Brexpiprazole in early- and late-onset psychotic disorders with complex neurodevelopmental and medical comorbidities: a case series

Introduction

Psychotic disorders occurring across the lifespan frequently present with diagnostic complexity when frequently accompanied by comorbidities such as neurodevelopmental abnormalities, structural brain lesions, congenital syndromes, or systemic medical conditions. Management in such cases requires careful differential diagnosis to exclude secondary causes and selection of antipsychotic therapy with favourable tolerability and behavioural stabilisation properties can be challenging. Brexpiprazole, a serotonin–dopamine activity modulator, may offer clinical advantages in patients with psychosis complicated by impulsivity, aggression, or significant somatic comorbidity.

Aims

This case series aims to present four clinically heterogeneous cases of psychosis across different age groups and illustrate (a) diagnostic challenges including organic and systemic contributors, and (b) clinical outcomes following treatment with brexpiprazole in complex presentations.

Methods

We describe four inpatients treated in a tertiary psychiatric setting: A 19-year-old male with mild intellectual disability (Raven score 69), frontoparietal developmental venous anomaly on MRI, severe aggression, impulsivity, and persecutory delusions (baseline PANSS 105). A 62-year-old woman, probable thalidomide survivor with congenital malformations and diabetes mellitus, presenting with persistent persecutory delusional disorder (baseline PANSS 119). A 56-year-old man with late-onset first psychotic episode and newly identified hypertension and microalbuminuria (94 mg/g), requiring extensive work-up for secondary causes. Comprehensive diagnostic assessment included neuroimaging, laboratory investigations, somatic evaluation, and structured psychopathology assessment (PANSS where applicable). Psychosocial interventions were implemented alongside pharmacotherapy. A 55‑year‑old woman with longstanding cerebellar ataxia, gait instability, and hypogonadotropic hypogonadism, admitted with jealous‑type delusions, intrusive beliefs, and verbal/somatic aggression. Raven’s testing excluded intellectual disability; MRI revealed no structural abnormalities. Baseline PANSS: 126.

Results

In the first two cases, brexpiprazole was initiated and well tolerated without emergent adverse effects or somatic deterioration. Case 1: After 3 weeks, aggression resolved during hospitalisation and PANSS decreased from 105 to 70 (30% reduction), with marked improvement in behavioural regulation and delusional intensity. Case 2: At 3 weeks, PANSS decreased from 119 to 77 (35% reduction), with substantial attenuation of persecutory ideation and improved engagement with care. The third case underscored the importance of systematic evaluation in late-onset psychosis, where renal and vascular findings prompted consideration of secondary organic causes. Case 4: Within 3 weeks, aggression subsided, insight increased, and preoccupation with jealous ideas decreased. PANSS improved from 126 to 70 (44% reduction). Diagnostic work-up remains ongoing.

Conclusions

These cases highlight the heterogeneity of psychotic presentations across the lifespan and reinforce the necessity of a structured diagnostic algorithm, particularly in late-onset or medically complex cases. Brexpiprazole demonstrated clinically meaningful symptom reduction and favourable tolerability in patients with neurodevelopmental vulnerability and significant medical comorbidity, including behavioural dysregulation and chronic somatic illness. A multidisciplinary framework integrating psychiatric, neurological, and systemic evaluation is essential for optimal management. Case-based evidence supports the potential role of brexpiprazole as a stabilizing agent in complex psychotic disorders beyond prototypical schizophrenia presentations.

References

No references