Case Report of Management of Severe Tardive Dyskinesia Induced by an Atypical Antipsychotic in a Schizophrenic Patient

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Case presentation This case report presents a 32-year-old male diagnosed with schizophrenia who developed TD after being treated with the atypical antipsychotic Aripiprazole and experienced symptoms four weeks post self-discontinuation. Despite the generally lower risk of extrapyramidal symptoms associated with atypical (second-generation) antipsychotics, the patient experienced significant involuntary facial and jaw movements that adversely affected his quality of life. Traditional management strategies were ineffective; however, by adjusting the previous medications and dosages, including Tetrabenazine, a recently approved medication for TD, the patient showed marked improvement in his symptoms. Conclusion This case highlights the importance of recognizing TD as a potential complication of aripiprazole and underscores the effectiveness of Tetrabenazine as a treatment option for managing this challenging condition. Case report Tardive dyskenisa schizophrenia antipyschoitcs SGAS Introduction Schizophrenia is a severe mental disorder that profoundly affects an individual's ability to think, feel, and behave normally. It typically manifests during late adolescence or early adulthood and impacts approximately 1% of the global population ( 1 ). The condition is characterized by abnormalities in brain circuits found in both the cortex and sub-cortex, which involve disruptions in various neurotransmitter systems, particularly dopamine and glutamate ( 2 , 3 ). Antipsychotics remain the primary treatment modality, targeting various neurotransmitter receptors, particularly dopamine receptors, with a focus on G protein-coupled receptors (GPCRs) ( 4 ). Since individuals respond differently to treatment, exploring various therapeutic approaches is essential ( 5 ). While antipsychotics are generally effective, they may lead to several physical issues, including metabolic, cardiovascular, and neurological complications ( 6 ). Neurological complications may include extrapyramidal symptoms (EPS), and seizures ( 7 ). Although it was previously believed that second-generation antipsychotics (SGAs) pose a lower risk of EPS compared to first-generation antipsychotics (FGAs), recent research indicates that this is not always the case. In clinical practice, over 60% of patients with bipolar disorder have reported experiencing moderate to severe EPS while being treated with SGA ( 8 ). Tardive dyskinesia (TD) is a type of extrapyramidal symptom (EPS) characterized by uncontrollable movements, primarily affecting the face and limbs. It is caused by agents that block dopamine receptors, such as antipsychotics. Notably, TD can persist even after discontinuation of the medication, leading to societal stigma and a diminished quality of life ( 9 ). It could also present up to weeks following antipsychotic discontinuation or dose reduction ( 10 ). Management strategies involve discontinuatino or lowering the dose of the antipsychotic, switching to atypical antipsychotics as the first-line treatment, with recently approved medications such as Deutetrabenazine, Valbenazine, and Tetrabenazine being utilized ( 11 , 12 ). These medications are vesicular monoamine transporter 2 (VMAT2) inhibitors. By supressing VMAT2, presynaptic dopamine packaging and releasing is reduced, and therefore, dopaminergic hyperactivity, which is the primary pathophyisiology of TD, is mitigated ( 13 ). These agents are FDA-approved and currently represent the most effective and targeted pharmacological treatments for TD ( 14 ). Here, we report an interesting case of a patient with schizophrenia who developed TD as a result of taking an atypical antipsychotic- which tend do not be associated with TD too much - Aripiprazole and was successfully treated through adjustments in medications and dosages, including the use of Tetrabenazine. Case presentation The patient is a 32-year-old male who was admitted to the emergency department with a chief complaint of severe difficulty controlling his jaw movements. During the interview, he exhibited no aggression or agitation and cooperated well with the psychiatrist. His mood appeared partially depressed, and his affect was restricted. His perception was affected by auditory and visceral hallucinations, as he reported hearing voices that told him he would never get better and that he would never be free. He also frequently sensed a device implanted in his stomach, caused restriction in his stomach capacity. His form of thought was goal directed; however, the content of his thoughts included persecutory delusions, specifically that the device in his stomach had been implanted by an unknown persons intending to harm him. Negative symptoms were evident, including partially diminished self-care, poverty of content of thought, restricted affect, and a lack of willingness. The patient reports experiencing mandibular dyskinesia for approximately two years, initially without significant impact on his daily life. However, the severity of the dyskinesia began to worsen in the several months leading up to his referral to the hospital. In his past psychiatric history, the patient was brought to the emergency department about four years ago by his family due to aggression, auditory hallucinations (specifically hearing a voice that said, "You will never escape from me"), visceral hallucinations (sensing that his stomach was occupied by a device), persecutory delusions (believing that a device had been implanted in his stomach to impede his eating and harm him), and negative symptoms, including restricted affect, poverty of speech, and diminished self-care. By the way, His psychotic symptoms were beginning years before and gradually getting worse. Based on his previous records and outpatient visits, and due to inadequate response to various prior antipsychotic regimens, such as risperidone and olanzapine, he was started on clozapine, gradually increased the dose to 100 mg/day. However, due to elevated liver enzymes (AST and ALT up to 70), which persisted, and the likelihood of poor follow-up after discharge, clozapine dose was reduced to 50 mg, and aripiprazole 10 mg was added to the treatment. Eventually, for the first time in years, the patient was seen with complete remission of positive symptoms and partial improvement in negative symptoms. Over the following two years, in sporadic visits, the patient’s positive symptoms remained in complete remission. However, following self-reducing and discontinuing aripiprazole after four weeks, tremors in the jaw and neck became evident. Subsequently, he was diagnosed with tardive dyskinesia. Following the development of tardive dyskinesia (TD), which was unresponsive to monotherapy with Clozapine, other strategies were attempted, such as adding Biperiden and Propranolol to Clozapine. Clozapine was the only antipsychotic that could be implemented to manage the patient's severe and chronic psychotic symptoms as well as TD. However, none of these strategies caused improvement in the patient’s TD. About one and a half years after these two years of ineffective treatment with various adjuvants to Clozapine, the patient met several other physicians and psychiatrists during sporadic and chaotic outpatient visits. He attempted to address his severe and undesirable jaw movements in addition to his psychotic symptoms. Yet, since none of the therapeutic management strategies were effective, he became disappointed in finding a viable solution, discontinued his visits to health care providers, and attempted to self-treat with various medications available at home for about six months. Upon re-evaluation after this period by the psychiatrist who had initially managed him during his first hospitalization, it was evident that the patient was severely affected by tardive dyskinesia. He was unable to eat properly due to dyskinetic jaw movements, which caused his jaw to remain open, leading to food spilling from his mouth. Additionally, he was unable to engage in normal conversations because of TD. The patient was fully psychotic, experiencing delusions of persecution, auditory and visceral hallucinations with the same content as before, and more severe negative symptoms. His mood was assessed as partially depressed due to the uncontrollable jaw movements, worsening his personal and interpersonal functions. Therefore, he was readmitted to psychiatric ward. In his past psychiatric history, except for the onset of schizophrenia at about 20 years old, he mentioned having tics that started about ten years ago, affecting head movements, but these were self-determined. In his family history, the patient has an identical monozygotic twin, who does not suffer from schizophrenia or other psychiatric disorders but has gastrointestinal symptoms. Upon reviewing his recent self-treated medication history, it was found that the patient was receiving Risperidone (4 mg), Clozapine (150 mg), Biperidine, Clonazepam, Propranolol, and Tetrabenazine. These medications were self-administered by the patient from leftover medications at home, at self-determined dosages. The patient did not know the exact dosages of the prescribed medications. In his social history, he was smoker but he refused to abuse any other substances. In physical examination, except abnormal severe movements in his facial expressions and mild tremors in neck and hands without any rigidity, everything was normal. His vital signs were appropriate and he did not have fever. The patient diagnosed as chronic schizophrenia with chronic adjustment disorder (depressed type) and abnormal movement disorder which seemed to be TD caused by Aripiprazole. During admission to the psychiatric ward, the diagnostic plan included ruling out other possible differential diagnoses and assessing the patient's basic physical condition. The patient underwent a brain MRI, electroencephalography (EEG), and various lab tests. Although the patient had a healthy monozygotic twin with no psychiatric or movement issues, but with gastrointestinal symptoms, serum ceruloplasmin tests and an ophthalmologic consultation for Kayser-Fleischer ring evaluation were requested to rule out other possible differential diagnose for the dyskinetic movements alongside psychotic symptoms (Wilson’s disease). The brain MRI showed normal skull base signal intensity and anatomic landmarks, no evidence of infarction or hemorrhage, however, few tiny T2w high signal intensity foci in the right frontal area were seen, which could have been due to microvascular ischemic changes, as reported by the radiologist. The EEG, which was performed in an awake state, consisted mostly of alpha waves. No epileptic waves or focal findings were observed. Some bursts of slowed waves were observed, however. The neurologist recommended investigation of metabolic causes or drug poisoning. Upon admission, the complete blood count (CBC) was normal except for a hemoglobin of 12.9 g/dl (normal range: 14–18 g/dl). ESR, biochemistry tests including FBS, renal and hepatic function tests, and lipid panel were normal. T3 and T4 were normal; however, the TSH was 6.48 MIU/L (normal range: 0.3–6.3 MUI/L), which by re-evaluating the test was reported as 5.28 MUI/L. CBC on the fifth day of admission was normal, except for hemoglobin of 13.1. Iron, TIBC, ferritin, and thyroid tests were evaluated and all were within normal limits (lab data is presented in Table 1 ). ECG was performed twice, and QTc was monitored during the course of treatment (initially 0.436 ms, and during inpatient management with medication and dosage adjustments, it decreased to 0.385 ms). Slit-lamp examination by an ophthalmologist ruled out a Kayser-Fleischer ring, and serum ceruloplasmin test was negative. Table 1 laboratory data of the patient Lab data Value Complete blood count WBC (cells/mcL) 4.8 RBC (million cells/mcL) 4.28 Haemoglobin (g/dl) 12.9 Haematocrit (%) 38.7 MCV (FL) 90.4 MCHC (pg) 30.1 RDW (%) 14.4 Platelets (platelets/mcL) 307 Biochemistry Fasting blood sugar (mg/dl) 75 Urea (mg/dl) 27 Creatinine (mg/dl) 1.0 Cholesterol (mg/dl) 160 Triglyceride (mg/dl) 81 HDL (mg/dl) 44 LDL (mg/dl) 99 electrolytes Ca (mg/dl) 10.0 Na (mmol/l) 137 K (mmol/l) 3.9 Liver biochemistry Alkaline Phosphatase (U/l) 92 AST (U/l) 14 ALT (U/l) 13 Hormone T4 (microg/dl) 8 T3 (ng/dl) 153 TSH (MIU/l) 6.48 (5.28 in follow-up) Ferritin (ng/ml) 81 Iron (mg/dl) 78 TIBC (mg/dl) 369 Serology CRP Negative Ceruloplasmin Negative According to therapeutic plan designed by the psychiatrist, risperidone was immediately discontinued. Due to the patient’s history of elevated liver enzymes, QTc calculations on ECG, and the absence of aggression or self-harm behaviors during the hospitalization, Clozapine was reduced to 25 mg, Tetrabenazine was increased (from 25mg 1-0-1 to 25mg 1-0.5-1), and he was started on Lorazepam1 mg (0–1/2 − 1/2), and Sertraline, as well as continuation of Biperiden 2 mg (0–1/2 − 1/2), and Propranolol (20mg BID). With the reduction of QTc, normal liver enzymes, and no reduction in hemoglobin, Clozapine was gradually increased to 100 mg/day. Tetrabenazine 6 mg (1/2 daily) was also administered, along with an increase in the biperiden dose (2mg, 1/2,-1/2 − 1/2 in the seventh post-admission day). During hospitalization, the patient’s dyskinetic movements and tremors significantly decreased, allowing him to close his mouth and chew food more effectively, with less food spilling during meals and fewer food stains on his clothes. He was also able to participate in conversations more effectively, as he could move his jaw better and showed improvement in articulation. He reported a decrease in both the frequency and severity of his psychotic symptoms, though there was not a full remission. The patient's mood improved; however, it remained slightly depressed, while other symptoms such as boredom and disappointment vanished. The psychiatrist believed that two weeks of sertraline was not enough for a complete improvement in the patient's mood, and it was possible that, with enough time and without increasing the dose, the patient would experience complete remission from the depressive episode. Additionally, negative symptoms partially improved. Ultimately, after 17 days of hospitalization, the patient was discharged in good general condition, with significant improvement in tardive dyskinesia (TD), partial remission of both positive and negative symptoms, and a near-euthymic mood. At discharge, the patient and his mother received comprehensive psychoeducation on symptoms, the treatment plan, potential interactions, the importance of avoiding self-medication, and the need to attend outpatient visits on time and in order. Discussion TD is a serious, often irreversible movement disorder characterized by involuntary, repetitive movements, typically affecting the orofacial region. It is associated with long-term use of dopamine receptor-blocking agents. Although atypical antipsychotics are generally considered to have a lower risk of TD compared to typical antipsychotics, cases of TD induced by atypical agents like risperidone and aripiprazole have been reported ( 15 , 16 ). In the present case, a 32-year-old male developed TD after two years of treatment with Aripiprazole for schizophrenia within four weeks following self-tapering down and stopping the usage of it. Aripiprazole, known for its unique mechanism as a partial agonist at dopamine D2 and serotonin 5-HT1A receptors and antagonist at 5-HT2A receptors ( 17 ), is considered to have a favorable side effect profile, with lower rates of metabolic and motor symptoms ( 18 , 19 ). However, rare cases of aripiprazole-induced TD have been reported ( 15 , 20 ). Management of TD focuses on prevention, early detection, and appropriate intervention. Guidelines recommend withdrawing the causative agent when possible ( 21 , 22 ). Switching to antipsychotics with lower D2 receptor affinity, such as Clozapine or Quetiapine, may alleviate symptoms ( 21 , 22 ). Vesicular monoamine transporter 2 (VMAT-2) inhibitors like deutetrabenazine and valbenazine are recommended treatments with strong evidence for efficacy ( 21 – 23 ). Other treatments with varying levels of evidence include Clonazepam, Ginkgo biloba, Amantadine, and Tetrabenazine ( 23 , 24 ). A study on 234 patients treated with aripiprazole showed a TD prevalence of 3.4%, and in most patients, TD did not resolve spontaneously following discontinuation of aripiprazole. Most patients in the mentioned study improved via treatment with Tetrabenazine ( 25 ). Other case reports have also showed TD evolvement following use of Aripiprazole ( 26 , 27 ). Additionally, a case report showed improvement of Aripiprazole-induced TD and dystonic symptoms following switching the medication to Quetiapine ( 28 ). Similar improving result were also reported with the use of Clozapine ( 29 , 30 ). risperidone was also reported to cause TD in some case reports ( 31 , 32 ). Tetrabenazine selectively and reversibly VMAT2, which is responsible for packaging dopamine, norepinephrine, serotonin, and histamine into synaptic vesicles in presynaptic neurons. By blocking VMAT2, tetrabenazine prevents dopamine storage in vesicles, leaving it exposed to degradation by monoamine oxidase (MAO) in the cytoplasm, thereby depleting presynaptic dopamine levels. This reduction in dopamine release decreases overstimulation of postsynaptic D2 receptors (particularly in the indirect pathway of the motor striatum), which are often hypersensitive in conditions like TD ( 33 , 34 ). Additionally, by lowering dopamine availability in the direct pathway, tetrabenazine further reduces hyperkinetic movements. Unlike irreversible VMAT inhibitors (e.g., reserpine), tetrabenazine’s effects are reversible and CNS-specific (due to its selectivity for VMAT2 over VMAT1), minimizing peripheral side effects. Its active metabolites (α- and β-hydroxytetrabenazine) prolong its dopamine-depleting action, providing symptomatic relief in TD without directly blocking dopamine receptors ( 33 ). This case report offers important clinical insights into the rare occurrence of TD induced by Aripiprazole, an atypical antipsychotic typically associated with a lower risk of extrapyramidal side effects. The case is notable for its clear documentation of symptom onset following self-discontinuation of Aripiprazole, as well as the observed improvement with Tetrabenazine—an agent with a well-established mechanism for managing hyperkinetic movement disorders. The inclusion of relevant literature and treatment guidelines enhances the report’s educational and clinical utility for practitioners managing similar cases. However, several limitations must be acknowledged. As a single case report, the findings cannot be generalized to broader populations and lack the statistical power of controlled studies. The absence of objective clinical assessment tools, such as the Abnormal Involuntary Movement Scale (AIMS), limits the ability to quantify symptom severity and response to treatment. The report also lacks extended follow-up data, which would be valuable in assessing the long-term efficacy and tolerability of Tetrabenazine. Despite these limitations, this case contributes meaningfully to the growing body of literature highlighting the potential for atypical antipsychotics to induce TD and reinforces the importance of monitoring, patient education, and early intervention in mitigating long-term adverse outcomes. This case highlights that TD can develop even with atypical antipsychotics as well, particularly following abrupt changes in dosing, suggesting that both chronic exposure and sudden withdrawal may play a role in its pathogenesis. The delayed onset and persistence of symptoms underscore the importance of close monitoring for movement disorders, even with medications traditionally considered to have lower extrapyramidal risk. The patient’s improvement with Tetrabenazine further supports its utility as an effective treatment option for managing TD. Clinicians should remain vigilant for early signs of TD, ensure patients are educated about medication adherence, and be prepared to adjust treatment promptly to prevent long-term complications. Conclusion In conclusion, tardive dyskinesia (TD) remains a serious and often distressing movement disorder that can arise from the long-term use of antipsychotics, primarily typical antipsychotics, though it can also occur with atypical antipsychotics. This case highlights the development of TD in a 32-year-old male patient with schizophrenia who experienced this complication within four weeks after self-tapering down and discontinuing Aripiprazole, which he had taken for two years. Furthermore, the results of this case report emphasize the promising role of Tetrabenazine in the management of TD, alongside other therapeutic strategies. Declarations Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Conflicts of interest/Competing interests The authors declare that they have no known competing financial interests or personal relationships that could have influenced this study. Ethics approval The study was approved by the ethical committee of Birjand University of Medical Sciences by the ethics code of IR.BUMS.REC.1403.283. Consent to participate The patient gave informed consent for both interviews and conduction of the report in a stable, non-psychotic state. Written Consent for publication The authors confirm that the participant gave consent for their data to be published anonymously. Availability of data and material Not applicable Code availability Not applicable Authors' contributions MM did the process of diagnosis and treatment. FF reviewed the documentation and prepared them for writing. both FF and DG wrote the draft. 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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-7176801","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":492414662,"identity":"cde8856a-24d6-42d7-b17c-f3f40e584e24","order_by":0,"name":"Farzad Fayedeh","email":"","orcid":"","institution":"Birjand University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Farzad","middleName":"","lastName":"Fayedeh","suffix":""},{"id":492414663,"identity":"75a336d4-8548-496b-9e89-8f01ecf020b8","order_by":1,"name":"Mahya Mojahedi","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA8UlEQVRIiWNgGAWjYFACHhDBxmDAwGBw4AOIyU6KloMzQExm4rQwgLUwg9mEtOi2nz3AdKOCT96cvXnjYZtf2+T5mBkYP3zMwa3F7ExeAnPOGTbDnT3HCg7n9t02bGNmYJacuQ2PlgM5Bsy5bWyMG27kGBzO7bnNCNTCxsyLT8v5N2At9hvuvzE4bNlz256wlhsQWxI33OAxOMzw43YiEVqAhgP9krzhTFrBwd6G28ltzIzN+P1yPsfwcU7FMdsNxw9v/vDjz23b+e3NBz98xKMFBA4wMByDsBjbwGQDfvUQUAOl/xCjeBSMglEwCkYaAABf0lXOhVWDmwAAAABJRU5ErkJggg==","orcid":"","institution":"Birjand University of Medical Sciences","correspondingAuthor":true,"prefix":"","firstName":"Mahya","middleName":"","lastName":"Mojahedi","suffix":""},{"id":492414664,"identity":"274e5606-6012-4182-a228-0c8f1b48f530","order_by":2,"name":"Danial Gharaie Amirabadi","email":"","orcid":"","institution":"Birjand University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Danial","middleName":"Gharaie","lastName":"Amirabadi","suffix":""}],"badges":[],"createdAt":"2025-07-21 11:23:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7176801/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7176801/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":88015806,"identity":"519615c9-296d-49db-ab4d-b9d7c909ab21","added_by":"auto","created_at":"2025-07-31 13:04:16","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":460010,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7176801/v1/1649f6b3-8584-40f9-8dbb-b5e482a10499.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Case Report of Management of Severe Tardive Dyskinesia Induced by an Atypical Antipsychotic in a Schizophrenic Patient","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSchizophrenia is a severe mental disorder that profoundly affects an individual's ability to think, feel, and behave normally. It typically manifests during late adolescence or early adulthood and impacts approximately 1% of the global population (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). The condition is characterized by abnormalities in brain circuits found in both the cortex and sub-cortex, which involve disruptions in various neurotransmitter systems, particularly dopamine and glutamate (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eAntipsychotics remain the primary treatment modality, targeting various neurotransmitter receptors, particularly dopamine receptors, with a focus on G protein-coupled receptors (GPCRs) (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Since individuals respond differently to treatment, exploring various therapeutic approaches is essential (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). While antipsychotics are generally effective, they may lead to several physical issues, including metabolic, cardiovascular, and neurological complications (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Neurological complications may include extrapyramidal symptoms (EPS), and seizures (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Although it was previously believed that second-generation antipsychotics (SGAs) pose a lower risk of EPS compared to first-generation antipsychotics (FGAs), recent research indicates that this is not always the case. In clinical practice, over 60% of patients with bipolar disorder have reported experiencing moderate to severe EPS while being treated with SGA (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eTardive dyskinesia (TD) is a type of extrapyramidal symptom (EPS) characterized by uncontrollable movements, primarily affecting the face and limbs. It is caused by agents that block dopamine receptors, such as antipsychotics. Notably, TD can persist even after discontinuation of the medication, leading to societal stigma and a diminished quality of life (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). It could also present up to weeks following antipsychotic discontinuation or dose reduction (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Management strategies involve discontinuatino or lowering the dose of the antipsychotic, switching to atypical antipsychotics as the first-line treatment, with recently approved medications such as Deutetrabenazine, Valbenazine, and Tetrabenazine being utilized (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). These medications are vesicular monoamine transporter 2 (VMAT2) inhibitors. By supressing VMAT2, presynaptic dopamine packaging and releasing is reduced, and therefore, dopaminergic hyperactivity, which is the primary pathophyisiology of TD, is mitigated (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). These agents are FDA-approved and currently represent the most effective and targeted pharmacological treatments for TD (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eHere, we report an interesting case of a patient with schizophrenia who developed TD as a result of taking an atypical antipsychotic- which tend do not be associated with TD too much - Aripiprazole and was successfully treated through adjustments in medications and dosages, including the use of Tetrabenazine.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eThe patient is a 32-year-old male who was admitted to the emergency department with a chief complaint of severe difficulty controlling his jaw movements. During the interview, he exhibited no aggression or agitation and cooperated well with the psychiatrist. His mood appeared partially depressed, and his affect was restricted. His perception was affected by auditory and visceral hallucinations, as he reported hearing voices that told him he would never get better and that he would never be free. He also frequently sensed a device implanted in his stomach, caused restriction in his stomach capacity. His form of thought was goal directed; however, the content of his thoughts included persecutory delusions, specifically that the device in his stomach had been implanted by an unknown persons intending to harm him. Negative symptoms were evident, including partially diminished self-care, poverty of content of thought, restricted affect, and a lack of willingness.\u003c/p\u003e\u003cp\u003eThe patient reports experiencing mandibular dyskinesia for approximately two years, initially without significant impact on his daily life. However, the severity of the dyskinesia began to worsen in the several months leading up to his referral to the hospital.\u003c/p\u003e\u003cp\u003eIn his past psychiatric history, the patient was brought to the emergency department about four years ago by his family due to aggression, auditory hallucinations (specifically hearing a voice that said, \"You will never escape from me\"), visceral hallucinations (sensing that his stomach was occupied by a device), persecutory delusions (believing that a device had been implanted in his stomach to impede his eating and harm him), and negative symptoms, including restricted affect, poverty of speech, and diminished self-care.\u003c/p\u003e\u003cp\u003eBy the way, His psychotic symptoms were beginning years before and gradually getting worse. Based on his previous records and outpatient visits, and due to inadequate response to various prior antipsychotic regimens, such as risperidone and olanzapine, he was started on clozapine, gradually increased the dose to 100 mg/day. However, due to elevated liver enzymes (AST and ALT up to 70), which persisted, and the likelihood of poor follow-up after discharge, clozapine dose was reduced to 50 mg, and aripiprazole 10 mg was added to the treatment. Eventually, for the first time in years, the patient was seen with complete remission of positive symptoms and partial improvement in negative symptoms.\u003c/p\u003e\u003cp\u003eOver the following two years, in sporadic visits, the patient’s positive symptoms remained in complete remission. However, following self-reducing and discontinuing aripiprazole after four weeks, tremors in the jaw and neck became evident. Subsequently, he was diagnosed with tardive dyskinesia. Following the development of tardive dyskinesia (TD), which was unresponsive to monotherapy with Clozapine, other strategies were attempted, such as adding Biperiden and Propranolol to Clozapine. Clozapine was the only antipsychotic that could be implemented to manage the patient's severe and chronic psychotic symptoms as well as TD. However, none of these strategies caused improvement in the patient’s TD.\u003c/p\u003e\u003cp\u003eAbout one and a half years after these two years of ineffective treatment with various adjuvants to Clozapine, the patient met several other physicians and psychiatrists during sporadic and chaotic outpatient visits. He attempted to address his severe and undesirable jaw movements in addition to his psychotic symptoms. Yet, since none of the therapeutic management strategies were effective, he became disappointed in finding a viable solution, discontinued his visits to health care providers, and attempted to self-treat with various medications available at home for about six months.\u003c/p\u003e\u003cp\u003eUpon re-evaluation after this period by the psychiatrist who had initially managed him during his first hospitalization, it was evident that the patient was severely affected by tardive dyskinesia. He was unable to eat properly due to dyskinetic jaw movements, which caused his jaw to remain open, leading to food spilling from his mouth. Additionally, he was unable to engage in normal conversations because of TD.\u003c/p\u003e\u003cp\u003eThe patient was fully psychotic, experiencing delusions of persecution, auditory and visceral hallucinations with the same content as before, and more severe negative symptoms. His mood was assessed as partially depressed due to the uncontrollable jaw movements, worsening his personal and interpersonal functions. Therefore, he was readmitted to psychiatric ward.\u003c/p\u003e\u003cp\u003eIn his past psychiatric history, except for the onset of schizophrenia at about 20 years old, he mentioned having tics that started about ten years ago, affecting head movements, but these were self-determined.\u003c/p\u003e\u003cp\u003eIn his family history, the patient has an identical monozygotic twin, who does not suffer from schizophrenia or other psychiatric disorders but has gastrointestinal symptoms.\u003c/p\u003e\u003cp\u003eUpon reviewing his recent self-treated medication history, it was found that the patient was receiving Risperidone (4 mg), Clozapine (150 mg), Biperidine, Clonazepam, Propranolol, and Tetrabenazine. These medications were self-administered by the patient from leftover medications at home, at self-determined dosages. The patient did not know the exact dosages of the prescribed medications.\u003c/p\u003e\u003cp\u003eIn his social history, he was smoker but he refused to abuse any other substances.\u003c/p\u003e\u003cp\u003eIn physical examination, except abnormal severe movements in his facial expressions and mild tremors in neck and hands without any rigidity, everything was normal. His vital signs were appropriate and he did not have fever.\u003c/p\u003e\u003cp\u003eThe patient diagnosed as chronic schizophrenia with chronic adjustment disorder (depressed type) and abnormal movement disorder which seemed to be TD caused by Aripiprazole.\u003c/p\u003e\u003cp\u003eDuring admission to the psychiatric ward, the diagnostic plan included ruling out other possible differential diagnoses and assessing the patient's basic physical condition. The patient underwent a brain MRI, electroencephalography (EEG), and various lab tests. Although the patient had a healthy monozygotic twin with no psychiatric or movement issues, but with gastrointestinal symptoms, serum ceruloplasmin tests and an ophthalmologic consultation for Kayser-Fleischer ring evaluation were requested to rule out other possible differential diagnose for the dyskinetic movements alongside psychotic symptoms (Wilson’s disease).\u003c/p\u003e\u003cp\u003eThe brain MRI showed normal skull base signal intensity and anatomic landmarks, no evidence of infarction or hemorrhage, however, few tiny T2w high signal intensity foci in the right frontal area were seen, which could have been due to microvascular ischemic changes, as reported by the radiologist. The EEG, which was performed in an awake state, consisted mostly of alpha waves. No epileptic waves or focal findings were observed. Some bursts of slowed waves were observed, however. The neurologist recommended investigation of metabolic causes or drug poisoning. Upon admission, the complete blood count (CBC) was normal except for a hemoglobin of 12.9 g/dl (normal range: 14–18 g/dl). ESR, biochemistry tests including FBS, renal and hepatic function tests, and lipid panel were normal. T3 and T4 were normal; however, the TSH was 6.48 MIU/L (normal range: 0.3–6.3 MUI/L), which by re-evaluating the test was reported as 5.28 MUI/L. CBC on the fifth day of admission was normal, except for hemoglobin of 13.1. Iron, TIBC, ferritin, and thyroid tests were evaluated and all were within normal limits (lab data is presented in Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). ECG was performed twice, and QTc was monitored during the course of treatment (initially 0.436 ms, and during inpatient management with medication and dosage adjustments, it decreased to 0.385 ms). Slit-lamp examination by an ophthalmologist ruled out a Kayser-Fleischer ring, and serum ceruloplasmin test was negative.\u003c/p\u003e\u003cdiv class=\"gridtable\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003elaboratory data of the patient\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003c/colgroup\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eLab data\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eValue\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"7\" rowspan=\"8\"\u003e\u003cp\u003eComplete blood count\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eWBC (cells/mcL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4.8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eRBC (million cells/mcL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4.28\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHaemoglobin (g/dl)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12.9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHaematocrit (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e38.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMCV (FL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e90.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMCHC (pg)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e30.1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eRDW (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePlatelets (platelets/mcL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e307\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"6\" rowspan=\"7\"\u003e\u003cp\u003eBiochemistry\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFasting blood sugar (mg/dl)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e75\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eUrea (mg/dl)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e27\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCreatinine (mg/dl)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCholesterol (mg/dl)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e160\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTriglyceride (mg/dl)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e81\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHDL (mg/dl)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e44\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eLDL (mg/dl)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e99\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eelectrolytes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCa (mg/dl)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10.0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNa (mmol/l)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e137\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eK (mmol/l)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eLiver biochemistry\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAlkaline Phosphatase (U/l)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e92\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAST (U/l)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eALT (U/l)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"5\" rowspan=\"6\"\u003e\u003cp\u003eHormone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eT4 (microg/dl)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eT3 (ng/dl)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e153\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTSH (MIU/l)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6.48 (5.28 in follow-up)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFerritin (ng/ml)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e81\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eIron (mg/dl)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e78\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTIBC (mg/dl)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e369\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eSerology\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCRP\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNegative\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCeruloplasmin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNegative\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/table\u003e\u003c/div\u003e\u003cp\u003eAccording to therapeutic plan designed by the psychiatrist, risperidone was immediately discontinued. Due to the patient’s history of elevated liver enzymes, QTc calculations on ECG, and the absence of aggression or self-harm behaviors during the hospitalization, Clozapine was reduced to 25 mg, Tetrabenazine was increased (from 25mg 1-0-1 to 25mg 1-0.5-1), and he was started on Lorazepam1 mg (0–1/2 − 1/2), and Sertraline, as well as continuation of Biperiden 2 mg (0–1/2 − 1/2), and Propranolol (20mg BID). With the reduction of QTc, normal liver enzymes, and no reduction in hemoglobin, Clozapine was gradually increased to 100 mg/day. Tetrabenazine 6 mg (1/2 daily) was also administered, along with an increase in the biperiden dose (2mg, 1/2,-1/2 − 1/2 in the seventh post-admission day).\u003c/p\u003e\u003cp\u003eDuring hospitalization, the patient’s dyskinetic movements and tremors significantly decreased, allowing him to close his mouth and chew food more effectively, with less food spilling during meals and fewer food stains on his clothes. He was also able to participate in conversations more effectively, as he could move his jaw better and showed improvement in articulation. He reported a decrease in both the frequency and severity of his psychotic symptoms, though there was not a full remission. The patient's mood improved; however, it remained slightly depressed, while other symptoms such as boredom and disappointment vanished. The psychiatrist believed that two weeks of sertraline was not enough for a complete improvement in the patient's mood, and it was possible that, with enough time and without increasing the dose, the patient would experience complete remission from the depressive episode. Additionally, negative symptoms partially improved.\u003c/p\u003e\u003cp\u003eUltimately, after 17 days of hospitalization, the patient was discharged in good general condition, with significant improvement in tardive dyskinesia (TD), partial remission of both positive and negative symptoms, and a near-euthymic mood. At discharge, the patient and his mother received comprehensive psychoeducation on symptoms, the treatment plan, potential interactions, the importance of avoiding self-medication, and the need to attend outpatient visits on time and in order.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eTD is a serious, often irreversible movement disorder characterized by involuntary, repetitive movements, typically affecting the orofacial region. It is associated with long-term use of dopamine receptor-blocking agents. Although atypical antipsychotics are generally considered to have a lower risk of TD compared to typical antipsychotics, cases of TD induced by atypical agents like risperidone and aripiprazole have been reported (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eIn the present case, a 32-year-old male developed TD after two years of treatment with Aripiprazole for schizophrenia within four weeks following self-tapering down and stopping the usage of it.\u003c/p\u003e\u003cp\u003eAripiprazole, known for its unique mechanism as a partial agonist at dopamine D2 and serotonin 5-HT1A receptors and antagonist at 5-HT2A receptors (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e), is considered to have a favorable side effect profile, with lower rates of metabolic and motor symptoms (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). However, rare cases of aripiprazole-induced TD have been reported (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eManagement of TD focuses on prevention, early detection, and appropriate intervention. Guidelines recommend withdrawing the causative agent when possible (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). Switching to antipsychotics with lower D2 receptor affinity, such as Clozapine or Quetiapine, may alleviate symptoms (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). Vesicular monoamine transporter 2 (VMAT-2) inhibitors like deutetrabenazine and valbenazine are recommended treatments with strong evidence for efficacy (\u003cspan additionalcitationids=\"CR22\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). Other treatments with varying levels of evidence include Clonazepam, Ginkgo biloba, Amantadine, and Tetrabenazine (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eA study on 234 patients treated with aripiprazole showed a TD prevalence of 3.4%, and in most patients, TD did not resolve spontaneously following discontinuation of aripiprazole. Most patients in the mentioned study improved via treatment with Tetrabenazine (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). Other case reports have also showed TD evolvement following use of Aripiprazole (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eAdditionally, a case report showed improvement of Aripiprazole-induced TD and dystonic symptoms following switching the medication to Quetiapine (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). Similar improving result were also reported with the use of Clozapine (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). risperidone was also reported to cause TD in some case reports (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eTetrabenazine selectively and reversibly VMAT2, which is responsible for packaging dopamine, norepinephrine, serotonin, and histamine into synaptic vesicles in presynaptic neurons. By blocking VMAT2, tetrabenazine prevents dopamine storage in vesicles, leaving it exposed to degradation by monoamine oxidase (MAO) in the cytoplasm, thereby depleting presynaptic dopamine levels. This reduction in dopamine release decreases overstimulation of postsynaptic D2 receptors (particularly in the indirect pathway of the motor striatum), which are often hypersensitive in conditions like TD (\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e). Additionally, by lowering dopamine availability in the direct pathway, tetrabenazine further reduces hyperkinetic movements. Unlike irreversible VMAT inhibitors (e.g., reserpine), tetrabenazine\u0026rsquo;s effects are reversible and CNS-specific (due to its selectivity for VMAT2 over VMAT1), minimizing peripheral side effects. Its active metabolites (α- and β-hydroxytetrabenazine) prolong its dopamine-depleting action, providing symptomatic relief in TD without directly blocking dopamine receptors (\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThis case report offers important clinical insights into the rare occurrence of TD induced by Aripiprazole, an atypical antipsychotic typically associated with a lower risk of extrapyramidal side effects. The case is notable for its clear documentation of symptom onset following self-discontinuation of Aripiprazole, as well as the observed improvement with Tetrabenazine\u0026mdash;an agent with a well-established mechanism for managing hyperkinetic movement disorders. The inclusion of relevant literature and treatment guidelines enhances the report\u0026rsquo;s educational and clinical utility for practitioners managing similar cases. However, several limitations must be acknowledged. As a single case report, the findings cannot be generalized to broader populations and lack the statistical power of controlled studies. The absence of objective clinical assessment tools, such as the Abnormal Involuntary Movement Scale (AIMS), limits the ability to quantify symptom severity and response to treatment. The report also lacks extended follow-up data, which would be valuable in assessing the long-term efficacy and tolerability of Tetrabenazine.\u003c/p\u003e\u003cp\u003eDespite these limitations, this case contributes meaningfully to the growing body of literature highlighting the potential for atypical antipsychotics to induce TD and reinforces the importance of monitoring, patient education, and early intervention in mitigating long-term adverse outcomes.\u003c/p\u003e\u003cp\u003eThis case highlights that TD can develop even with atypical antipsychotics as well, particularly following abrupt changes in dosing, suggesting that both chronic exposure and sudden withdrawal may play a role in its pathogenesis. The delayed onset and persistence of symptoms underscore the importance of close monitoring for movement disorders, even with medications traditionally considered to have lower extrapyramidal risk. The patient\u0026rsquo;s improvement with Tetrabenazine further supports its utility as an effective treatment option for managing TD. Clinicians should remain vigilant for early signs of TD, ensure patients are educated about medication adherence, and be prepared to adjust treatment promptly to prevent long-term complications.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, tardive dyskinesia (TD) remains a serious and often distressing movement disorder that can arise from the long-term use of antipsychotics, primarily typical antipsychotics, though it can also occur with atypical antipsychotics. This case highlights the development of TD in a 32-year-old male patient with schizophrenia who experienced this complication within four weeks after self-tapering down and discontinuing Aripiprazole, which he had taken for two years. Furthermore, the results of this case report emphasize the promising role of Tetrabenazine in the management of TD, alongside other therapeutic strategies.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cul\u003e\n\u003cli\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\n\u003cul\u003e\n\u003cli\u003e\u003cstrong\u003eConflicts of interest/Competing interests\u003c/strong\u003e\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eThe authors declare that they have no known competing financial interests or personal relationships that could have influenced this study.\u003c/p\u003e\n\n\u003cul\u003e\n\u003cli\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eThe study was approved by the ethical committee of Birjand University of Medical Sciences by the ethics code of IR.BUMS.REC.1403.283.\u003c/p\u003e\n\n\u003cul\u003e\n\u003cli\u003e\u003cstrong\u003eConsent to participate\u003c/strong\u003e\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eThe patient gave informed consent for both interviews and conduction of the report in a stable, non-psychotic state.\u003c/p\u003e\n\n\u003cul\u003e\n\u003cli\u003e\u003cstrong\u003eWritten Consent for publication\u003c/strong\u003e\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eThe authors confirm that the participant gave consent for their data to be published anonymously.\u003c/p\u003e\n\n\u003cul\u003e\n\u003cli\u003e\u003cstrong\u003eAvailability of data and material\u003c/strong\u003e\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eNot applicable \u003c/p\u003e\n\n\u003cul\u003e\n\u003cli\u003e\u003cstrong\u003eCode availability\u003c/strong\u003e\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eNot applicable \u003c/p\u003e\n\n\u003cul\u003e\n\u003cli\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eMM did the process of diagnosis and treatment. FF reviewed the documentation and prepared them for writing. both FF and DG wrote the draft. MM reviewed and revised the draft. all authors reviwed and confirmed the final draft\u003c/p\u003e\n"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eFayedeh F, Khorashadizadeh S, Yousefi M, Abbasifar S, Erfanian N, Rafiee M, et al. CTLA-4 expression and polymorphisms in Schizophrenia; a systematic review of literature. Molecular Biology Reports. 2024;51(1):431.\u003c/li\u003e\n\u003cli\u003eVolk D, Jenkins A, Lidstone P, Lewis D. Chapter 38-Schizophrenia. Rosenberg\u0026rsquo;s Molecular and Genetic Basis of Neurological and Psychiatric Disease. 2020:653-62.\u003c/li\u003e\n\u003cli\u003eMcCutcheon RA, Marques TR, Howes OD. Schizophrenia\u0026mdash;an overview. JAMA psychiatry. 2020;77(2):201-10.\u003c/li\u003e\n\u003cli\u003eStępnicki P, Kondej M, Kaczor AA. Current concepts and treatments of schizophrenia. 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Journal of clinical pharmacy and therapeutics. 2012;37(3):370-2.\u003c/li\u003e\n\u003cli\u003eJoe S, Park J, Lim J, Park C, Ahn J. Remission of irreversible aripiprazole-induced tardive dystonia with clozapine: a case report. BMC psychiatry. 2015;15:1-5.\u003c/li\u003e\n\u003cli\u003eTomruk NB, Saatcioglu O, Yildizhan E, Alpay N. Aripiprazole-induced tardive dyskinesia treated with quetiapine: a case report. Acta Neuropsychiatrica. 2011;23(4):188-90.\u003c/li\u003e\n\u003cli\u003eHong KS, Cheong SS, Woo J-M, Kim E. Risperidone-induced tardive dyskinesia. American Journal of Psychiatry. 1999;156(8):1290-.\u003c/li\u003e\n\u003cli\u003eVasudevan O, Pinto DA, Gopinath P. Risperidone induced tardive dyskinesia-a case report. Indian Journal of Psychiatry. 2002;44(4):384-6.\u003c/li\u003e\n\u003cli\u003eStahl SM. Mechanism of action of vesicular monoamine transporter 2 (VMAT2) inhibitors in tardive dyskinesia: reducing dopamine leads to less \u0026ldquo;go\u0026rdquo; and more \u0026ldquo;stop\u0026rdquo; from the motor striatum for robust therapeutic effects. CNS spectrums. 2018;23(1):1-6.\u003c/li\u003e\n\u003cli\u003eWarren B, Vanderhoef D, Johnson J. VMAT2 inhibitors for the treatment of tardive dyskinesia. Issues in Mental Health Nursing. 2022;43(1):22-31.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"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":"Case report, Tardive dyskenisa, schizophrenia, antipyschoitcs, SGAS","lastPublishedDoi":"10.21203/rs.3.rs-7176801/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7176801/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eIntroduction\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTardive dyskinesia (TD) is a debilitating movement disorder often resulting from the prolonged use of antipsychotic medications, especially high-potency typical (first-generation) antipsychotics.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase presentation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis case report presents a 32-year-old male diagnosed with schizophrenia who developed TD after being treated with the atypical antipsychotic Aripiprazole and experienced symptoms four weeks post self-discontinuation. Despite the generally lower risk of extrapyramidal symptoms associated with atypical (second-generation) antipsychotics, the patient experienced significant involuntary facial and jaw movements that adversely affected his quality of life. Traditional management strategies were ineffective; however, by adjusting the previous medications and dosages, including Tetrabenazine, a recently approved medication for TD, the patient showed marked improvement in his symptoms.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis case highlights the importance of recognizing TD as a potential complication of aripiprazole and underscores the effectiveness of Tetrabenazine as a treatment option for managing this challenging condition.\u003c/p\u003e","manuscriptTitle":"Case Report of Management of Severe Tardive Dyskinesia Induced by an Atypical Antipsychotic in a Schizophrenic Patient","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-31 12:40:10","doi":"10.21203/rs.3.rs-7176801/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":"2b20ff94-a02f-46e4-9669-b090feb85e10","owner":[],"postedDate":"July 31st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-07-31T12:40:12+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-31 12:40:10","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7176801","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7176801","identity":"rs-7176801","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}