Vol. 7, Issue 2, Part A (2025)

Disruptive Mood Dysregulation Disorder is defined by chronic irritability and recurrent, severe temper outbursts, while Autism Spectrum Disorder, a neurodevelopmental condition marked by social-communication deficits and restricted behaviours, frequently presents with overlapping irritability and aggression. Although risperidone and aripiprazole are FDA-approved for irritability in autism, treatment guidelines for Disruptive Mood Dysregulation Disorder remain limited, especially in refractory cases. We present the case of a 15-year-old male with autism, generalized anxiety disorder, and attention-deficit hyperactivity disorder, who was diagnosed with comorbid disruptive mood dysregulation disorder after escalating aggression and mood dysregulation. At the time of presentation, he was taking fluoxetine, clonidine, and hydroxyzine, with prior trials of risperidone and aripiprazole discontinued due to lack of efficacy. Valproate and methylphenidate were initiated and later optimized, with further adjustments in clonidine, hydroxyzine, and oral paliperidone, but symptoms persisted. In April 2025, he was transitioned to paliperidone palmitate injections given monthly. Over three months, he demonstrated mood stabilization, reduced irritability, and a significant decline in anger outbursts. This case illustrates the therapeutic challenges in managing Disruptive Mood Dysregulation Disorder in the context of autism and suggests that long-acting injectable antipsychotics may be beneficial in treatment-resistant cases, particularly where adherence and sustained control are priorities. While evidence for their use in pediatric populations remains scarce, this case highlights the potential role of paliperidone palmitate in refractory mood dysregulation and underscores the urgent need for evidence-based guidelines to better inform clinical management of Disruptive Mood Dysregulation Disorder.