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Neuroleptic-induced dystonia is a source of great concern in clinical practice because of its iatrogenic nature which can potentially lead to life-threatening conditions. Since all neuroleptics (antipsychotics) share the ability to block the dopamine D2-type receptors (D2Rs) that are highly enriched in the striatum, this drug-induced dystonia is thought to be caused by decreased striatal D2R activity. However, how associations of striatal D2R inactivation with dystonia are formed remains elusive.A growing body of evidence suggests that imbalanced activities between D1R-expressing medium spiny neurons and D2R-expressing medium spiny neurons (D1-MSNs and D2-MSNs) in the striatal striosome-matrix system underlie the pathophysiology of various basal ganglia disorders including dystonia. Given the specificity of the striatal dopamine D1 system in ‘humans’, this article highlights the striatal striosome hypothesis in causing ‘repetitive’ and ‘stereotyped’ motor symptoms which are key clinical features of dystonia. It is suggested that exposure to neuroleptics may reduce striosomal D1-MSN activity and thereby cause dystonia symptoms. This may occur through an increase in the striatal cholinergic activity and the collateral inhibitory action of D2-MSNs onto neighbouring D1-MSNs within the striosome subfields. The article proposes a functional pathology of the striosome-matrix dopamine system for neuroleptic-induced acute dystonia or neuroleptic-withdrawal dystonia. A rationale for the effectiveness of dopaminergic or cholinergic pharmacotherapy is also provided for treating dystonias. This narrative review covers various aspects of the relevant field and provides a detailed discussion of the mechanisms of neuroleptic-induced dystonia.

Drug-induced movement disorders (DIMDs) are associated with use of dopamine receptor blocking agents (DRBAs), including antipsychotics. The most common forms are drug-induced parkinsonism (DIP), dystonia, akathisia, and tardive dyskinesia (TD). Although rare, neuroleptic malignant syndrome (NMS) is a potentially life-threatening consequence of DRBA exposure. Recommendations for anticholinergic use in patients with DIMDs were developed on the basis of a roundtable discussion with healthcare professionals with extensive expertise in DIMD management, along with a comprehensive literature review. The roundtable agreed that “extrapyramidal symptoms” is a non-specific term that encompasses a range of abnormal movements. As such, it contributes to a misconception that all DIMDs can be treated in the same way, potentially leading to the misuse and overprescribing of anticholinergics. DIMDs are neurobiologically and clinically distinct, with different treatment paradigms and varying levels of evidence for anticholinergic use. Whereas evidence indicates anticholinergics can be effective for DIP and dystonia, they are not recommended for TD, akathisia, or NMS; nor are they supported for preventing DIMDs except in individuals at high risk for acute dystonia. Anticholinergics may induce serious peripheral adverse effects (e.g., urinary retention) and central effects (e.g., impaired cognition), all of which can be highly concerning especially in older adults. Appropriate use of anticholinergics therefore requires careful consideration of the evidence for efficacy (e.g., supportive for DIP but not TD) and the risks for serious adverse events. If used, anticholinergic medications should be prescribed at the lowest effective dose and for limited periods of time. When discontinued, they should be tapered gradually. Graphical Abstract

Abstract Background and Hypothesis Drug-induced dystonia and dyskinesia are associated with increased all-cause mortality, with limited data on cause-specific mortality. We aim to confirm mortality risk and cause-specific mortality in drug-induced acute dystonia or tardive dyskinesia. Study Design From Taiwan’s National Health Insurance Database (2015–2021), we identified adults with ≥2 psychiatrist- or neurologist-confirmed diagnoses of drug-induced acute dystonia or tardive dyskinesia, and created 1:4 age- and sex-matched population controls and an unaffected sibling cohort. Outcomes included all-cause, natural-cause, and unnatural-cause mortality expressed as hazard ratios (HRs) with 95% confidence intervals (CIs). Multivariable Cox models were adjusted for sex, age, urbanization, socioeconomic status, and comorbidities. Study Results A total of 2862 patients and 11 448 matched controls were identified. Mean age was 64.6 years, 67.2% female, mean follow-up duration was 4.5 years. Drug-induced acute dystonia or tardive dyskinesia was associated with significant excess risk of all-cause (HR = 1.51, 95% CI 1.36–1.67), natural-cause (1.39, 1.25–1.55), and unnatural-cause (3.67, 2.42–5.54) mortality. For natural-cause mortality, mortality risk was elevated for endocrine, nutritional, and metabolic diseases; mental and behavioral disorders; nervous, circulatory, and respiratory system diseases; but reduced for neoplasms. For unnatural-cause mortality, both accidents and suicides revealed higher mortality risks. Results were similar across age groups and ten psychiatric comorbidities. Sex subgroup analysis revealed higher suicide mortality risk in females than males. Conclusions Drug-induced acute dystonia and tardive dyskinesia are associated with elevated all-cause, natural-cause, unnatural-cause, and cause-specific mortalities, highlighting the need for targeted interventions to prevent these specific causes of deaths.

Medication-induced dystonia (MID) is a movement disorder (MD), characterized by involuntary sustained or intermittent muscle contractions, causing abnormal, often repetitive, movements, postures, or both. Although MID is commonly associated with the use of antipsychotics, it also occurs with many other medications widely used in clinical practice. A systematic literature search (from inception to November 2023), using the PubMed and Embase databases, was conducted without language restriction for articles reporting on MID in people without pre-existing MDs, and this for all potentially relevant non-antipsychotic medications. A narrative synthesis of the available evidence was undertaken. MID is common (1 to 10%) with certain antiemetics. Selective serotonin reuptake inhibitors and the antiepileptics valproate, carbamazepine, and lamotrigine are rarely (0.01 to 0.1%) or very rarely (<0.01%) associated with MID. All other medications are very rarely (<0.01%) associated with MID or have a risk that cannot be precisely estimated. The actual rate of dystonic reactions with most non-antipsychotic agents remains unknown, owing to misdiagnosis and underreporting in the scientific literature. In general, MID seems to occur more often in children and adolescents, even with a single low dose, and with polymedication. In most cases, MID is acute in onset (occurring within hours to days) and involves the head and neck. Although MID is most common with dopamine receptor-blocking antiemetics, many other medications may also produce dystonic reactions, particularly in children and adolescents. Although such incidents remain rare, there are indications that MID is underreported for many classes of medications.

Background Extrapyramidal symptoms affect an average of 37%, with a maximum prevalence of 71.4%, among individuals on antipsychotics. About one in five patients experiences Parkinsonism, and more than one in ten experiences akathisia. These symptoms can significantly increase relapse rates, elevate healthcare costs (approximately $27,408), and contribute to stigmatization. In Tigray, where antipsychotic use is rising, data on Extrapyramidal symptoms are limited. This study aimed to fill this research gap to better patient care and management. Objectives The aim of this study was to determine the prevalence of Extrapyramidal symptoms associated with antipsychotic medications. Additionally, it sought to identify factors contributing to these side effects among patients. Methods This study was conducted across five public hospitals in the Tigray region, utilizing a comprehensive approach that included face-to-face interviews, direct observations, card reviews, and physical examinations. A total of 834 participants were selected through a multistage sampling technique to ensure representativeness, using the Extra Pyramidal Symptom Rating Scale (ESRS) for standardized evaluation. Data collected were analyzed using SPSS version 27. Result The study findings showed that the prevalence rates of Parkinsonism, Akathisia, Dystonia, and Tardive Dyskinesia were 9.9% , 6.9% , 5.0% , and 2.4% , respectively. The multivariate analysis revealed several common risk factors associated with these extrapyramidal symptoms. Both Parkinsonism and Akathisia were significantly associated with various factors, including the type of antipsychotic medication, illness relapse, comorbid medical conditions, anticholinergic medication, perceived stigma, and current khat use. Additionally, Parkinsonism was associated with the type of mental illness. Dystonia was also associated with marital status, anticholinergic medication, perceived stigma, and tobacco use. Lastly, Tardive Dyskinesia was associated with educational status and medication adherence. Conclusion and recommendations Although Extrapyramidal symptoms were reported at lower rates than in previous studies, psychiatry professionals should routinely screen for EPS and tailor treatment to patient-specific factors. Efforts to reduce stigma around these side effects are also essential to improve patient outcomes.

ObjectivesTo measure the incidence of movement side effects of antipsychotic drugs in adults with intellectual disability and compare rates with adults without intellectual disability.DesignCohort study using data from The Health Improvement Network.SettingUK primary care.ParticipantsAdults with intellectual disability prescribed antipsychotic drugs matched to a control group of adults without intellectual disability prescribed antipsychotic drugs.Outcome measuresNew records of movement side effect including acute dystonias, akathisia, parkinsonism, tardive dyskinaesia and neuroleptic malignant syndrome.Results9013 adults with intellectual disability and a control cohort of 34 242 adults without intellectual disability together contributed 148 709 person-years data. The overall incidence of recorded movement side effects was 275 per 10 000 person-years (95% CI 256 to 296) in the intellectual disability group and 248 per 10 000 person-years (95% CI 237 to 260) in the control group. The incidence of any recorded movement side effect was significantly greater in people with intellectual disability compared with those without (incidence rate ratio 1.30, 95% CI 1.18 to 1.42, p<0.001, after adjustment for potential confounders), with parkinsonism and akathisia showing the greatest difference between the groups. Neuroleptic malignant syndrome, although occurring infrequently, was three times more common in people with intellectual disability-prescribed antipsychotic drugs (incidence rate ratio 3.03, 95% CI 1.26 to 7.30, p=0.013). Differences in rates of movement side effects between the groups were not due to differences in the proportions prescribed first and second-generation antipsychotic drugs.ConclusionsThis study provides evidence to substantiate the long-held assumption that people with intellectual disability are more susceptible to movement side effects of antipsychotic drugs. Assessment for movement side effects should be integral to antipsychotic drug monitoring in people with intellectual disability. Regular medication review is essential to ensure optimal prescribing in this group.

Metoclopramide is a dopamine-2 antagonist and is generally used as an antiemetic in clinical practice. Extrapyramidal reactions are the important adverse effects of metoclopramide which are reported in 0.2% of cases. In young children, the incidence can extend up to 25%. Metoclopramide-induced EPS include acute dystonia, tardive dyskinesia, parkinsonism, akathisia, and malignant neuroleptic syndrome. We are reporting a single dose of metoclopramide induced acute dystonia in an adolescent girl, which caused lot of anxiety in the patient and the parents which responded to oral diphenhydramine.

BackgroundThe aim of this systematic review and meta-analysis is to evaluate and compare the prevalence rates of spontaneous movement disorders (SMDs), including dyskinesia, parkinsonism, akathisia and dystonia, in antipsychotic-naïve individuals with chronic psychosis and first-episode psychosis (FEP) and gain a more nuanced understanding of factors influencing their presence.MethodsSeveral literature databases were systematically searched and screened based on predetermined eligibility criteria. Included articles underwent risk of bias assessment. The prevalence rates of SMDs were calculated using a random-effects model.ResultsOut of 711 articles screened, 27 were included in this meta-analysis. The pooled prevalence of spontaneous dyskinesia was 7% (3% FEP and 17% chronic schizophrenia) across 24 studies (95% CI 3 to 11; I2=94%, p<0.01) and 15% for spontaneous parkinsonism (14% FEP and 19% chronic schizophrenia) in 21 studies (95% CI 12 to 20; I2=81%, p<0.01). A meta-regression analysis found a significant positive correlation between age (p<0.05) and duration of untreated psychosis (DUP) (p<0.05) with dyskinesia but not parkinsonism prevalence. Akathisia and dystonia appear to be both less studied and less frequent in occurrence with a pooled prevalence of 4% (95% CI: 3 to 6; I2=0%, p=0.65) for akathisia in eight studies and a mean prevalence of 6% (range 0%–16%) for dystonia in five studies.ConclusionThe presence of varying degrees of neurodysfunction in antipsychotic-naïve patients with schizophrenia underscores the need for individualised treatment approaches that consider each patient’s unique predisposition and neuromotor profile. Further research is warranted into the role of specific SMDs and risk factors including sex, race and diagnostic variations.PROSPERO registration numberCRD42024501951.

Cannabis withdrawal syndrome (CWS) presents with irritability, anxiety and sleep disturbances within a week of stopping cannabis use. This case highlights a young woman with a medical history of recurrent hospitalisations due to intractable nausea and vomiting related to heavy, prolonged cannabis use and acute dystonic reactions secondary to haloperidol. The patient presented with intractable nausea, vomiting and frequent hot bathing five days after her last cannabis use. She developed an acute dystonic reaction to low-dose metoclopramide, a commonly used antiemetic, potentially exacerbated by cannabis’s inhibition of drug-metabolising enzymes. We also highlight key differences between CWS and cannabis hyperemesis syndrome (CHS).