Short communicationPropranolol therapy for Tardive dyskinesia: A retrospective examination
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.
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