Tardive syndrome encompasses a range of persistent hyperkinetic, hypokinetic, and sensory phenomena resulting from chronic exposure to dopamine receptor blocking agents (DRBAs). Tardive dyskinesia, the most well-known form, involves repetitive oral-buccal-lingual movements and other similar motions in the limbs, trunk, or pelvis. Tardive dystonia, characterized by dystonia as the main feature, often includes retrocollis and oromandibular dystonia. Other manifestations of tardive syndrome include tardive akathisia (restlessness and an urge to move), tardive tourettism (motor and phonic tics), tardive tremor (postural and kinetic tremors), and tardive pain (chronic pain in areas like the mouth, tongue, or genital region without physical findings).

Tardive parkinsonism, a controversial diagnosis, refers to persistent Parkinson-like symptoms even after discontinuation of DRBAs. However, it is debated whether this represents drug-induced parkinsonism or the onset of idiopathic Parkinson’s disease coincident with DRBA use. The term "tardive syndrome" serves as an umbrella term for all these conditions, with tardive dyskinesia being a subset within it. Understanding the various types of tardive phenomena is essential for diagnosing and managing these complex and often distressing conditions associated with DRBA therapy.

Reference: Truong DD, Frei K. Setting the record straight: The nosology of tardive syndromes. Parkinsonism Relat Disord. 2019;59:146-150. doi: 10.1016/j.parkreldis.2018.11.025. 

This Delphi consensus study addresses inconsistent terminology around tardive dyskinesia (TD) and the broader group of tardive movement disorders caused by dopamine receptor blocking agents (DRBAs). The authors explain that TD was originally used to describe delayed-onset oral-buccal-lingual movements, but the term gradually expanded to include multiple tardive presentations, including tardive dystonia, akathisia, myoclonus, tics, tremor, and rare tardive pain. Because these conditions may differ in presentation, pathophysiology, and treatment response, inconsistent use of “TD” and “tardive syndrome” can create confusion in clinical practice, research, and treatment trials. To address this, the study convened an expert Delphi panel of movement disorder neurologists, psychiatrists, and a clinical researcher to establish clearer nomenclature.

Across the Delphi rounds, the panel reached consensus that “tardive syndrome” should be used as the umbrella term for the full group of persistent tardive disorders related to DRBA exposure. The authors recommend reserving “tardive dyskinesia” for the specific subtype involving oral-buccal-lingual stereotypy, with or without chorea of the extremities. They also recommend avoiding the abbreviation “TS” because it could be confused with Tourette syndrome. Overall, the paper argues that clearer terminology is more than a semantic issue: it can improve communication among clinicians, reduce misinterpretation in the literature, support more consistent diagnosis, and help distinguish tardive phenomenologies that may require different assessment and management approaches.

Reference: Frei K, Scott A, Caroff SN, et al. Tardive Dyskinesia versus Tardive Syndrome. What Is in a Name? Parkinsonism Relat Disord. 2025 Apr;133:107295. doi: 10.1016/j.parkreldis.2025.107295.

This case report describes a 52-year-old woman with schizophrenia who developed tardive sensory syndrome (TSS) after approximately 3 months of treatment with lurasidone. Her symptoms were notable for mandibular sensory paresthesia and pain, without the more commonly recognized abnormal involuntary movements often associated with tardive syndromes, such as orofacial dyskinesia, tremor, rigidity, dystonia, or bradykinesia. The patient had previously been treated with several antipsychotics, but lurasidone had most recently been started after olanzapine was discontinued because of weight gain. To rule out other causes, clinicians conducted an extensive evaluation, including laboratory testing, brain CT imaging, and dental consultation, all of which were unrevealing. Based on the clinical features and exclusion of secondary causes, TSS was suspected, and her baseline Extrapyramidal Symptom Rating Scale (ESRS) score was 18 before her antipsychotic regimen was changed.

After lurasidone was discontinued and the patient was switched to quetiapine, her sensory symptoms improved markedly. Within 1 month, her ESRS score improved by 65%, falling from 18 to 6, and by 6 months her pain had fully resolved, with a visual analog pain score of 0/10. The authors suggest that this may be the first reported case of TSS associated with lurasidone and review several possible mechanisms, including dopamine receptor effects, serotonergic involvement, and oxidative stress-related injury. They also note that although second-generation antipsychotics are often viewed as carrying a lower risk of tardive syndromes, they are not risk-free. Overall, the report highlights the importance of recognizing painful sensory symptoms as a possible tardive phenomenon and considering medication changes promptly when these symptoms emerge.

Reference: Lin MC, Chang YY, Lee Y, Wang LJ. Tardive sensory syndrome related to lurasidone: A case report. World J Psychiatry. 2023 Mar 19;13(3):126-130. doi: 10.5498/wjp.v13.i3.126.

Withdrawal-emergent dyskinesia (WED) is a transient movement disorder that appears after rapid taper or abrupt discontinuation of antipsychotics. Unlike classic tardive dyskinesia (TD), WED usually improves within weeks. This case describes a 13-year-old with disruptive mood dysregulation disorder and attention-deficit hyperactivity disorder who developed reversible oral dyskinesia during inpatient care after ziprasidone was stopped and methylphenidate was up-titrated. Symptoms (facial grimacing, mouth twitching) emerged within a day of antipsychotic cessation, were managed with benztropine and brief ziprasidone, and ultimately resolved as stimulants were tapered and bupropion was started.

The authors suggest dopamine D2 receptor hypersensitivity from prior antipsychotic exposure, unmasked by rapid withdrawal and amplified by stimulant-driven dopaminergic tone, as a plausible mechanism. A serotonin-syndrome-like process was considered but not supported clinically. Key practice points: avoid abrupt antipsychotic discontinuation, consider slower tapers and cross-titration to lower-dopaminergic or non-stimulant agents, and recognize WED/pseudo-tardive presentations as distinct from persistent TD. Heightened clinician awareness is especially important in pediatric populations where antipsychotics and stimulants are commonly co-managed.

Reference: Haji Rahman R, Dharmapuri S. Oral Dyskinesia in a Pediatric Patient Following Concurrent Use of Neuroleptics and Stimulants: Treatment Strategy Considerations to Avert Avoidable Adverse Side Effects. Cureus. 2023;15(4):e38294. doi: 10.7759/cureus.38294.

Antipsychotic medications are widely used for psychiatric conditions, but they are associated with significant side effects, including drug-induced movement disorders (DIMDs) like drug-induced parkinsonism, acute dystonia, tardive dyskinesia (TD), and neuroleptic malignant syndrome (NMS). These side effects can be debilitating, especially with polypharmacy or higher doses. While anticholinergic medications are sometimes used to treat DIMDs, they carry additional risks, particularly in older adults or those taking multiple medications with anticholinergic properties. These medications can be effective for conditions like drug-induced parkinsonism but are harmful for TD, akathisia, or NMS.

The expert panel stresses the importance of accurate diagnosis and tailored treatment for DIMDs, as these disorders respond differently to treatment. Anticholinergics are helpful for certain DIMDs like drug-induced parkinsonism and acute dystonia but are contraindicated for TD and NMS. Over-prescription of anticholinergics, especially in vulnerable populations, can lead to cognitive dysfunction, delirium, and increased mortality risk. The panel advocates for better education on the use of anticholinergics, proper tapering strategies, and further research on alternative treatments. Clinicians are also encouraged to avoid grouping all DIMDs under "extrapyramidal symptoms," as each requires a specific treatment approach.

Reference: Vanegas-Arroyave N, Caroff SN, Citrome L, et al. An Evidence-Based Update on Anticholinergic Use for Drug-Induced Movement Disorders. CNS Drugs. 2024;38(4):239-254. doi: 10.1007/s40263-024-01078-z.

This case report presents a 25-year-old female with tardive dyskinesia and tardive dystonia, which were refractory to valbenazine treatment. The patient, previously diagnosed with bipolar disorder and treated with antipsychotics, developed symptoms such as right-sided neck dystonia and oral dyskinesia after switching from quetiapine to lurasidone. After unsuccessful attempts with various therapies, the patient was admitted for electroconvulsive therapy (ECT), which significantly improved her symptoms, reducing her Abnormal Involuntary Movement Scale score from 10 to 2 after 12 sessions.

A literature review was conducted, encompassing 27 studies that included 50 patients treated with ECT for tardive dyskinesia and tardive dystonia. The review found that 84% of patients with tardive dyskinesia and 91% with tardive dystonia showed partial or full responses to ECT. However, the effects of ECT were variable, with some patients experiencing only temporary relief, while others had prolonged improvement. Despite the promising results, the exact mechanism of ECT’s efficacy in treating these conditions remains unclear. The study highlighted the need for further research, particularly randomized controlled trials, to better understand the role of ECT in managing treatment-resistant tardive dyskinesia and dystonia.

Reference: Irinaka K, Itoh Y, Yoshizawa K, et al. Successful Electroconvulsive Therapy for Tardive Dyskinesia and Tardive Dystonia Refractory to Valbenazine Treatment: A Case Report and Narrative Literature Review. Clin Psychopharmacol Neurosci. 2024;22(4):688-696. doi: 10.9758/cpn.24.1185

Antipsychotic (neuroleptic) medications are widely used for chronic mental illnesses such as schizophrenia but can cause movement disorders, including tardive dyskinesia (TD). TD often presents as repetitive involuntary movements of the mouth and face. Because oxidative stress has been proposed as a contributor to TD, vitamin E has been studied as a potential adjunct to prevent TD from worsening or to reduce symptoms. This review evaluated the clinical effects of vitamin E in adults with schizophrenia or other chronic mental illness who developed antipsychotic-induced TD while remaining on antipsychotic therapy. It also examined whether effects persist over time or are stronger in early-onset TD (<5 years).

Across 13 small, poorly reported randomized trials (478 participants), vitamin E did not show clear benefit over placebo for clinically important improvement in TD symptoms (low-quality evidence). However, limited evidence suggested vitamin E might reduce the risk of symptom deterioration compared with placebo. The review found no reliable differences in adverse effects, extrapyramidal symptoms, or study dropouts. Patient-centered outcomes like quality of life and social functioning were not reported, and there were no trial data to assess vitamin E specifically in early-onset TD. Overall, the authors conclude vitamin E may help protect against TD worsening but does not appear to meaningfully improve established TD. They also call for larger, higher-quality trials to better define its role.

Reference: Soares-Weiser K, Maayan N, Bergman H. Vitamin E for antipsychotic-induced tardive dyskinesia. Cochrane Database Syst Rev. 2018 Jan 17;1(1):CD000209. doi: 10.1002/14651858.CD000209.pub3.

Authors of this case report describe a 68-year-old woman who developed acute orofacial dystonia shortly after starting promethazine-chlordiazepoxide for anxiety and sleep support. She had a history of generalized anxiety disorder, hypertension, and partial thyroidectomy, and had previously been treated with several psychiatric medications without extrapyramidal side effects. On the second day after starting promethazine-chlordiazepoxide, she developed involuntary orofacial movements and slurred speech. The suspected medication was discontinued, but her symptoms persisted despite additional treatment with clonazepam and other supportive therapies. After two months of ongoing dystonia, botulinum toxin injection led to significant improvement.

The authors conclude that promethazine was the most likely cause of the acute dystonic reaction, even though the patient did not have the usual risk factors such as younger age or male sex. They note that ischemic changes seen on MRI in the basal ganglia and periventricular regions may have increased her susceptibility. The report highlights that acute dystonia can occur rapidly after exposure to dopamine receptor antagonists or related agents and underscores the need for clinicians to remain alert to this potential adverse effect of promethazine. It also suggests that botulinum toxin may be helpful when symptoms are prolonged or do not respond to more conventional measures.

Reference: Zhang R, Lai J, Huang J. Acute onset of orofacial dystonia from promethazine treatment: A case report. Medicine (Baltimore). 2019;98(43):e17675. doi: 10.1097/MD.0000000000017675.

Painless legs and moving toes syndrome is a rare movement disorder characterized by semi-continuous, involuntary toe movements without associated pain. This report describes a 48-year-old woman with the condition in the context of chronic neuroleptic use. Her symptoms initially presented in one foot and later progressed to both, causing painful calluses. Treatment with benztropine alleviated her toe movements but induced orofacial dyskinesias, while amantadine caused truncal dyskinesias. The discontinuation of aripiprazole and initiation of clonazepam eventually improved her symptoms.

The syndrome's pathophysiology remains unclear, though it may involve altered sensory afferent pathways leading to abnormal motor efferent activity. Diagnosis is clinical, and treatment often involves trial-and-error combinations of medications such as clonazepam, baclofen, and gabapentin. Due to its rarity, there are no established treatment guidelines, but this case highlights the importance of individualized therapeutic approaches and careful management of associated movement disorders.

Reference: Nagarajan E, Digala LP, Bollu PC. Painless Legs and Moving Toes Presenting as a Tardive Phenomenon: Case Report and Review of the Literature. J Neurosci Rural Pract. 2020;11(2):341-342. doi: 10.1055/s-0040-1709267. 

The pathophysiology of tardive dyskinesia (TD) involves prolonged dopamine receptor blockade, leading to receptor supersensitivity and oxidative damage in the striatum. This case report discusses a 62-year-old male patient presenting with involuntary tongue movements and a history of long-term antidepressant and mood stabilizer use. The patient exhibited moderate spontaneous tongue movements and mild distress, as assessed using the Abnormal Involuntary Movement Scale. Management included altering his medication regimen by switching to clonazepam and clozapine, performing coronoplasty to prevent trauma from tongue movements, and providing counseling to improve his psychosocial well-being. These measures significantly reduced the severity of his symptoms.

Preventive strategies include altering antipsychotic regimens, reducing dosages, and considering second-generation antipsychotics or vesicular monoamine transporter 2 inhibitors. The case underscores the importance of early diagnosis and comprehensive management, including collaboration between oral physicians and psychiatrists, to mitigate the functional and psychosocial impact of TD, particularly in geriatric patients.

Reference: Ruparelia P, Pandya U, Gill N, Verma O. Restless tongue: Lingual Tardive Dyskinesia - A rare case report. J Oral Biol Craniofac Res. 2022;12(1):99-101. doi: 10.1016/j.jobcr.2021.10.006.

The underlying causes of tardive syndrome (TS) are not entirely understood, but hypotheses suggest dopaminergic receptor hypersensitivity and oxidative stress as potential contributors. Diagnosis typically requires symptoms to persist for at least a month after discontinuing the drug, and it can be challenging to differentiate from other similar conditions.

The treatment of TS involves a multifaceted approach. First, determining the offending drug and considering whether discontinuation or replacement with atypical antipsychotics like quetiapine or clozapine is possible. Vesicular monoamine transporter-2 inhibitors such as tetrabenazine, deutetrabenazine, and valbenazine are commonly used to manage symptoms by reducing dopamine availability in the synapse. These agents are often more effective with fewer side effects than older treatments like tetrabenazine. In refractory cases, other treatments, including benzodiazepines like clonazepam, amantadine for parkinsonism, and botulinum toxin for dystonia, can be considered. For severe cases, deep brain stimulation of the globus pallidus interna has shown promise in improving symptoms, particularly in patients who do not respond to medical treatments. Further research is needed to refine treatment strategies and understand the complex mechanisms of TS.

Reference: Badarny S, Nassar R, Badarny Y. Tardive Syndrome Is a Mysterious Phenomenon with Different Clinical Manifestations-Review. J Clin Med. 2023;12(4):1498. doi: 10.3390/jcm12041498. 

Tardive dyskinesia (TD) is most commonly linked to long-term use of dopamine receptor blocking drugs (DRBDs), such as antipsychotics. However, there has been some exploration of whether non-DRBD medications, like antidepressants, can also trigger similar movement disorders. While some case reports suggest a potential link between these drugs and TD-like symptoms, the majority of these cases involve patients with prior or concurrent DRBD exposure, making it difficult to establish a definitive cause. 

Reviewing the literature on TD induced by non-DRBDs reveals that most reported cases involve concurrent or prior use of DRBDs, further complicating the causality of TD in these instances. Some reports also fail to exclude other potential causes of dyskinesia, such as primary brain disorders. A small subset of cases suggests that antidepressants, like serotonin reuptake inhibitors and tricyclic antidepressants, may exacerbate or unmask TD that was previously latent due to DRBD exposure. The current consensus leans toward the understanding that non-DRBD medications likely do not directly cause TD but may contribute to its emergence in individuals with a history of DRBD use. Therefore, TD-like syndromes in patients without any DRBD exposure should be considered exceedingly rare, and such cases require thorough evaluation to rule out other explanations.

Reference: D'Abreu A, Friedman JH. Tardive Dyskinesia-like Syndrome Due to Drugs that do not Block Dopamine Receptors: Rare or Non-existent: Literature Review. Tremor Other Hyperkinet Mov (N Y). 2018;8:570. doi: 10.7916/D8FF58Z9. 

Researchers of this multi-phase study evaluated a video-based artificial intelligence (AI) algorithm designed to detect and assess the severity of tardive dyskinesia (TD) in patients taking antipsychotics. Across three studies involving 351 participants and nearly 4,000 video clips, the algorithm analyzed facial and upper body movements captured via smartphone. Compared to clinician-rated Abnormal Involuntary Movement Scale scores, the model achieved a high area under the curve of 0.85 to 0.98 and outperformed trained raters in sensitivity, specificity, and reliability (Cohen’s κ = 0.61 vs 0.57). It also demonstrated consistent performance across demographic subgroups and could pinpoint specific body regions with abnormal movements.

The findings highlight the algorithm’s potential to close the diagnostic gap for TD, which affects up to 2.6 million people in the United States, though only about 40,000 currently receive treatment. With psychiatric care strained by limited time and resources, this scalable AI tool offers an efficient solution for earlier detection and monitoring. Early identification enables timely interventions, whether this be medication adjustments or symptom management, before TD becomes irreversible. As such, this technology could improve outcomes and reduce the burden of long-term disability in patients at risk for TD.

Reference: Sterns AA, Hughes JW, Grimm B, et al. Detecting Tardive Dyskinesia Using Video-Based Artificial Intelligence. J Clin Psychiatry. 2025;86(3):25m15792. doi: 10.4088/JCP.25m15792.

Antidepressant-induced movement disorders are uncommon adverse drug reactions, and the risk may vary by drug and antidepressant class. Authors of this study used reports from VigiBase (the World Health Organization global pharmacovigilance database) from January 1967 to February 2017 to evaluate whether movement disorders were reported disproportionately often with antidepressants. Using a case/non-case design, the authors calculated reporting odds ratios (RORs) for nine movement-disorder subtypes. They then adjusted those RORs for age, sex, co-reported drugs that can induce movement disorders, and drugs used to treat movement disorders.

Among 14,270,446 total reports, 1,027,405 (7.2%) involved at least one antidepressant, and 29,253 (2.8% of those) included a movement disorder. The cohort skewed female (female/male ratio 2.15) with a mean age of about 51 years. Antidepressants overall showed increased reporting for all movement-disorder subtypes, strongest for bruxism and weakest for tics. Most antidepressant classes also showed significant associations across subtypes, with restless legs syndrome showing a class-specific signal only for serotonin reuptake inhibitors. Several antidepressants appeared more strongly associated. Commonly implicated agents included citalopram, paroxetine, duloxetine, and mirtazapine, and additional signals were reported for multiple other antidepressants. The authors conclude these findings suggest potential harmful associations that warrant clinical vigilance and early monitoring. However, they emphasize the analysis is exploratory and should be refined by future epidemiologic studies.

Reference: Revet A, Montastruc F, Roussin A, et al. Antidepressants and movement disorders: a postmarketing study in the world pharmacovigilance database. BMC Psychiatry. 2020 Jun 16;20(1):308. doi: 10.1186/s12888-020-02711-z.

This case report describes a 57-year-old woman with treatment-resistant major depression who developed severe tardive akathisia after combination therapy with escitalopram and the antipsychotic olanzapine. Despite stopping both medications and trying standard treatments for akathisia, her inner restlessness, inability to sit still, pacing, and severe distress persisted, leading to suicidal thoughts and hospitalization. A single-photon emission CT scan ruled out Parkinson’s disease, and her akathisia was rated as severe (5/5) on the Barnes Akathisia Rating Scale. The case underscores how akathisia is often missed or misattributed to anxiety or the primary illness, prompting medication increases that can worsen symptoms.

With standard options exhausted, the team and patient proceeded with electroconvulsive therapy (ECT). After 12 ECT sessions, both tardive akathisia and depressive symptoms went into complete remission, with no residual movement symptoms or ECT-related adverse effects. She remained well two years later on maintenance clomipramine. The authors note that selective serotonin reuptake inhibitors and antipsychotics, especially in combination, can induce extrapyramidal side effects such as akathisia, which is particularly difficult to treat and lacks clear guidelines. They present this as one of the first reports of full remission of tardive akathisia and depression with ECT, highlighting the need for greater clinical awareness, cautious polypharmacy, and further research on ECT and other potential treatments.

Reference: Emmanuel T. Remission of treatment-resistant depression with tardive akathisia with electroconvulsive therapy. BMJ Case Rep. 2019 Sep 18;12(9):e229714. doi: 10.1136/bcr-2019-229714.