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In This Article
 »  Abstract
 » Introduction
 » Case Report
 » Discussion
 » Acknowledgement
 »  References

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 Table of Contents    
Year : 2011  |  Volume : 43  |  Issue : 5  |  Page : 601-602

Quadriparesis and dysarthria due to tetrabenazine therapy in a child with rheumatic chorea

Department of Pediatrics, Lokmanya Tilak Municipal General Hospital and Medical College, Sion, Mumbai 400 022, India

Date of Submission28-Jan-2011
Date of Decision16-Feb-2011
Date of Acceptance01-Jul-2011
Date of Web Publication15-Sep-2011

Correspondence Address:
Syed Ahmed Zaki
Department of Pediatrics, Lokmanya Tilak Municipal General Hospital and Medical College, Sion, Mumbai 400 022
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0253-7613.84982

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 » Abstract 

Tetrabenazine (TBZ) is widely used to treat hyperkinetic movement disorders in adults; however, published experience with the drug in children is limited. Common side effects of TBZ include drowsiness, sedation, weakness, Parkinsonism, depression, and acute akathisia, all of which are reversible with decreased doses. We report here a 7-year-old girl with rheumatic chorea who developed acute akinesia of all four limbs and dysarthria due to TBZ therapy. Withdrawal of the drug led to rapid improvement within 18 hours.

Keywords: Dysarthria, parkinsonism, quadriparesis, rheumatic chorea, tetrabenazine

How to cite this article:
Zaki SA, Lad V, Shanbag P. Quadriparesis and dysarthria due to tetrabenazine therapy in a child with rheumatic chorea. Indian J Pharmacol 2011;43:601-2

How to cite this URL:
Zaki SA, Lad V, Shanbag P. Quadriparesis and dysarthria due to tetrabenazine therapy in a child with rheumatic chorea. Indian J Pharmacol [serial online] 2011 [cited 2023 Dec 3];43:601-2. Available from: https://www.ijp-online.com/text.asp?2011/43/5/601/84982

 » Introduction Top

Tetrabenazine (TBZ) was initially synthesized in 1950s as an antipsychotic drug. [1] Although it has been widely used for the treatment of hyperkinetic movement disorders in adults, reports of its use in pediatric population are limited. [2] Very few adverse drug reactions have been reported in children. [2] We report here a child with rheumatic chorea who developed acute akinesia of all four limbs and dysarthria on TBZ therapy.

 » Case Report Top

A 7-year-old girl was admitted with complaints of excessive sleepiness for one day, weakness in all four limbs for eight hours, and inability to speak for four hours. There was no history of fever, vomiting, bowel/bladder complaints, abdominal pain, jaundice, convulsion, or recent vaccination. Two days back, she was diagnosed to have rheumatic heart disease with chorea at a private clinic and was started on enalapril (0.3 mg/kg/day) and benzathine penicillin prophylactically. Echocardiography showed moderate mitral regurgitation, mild tricuspid, and pulmonary regurgitation. TBZ (100 mg/day in three divided doses) was prescribed for her chorea. Her development and family history were normal. On admission, she was afebrile with a heart rate of 96/min, respiratory rate of 24/min, and blood pressure of 98/70 mmHg. There was no pallor or icterus. Throat examination was normal. Cardiovascular examination revealed a pansystolic murmur of grade IV in the mitral area. She was able to comprehend but could not vocalize. Cranial nerve examination was normal. Tone was decreased in all four limbs. Power was 2/5 in all four limbs. Abdominal reflex was present and plantars were flexors bilaterally. Deep tendon reflexes were normal in all four limbs and there was no truncal weakness. There were no meningeal signs or involuntary movements. Rest of the systemic examination was normal. Last dose of TBZ was taken 9 hours earlier. On the basis of history and examination, an adverse effect of TBZ was suspected. One hour after admission, she started vocalizing. Power in all four limbs gradually increased and within 18 hours, she was able to walk. Involuntary movements reappeared in both the upper and lower limbs for which she was started on haloperidol, as patient refused to take TBZ again. This can be labeled as a type A class of adverse effect. It can be considered as probable/likely adverse drug reaction as per causality assessment of suspected adverse drug reaction. [3] After two days, she was discharged and on follow-up after two months, the involuntary movements are well controlled by haloperidol.

 » Discussion Top

TBZ is a benzoquinolizine derivative with the chemical name - 2-oxo-3-isobutyl-9,10-dimethoxy-1, 2, 3, 4, 6,7-hexahydrobenzo[a] quinolizine. [1] Although the drug never gained wide usage as an antipsychotic, it was found beneficial in hyperkinetic movement disorders. During the last two decades, TBZ has been used in a multitude of movement disorders like tardive dyskinesia, dystonia, tremor, choreic syndromes, primary and secondary dystonia, and tic disorders. [1] TBZ acts mainly as a reversible high-affinity inhibitor of monoamine uptake into granular vesicles of presynaptic neurons by binding selectively to vesicular monoamine transporter-2 (VMAT-2). [1],[4],[5] Also, it has been found that at high doses, TBZ blocks dopamine D2 receptors. [1],[4] The VMAT-2 is found mainly in the central nervous system and transports serotonin, dopamine, norepinephrine, and histamine into vesicles for storage. [4] TBZ more selectively depletes dopamine than other monoamines. [5] VMAT-2 binding and monoamine depletion by TBZ are reversible and are not modified by long-term treatment. [1] Although VMAT2 is located solely in the central nervous system, VMAT-1 is localized in the peripheral nervous system, accounting for the adverse effects such as orthostatic hypotension, abdominal pain, and diarrhea.

TBZ can be administered with food, has an oral absorption of at least 75% and a bioavailability of 0.049 ΁ 0.032. [4] It is rapidly metabolized in liver by carbonyl reductase into two compounds: Alpha (active form) and beta-dihydro-TBZ (inert form) (HTBZ). The C max of both forms is reached within 1.5 hours after dosing. Both alpha and beta forms of HTBZ have a high bioavailability and are less protein-bound (44 to 59%) in contrast to TBZ (83 to 88%). [4] In vitro studies indicate that a-HTBZ and b-HTBZ are O-dealkylated and hydroxylated by human liver microsomes. [4] Elimination of TBZ and its metabolites is primarily renal. It should not be prescribed for patients with suicidal tendencies, those with untreated or inadequately treated depression, or for patients with hepatic impairment. [4] It should not be used in conjunction with monoamine oxidase inhibitors or reserpine. Common side effects of TBZ include drowsiness, sedation, weakness,  Parkinsonism More Details, depression, and acute akathisia, all of which are reversible with decreased dose. Several studies have observed that younger patients tolerate TBZ better than the elderly. Other rare side effects include insomnia, loss of voice nervousness/anxiety, neuroleptic malignant syndrome, nausea and vomiting, tremor, memory problems, confusion, increased QT interval, orthostatic hypotension, balance and gait difficulties, dizziness, diarrhea, headaches, hallucinations, paresthesia, pharyngeal spasm and pain, blurred vision, dysphagia, panic attacks, paranoia, and suicide. [1],[4],[5] Dysarthria as an adverse effect of TBZ has not been reported in literature. The mechanism is probably similar to that seen in Parkinson's disease. The loss of volume, pitch, range, and intonation in the voice could be due to incoordination and reduced activity of muscles that control the speech mechanism. As the child was conscious and had an intact gag reflex, direct laryngoscopy to visualize the vocal cords was not attempted. TBZ should be started at 12.5 mg/d, and every week, the dose may be increased by 12.5 mg/d, dividing the drug in 3-times daily dose. [4],[5] The drug is titrated slowly to identify the lowest and best tolerated effective dose. [1],[4],[5] The patient in our case was started abruptly on a very high dose of TBZ, thereby increasing the chances of adverse reactions. It is recommended that patients who require doses greater than 50 mg/day should undergo genotyping for CYP 2D6 to determine whether they are poor, extensive, or intermediate metabolizers. [4],[5] As the drug is titrated to clinical effect and the genotyping has no impact on the clinical assessment of the patient, it is up to the provider to determine if this test should be performed. [5]

Most drug-related side effects can be alleviated by lowering the dose. [1],[4],[5] Since the half-life is short, side effects tend to wane quickly. [5] Tapering of the TBZ dose is not needed when the drug is being discontinued. Recurrence of chorea occurs within 12 to 18 hours of the withdrawal of TBZ. [4] However, the severity of involuntary movements does not worsen after withdrawal. If treatment is interrupted for less than five days, the previous maintenance dose can be resumed with no titration. [4]

 » Acknowledgement Top

We would like to thank the Dean of our institution for permitting us to publish this manuscript.

 » References Top

1.Paleacu D. Tetrabenazine in the treatment of Huntington's disease. Neuropsychiatr Dis Treat 2007;3:545-51.  Back to cited text no. 1
2.Jain S, Greene PE, Frucht SJ. Tetrabenazine therapy of pediatric hyper kinetic movement disorders. Mov Disord 2006;21:1966-72.  Back to cited text no. 2
3.Edwards IR, Aronson JK. Adverse drug reactions: Definitions, diagnosis and management. Lancet 2000;356:1255-9.  Back to cited text no. 3
4.Yero T, Rey JA. Tetrabenazine (Xenazine), An FDA-Approved Treatment Option For Huntington's Disease-Related Chorea. P T 2008;33:690-4.  Back to cited text no. 4
5.Frank S. Tetrabenazine: The first approved drug for the treatment of chorea in US patients with Huntington disease. Neuropsychiatr Dis Treat 2010;6:657-65.  Back to cited text no. 5

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