Purpose of review Adolescents with neurodevelopmental disorders (NDDs) often display challenging behaviors such as hypersexuality, severe irritability, and aggression. This review emphasizes current management strategies, focusing on the evaluation of problematic behaviors and considering both pharmacological and nonpharmacological options, as well as their level of evidence in the current literature. Recent findings Hypersexuality in adolescents with NDDs may result from conditions such as precocious puberty, polycystic ovary syndrome, neurologic disorders, trauma, or medication effects. Management should be etiology-based; limited evidence suggests selective serotonin reuptake inhibitors (SSRIs) and opioid antagonists may help in compulsive sexual behavior, though data in youth remain scarce. Irritability is most consistently improved with atypical antipsychotics, particularly risperidone and aripiprazole. Adjunctive options include NMDA modulators, stimulants, alpha-2 agonists, and anti-inflammatory or nutraceutical agents. Aggression management relies on antipsychotics, with clozapine considered for refractory cases; benzodiazepines, guanfacine, sertraline, and investigational agents such as vafidemstat show early promise. Psychotherapeutic and family-based interventions remain essential. Summary Effective care requires holistic evaluation, elimination of iatrogenic contributors, and individualized treatment. Combining behavioral therapies with judicious medication use can improve functioning and safety. Emerging pharmacologic and biologic strategies warrant further investigation in this vulnerable population.
Greydanus et al. (2026) studied this question.