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• W3000317468 abstract "Huntington's disease (HD) is an inherited autosomal-dominant progressive neurodegenerative disorder without any hitherto-established curative or disease-modifying treatments. Most patients with advanced HD can scarcely live alone because of the choreic movements and declined cognitive functions with psychiatric symptoms. We report a case of successful symptomatic treatment for choreic movements as well as psychiatric symptoms for an HD patient with brexpiprazole, a partial dopamine D2 receptor agonist-antipsychotic, who was successfully discharged from the hospital; the patient otherwise had no choice but to be continuously hospitalized in a neuropsychiatric unit. To the best of our knowledge, this is the first case report of treatment of an HD patient with brexpiprazole. The patient was a 41-year-old man with a 7-year history of suffering from chorea and cognitive decline, in whom the diagnosis of HD was confirmed by molecular genetic testing; the causative gene contained as many as 56 cytosine-adenine-guanine repeats. Owing to his impulsivity and aggression, he often hit his face and was sometimes covered in blood. Therefore, he was hospitalized in the neuropsychiatric unit of our hospital. On admission, he needed assistance with walking due to his postural instability and chorea, which consisted of brief, abrupt, irregular, and unpredictable movements of his limbs and torso along with a darting tongue. We decided not to treat him with tetrabenazine, a vesicular monoamine transporter 2 inhibitor, which makes psychiatric symptoms worse, because he had suicidal intention, anxiety, and aggression. Moreover, other antipsychotics, such as olanzapine and aripiprazole, were not options because he had aspiration pneumonia and rhabdomyolysis, and both symptoms would have gotten worse due to oversedation along with the extrapyramidal symptoms observed in these drug classes. Thus, we started with brexpiprazole, instead of olanzapine and aripiprazole, at 1 mg/day with the dose increased up to 2 mg/day over a period of 2 weeks. Dramatic improvement of the motor and psychiatric symptoms was observed, without any obvious side-effects. His score on the motor sub-item of the Unified Huntington's Disease Scale (UHDRS1; best: 0, worst: 128), which had been 61 prior to the start of treatment with brexpiprazole, decreased to 38 after 6 weeks of treatment with the drug. Furthermore, the scores on all items associated with postural instability, such as gait, tandem gait, and pull test score in the UHDRS, decreased from 2, 3, and 1 to 1, 1, and 0 after treatment, respectively, which indicates amelioration of postural instability. In his daily situation, we observed that his postural instability improved markedly and his gait became so smooth and stable that he was able to climb up stairs without assistance in the ward. The choreiform movements were moderately decreased. His daily living abilities improved to the point where the score on the Functional Independence Measure (best: 126, worst: 18), which had been 97 at admission, increased to 111. His psychomotor aggression, agitation, and suicidal behaviors disappeared altogether. After 8 weeks of treatment with brexpiprazole, he could be discharged from the hospital. Aripiprazole, a dopamine system stabilizer through its unique mechanism of dopamine D2 receptor partial agonist, is an option for the treatment of chorea in HD patients because it is hypothesized that chorea in HD is related to overstimulation of the dopaminergic receptor of the striatum. A small crossover study showed that patients showed better tolerability, without much sedation or sleepiness, for aripiprazole compared to other antipsychotics.2 Brexpiprazole, the newest dopamine D2 partial agonist antipsychotic, might have an advantage over aripiprazole for the treatment of choreic movements in HD because the intrinsic activity at D2 receptors of brexpiprazole is assumed to be approximately two-thirds that of aripiprazole.3 Also, brexpiprazole has much greater potency at the 5HT1A, 5HT2A, and alpha 1B receptor compared to aripiprazole, making it a more favorable antipsychotic in terms of avoidance of oversedation and extrapyramidal signs.4 In fact, an open-label randomized controlled trial demonstrated that brexpiprazole was more effective than aripiprazole for impulsiveness and that brexpiprazole was well tolerated with lower incidence of extrapyramidal symptoms (akathisia and dystonic events) and sedation than aripiprazole.5 Moreover, our case showed remarkable improvement in choreic movements and postural instability, which may be attributed to brexpiprazole's stabilization effect on the dopamine system in the basal ganglia, including the caudate nucleus. In addition, brexpiprazole has partial agonistic and antagonistic activities at the serotonin 5HT1A and 5HT2A receptors, respectively,4 which presumably contribute to its therapeutic effect on psychiatric symptoms.6 Furthermore, antidepressant properties are greater with brexpiprazole than aripiprazole due to its stronger activity at the serotonin 5HT1A receptor.6 As for olanzapine, no randomized control studies have compared the efficacy and safety of brexpiprazole versus olanzapine. However, our choice had rationale because a network meta-analysis revealed that olanzapine tends to have a more sedative effect than brexpiprazole, but not significantly.7 Our case suggests that brexpiprazole may be a clinically useful treatment option for HD. However, we should emphasize that this is just a single case report. Further clinical trials are warranted to endorse the findings. Informed consent for publication of the patient's clinical details was obtained from the patient's parent. Off-label use in the treatment was approved by the local Ethics Committee. The authors declare that they have no conflict of interest about this letter." @default.
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• W3000317468 date "2020-02-07" @default.
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• W3000317468 title "Effectiveness of brexpiprazole in the treatment in a patient with Huntington's disease" @default.
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• W3000317468 doi "https://doi.org/10.1111/pcn.12982" @default.
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