Tardive Dyskinesia After Aripiprazole Treatment That Improved With Tetrabenazine, Clozapine, and Botulinum Toxin

Abstract

We report on a patient with tardive dyskinesia (TDK) treated with aripiprazole, a third-generation antipsychotic with partial D2 agonist-antagonist activity at both the dopamine and serotonin receptors. The patient’s condition improved with administration of a combination of tetrabenazine, botulinum toxin, and clozapine, which has previously not been used. We suggest that this treatment combination may have potential benefits for patients with TDK. After aripiprazole discontinuation, the patient was treated with clozapine (150 mg/day) and biperiden (8 mg/day). Due to a lack of improvement, we administered 300 units (intramuscularly; IM) of botulinum toxin into the paravertebral muscles every 3 months and 1,000 units IM every 4 months in addition to tetrabenazine (75 mg/day) and biperiden (8 mg/day). The patient stopped this treatment, at which point TDK reappeared. After starting a treatment regimen of clozapine (100 mg/day), tetrabenazine (75 mg/day), and botulinum toxin (300 units IM), the patient’s symptoms remitted.

Drug-induced dyskinesias, can they be prevented?

“…Aguilar et al reported an aripiprazole-induced TD case in which botulinum toxin was used in combination with clozapine and tetrabensin. After the therapy was started, the patient's health improved significantly, and the dyskinetic symptoms were minimized [14]. The authors suggest that this combination of drugs, which has not been used before, may be of benefit to TD patients.…”

“…There is a reported case of a patient with TD induced with aripiprazole, which proves the therapeutic effect of clozapine. Clozapine was used in combination therapy with tetrabenazine and botulinum toxin [14]. Even though the drug has some restrictions (risk of agranulocytosis), it may be an effective alternative in the treatment of drugresistant TD.…”

“…Opisano przypadek pacjentki z TD indukowanym arypiprazolem, który potwierdza skuteczność działania terapeutycznego klozapiny, zastosowanej w terapii skojarzonej wraz z tetrabenazyną i toksyną botulinową [14]. Chociaż lek ma pewne ograniczenia (ryzyko agranulocytozy), może być skuteczną alternatywą w leczeniu nieodwracalnego TD.…”

“…Aguilar i inni opisali przypadek TD wywołanym przyjmowaniem arypiprazolu, w którym toksyna botulinowa znalazła zastosowanie w skojarzeniu z klozapiną i tetrabenzyną. Po wdrożeniu takiej terapii stan zdrowia pacjentki uległ znaczącej poprawie, a objawy dyskinetyczne zostały zminimalizowane [14]. Autorzy sugerują, że taka kombinacja leków, wcześniej nie stosowana może być korzystna u pacjentów z TD.…”

Treatment of Dystonia: Medications, Neurotoxins, Neuromodulation, and Rehabilitation

“…One exception is clozapine, a D4 receptor blocker (with relative sparing of D2 receptors), a drug that generally does not carry a significant risk of parkinsonism or tardive syndromes. Clozapine requires frequent blood draws to monitor for agranulocytosis but has shown efficacy in addressing tardive syndromes [49,52,53].…”