Elsevier

Parkinsonism & Related Disorders

Volume 32, November 2016, Pages 124-126
Parkinsonism & Related Disorders

Short communication
Propranolol therapy for Tardive dyskinesia: A retrospective examination

https://doi.org/10.1016/j.parkreldis.2016.09.004Get rights and content

Highlights

  • There are no approved treatments for Tardive dyskinesia (TD).

  • 47 patients with TD were examined retrospectively for response to propranolol.

  • 64% responded, 77% of these to a moderate or significant level.

  • Propranolol was well tolerated.

Abstract

Objective

To examine the tolerability and effectiveness of propranolol in treating tardive dyskinesia (TD).

Background

TD is a disabling, often irreversible, movement disorder that results from chronic therapy with dopamine receptor blocking drugs. There are no treatments currently approved for this disorder. Propranolol, a β-adrenergic blocker, has been reported to alleviate TD in case series and reports.

Methods

Retrospective database search of the Emory movement disorder clinic for TD patients treated with propranolol. All patients identified with at least one follow-up evaluation had records reviewed and responsiveness assessed. Logistic regression analysis examined for predictors of response.

Results

Forty-seven patients were analyzed, mean age 63 years. Neuroleptics were discontinued in all patients and duration of TD at the time propranolol was initiated 17 months. Mean severity of TD, based on a 0–3 scale (0 = none, 1 = mild, 2 = moderate, 3 = severe) was 2.2. Mean response, based on a 0–3 scale (0 = no response, 1 = mild response, 2 = moderate response, 3 = complete or near-complete response) was 1.4. Propranolol resulted in improvement in 64% and 77% of those had a moderate to complete or near-complete response. Mean daily dose was 69 mg and duration of therapy 14 months. Three patients stopped the propranolol due to adverse effects: hypotension (2), nightmares (1). Severity of TD and duration of propranolol therapy were associated with response.

Conclusion

Low dose propranolol appears to be well tolerated and effective in treating TD. A prospective randomized trial is warranted.

Introduction

Tardive dyskinesia (TD), a significant public health problem, is an iatrogenic movement disorder caused by exposure to dopamine-receptor antagonists which are used to treat psychiatric disease, gastrointestinal disorders and migraine [1]. It can cause abnormal movement disorders in any body part although the orofacial region is most common. The type of movement disorder can be varied including syndromes with chorea, stereotypy, dystonia, tics, myoclonus and akathisia. TD can be very disabling causing difficulty speaking, chewing, swallowing and tongue mutilation in the orofacial cases. Truncal and limb movements are even more impactful including limb chorea, truncal dystonia, rhythmic rocking or thrusting motions, and respiratory dyskinesia, which can be life threatening [2]. Data have shown that approximately 87% of cases are irreversible after 3 years of follow-up following discontinuation of the inciting agent [3]. Both typical and atypical antipsychotics can cause TD and prescribing data have shown a threefold increase in the use of these drugs, mostly for nonpsychotic symptoms [4]. Considering the incidence, prevalence and reversibility figures nearly a million Americans treated for psychiatric issues alone are afflicted with this disorder [1] and this number increases when considering those with gastrointestinal (GI) illness and migraine. The pathophysiology of TD is complex but central is the development of increased density and sensitivity of the dopamine receptors [5].

Despite significant disability and rising prevalence, there are no medications specifically approved for the treatment for TD and inappropriate management is common. Currently, the most common class of drugs used are vesicular monoamine transporter 2 (VMAT2) inhibitors, such as tetrabenazine, which deplete dopamine. While often effective, tetrabenazine is not well tolerated, particularly by the elderly, because of drug-induced parkinsonism, akathisia and depression [1]. Further, the only drugs in development for TD at this time are other VMAT2 inhibitors [6].

Propranolol, a β-adrenergic blocker, was FDA-approved in 1967 for cardiovascular disease and is used in other disorders such as migraine, essential tremor, akathisia and anxiety. We recently published several cases demonstrating a significant response of TD to propranolol [7]. As a result of this experience propranolol is frequently used in our clinic to treat this disorder. This treatment for TD has biological plausibility as it has been shown that propranolol modulates dopaminergic activity through presynaptic attenuation of dopamine efflux [8]. The purpose of this retrospective study was to further examine the tolerability and effectiveness of propranolol in treating TD.

Section snippets

Patients

Approval was obtained through an expedited review process from the Emory institutional review board for development of a patient database and medical record review in the movement disorder clinic. We performed a database search of Emory movement disorder clinic for TD patients (using ICD 9 code 333.85) treated with propranolol from 2006 to 2015. This was followed by a record review of all cases found who had at least one follow-up visit. Data collected from the records included: age, duration

Results

There were 58 patients in our database with TD and a history of being treated with propranolol. Of these we excluded 11: nine without follow-up, one who was prescribed but did not take propranolol, and one who did not have a diagnosis TD. Forty-seven patients were evaluated and all of them stopped neuroleptics prior to propranolol therapy. The mean age at presentation was 62.95 years (SD 15.47), 79% were women, mean duration of neuroleptic therapy before onset of TD was 77.47 months (SD 94.65),

Discussion

Propranolol was examined in the early 1980s as a possible treatment for TD. The reports were mostly open label single cases or case series (26 total subjects, largest series was 10 subjects) with one double-blind, crossover design study of four additional subjects [9] [10]. Over 50% of the patients were reported to have a rapid response to doses of </ = 80 mg. The blinded study did not show rapid response but two patients did demonstrate significant long term benefit. They utilized 10 times the

Conflicts of interest

None.

Disclosures

Dr. Martin has the following disclosures: Honoraria: Teva, Apple Inc.

Dr. Scorr and Dr. Armstrong have nothing to disclose.

Dr. Factor has the following disclosures: Honoraria: Neurocrine, Lundbeck, Auspex/Teva, Avanir, Cynapsus, Adamas, UCB. Grants: Ipsen, Allergan, Medtronics, Auspex, US World Meds, Pharm-Olam, Cynapsus Therapeutics, Solstice, CHDI Foundation, Michael J. Fox Foundation, NIH. Royalties: Demos, Blackwell Futura for textbooks, Uptodate

Author contributions

J. Hatcher-Martin: Drafting and revising manuscript, Study concept or design, Analysis or interpretation of data, Acquisition of data.

K.A. Armstrong: Revising the manuscript for content, analysis or interpretation of data, Statistical analysis.

L.M. Scorr: Revising the manuscript for content, analysis or interpretation of data, Statistical analysis.

S.A. Factor: Drafting and revising manuscript, Study concept or design, Analysis or interpretation of data, Acquisition of data, Study supervision or

Funding

JMHM was supported by the National Parkinson's Foundation and the Bumpus Foundation. KAA was supported by NINDS 5U10NS077366-05. SAF was supported by The Sartain Lanier Family Foundation, Inc and NINDS 5U10NS077366-05. LMS was supported by the Dystonia Medical research Foundation.

References (15)

  • L.J. Cloud et al.

    Tardive dyskinesia: therapeutic options for an increasingly common disorder

    Neurotherapeutics

    (2014)
  • M.R. Samie et al.

    Life-threatening tardive dyskinesia caused by metoclopramide

    Mov. Disord.

    (1987)
  • D. Zutshi et al.

    Tardive syndromes are rarely reversible after discontinuing dopamine receptor blocking agents: experience from a university-based movement disorder clinic

    Tremor Other Hyperkinetic Mov.

    (2014)
  • M. Olfson et al.

    National trends in the office-based treatment of children, adolescents, and adults with antipsychotics

    Arch. Gen. Psychiatry

    (2012)
  • S. Silvestri et al.

    Increased dopamine D2 receptor binding after long-term treatment with antipsychotics in humans: a clinical PET study

    Psychopharmacol. Berl.

    (2000)
  • C.F. O'Brien et al.

    NBI-98854, a selective monoamine transport inhibitor for the treatment of tardive dyskinesia: a randomized, double-blind, placebo-controlled study

    Mov. Disord.

    (2015)
  • S.A. Factor

    Propranolol therapy for tardive dyskinesia revisited

    Mov. Disord.

    (2012)
There are more references available in the full text version of this article.

Cited by (0)

View full text