alternative agents in essential tremor therapy: double-blind placebo-controlled study of alprazolam and acetazolamide. Neurological Science 2000;21:315-7. - PubMed

Additional references

Bain 1997
    1. Bain PG. The effectiveness of treatments for essential tremor. Neurology 1997;3:305-21.
Bain 1998
    1. Bain PG. Clinical measurement of tremor. Movement Disorders 1998;13(Suppl 3):77-80. - PubMed
Bain 2000a
    1. Bain P, Brin M, Deuschl G, Elble R, Jankovic J, Findley L, et al. Criteria for the diagnosis of essential tremor. Neurology 2000;54(Suppl 4):S7. - PubMed
Bain 2000b
    1. Bain PG. Tremor assessment and quality of life measurements. Neurology 2000;54(Suppl 4):S26-9. - PubMed
Busenbark 1991
    1. Busenbark KL, Nash J, Nash S, Hubble JP, Koller WC. Is essential tremor benign? Neurology 1991;41:1982-3. - PubMed
Chouinard 1997
    1. Chouinard S, Luois ED, Fahn S. Agreement among movement disorder specialists on the clinical diagnosis of essential tremor. Movement Disorders 1997;12(6):973-6. - PubMed
Deuschl 1998
    1. Deuschl G, Bain P, Brin M. Consensus statement of the Movement Disorder Society on tremor. Movement Disorders 1998;14(Suppl 3):s2-23. - PubMed
Deuschl 2000
    1. Deuschl G, Koller WC. Essential tremor. Neurology 2000;54(Suppl 4):S1. - PubMed
Fahn 1993
    1. Fahn S, Tolosa E, Marin C. Clinical rating scale for tremor. In: Jankovic J, Tolosa E, editors(s). Parkinson's Disease and Movement Disorders. 6th edition. Baltimore, MD: Williams & Wilkins, 1993.
Findley 1995
    1. Findley LJ, Koller W. Definitions and behavioural classifications. In: Findley LJ, Koller W, editors(s). Handbook of Tremor Disorders. New York: Dekker, 1995:1-5.
Haerer 1992
    1. Haerer AF, Anderson DW, Schoenberg BS. Prevalence of essential tremor: results from the Copiah County study. Archives of Neurology 1992;39:750-1. - PubMed
Hansten 2004
    1. Hansten PD, Horn JR. Managing Clinically Important Drug Interactions. 4th edition. St. Louis, MO: Facts & Comparisons, 2004.
Higgins 2003
    1. Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003;327:557-60. - PMC - PubMed
Higgins 2011
    1. Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. www.cochrane-handbook.org.
Jankovic 1996
    1. Jankovic J, Schwartz K, Clemence J. A randomized, double-blind, placebo controlled study to evaluate botulinum toxin type A in essential tremor. Movement Disorders 1996;11:250-6. - PubMed
Jankovic 2002
    1. Jankovic J. Essential tremor: a heterogeneous disorder. Movement Disorders 2002;17:638-44. - PubMed
Koller 1986
    1. Koller W, Biary N, Cone S. Disability in essential tremor: effect of treatment. Neurology 1986;36:1001-4. - PubMed
Koller 1989
    1. Koller WC, Vetere-Overfield B. Acute and chronic effects of propranolol and primidone in essential tremor. Neurology 1989;39:1587-8. - PubMed
Kralic 2005
    1. Kralic JE, Criswell HE, Osterman JL, O'Buckley TK, Wilkie ME, Matthews DB, et al. Genetic essential tremor in gamma-aminobutyric acid A receptor alpha1 subunit knockout mice. The Journal of Clinical Investigation 2005;115:774-9. - PMC - PubMed
Louis 1998
    1. Louis ED, Ford B, Lee H. Diagnostic criteria for essential tremor. Archives of Neurology 1998;55:823-8. - PubMed
Louis 2001a
    1. Louis ED. Clinical practice, essential tremor. New England Medical Journal 2001;342(12):887-91. - PubMed
Louis 2001b
    1. Louis ED, Barnes L, Wendt KJ, Ford B, Sangiorgio M, Tabbal S, et al. A teaching videotape for the assessment of essential tremor. Movement Disorders 2001;16:89-93. - PubMed
Louis 2005
    1. Louis ED. Essential tremor. Lancet Neurology 2005;4:100-10. - PubMed
Louis 2010
    1. Louis ED, Ferreira JJ. How common is the most common adult movement disorder? Update on the worldwide prevalence of essential tremor. Movement Disorders 2010;25(5):534-41. - PubMed
Pahwa 2003
    1. Pahwa R, Lyons KE. Essential tremor: differential diagnosis for the development of novel therapeutics. American Journal of Medicine 2003;115:134-42. - PubMed
Rejput 1984
    1. Rajput AH, Offord KP, Beard CM, Kurland LT. Essential tremor in Rochester, Minnesota: a 45-year study. Journal of Neurology, Neurosurgery and Psychiatry 1984;47:466-70. - PMC - PubMed
Salemi 1994
    1. Salemi G, Savettieri G, Rocca WA, Meneghini F, Saporito V, Morgante L, et al. Prevalence of essential tremor: a door to-door survey in Terrasini, Sicily. Neurology 1994;44:61-4. - PubMed
Sibbald 1998
    1. Sibbald B, Roberts C. Understanding controlled trials: crossover trials. BMJ 1998;316(7146):1719-20. - PMC - PubMed
Snow 1989
    1. Snow B, Wiens M, Hertzman C, Calne D. A community survey of Parkinson's disease. Canadian Medical Association Journal 1989;141:418-24. - PMC - PubMed
Sullivan 2004
    1. Sullivan KL, Hauser RA, Zesiewicz TA. Essential Tremor Epidemiology, Diagnosis, and Treatment. Philadelphia, PA: Lippincott Williams & Wilkins, 2004. - PubMed
Thompson 1984
    1. Thompson C, Lang A, Parkes JD, Marsden CD. A double-blind trial of clonazepam in benign essential tremor. Clinical Neuropharmacology 1984;7:83-8. - PubMed
Wasielewski 1998
    1. Wasielewski PG, Burns JM, Koller WC. Pharmacologic treatment of tremor. Movement Disorders 1998;13(Suppl 3):90-100. - PubMed
Zappia 2013
    1. Zappia M, Albanese A, Bruno E, Colosimo C, Filippini G, Martinelli P, et al, Italian Movement Disorders Association (DISMOV-SIN) Essential Tremor Committee. Treatment of essential tremor: a systematic review of evidence and recommendations from the Italian Movement Disorders Association. Journal of Neurology 2013;260(3):714-40. - PubMed
Zesiewicz 2002
    1. Zesiewicz TA, Encarnacion E, Hauser RA. Management of essential tremor. Current Neurology and Neuorscience Reports 2002;2:324-30. - PubMed
Zesiewicz 2005
    1. Zesiewicz TA, Elble R, Louis ED, Hauser RA, Sullivan KL, Dewey RB Jr, et al. Practice parameter: therapies for essential tremor: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2005;64(12):2008-20. - PubMed
Zesiewicz 2011
    1. Zesiewicz TA, Elble RJ, Louis ED, Gronseth GS, Ondo WG, Dewey RB Jr, et al. Evidence-based guideline update: treatment of essential tremor: report of the Quality Standards subcommittee of the American Academy of Neurology. Neurology 2011;77(19):1752-5. - PMC - PubMed

Publication types

LinkOut - more resources