Efektivitas augmentasi farmakologis dan non farmakologis pada skizofrenia resisten terapi: A narrative review
DOI: https://doi.org/10.33024/hjk.v20i6.3396
Augmentation Therapy Clozapine Treatment-Resistant Schizophrenia
Abstract
Background: Treatment-resistant schizophrenia (TRS) affects approximately 20–30% of patients with schizophrenia and is associated with poor prognosis, recurrent hospitalization, and increased suicide risk. TRS is linked to complex neurobiological mechanisms beyond dopaminergic dysfunction, including glutamatergic abnormalities and neuroinflammation.
Purpose: To review the definition, pathophysiology, and management strategies of TRS, particularly pharmacological and non-pharmacological augmentation approaches.
Method: A narrative review was conducted using literature from PubMed, ScienceDirect, and Google Scholar, including original studies, systematic reviews, meta-analyses, and clinical guidelines related to TRS and augmentation therapy.
Discussion: Clozapine remains the gold-standard treatment for TRS, although a substantial proportion of patients show inadequate response. Pharmacological augmentation strategies such as lamotrigine, N-acetylcysteine, and memantine, as well as non-pharmacological interventions including electroconvulsive therapy (ECT) and cognitive remediation therapy, have demonstrated potential benefits in selected patients.
Conclusion: TRS is a complex and heterogeneous condition requiring individualized and multimodal treatment approaches. Optimization of clozapine and evidence-based augmentation strategies may improve clinical outcomes and quality of life in patients with TRS.
Keywords: Augmentation Therapy; Clozapine; Treatment-Resistant Schizophrenia.
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References
Cahaya, N., Kristina, S. A., Widayanti, A. W., & Green, J. (2022). Interventions to improve medication adherence in people with schizophrenia: a systematic review. Patient preference and adherence, 2431-2449.
Chakrabarti, S. (2021). Clozapine resistant schizophrenia: newer avenues of management. World journal of psychiatry, 11(8), 429.
Citrawati, N. K., & Candra, D. G. (2025). Literature Review of Technology-Based Therapy for Schizophrenia Sufferers. Jurnal Keperawatan Dan Fisioterapi (JKF), 7(2), 177-181.
Hegde, N. C., Mishra, B. R., Mohapatra, D., Srinivasan, A., & Maiti, R. (2026). Augmentation of clozapine with dextromethorphan in treatment-resistant schizophrenia: A randomized, group sequential adaptive design, controlled clinical trial. Asian Journal of Psychiatry, 104919.
Howes, O. D., McCutcheon, R., Agid, O., De Bartolomeis, A., Van Beveren, N. J., Birnbaum, M. L., & Correll, C. U. (2017). Treatment-resistant schizophrenia: treatment response and resistance in psychosis (TRRIP) working group consensus guidelines on diagnosis and terminology. American Journal of Psychiatry, 174(3), 216-229.
Kane, J. M., Agid, O., Baldwin, M. L., Howes, O., Lindenmayer, J. P., Marder, S., & Correll, C. U. (2019). Clinical guidance on the identification and management of treatment-resistant schizophrenia. The Journal of clinical psychiatry, 80(2), 18com12123-18com12123.
Keepers, G. A., Fochtmann, L. J., Anzia, J. M., Benjamin, S., Lyness, J. M., Mojtabai, R., & (Systematic Review). (2020). The American Psychiatric Association practice guideline for the treatment of patients with schizophrenia. American Journal of Psychiatry, 177(9), 868-872.
Lopes, J. J., Carruthers, S. P., Meyer, D., Dean, B., & Rossell, S. L. (2024). Glutamatergic neurotransmission in schizophrenia: A systematic review and quantitative synthesis of proton magnetic resonance spectroscopy studies across schizophrenia spectrum disorders. Australian & New Zealand Journal of Psychiatry, 58(11), 930-951.
McCutcheon, R. A., Reis Marques, T., & Howes, O. D. (2020). Schizophrenia—an overview. JAMA psychiatry, 77(2), 201-210.
Merritt, K., McCutcheon, R. A., Aleman, A., Ashley, S., Beck, K., & Block, W. (2023). Variability and magnitude of brain glutamate levels in schizophrenia: a meta and mega-analysis. Molecular psychiatry, 28(5), 2039-2048.
Mishra, A., Maiti, R., Mishra, B. R., & Srinivasan, A. (2023). Augmentation strategies for partial or non-responders to clozapine in patients with schizophrenia: A Bayesian network meta-analysis of randomized controlled trials. Clinical Psychopharmacology and Neuroscience, 22(2), 232.
National Institute for Health and Care Excellence. (2024). Psychosis and schizophrenia in adults: prevention and management Clinical guideline. Diakses dari: www.nice.org.uk/guidance/cg178
Siskind, D., Siskind, V., & Kisely, S. (2017). Clozapine response rates among people with treatment-resistant schizophrenia: data from a systematic review and meta-analysis. The Canadian Journal of Psychiatry, 62(11), 772-777.
Smart, S. E., Kępińska, A. P., Murray, R. M., & MacCabe, J. H. (2021). Predictors of treatment resistant schizophrenia: a systematic review of prospective observational studies. Psychological medicine, 51(1), 44-53.
Speers, L. J., & Bilkey, D. K. (2025). Inflammation in schizophrenia: the role of disordered oscillatory mechanisms. Cells, 14(9), 650.
Wold, K. F., Kreis, I. V., Åsbø, G., Flaaten, C. B., Widing, L., Engen, M. J., & Melle, I. (2024). Long-term clinical recovery and treatment resistance in first-episode psychosis: a 10-year follow-up study. Schizophrenia, 10(1), 69.
Yada, Y., Yoshimura, B., & Kishi, Y. (2015). Correlation between delay in initiating clozapine and symptomatic improvement. Schizophrenia research, 168(1-2), 585-586.
Yeh, T. C., Correll, C. U., Yang, F. C., Chen, M. H., Tseng, P. T., Hsu, C. W., & Liang, C. S. (2023). Pharmacological and nonpharmacological augmentation treatments for clozapine-resistant schizophrenia: a systematic review and network meta-analysis with normalized entropy assessment. Asian journal of psychiatry, 79, 103375.
Zhang, M. H., Zhang, J., Cai, H., Liu, Y., Han, T., Wang, Y. F., & Ji, X. (2025). Mapping aggressive behaviors and testosterone among schizophrenia patients in acute stage. Schizophrenia, 11(1), 157.
Zulaikha, A., & Furqani, M. H. (2024). Pengobatan resistensi antipsikotik pada pasien skizofrenia. Usada Nusantara: Jurnal Kesehatan Tradisional, 2(1), 151-161.
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