Successful Use of Sertindole for Severe Behavioral Dyscontrol in a Pediatric Case of Syndromic Autism Spectrum Disorder

Introduction

Autism spectrum disorder (ASD) is commonly coupled with a multitude of maladaptive challenging behaviors. Pharmacotherapy is indicated once psychosocial and educational interventions fail. A sound evidence base supports the use of atypical antipsychotics (AAPs) to address these behavioral facets. This is reflected in FDA approval of both risperidone and aripiprazole to tackle severe irritability (self-injury, tantrums, and aggression). Unfortunately, these agents are plagued with a myriad of side effects in this population who are at a heightened risk by virtue of diagnostic vulnerability and young age.

In this study, the author reported a case of syndromic ASD and moderate intellectual disability (ID) with a severe behavioral component that failed multiple psychotropic trials and developed metabolic and neuroendocrinal side effects, which ultimately responded to the AAP sertindole (at 12 mg/d) that brought about marked clinical improvement, reversed side effects, and above all, was well tolerated. Response was well sustained over the 6-month duration at the time of writing this report.

Case Vignette

A 9-year-old Egyptian boy, long diagnosed as syndromic ASD with moderate ID and following up with Developmental Pediatrics, was referred with associated neurobehavioral syndrome with difficult-to-treat self-injurious behaviors (SIBs, including eye poking, morsicatio palpebrarum, and onychotillomania), heteroaggression, hyperactivity, and multiple motor tics (sniffing and shoulder shrugging).

Mental Status Examination: General Appearance/Behavior: Portly habitus (48 kg). Dysmorphic. Poor eye contact. Detached. Lack of facial gestures. Obstreperous. Hyperactive. Multiple motor tics (sniffing, shoulder shrugging). Multiple callosities. Speech: delayed echolalia. Sing-song lallation. Mood/Affectivity: erratic/labile. Thought: reported idiosyncratic interests (collecting enormous amounts of paper clips and sorting by colors). Perception: hypersensitivity to sounds (covers his ears repeatedly). Cognition: looks distractible. Insight: Poor.

Work-up pursued is depicted in Table 1.

The patient has already been through multiple psychotropic trials with mediocre response at best; sleep has improved (7 hours) and psychomotor activity a little bit lessened, but both aggressivity and SIBs remained the same throughout, as reported by parents.

Sequential Trials, Medications Chart, Untoward Effects, and Clinical Outcome are shown in Table 2. Lack of efficacy and/or intolerability issues were the reasons behind prematurely aborting these trails.

Given the sluggish clinical response and side effects on these trials, we opted to embark on a time-bound trial of sertindole, basically for its metabolic friendly profile. Parents' consent was obtained beforehand.

Table 3 portrays the sertindole trial.

As shown, the outcome was remarkable, spanning different target symptoms. This was coupled with excellent metabolic and neurohormonal profile.

Of note, QTc remained within normal range all through.

This response was well sustained over the duration of 6 months at the time of writing this report.

Discussion

ASD is associated with a host of challenging behaviors that are impairing, and constitute a focus of clinical attention, primary cause of referral to child psychiatrists, and a target for psychopharmacologic interventions. Only risperidone (5–16 years) and aripiprazole (6–17 years) are FDA approved to address these behavioral facets once psychological and educational approaches (e.g., Applied Behavioral Analysis, Sensory Integration) are ineffective, inaccessible, or unaffordable. Aman et al. (2003) showed 45% of ASD are medicated. These behaviors include attention-deficit/hyperactivity disorder-like symptoms, tics and stereotypies, autoaggression and heteroaggression, irritability and mood and anxiety symptoms, disturbed eating and sleeping patterns, and sexually inappropriate behaviors (Naguy and Al-Tajali 2015).

Unfortunately, the use of these AAPs is fraught with a multitude of cardiometabolic and neurohormonal syndromes.

Sertindole is one of only a few metabolic friendly AAPs, with Extrapyramidal syndromes equal to placebo, and, promising procognitive actions. Unfortunately, it was withdrawn from U.S. markets for cardiotoxicity concerns (Naguy 2016), but is still available in Europe and other parts of world, including this country. Eckardt et al. (2002) refuted these concerns. They have demonstrated that QT and MAP in case of sertindole are cycle-length independent, no effects on transmural or interventricular dispersion of reploarization, and no early after-depolarizations. This might be ascribed to α1 blockade and/or I Na inhibition pharmacologic properties of sertindole.

To our knowledge, this is the first pediatric case reporting the use of sertindole in autism, which was both effective and tolerable. This might open new venues to such complicated clinical scenarios.