Therapizing Schizophrenia Therapies: How the Unmet Needs of TRS Patients Highlights the Need for Alternatives
DOI:
https://doi.org/10.47611/jsrhs.v13i4.8195Keywords:
treatment of schizophrenia, treatment-resistant schizophrenia, schizophrenia, therapies for schizophreniaAbstract
Schizophrenia is a disorder of which there is no known cause right now. The most researched theory is that there are increased levels of dopamine in the brain. Schizophrenia is generally treated with antipsychotics targeting the dopamine system to reduce the patient’s positive and cognitive symptoms. These medications do not effectively treat schizophrenia for all patients, so more research into alternative therapeutics is necessary. Treatment-resistant schizophrenia (TRS) occurs when patients don’t respond to the treatment they’ve been put on. Patients with TRS are at a higher risk of suicide or substance abuse as well as unemployment. Healthcare costs are also much higher for TRS patients than those with schizophrenia. As for treatment, if other medication for TRS patients does not aid in reducing their symptoms then clozapine is prescribed. Clozapine can reduce the risk of a relapse in symptoms, the risk of suicide, and the craving of substances. Combining antipsychotics can also be helpful in treatment. Some patients, however, do not respond to any of these treatments. This could be due to the treatment all targeting dopamine receptors as that is the widely studied cause of schizophrenia. Getting treatment for the patients who don’t respond to the existing ones means that there should be more exploring into the different causes of schizophrenia.
Downloads
References or Bibliography
Albert, P. (2012). Drugs for kids: Good or bad? Journal of Psychiatry and Neuroscience, 37(5), 293–295. https://doi.org/10.1503/jpn.120140
Bitter, I., Dossenbach, M. R. K., Brook, S., Feldman, P. D., Metcalfe, S., Gagiano, C. A., Füredi, J., Bartko, G., Janka, Z., Banki, C. M., Kovacs, G., & Breier, A. (2004b). Olanzapine versus clozapine in treatment-resistant or treatment-intolerant schizophrenia. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 28(1), 173–180. https://doi.org/10.1016/j.pnpbp.2003.09.033
Bogers, J. P., Schulte, P. F., Van Dijk, D., Bakker, B., & Cohen, D. (2016). Clozapine Underutilization in the Treatment of Schizophrenia. Journal of Clinical Psychopharmacology, 36(2), 109–111. https://doi.org/10.1097/jcp.0000000000000478
Bondolfi, G., Dufour, H., Patris, M., May, J. P., Billeter, U., Eap, C. B., & Baumann, P. (1998). Risperidone Versus Clozapine in Treatment-Resistant Chronic Schizophrenia: A Randomized Double-Blind Study. American Journal of Psychiatry, 155(4), 499–504. https://doi.org/10.1176/ajp.155.4.499
Brunette, M. F., Drake, R. E., Xie, H., McHugo, G. J., & Green, A. I. (2005). Clozapine Use and Relapses of Substance Use Disorder Among Patients With Co-occurring Schizophrenia and Substance Use Disorders. Schizophrenia Bulletin, 32(4), 637–643. https://doi.org/10.1093/schbul/sbl003
Carbon, M., & Correll, C. U. (2014). Thinking and acting beyond the positive: the role of the cognitive and negative symptoms in schizophrenia. CNS Spectrums, 19(S1), 35–53. https://doi.org/10.1017/s1092852914000601
Cognitive-Behavioral Therapy for Schizophrenia: A Review : Journal of Psychiatric Practice®. (n.d.). LWW. https://journals.lww.com/practicalpsychiatry/abstract/2004/01000/cognitive_behavioral_therapy_for_schizophrenia__a.2.aspx
Coyle, J. T. (2006). Glutamate and Schizophrenia: Beyond the Dopamine Hypothesis. Cellular and Molecular Neurobiology, 26(4–6), 363–382. https://doi.org/10.1007/s10571-006-9062-8
Eggers, A. E. (2013). A serotonin hypothesis of schizophrenia. Medical Hypotheses, 80(6), 791–794. https://doi.org/10.1016/j.mehy.2013.03.013
Fakra, E., & Azorin, J. M. (2012). Clozapine for the treatment of schizophrenia. Expert Opinion on Pharmacotherapy, 13(13), 1923–1935. https://doi.org/10.1517/14656566.2012.709235
Fakra, E., & Azorin, J. M. (2012b). Clozapine for the treatment of schizophrenia. Expert Opinion on Pharmacotherapy, 13(13), 1923–1935. https://doi.org/10.1517/14656566.2012.709235
Farooq, S., Choudry, A., Cohen, D., Naeem, F., & Ayub, M. (2018). Barriers to using clozapine in treatment-resistant schizophrenia: systematic review. BJPsych Bulletin, 43(1), 8–16. https://doi.org/10.1192/bjb.2018.67
Farooq, S., & Taylor, M. (2011). Clozapine: dangerous orphan or neglected friend? The British Journal of Psychiatry, 198(4), 247–249. https://doi.org/10.1192/bjp.bp.110.088690
Griffiths, K., Millgate, E., Egerton, A., & MacCabe, J. H. (2021). Demographic and clinical variables associated with response to clozapine in schizophrenia: a systematic review and meta-analysis. Psychological Medicine, 51(3), 376–386. https://doi.org/10.1017/s0033291721000246
Hartling, L., Abou-Setta, A. M., Dursun, S., Mousavi, S. S., Pasichnyk, D., & Newton, A. S. (2012). Antipsychotics in Adults With Schizophrenia: Comparative Effectiveness of First-Generation Versus Second-Generation Medications. Annals of Internal Medicine, 157(7), 498.
https://doi.org/10.7326/0003-4819-157-7-201210020-00525
Hellewell, J. S. E. (1999). Treatment-Resistant Schizophrenia: Reviewing the Options and Identifying the Way Forward. In J Clin Psychiatry (Vols. 60–60, Issue suppl 23, pp. 14–19). https://www.psychiatrist.com/wp-content/uploads/2021/02/18428_treatment-resistant-schizophrenia-reviewing-options.pdf
Heres, S., Davis, J., Maino, K., Jetzinger, E., Kissling, W., & Leucht, S. (2006). Why Olanzapine Beats Risperidone, Risperidone Beats Quetiapine, and Quetiapine Beats Olanzapine: An Exploratory Analysis of Head-to-Head Comparison Studies of Second-Generation Antipsychotics. American Journal of Psychiatry, 163(2), 185–194. https://doi.org/10.1176/appi.ajp.163.2.185
Higley, M. J., & Picciotto, M. R. (2014). Neuromodulation by acetylcholine: examples from schizophrenia and depression. Current Opinion in Neurobiology, 29, 88–95. https://doi.org/10.1016/j.conb.2014.06.004
Howes, O. D., McCutcheon, R., Agid, O., De Bartolomeis, A., Van Beveren, N. J., Birnbaum, M. L., Bloomfield, M. A., Bressan, R. A., Buchanan, R. W., Carpenter, W. T., Castle, D. J., Citrome, L., Daskalakis, Z. J., Davidson, M., Drake, R. J., Dursun, S., Ebdrup, B. H., Elkis, H., Falkai, P., . . . 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. https://doi.org/10.1176/appi.ajp.2016.16050503
Identifying Gene-Environment Interactions in Schizophrenia: Contemporary Challenges for Integrated, Large-scale Investigations” - Google Search. (n.d.). https://www.google.com/search?q=Identifying+Gene-Environment+Interactions+in+Schizophrenia%3A+Contemporary+Challenges+for+Integrated%2C+Large-scale+Investigations%E2%80%9D&rlz=1C9BKJA_enUS1078US1078&oq=Identifying+Gene-Environment+Interactions+in+Schizophrenia%3A+Contemporary+Challenges+for+Integrated%2C+Large-scale+Investigations%E2%80%9D&gs_lcrp=EgZjaHJvbWUyBggAEEUYOdIBBzQ3MWowajeoAgqwAgE&hl=en-US&sourceid=chrome-mobile&ie=UTF-8
Kane, J. M., Agid, O., Baldwin, M. L., Howes, O., Lindenmayer, J. P., Marder, S., Olfson, M., Potkin, S. G., & Correll, C. U. (2019). Clinical Guidance on the Identification and Management of Treatment-Resistant Schizophrenia. The Journal of Clinical Psychiatry, 80(2). https://doi.org/10.4088/jcp.18com12123
Lally, J., & MacCabe, J. H. (2015). Antipsychotic medication in schizophrenia: a review. British Medical Bulletin, 114(1), 169–179. https://doi.org/10.1093/bmb/ldv017
Leung, C. C. Y., Gadelrab, R., Ntephe, C. U., McGuire, P. K., & Demjaha, A. (2019). Clinical Course, Neurobiology and Therapeutic Approaches to Treatment Resistant Schizophrenia. Toward an Integrated View. Frontiers in Psychiatry, 10. https://doi.org/10.3389/fpsyt.2019.00601
Masi, G., & Liboni, F. (2011). Management of Schizophrenia in Children and Adolescents. Drugs, 71(2), 179–208. https://doi.org/10.2165/11585350-000000000-00000
Matrone, M., Kotzalidis, G. D., Romano, A., Bozzao, A., Cuomo, I., Valente, F., Gabaglio, C., Lombardozzi, G., Trovini, G., Amici, E., Perrini, F., De Persis, S., Iasevoli, F., De Filippis, S., & De Bartolomeis, A. (2022). Treatment-resistant schizophrenia: Addressing white matter integrity, intracortical glutamate levels, clinical and cognitive profiles between early- and adult-onset patients. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 114, 110493. https://doi.org/10.1016/j.pnpbp.2021.110493
Meltzer, H. (1999). The Role of Serotonin in Antipsychotic Drug Action. Neuropsychopharmacology, 21(2), 106S-115S. https://doi.org/10.1016/s0893-133x(99)00046-9/PMC4159061/
Meltzer, H. Y. (1997). Treatment-Resistant Schizophrenia - The Role of Clozapine. Current Medical Research and Opinion, 14(1), 1–20. https://doi.org/10.1185/03007999709113338
Muscatello, M. R. A., Bruno, A., De Fazio, P., Segura-Garcia, C., Pandolfo, G., & Zoccali, R. (2014). Augmentation strategies in partial responder and/or treatment-resistant schizophrenia patients treated with clozapine. Expert Opinion on Pharmacotherapy, 15(16), 2329–2345. https://doi.org/10.1517/14656566.2014.956082
Newman-Tancredi, A., & Kleven, M. S. (2011). Comparative pharmacology of antipsychotics possessing combined dopamine D2 and serotonin 5-HT1A receptor properties. Psychopharmacology, 216(4), 451–473. https://doi.org/10.1007/s00213-011-2247-y
Nord, M., & Farde, L. (2010). Antipsychotic Occupancy of Dopamine Receptors in Schizophrenia. CNS Neuroscience & Therapeutics, 17(2), 97–103. https://doi.org/10.1111/j.1755-5949.2010.00222.x
Pandarakalam, J. P. (2019). Combination Therapy for Treatment Resistant Schizophrenia. In British Journal of Medical Practitioners (Vol. 12, p. a015). https://www.bjmp.org/files/2019-12-2/bjmp-2019-12-2-a016.pdf
Pandey, A., & Kalita, K. N. (2022). Treatment-resistant schizophrenia: How far have we traveled? Frontiers in Psychiatry, 13. https://doi.org/10.3389/fpsyt.2022.994425
Patel, K. R., Cherian, J., Gohil, K., & Atkinson, D. (2014, September 1). Schizophrenia: Overview and Treatment Options. PubMed Central (PMC). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4159061/
Patel, K. R., Cherian, J., Gohil, K., & Atkinson, D. (2014, September 1). Schizophrenia: Overview and Treatment Options. PubMed Central (PMC). https://www.ncbi.nlm.nih.gov/pmc/articlesMeltzer, H. (1999). The Role of Serotonin in Antipsychotic Drug Action. Neuropsychopharmacology, 21(2), 106S-115S. https://doi.org/10.1016/s0893-133x(99)00046-9
Second-generation antipsychotic medications: Pharmacology, administration, and side effects. MediLib. https://medilib.ir/uptodate/show/14776
Severance, E. G., Dickerson, F. B., & Yolken, R. H. (2018). Autoimmune phenotypes in schizophrenia reveal novel treatment targets. Pharmacology & Therapeutics, 189, 184–198. https://doi.org/10.1016/j.pharmthera.2018.05.005
Smart, S. E., Kępińska, A. P., Murray, R. M., & MacCabe, J. H. (2019). Predictors of treatment resistant schizophrenia: a systematic review of prospective observational studies. Psychological Medicine, 51(1), 44–53. https://doi.org/10.1017/s0033291719002083
Tauber, A. I. (2015). Reconceiving autoimmunity: An overview. Journal of Theoretical Biology, 375, 52–60. https://doi.org/10.1016/j.jtbi.2014.05.029
Townsend, L. K., Peppler, W. T., Bush, N. D., & Wright, D. C. (2018). Obesity exacerbates the acute metabolic side effects of olanzapine. Psychoneuroendocrinology, 88, 121–128. https://doi.org/10.1016/j.psyneuen.2017.12.004
Trifu, S., Kohn, B., Vlasie, A., & Patrichi, B. E. (2020). Genetics of schizophrenia (Review). Experimental and Therapeutic Medicine. https://doi.org/10.3892/etm.2020.8973
Van Os, J., Kenis, G., & Rutten, B. P. F. (2010). The environment and schizophrenia. Nature, 468(7321), 203–212. https://doi.org/10.1038/nature09563
Vita, A., Minelli, A., Barlati, S., Deste, G., Giacopuzzi, E., Valsecchi, P., Turrina, C., & Gennarelli, M. (2019). Treatment-Resistant Schizophrenia: Genetic and Neuroimaging Correlates. Frontiers in Pharmacology, 10. https://doi.org/10.3389/fphar.2019.00402
Zhang, J. P., Gallego, J. A., Robinson, D. G., Malhotra, A. K., Kane, J. M., & Correll, C. U. (2013). Efficacy and safety of individual second-generation vs. first-generation antipsychotics in first-episode psychosis: a systematic review and meta-analysis. The International Journal of Neuropsychopharmacology, 16(6), 1205–1218. https://doi.org/10.1017/s1461145712001277
Published
How to Cite
Issue
Section
Copyright (c) 2024 Maaheen Ghumman; Makaila Furderer, Kokila Beri
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Copyright holder(s) granted JSR a perpetual, non-exclusive license to distriute & display this article.
