Treatment-Resistant Schizoaffective Disorder in Alcohol Dependence: A Case Report

Treatment-Resistant Schizoaffective Disorder in Alcohol Dependence: A Case Report | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Treatment-Resistant Schizoaffective Disorder in Alcohol Dependence: A Case Report Sonam Saxena, Shruti Garg, Niharika Meena This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7554183/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Schizophrenia and schizoaffective disorder are complex psychotic disorders characterized by symptoms such as delusions, hallucinations, and cognitive impairment. These disorders are often exacerbated by comorbid substance use disorder (SUD), leading to more severe disability and poorer outcomes compared to those without SUD. The frequent co-occurrence of schizophrenia with alcohol use disorder (AUD) or other substances may be linked to dysfunctions in brain reward circuitry and shared neurobiological pathways. Effective management typically involves a combination of pharmacological treatments and complementary therapeutic approaches to address both the psychotic disorder and the substance use disorder. This case report presents a 50-year-old man with a history of alcohol and tobacco dependence, who displayed increased alcohol consumption and neglect of pleasurable activities, alongside symptoms indicative of schizoaffective disorder. Medical investigations, including blood tests, chest X-ray and NCCT Head, revealed no significant abnormalities. Serial mental status examinations led to a diagnosis of Mental and Behavioral Disorder due to Alcohol Dependence Syndrome (ADS) with Schizoaffective Disorder. Initial treatment with second-generation antipsychotics and mood stabilizers provided limited improvement. A subsequent switch to first-generation antipsychotics yielded only a partial response, classifying the patient as treatment-resistant. The introduction of clozapine resulted in significant clinical improvement, enhancing social functioning and achieving remission, while avoiding polypharmacy and minimizing metabolic side effects. Schizoaffective Disorder Alcohol Use Disorder Treatment Resistance Dual Diagnosis Clozapine Figures Figure 1 Figure 2 Introduction Schizoaffective disorder is a complex and chronic psychiatric condition that lies at the intersection of schizophrenia and mood disorders .¹ It manifests as a combination of psychotic features, such as hallucinations or delusions, alongside disturbances in mood, including depression or mania .² The illness often follows a fluctuating course, leading to significant reductions in social, occupational, and overall functional capacities .³ Successful management is frequently challenging because it requires interventions that address both the psychotic and affective components of the disorder simultaneously.⁴ The situation becomes even more complicated when schizoaffective disorder coexists with substance use disorders (SUD) .⁵ Among these, alcohol use disorder (AUD) is particularly prevalent .⁶ Studies consistently demonstrate that individuals with schizophrenia spectrum disorders are more likely to develop alcohol dependence compared to the general population .⁷ Estimates suggest that one-quarter to half of these patients may engage in harmful drinking over their lifetimes .⁸ The reasons for this overlap appear multifactorial .⁹Neurobiological mechanisms, including dysregulation of dopamine and glutamate pathways, underlie vulnerability to both psychosis and addictive behaviors .Cognitive dysfunction, impulsivity, impaired social support networks, and environmental stressors contribute further to this comorbidity .The clinical implications of combining chronic alcohol misuse with schizoaffective illness are wide-ranging . Patients have poorer therapeutic responses and they face higher relapse risk and more frequent hospitalizations .¹⁰Pharmacological management also becomes more complex because alcohol may interact with psychiatric medications and impair their metabolism . Moreover, substance misuse produces psychosocial disruption- hampering employment, financial security, interpersonal relationships, and caregiving systems .¹¹ These combined challenges call for integrated, multidisciplinary approaches that simultaneously address psychiatric stabilization and addictive behaviors .¹² This report presents a middle-aged man in India with treatment-resistant schizoaffective disorder and a long history of alcohol dependence . It highlights diagnostic considerations, treatment strategies, and ethical aspects of delivering care under mental health legislation . Case Presentation Demographic Information and Personal Background The patient, here referred to as Mr. O, is a 50-year-old Indian male from a disadvantaged socioeconomic environment. He completed high school but did not pursue higher education. Early in adulthood, he worked as a vegetable vendor and later shifted to labor-based employment. Over time, his psychiatric illness diminished his functional and occupational capacity, leading to loss of steady work and increasing financial strain. No significant hereditary contribution to mental illness was identified in his family history. Medical investigations revealed no comorbid illnesses such as diabetes, hypertension, or chronic liver damage. Substance Use History Mr. O reported consuming alcohol regularly for 33 years, beginning in late adolescence. This long-standing dependence eventually became habitual, with significant impairment in health and functioning. He also smoked tobacco concurrently. His last recorded alcohol consumption was 20 days prior to hospital admission. Despite this temporary abstinence, his case clearly fulfilled the diagnosis of alcohol dependence syndrome due to the chronicity and compulsive nature of his use . Psychiatric Symptom Evolution Psychiatric manifestations appeared roughly 14 years after the onset of sustained drinking. Initially, his family noticed changes in behavior, which worsened steadily over a three-year period. Prominent symptoms included persistent grandiose delusions, public disinhibition, neglect of personal hygiene, inappropriate social behaviors, and disorganized conduct such as hoarding trash or undressing in public. These actions attracted stigma and strained his social network. He was also noted to talk loudly to himself in public, suggesting auditory hallucinations or a heightened thought disorder. As symptoms progressed, irritability and unpredictability increased, leading to significant interpersonal conflict and a marked decline in his occupational and daily functioning. Mental State Examination On mental status examination, Mr. O presented with elevated mood and a euphoric affect. His speech was pressured and tangential, often irrelevant, with a flight of ideas. Thought content was dominated by clearly defined grandiose delusions. He exhibited increased psychomotor activity and lacked coherent self-reflection about his condition. Cognitive assessment revealed impaired judgment, reduced concentration, and distractibility. His level of insight into the illness was profoundly deficient, consistent with chronic psychosis . Diagnostic Impression Using ICD-10 criteria, he was diagnosed with schizoaffective disorder, bipolar type (F25.0). In parallel, based on his prolonged alcohol use trajectory and current state of abstinence, he received the diagnosis of alcohol dependence syndrome under care. Standard laboratory testing, chest imaging, and neuroimaging did not reveal abnormalities, indicating that despite years of alcohol misuse, no immediate systemic organ damage had manifested . Interventions and Hospital Course Mr. O required inpatient care and was admitted under Section 89 of the Indian Mental Healthcare Act (2017), which justifies involuntary treatment when patients lack capacity for informed decision-making and pose risk to themselves or the community. His admission to a dual-diagnosis facility allowed simultaneous focus on his psychiatric illness and alcohol abuse history . Pharmacological treatment was initiated with sodium valproate 500 mg/day, later titrated to 1200 mg/day to stabilize affective symptoms. Lorazepam (2 mg/day) was used early to manage agitation but was switched to clonazepam (0.5 mg) due to its longer duration of action and greater tolerability. Trials of risperidone and haloperidol were attempted but led to inadequate control of psychotic symptoms, in addition to producing adverse extrapyramidal reactions. These medications were withdrawn. Given poor response, clozapine was considered despite being reserved typically for refractory psychotic cases. It was started at 12.5 mg/day and titrated to 25 mg/day. To minimize side effects, trihexyphenidyl was also prescribed. This regimen produced robust improvement: psychotic features diminished, his communication became more organized, and self-care significantly improved. Family members observed better social interactions and welcomed reduction in disruptive public behavior. Concurrently, non-pharmacological interventions were emphasized. Psychoeducation sessions conveyed the nature of psychiatric illness, the necessity of ongoing treatment, and the risks of relapse. Family therapy sessions enabled relatives to support adherence and manage stress. Structured rehabilitation programs provided guidance on relapse prevention and craving control. Abstinence monitoring strategies and outpatient follow-up plans were firmly established before discharge. After stabilization, Mr. O was discharged on maintenance with clozapine, valproate, clonazepam, and trihexyphenidyl, alongside scheduled psychiatric follow-ups and mandatory blood monitoring given clozapine-associated risks . Conclusion This report demonstrates the difficulties in detecting and treating schizoaffective disorder in people with concomitant AUD .Poor insight, cognitive impairments, and nonadherence hampered traditional therapeutic response .Clozapine, while often reserved for refractory cases, proved critical in attaining symptom management and functional improvement. Clozapine appears to be helpful in dual diagnosis individuals with psychosis and substance use disorders, probably due to its unique neuroreceptor profile and higher efficacy over other antipsychotics .Ethical management, which includes permission, family involvement, and multidisciplinary treatment, is critical, particularly for patients who require compulsory hospitalisation under mental health legislation. The case reinforces the significance of a comprehensive, ethical, and integrated approach to treating dual diagnosis cases .Clozapine remains a valuable treatment modality in managing resistant psychotic symptoms and improving patient quality of life, even in the context of chronic substance use. Declarations Ethics approval and consent to participate Not applicable. The case report is based on retrospective clinical information and anonymized data. Consent for publication Written informed consent was obtained from the patient for publication of this case report, including clinical details. The consent form is available with the corresponding author and can be provided upon request. Availability of data and materials Not applicable. Competing interests The authors declare that they have no competing interests. Funding The authors received no external funding for this case report. Authors’ contributions SS conceptualized the case report and coordinated the drafting. SG supervised clinical care and contributed to manuscript revisions. NM assisted in literature review and formatting. All authors read and approved the final manuscript. Acknowledgements We acknowledge the patient and his caregivers for their cooperation and consent to share his clinical details. Authors’ information Not applicable. References Buckley PF, Miller BJ, Lehrer DS, Castle DJ. Psychiatric comorbidities and schizophrenia. Schizophr Bull. 2009;35(2):383–402. Green MF, Nuechterlein KH. Should schizophrenia be treated as a neurocognitive disorder? Schizophr Bull. 1999;25(2):309–319. Volkow ND, Fowler JS. Addiction and the orbitofrontal cortex. Cereb Cortex. 2000;10(3):318–325. Blanchard JJ, Brown SA. Substance use and course of illness in schizophrenia. Clin Psychol Rev. 1998;18(2):201–220. Leucht S, et al. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia. Lancet. 2013;382(9896):951–962. McLellan AT, Koob GF, Volkow ND. Precipitated withdrawal from alcohol and opioids. Am J Psychiatry. 2014;171(10):1101–1107. Buckley PF. Prevalence and consequences of dual diagnosis. J Clin Psychiatry. 2006;67(Suppl 7):5–9. Mueser KT, Noordsy DL, Drake RE, Fox L. Integrated Treatment for Dual Disorders: A Guide to Effective Practice. New York: Guilford Press; 2003. Pompili M, et al. Substance abuse and suicide risk among schizophrenia patients. Schizophr Res. 2009;119(1–3):253–254. Kirkpatrick B, Buchanan RW. Schizophrenia as a syndrome. Compr Psychiatry. 1990;31(4):255–269. Addington J, Saeedi H, Addington D. Cognitive functioning in first episode psychosis. Schizophr Res. 2005;78(1):35–43. Mueser KT, et al. Substance abuse in schizophrenia: demographic and clinical correlates. Schizophr Bull. 1990;16(1):31–56. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7554183","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":511563432,"identity":"ddc0e670-a025-4cbf-9969-d58650d3b7b6","order_by":0,"name":"Sonam Saxena","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABEklEQVRIiWNgGAWjYDCCA6hcCTl+EJVQQLwWC2PJBpAWA+K1VCRuAIvg0cJ3+wDzh4877KLl288YPi6okUjcfH514ocHBgzy/GIHsGqRPJfAJjnzTHLuhjNpycYzjkkYb7vxdrME0GGGM2cnYNVicIaBjZm3jTl3A0PyMWkeNgnZbTfObgBpSTC4jVML82fetvrc+f0P23/z/JNg3Dzj7OYfBLQwSPO2Hc5tuJF8DGidhOIG/t5teG2RPMPYJjmz7XjuhhvPkqV5+ySMJW7wbrNIMJDA6Re+M8yHP3xsqwY6LMfwM8+3Ojn+/rObb/6osJHnl8auhYGBsQFNQAKsUgKHcqyA/wApqkfBKBgFo2AEAAD0TmIx6Sov3QAAAABJRU5ErkJggg==","orcid":"","institution":"Institute of Human Behaviour and Allied Sciences (IHBAS)","correspondingAuthor":true,"prefix":"","firstName":"Sonam","middleName":"","lastName":"Saxena","suffix":""},{"id":511563433,"identity":"904a20b6-d2b3-4b3c-8979-005f4eed75f4","order_by":1,"name":"Shruti Garg","email":"","orcid":"","institution":"Institute of Human Behaviour and Allied Sciences (IHBAS)","correspondingAuthor":false,"prefix":"","firstName":"Shruti","middleName":"","lastName":"Garg","suffix":""},{"id":511563434,"identity":"8091d9f9-995c-4174-ac31-ab08f159e6dc","order_by":2,"name":"Niharika Meena","email":"","orcid":"","institution":"Institute of Human Behaviour and Allied Sciences (IHBAS)","correspondingAuthor":false,"prefix":"","firstName":"Niharika","middleName":"","lastName":"Meena","suffix":""}],"badges":[],"createdAt":"2025-09-07 05:38:19","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7554183/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7554183/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":90896168,"identity":"06d1df3a-62ff-47f4-b011-b2d0a934d915","added_by":"auto","created_at":"2025-09-09 11:37:22","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":99317,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend.\u003c/p\u003e","description":"","filename":"Figure300.png","url":"https://assets-eu.researchsquare.com/files/rs-7554183/v1/7f79c8aaac9ac181908a9142.png"},{"id":90896178,"identity":"2a3accef-f025-439c-a85f-613b548c9412","added_by":"auto","created_at":"2025-09-09 11:37:23","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":287106,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend.\u003c/p\u003e","description":"","filename":"FIG2.png","url":"https://assets-eu.researchsquare.com/files/rs-7554183/v1/b091656c9a4b175b4a676de5.png"},{"id":91415304,"identity":"1ca33f28-21b6-4e60-a218-f8da9e8f1573","added_by":"auto","created_at":"2025-09-16 09:17:12","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":695551,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7554183/v1/b01c9ff1-9c41-4d31-bcbf-408b1d902396.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Treatment-Resistant Schizoaffective Disorder in Alcohol Dependence: A Case Report","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSchizoaffective disorder is a complex and chronic psychiatric condition that lies at the intersection of schizophrenia and mood disorders .\u0026sup1; It manifests as a combination of psychotic features, such as hallucinations or delusions, alongside disturbances in mood, including depression or mania .\u0026sup2;\u003c/p\u003e\u003cp\u003eThe illness often follows a fluctuating course, leading to significant reductions in social, occupational, and overall functional capacities .\u0026sup3;\u003c/p\u003e\u003cp\u003eSuccessful management is frequently challenging because it requires interventions that address both the psychotic and affective components of the disorder simultaneously.⁴\u003c/p\u003e\u003cp\u003eThe situation becomes even more complicated when schizoaffective disorder coexists with substance use disorders (SUD) .⁵\u003c/p\u003e\u003cp\u003eAmong these, alcohol use disorder (AUD) is particularly prevalent .⁶\u003c/p\u003e\u003cp\u003eStudies consistently demonstrate that individuals with schizophrenia spectrum disorders are more likely to develop alcohol dependence compared to the general population .⁷\u003c/p\u003e\u003cp\u003eEstimates suggest that one-quarter to half of these patients may engage in harmful drinking over their lifetimes .⁸\u003c/p\u003e\u003cp\u003eThe reasons for this overlap appear multifactorial .⁹Neurobiological mechanisms, including dysregulation of dopamine and glutamate pathways, underlie vulnerability to both psychosis and addictive behaviors .Cognitive dysfunction, impulsivity, impaired social support networks, and environmental stressors contribute further to this comorbidity .The clinical implications of combining chronic alcohol misuse with schizoaffective illness are wide-ranging .\u003c/p\u003e\u003cp\u003ePatients have poorer therapeutic responses and they face higher relapse risk and more frequent hospitalizations .\u0026sup1;⁰Pharmacological management also becomes more complex because alcohol may interact with psychiatric medications and impair their metabolism .\u003c/p\u003e\u003cp\u003eMoreover, substance misuse produces psychosocial disruption- hampering employment, financial security, interpersonal relationships, and caregiving systems .\u0026sup1;\u0026sup1;\u003c/p\u003e\u003cp\u003eThese combined challenges call for integrated, multidisciplinary approaches that simultaneously address psychiatric stabilization and addictive behaviors .\u0026sup1;\u0026sup2;\u003c/p\u003e\u003cp\u003eThis report presents a middle-aged man in India with treatment-resistant schizoaffective disorder and a long history of alcohol dependence .\u003c/p\u003e\u003cp\u003eIt highlights diagnostic considerations, treatment strategies, and ethical aspects of delivering care under mental health legislation .\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eDemographic Information and Personal Background\u003c/h2\u003e\u003cp\u003eThe patient, here referred to as Mr. O, is a 50-year-old Indian male from a disadvantaged socioeconomic environment. He completed high school but did not pursue higher education. Early in adulthood, he worked as a vegetable vendor and later shifted to labor-based employment. Over time, his psychiatric illness diminished his functional and occupational capacity, leading to loss of steady work and increasing financial strain. No significant hereditary contribution to mental illness was identified in his family history. Medical investigations revealed no comorbid illnesses such as diabetes, hypertension, or chronic liver damage.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eSubstance Use History\u003c/h3\u003e\n\u003cp\u003eMr. O reported consuming alcohol regularly for 33 years, beginning in late adolescence. This long-standing dependence eventually became habitual, with significant impairment in health and functioning. He also smoked tobacco concurrently. His last recorded alcohol consumption was 20 days prior to hospital admission. Despite this temporary abstinence, his case clearly fulfilled the diagnosis of alcohol dependence syndrome due to the chronicity and compulsive nature of his use .\u003c/p\u003e\n\u003ch3\u003ePsychiatric Symptom Evolution\u003c/h3\u003e\n\u003cp\u003ePsychiatric manifestations appeared roughly 14 years after the onset of sustained drinking. Initially, his family noticed changes in behavior, which worsened steadily over a three-year period. Prominent symptoms included persistent grandiose delusions, public disinhibition, neglect of personal hygiene, inappropriate social behaviors, and disorganized conduct such as hoarding trash or undressing in public. These actions attracted stigma and strained his social network.\u003c/p\u003e\u003cp\u003eHe was also noted to talk loudly to himself in public, suggesting auditory hallucinations or a heightened thought disorder. As symptoms progressed, irritability and unpredictability increased, leading to significant interpersonal conflict and a marked decline in his occupational and daily functioning.\u003c/p\u003e\n\u003ch3\u003eMental State Examination\u003c/h3\u003e\n\u003cp\u003eOn mental status examination, Mr. O presented with elevated mood and a euphoric affect. His speech was pressured and tangential, often irrelevant, with a flight of ideas. Thought content was dominated by clearly defined grandiose delusions. He exhibited increased psychomotor activity and lacked coherent self-reflection about his condition. Cognitive assessment revealed impaired judgment, reduced concentration, and distractibility. His level of insight into the illness was profoundly deficient, consistent with chronic psychosis .\u003c/p\u003e\n\u003ch3\u003eDiagnostic Impression\u003c/h3\u003e\n\u003cp\u003eUsing ICD-10 criteria, he was diagnosed with schizoaffective disorder, bipolar type (F25.0). In parallel, based on his prolonged alcohol use trajectory and current state of abstinence, he received the diagnosis of alcohol dependence syndrome under care. Standard laboratory testing, chest imaging, and neuroimaging did not reveal abnormalities, indicating that despite years of alcohol misuse, no immediate systemic organ damage had manifested .\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eInterventions and Hospital Course\u003c/h2\u003e\u003cp\u003eMr. O required inpatient care and was admitted under Section 89 of the Indian Mental Healthcare Act (2017), which justifies involuntary treatment when patients lack capacity for informed decision-making and pose risk to themselves or the community. His admission to a dual-diagnosis facility allowed simultaneous focus on his psychiatric illness and alcohol abuse history .\u003c/p\u003e\u003cp\u003ePharmacological treatment was initiated with sodium valproate 500 mg/day, later titrated to 1200 mg/day to stabilize affective symptoms. Lorazepam (2 mg/day) was used early to manage agitation but was switched to clonazepam (0.5 mg) due to its longer duration of action and greater tolerability.\u003c/p\u003e\u003cp\u003eTrials of risperidone and haloperidol were attempted but led to inadequate control of psychotic symptoms, in addition to producing adverse extrapyramidal reactions. These medications were withdrawn.\u003c/p\u003e\u003cp\u003eGiven poor response, clozapine was considered despite being reserved typically for refractory psychotic cases. It was started at 12.5 mg/day and titrated to 25 mg/day. To minimize side effects, trihexyphenidyl was also prescribed. This regimen produced robust improvement: psychotic features diminished, his communication became more organized, and self-care significantly improved. Family members observed better social interactions and welcomed reduction in disruptive public behavior.\u003c/p\u003e\u003cp\u003eConcurrently, non-pharmacological interventions were emphasized. Psychoeducation sessions conveyed the nature of psychiatric illness, the necessity of ongoing treatment, and the risks of relapse. Family therapy sessions enabled relatives to support adherence and manage stress. Structured rehabilitation programs provided guidance on relapse prevention and craving control. Abstinence monitoring strategies and outpatient follow-up plans were firmly established before discharge.\u003c/p\u003e\u003cp\u003eAfter stabilization, Mr. O was discharged on maintenance with clozapine, valproate, clonazepam, and trihexyphenidyl, alongside scheduled psychiatric follow-ups and mandatory blood monitoring given clozapine-associated risks .\u003c/p\u003e\u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis report demonstrates the difficulties in detecting and treating schizoaffective disorder in people with concomitant AUD .Poor insight, cognitive impairments, and nonadherence hampered traditional therapeutic response .Clozapine, while often reserved for refractory cases, proved critical in attaining symptom management and functional improvement.\u003c/p\u003e\u003cp\u003eClozapine appears to be helpful in dual diagnosis individuals with psychosis and substance use disorders, probably due to its unique neuroreceptor profile and higher efficacy over other antipsychotics .Ethical management, which includes permission, family involvement, and multidisciplinary treatment, is critical, particularly for patients who require compulsory hospitalisation under mental health legislation.\u003c/p\u003e\u003cp\u003eThe case reinforces the significance of a comprehensive, ethical, and integrated approach to treating dual diagnosis cases .Clozapine remains a valuable treatment modality in managing resistant psychotic symptoms and improving patient quality of life, even in the context of chronic substance use.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthics approval and consent to participate\u003c/p\u003e\n\u003cp\u003eNot applicable. The case report is based on retrospective clinical information and anonymized data.\u003c/p\u003e\n\u003cp\u003eConsent for publication\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient for publication of this case report, including clinical details. The consent form is available with the corresponding author and can be provided upon request.\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003eCompeting interests\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003eFunding\u003c/p\u003e\n\u003cp\u003eThe authors received no external funding for this case report.\u003c/p\u003e\n\u003cp\u003eAuthors\u0026rsquo; contributions\u003c/p\u003e\n\u003cp\u003eSS conceptualized the case report and coordinated the drafting. SG supervised clinical care and contributed to manuscript revisions. NM assisted in literature review and formatting. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003eAcknowledgements\u003c/p\u003e\n\u003cp\u003eWe acknowledge the patient and his caregivers for their cooperation and consent to share his clinical details.\u003c/p\u003e\n\u003cp\u003eAuthors\u0026rsquo; information\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBuckley PF, Miller BJ, Lehrer DS, Castle DJ. Psychiatric comorbidities and schizophrenia. Schizophr Bull. 2009;35(2):383\u0026ndash;402.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGreen MF, Nuechterlein KH. Should schizophrenia be treated as a neurocognitive disorder? Schizophr Bull. 1999;25(2):309\u0026ndash;319.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eVolkow ND, Fowler JS. Addiction and the orbitofrontal cortex. Cereb Cortex. 2000;10(3):318\u0026ndash;325.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBlanchard JJ, Brown SA. Substance use and course of illness in schizophrenia. Clin Psychol Rev. 1998;18(2):201\u0026ndash;220.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLeucht S, et al. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia. Lancet. 2013;382(9896):951\u0026ndash;962.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMcLellan AT, Koob GF, Volkow ND. Precipitated withdrawal from alcohol and opioids. Am J Psychiatry. 2014;171(10):1101\u0026ndash;1107.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBuckley PF. Prevalence and consequences of dual diagnosis. J Clin Psychiatry. 2006;67(Suppl 7):5\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMueser KT, Noordsy DL, Drake RE, Fox L. Integrated Treatment for Dual Disorders: A Guide to Effective Practice. New York: Guilford Press; 2003.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePompili M, et al. Substance abuse and suicide risk among schizophrenia patients. Schizophr Res. 2009;119(1\u0026ndash;3):253\u0026ndash;254.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKirkpatrick B, Buchanan RW. Schizophrenia as a syndrome. Compr Psychiatry. 1990;31(4):255\u0026ndash;269.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAddington J, Saeedi H, Addington D. Cognitive functioning in first episode psychosis. Schizophr Res. 2005;78(1):35\u0026ndash;43.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMueser KT, et al. Substance abuse in schizophrenia: demographic and clinical correlates. Schizophr Bull. 1990;16(1):31\u0026ndash;56.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Schizoaffective Disorder, Alcohol Use Disorder, Treatment Resistance, Dual Diagnosis, Clozapine","lastPublishedDoi":"10.21203/rs.3.rs-7554183/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7554183/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eSchizophrenia and schizoaffective disorder are complex psychotic disorders characterized by symptoms such as delusions, hallucinations, and cognitive impairment. These disorders are often exacerbated by comorbid substance use disorder (SUD), leading to more severe disability and poorer outcomes compared to those without SUD. The frequent co-occurrence of schizophrenia with alcohol use disorder (AUD) or other substances may be linked to dysfunctions in brain reward circuitry and shared neurobiological pathways. Effective management typically involves a combination of pharmacological treatments and complementary therapeutic approaches to address both the psychotic disorder and the substance use disorder.\u003c/p\u003e\u003cp\u003eThis case report presents a 50-year-old man with a history of alcohol and tobacco dependence, who displayed increased alcohol consumption and neglect of pleasurable activities, alongside symptoms indicative of schizoaffective disorder. Medical investigations, including blood tests, chest X-ray and NCCT Head, revealed no significant abnormalities. Serial mental status examinations led to a diagnosis of Mental and Behavioral Disorder due to Alcohol Dependence Syndrome (ADS) with Schizoaffective Disorder. Initial treatment with second-generation antipsychotics and mood stabilizers provided limited improvement. A subsequent switch to first-generation antipsychotics yielded only a partial response, classifying the patient as treatment-resistant. The introduction of clozapine resulted in significant clinical improvement, enhancing social functioning and achieving remission, while avoiding polypharmacy and minimizing metabolic side effects.\u003c/p\u003e","manuscriptTitle":"Treatment-Resistant Schizoaffective Disorder in Alcohol Dependence: A Case Report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-09 11:37:17","doi":"10.21203/rs.3.rs-7554183/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e205a4ac-da3d-489d-abba-d4faace1e6cb","owner":[],"postedDate":"September 9th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-09-16T09:09:05+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-09 11:37:17","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7554183","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7554183","identity":"rs-7554183","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}