From antipsychotic polypharmacy to functional recovery: a case report on rationalization with clozapine and long-acting aripiprazole

Background: Antipsychotic polypharmacy remains a common yet controversial strategy in the management of severe psychotic disorders, particularly in treatment-resistant cases. Although frequently used in clinical practice, evidence supporting its long-term efficacy is limited, and it is associated with an increased burden of adverse effects, including sedation, metabolic complications, and reduced functional capacity (1,2). Clinical guidelines generally recommend antipsychotic monotherapy, with clozapine as the gold standard for treatment-resistant schizophrenia (5). However, real-world patients often present with diagnostic complexity, including overlap between schizophrenia and schizoaffective disorder, as well as issues related to adherence and repeated relapses (3). In such cases, rationalization of pharmacological regimens becomes a key but challenging intervention.

Case Presentation: We report the case of a 38-year-old male with a long-standing diagnosis of paranoid schizophrenia, with a differential diagnosis of schizoaffective disorder due to prominent affective symptoms during multiple episodes. The patient had a history of frequent psychiatric admissions, poor adherence to treatment, and progressive social and occupational deterioration. He was admitted to an acute psychiatric unit presenting with severe behavioral disorganization, persecutory delusions, irritability, and affective lability.

At the time of admission, the patient was receiving extensive pharmacological treatment, including high-dose risperidone (with previous trials of long-acting formulations), olanzapine, levomepromazine, and valproate at 1500 mg/day. Despite this regimen, symptom control was incomplete, and the patient exhibited significant adverse effects, including marked sedation, emotional blunting, and limited engagement, consistent with the known risks of antipsychotic polypharmacy (1,4). The clinical picture raised concerns about iatrogenic burden contributing to functional impairment.

A structured pharmacological rationalization strategy was implemented. Antipsychotics with limited efficacy were progressively tapered and discontinued. Clozapine was introduced and titrated up to 300 mg/day, with careful monitoring, following established recommendations for treatment-resistant psychosis (5). In addition, long-acting injectable aripiprazole (bi-monthly formulation) was initiated to address adherence difficulties and to provide partial dopaminergic agonism, potentially improving both positive symptoms and affective instability (6).

Results: Over a follow-up period of several weeks, the patient demonstrated a marked clinical improvement. There was a significant reduction in persecutory ideation and behavioral disorganization, along with improved affective regulation. The patient became more engaged in the therapeutic milieu and showed better interpersonal functioning. Importantly, the reduction of pharmacological burden was associated with decreased sedation, improved cognitive clarity, and enhanced participation in daily activities. No major adverse effects related to clozapine were observed during the titration phase.

Conclusions: This case highlights the clinical relevance of treatment rationalization in patients with complex psychotic disorders and extensive antipsychotic polypharmacy. The combination of clozapine and long-acting injectable aripiprazole may represent a valuable therapeutic strategy in selected cases, particularly where treatment resistance, adherence issues, and diagnostic ambiguity coexist (6,7). Beyond symptom reduction, simplifying pharmacological regimens may contribute to improved subjective experience and functional recovery. These findings support the need for individualized, dynamic treatment approaches and further research into optimized strategies for managing severe psychotic disorders.

References

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