{'fraction_non_alphanumeric': 0.03014265991716521, 'fraction_numerical': 0.01150483202945237, 'mean_word_length': 5.44, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Dose-Dependent Aripiprazole-Induced Stuttering in a Child With Mild Intellectual Disability.

To the Editor: An 11-year-old Kuwaiti boy with mild intellectual disability (nonsyndromic, nonepileptic, verbal, 35 Kg) was referred from developmental pediatrics for behavioral dyscontrol that failed to respond to behavioral modification. No environmental or medical causes for this behavioral decompensation could be detected. He has been trialled previously on risperidone with favorable outcome but at the expense of enormous weight gain. At parents’ request, swapping to the more metabolic friendly aripiprazole was pursued. He was started on 2 mg/d for a week. The dose was uptitrated to 5 mg/d over 2 weeks with only mediocre response. At 10 mg/d after 4 weeks, parents reported a tangible response in accordance with school records (special setting). However, at that dose, parents have noticed their child beginning to stutter. Neurological examination was unrevealing. Oto-rhino-laryngological consult was summoned with negative yield. Blood levels were obtained and read 85 ng/mL (ruled out toxic levels). Electroencephalogram was performed to rule out/in a remote possibility of epileptogenicity and nothing abnormal detected. Although no other (somatic/psychic) concomitants of anxiety could be probed on mental status examination, we adopted a rather lower threshold to introduce clonazepam at 0.75 mg/d. After 2 weeks, no improvement was seen regarding stuttering, which becomes socially embarrassing. Clonazepam was discontinued. Aripiprazole dose was reduced to 5 mg/d. Stuttering, lo and behold, has totally abated over 10 days. Behavioral facets, unfortunately, re-emerged. With cautiously increasing the dose back to 10 mg, stuttering reappeared. Naranjo Adverse Drug Reaction Probability scale scored 9 (definite). Aripiprazole, as the culprit agent, was then discontinued and replaced with risperidone again at 1 mg/d. Add-on metformin 1000 mg/d was coprescribed, and a dietary advice was sought out. Two months have elapsed at time of writing this report, and the child keeps faring well on risperidone with great tolerability. No stuttering anymore. Parents’ viva voce consent to report this case anonymously was obtained beforehand. Stuttering (or stammering/DSM-5 childhood-onset fluency disorder) describes disturbance in both timing and fluency of speech inappropriate to age. This is typified with the repetition and prolongation of sounds and syllables. Cluttering is the visual analogue of stuttering. Two types of stuttering are characterized in literature; viz. as developmental and nondevelopmental (acquired). Nondevelopmental stuttering may begin suddenly at any age and may be seen rarely due to the adverse effects of drugs.1 Nondevelopmental stuttering is rare and possibly dose-dependent side effect that has been reported with antipsychotics.2 Early reports suggested that antipsychotic-induced stuttering can be envisioned as an extrapyramidal syndrome.3 This has, however, been debunked by the fact that add-on anticholinergic benztropine failed to bring about any efficacy. Some has opined that stuttering could be a harbinger of future seizure.4 By contrast, developmental stuttering, based on functional imaging studies, has been ascribed to increased hyperdopaminergic tone in striatum, and hence the robust response to antipsychotic treatment, including aripiprazole.5 Abnormal patterns of cerebral hemispheric dominance in both anterior and posterior language areas might also be contributory.6 Immune-based mechanisms were also suggested as PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection).7 Aripiprazole-induced stuttering has similarly been reported previously in a 34-year-old woman with paranoid schizophrenia at 30 mg.8 In our case, stuttering developed at a relatively low dose. Intellectual disability population might have a heightened vulnerability. Mechanistically, it is difficult to explain the differential effects of risperidone, which has a potent dopaminergic D2 blockade. Aripiprazole D2 tenacity could be a factor.9 Psychotropic-induced dysarthria, including stuttering, should always alert clinicians to possible neurotoxicity. If this is ruled out, nondevelopmental stuttering might be a American Journal of Therapeutics 0, 1–2 (2020)