Trichotieromania and Alopecia Areata Triggered by Aripiprazole-Methylphenidate Combo in an Autistic Child: The Nexus of Impulsivity-Compulsivity

Impulsivity-Compulsivity

Traditionally, compulsive disorders and impulsive disorders were regarded at opposite polarities- the former driven by harm-avoidance and the latter by reward-seeking. Convergent evidence from translational studies now suggests a shared tendency toward behavioural disinhibition, from failures in top-down cortical control of fronto-striatal circuits or overactivity within the striatal circuity. Neurocognitive models posit the existence of separate yet intercommunicating compulsive and impulsive cortico-striatal circuits differentially modulated by neurotransmitters. Anatomical overlap between these functional systems does exist, so that what starts out as a problem in the impulsive circuit may end up as a problem in the compulsive circuit and vice versa.¹

Both autism spectrum disorder (ASD) and trichotillomania (TTM) share the same neurocircuity, that is, fronto-striatal, hence, it comes as no surprise, that both conditions are closely interrelated. This is amply exemplified in the following report.

Case Vignette

A 9-year-old male Kuwaiti boy presented to our outpatient clinic in accompaniment of his parents for long-standing ADHD-like symptom profile and episodic behavioral dyscontrol. He was long diagnosed, in developmental paediatrics, as essential low-functioning ASD, mild ID, non-verbal, non-epileptic and enrolled in special schooling. As reported by parents, he was hyperactive, cranky, disruptive with continuous body rocking movements and disturbed sleep (difficulty falling asleep and frequent nocturnal awakenings). There was escalating aggression lately and he was suspended from school. He was meticulously scrutinized for medical and environmental causations that could be contributory to this behavioral decompensation with negative yield. He was metabolically prone (50 kg) with strong family history of T1D. He was started on aripiprazole (ARIP) 2 mL/d nocte. Methylphenidate-IR (MPH) 5 mg tds was then introduced. A tangible improvement was noticed over few days with great somatic tolerability, as reported by parents and he was able to go back to school. ARIP and MPH were both increased to 5 mL and 30 mg/d respectively, over a week, with better behavioural response. On this regimen, patient was noticed to engage in a compulsive habit of rubbing and removing his scalp hair and eyebrows as well leaving bald patches especially over temples- alopecia areata. This has never been reported by parents before. Diversion techniques were helpful initially but only temporarily. He would soon indulge into these behaviours over and over again. If prevented by his parents, he would turn frenzy and destructive. This was clearly distressing to parents and requested to stop medications altogether. ARIP and MPH were then phased out. To our surprise, these complex behaviours have totally abated in a week but at the expense of behavioural deterioration. Drug-related trichotieomania (vide infra) was entertained retrospectively with Naranjo Adverse Drug Reaction Scale scoring 7 (‘probable’). He was shifted to risperidone (RISP) (1 mL/d on 2 divided doses) in lieu, with metformin (1000 mg/d) from outset. Dietary advice was also summoned. He responded favourably to RISP with better behavioural facets and most importantly, no trichotieromania was observed. Weight plateaued at 44 kg. Only S. PRL was high at 350 U but asymptomatically. Sixteen weeks have elapsed at time of writing this report, and he keeps faring well with no tolerability issue. He is also being engaged in OT sessions. Parents’ viva voce consent was obtained beforehand to report this case anonymously.

Discussion

Trichotillomania (TTM),² or hair-pulling, is currently classified, in DSM-5, as an OCD-related disorder resulting in hair loss. Term was first coined by Francois Henri Hallopeau in 1889.

Certain variants, although less common than TTM, have been described in literature. These include trichorrhizophagia, where patients eat roots of plugged hair which could result in trichophytobezoar and the rare Rapunzel’s syndrome.³ Trichotemnomania is compulsive habit to remove hair by shaving. Trichodaganomania is a compulsive habit of biting one’s own hair. Trichoteiromania is a compulsive habit of rubbing one’s hair—as in our case here.

Working differential in this report include de novo RRBs (repetitive and restricted behaviours) as part of ASD⁴—this is unlikely as these tend to be seen earlier on and represent high-order behaviours for a low-functioning ASD. Another possibility is MPH-exacerbated OCRD (obsessive-compulsive related disorders)—again, this seems unlikely given the ego-syntonic nature of these behaviours and the explosive reactions to interruption. Last but not least, it could be part of DDS (dopamine dysregulation syndrome). DDS/hedonic homeostatic syndrome (AKA as Lees’ syndrome) has been described with dopamine replacement therapy in Parkinson disease, where impulse dyscontrol is secondary to excessive dopamine stimulation. Given the temporal relationship between trichotieromania in this report to starting meds, disappearance on halting meds, absence of other alternative explanations, and the robust response to tight D2 blockade by risperidone, these make DDS very likely and might be mechanistically attributed to boosting of DA tone in PFC by MPH and partial DA agonistic activity (70%) by aripiprazole. MPH-IR pharmacokinetics might account for the rapid appearance/disappearance of trichotieromania in challenging-dechallenging paradigm. ARIP has been reported to also disinhibit impulses, and FDA has warned against it since 2016.

In tandem with this case, we have previously reported on two cases with iatrogenic oniomania related to aripiprazole and MPH,⁵ although in neurotypical subjects. Also, we have reported before on punding in an autistic child on the same combo.⁶

ASD population might be at heightened vulnerability by virtue of young age, male gender, and neuro-disability. It behooves clinicians to be vigilant to such iatrogenic behavioural syndromes where potent DA blockade is then indicated.