Polifarmasi antipsikotik pada pasien skizofrenia terhadap rasionalitas klinis dalam perspektif neurobiologi dan evidence-based: A narrative review
DOI: https://doi.org/10.33024/hjk.v20i6.3427
Augmentation Therapy Clozapine Treatment-Resistant Schizophrenia
Abstract
Background: Schizophrenia is a chronic psychiatric disorder characterized by positive symptoms, negative symptoms, and cognitive impairment resulting from neurotransmitter dysregulation, particularly within the dopaminergic system. Although antipsychotic monotherapy remains the standard treatment, a substantial proportion of patients experience inadequate clinical response, leading to the use of antipsychotic polypharmacy (APP), defined as the concurrent administration of two or more antipsychotic agents.
Puporse: To review the neurobiological rationale, clinical indications, efficacy, and safety of antipsychotic polypharmacy in the management of schizophrenia based on current evidence.
Method: A narrative review was conducted to examine scientific evidence regarding the use of antipsychotic polypharmacy in patients with schizophrenia. A systematic literature search was performed using the PubMed, ScienceDirect, and Google Scholar databases. Search strategies employed the keywords “schizophrenia,” “antipsychotic polypharmacy,” “antipsychotic combination,” “treatment-resistant schizophrenia,” “clozapine augmentation,” and “neurobiology,” used either individually or in various combinations with Boolean operators (AND and OR). The search covered publications from 2013 to 2026 in English and Indonesian. Ultimately, 18 relevant and usable articles were selected for the review.
Results: APP continues to be widely prescribed, particularly in patients with severe symptoms, recurrent relapse, or treatment-resistant schizophrenia (TRS). Evidence suggests that APP may improve symptom control, especially negative symptoms, and reduce rehospitalization rates compared with antipsychotic monotherapy. Clozapine augmentation with agents such as aripiprazole or amisulpride has demonstrated potential benefits in refractory cases. However, APP is associated with an increased risk of metabolic disturbances, hyperprolactinemia, drug interactions, and excessive antipsychotic exposure, necessitating careful patient selection and monitoring.
Conclusion: Antipsychotic polypharmacy may provide clinical benefits in selected patients with schizophrenia, particularly those with inadequate response to monotherapy. Nevertheless, its use should be individualized, guided by evidence-based recommendations, and balanced against the potential risks of adverse effects and overtreatment.
Keywords: Augmentation Therapy; Clozapine; Treatment-Resistant Schizophrenia.
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