Tardive Syndromes Research Articles

Amisulpride-induced myoclonus: A unique tardive syndrome

Amisulpride-induced myoclonus: A unique tardive syndrome

Management of tardive dyskinesia and tardive dystonia with clozapine: A retrospective study

AimThis retrospective study aimed to evaluate the long-term effectiveness of switching to clozapine in the management of tardive syndromes (TS). MethodologyThe treatment records of patients who had TS at the time of starting clozapine, were reviewed and demographic and clinical data was extracted on a predesigned performa. ResultsAbout three-fourth (74.2 %) of the study subjects had tardive dystonias and two-third (69.7 %) had tardive dyskinesia at the time of starting clozapine. About half (48.5 %) of the patients had both tardive dystonia and dyskinesia. A small proportion (13.6 %) also had tardive akathisia at the time of starting clozapine. About three-fourth (72.2 %) of the patients had >50 % reduction, and about two-third (66.6 %) of the patients had >75 % reduction and nearly half (54.5 %) of the patients had complete resolution of dyskinesia at the last follow-up. Similar trends were seen in reduction in dystonia, i.e., >50 % reduction in 74.3 %, >75 % reduction in 62.2 % and complete resolution was seen in 56.1 %. ConclusionsThe present study suggest that clozapine is useful in the management of drug induced tardive dyskinesia and tardive dystonia.

The Outcome of Antipsychotics-induced Tardive Syndromes: A Ten-year Follow-up Study.

Tardive syndrome (TS) is an umbrella term used to describe a group of abnormal movement disorders caused by chronic exposure to dopamine receptor blocking agents. Few follow-up studies have been performed on the outcome of TS in patients using antipsychotics. The purpose of our study was to investigate the prevalence, incidence, remission rate, and factors associated with remission in patients using antipsychotics. This retrospective cohort study consisted of 123 patients who received continuous treatment of antipsychotics in a medical center in Taiwan, from April 1, 2011 to May 31, 2021. We assessed the demographic and clinical characteristics, prevalence, incidence, remission rate, and factors associated with remission in patients using antipsychotics. TS remission was defined as a Visual Analogue Scale score ≤ 3. Of the 92 patients who completed the 10-year follow-up, 39 (42.4%) were found to have at least one episode of TS, with tardive dyskinesia (TD) being the most prevalent subtype (51.3%). With regard to concurrent physical illness, a history of extrapyramidal symptoms were significant risk factors for TS. During the 10-year follow-up period, the remission rate of TS was 74.3%. The use of antioxidants including vitamin B6 and piracetam was related to the remission of TS. Patients with tardive dystonia had a higher remission rate (87.5%) compared to TD (70%). Our study suggests that TS may be a treatable condition, and the key to a better outcome is early detection and prompt intervention, including closely monitoring antipsychotics-related TS symptoms and using antioxidants.

Overview of Movement Disorders Secondary to Drugs.

Drug-induced movement disorders affect a significant percentage of individuals, and they are commonly overlooked and underdiagnosed in clinical practice. Many comorbidities can affect these individuals, making the diagnosis even more challenging. Several variables, including genetics, environmental factors, and aging, can play a role in the pathophysiology of these conditions. The Diagnostic and Statistical Manual of Mental Disorders (DSM) and the International Statistical Classification of Diseases and Related Health Problems (ICD) are the most commonly used classification systems in categorizing drug-induced movement disorders. This literature review aims to describe the abnormal movements associated with some medications and illicit drugs. Myoclonus is probably the most poorly described movement disorder, in which most of the reports do not describe electrodiagnostic studies. Therefore, the information available is insufficient for the diagnosis of the neuroanatomical source of myoclonus. Drug-induced parkinsonism is rarely adequately evaluated but should be assessed with radiotracers when these techniques are available. Tardive dyskinesias and dyskinesias encompass various abnormal movements, including chorea, athetosis, and ballism. Some authors include a temporal relationship to define tardive syndromes for other movement disorders, such as dystonia, tremor, and ataxia. Antiseizure medications and antipsychotics are among the most thoroughly described drug classes associated with movement disorders.

Heterogeneous tardive syndromes are still treatable with quetiapine

This article presents a case of classical tardive dyskinesia, apparent since at least 1997 when tetrabenazine and clonazepam were prescribed to the patient in addition to risperidone. However, the patient's mental health had been well controlled until sudden cessation of risperidone and the subsequent development of severe classical tardive dyskinesia, tardive dystonia and tardive tics. The authors describe the proposed pathophysiology of tardive dyskinesia, the impure nature of tardive syndromes, the underdiagnosis of tardive tics but eventual successful treatment with quetiapine.

Treatment of tardive dystonia: A review

Tardive dystonia (TD), the second most common but most disabling form of tardive syndrome, was initially described in 1982. It is caused by exposure to dopamine receptor blocking agents including antipsychotics and antiemetics. It most commonly presents as cranial or cervical dystonia. Characteristics suggestive of a TD diagnosis include a young age of onset, male predominance, and the higher prevalence of phasic cervical dystonia and retrocollis. Treatment of TD is limited. In this paper we review the literature on treatment options for TD as well as discussing a strategic approach. Options include use of clozapine which appears to have anti-dystonia properties. Other medications reported on with limited evidence include VMAT2 inhibitors, anticholinergics, clonazepam, and baclofen. Botulinum toxin has been shown to provide relief in TD in a manner similar to primary dystonia. The largest literature is on the use of deep brain stimulation (DBS) of the globus pallidus pars interna which includes blinded studies. We finish with providing an algorithm based on current knowledge.

Early onset tardive syndromes associated with Lurasidone in patients with mood disorders: A case series and literature review

• The incidence of tardive syndromes on antipsychotics is cumulative and screening as early as one month may enhance the opportunity for early detection and treatment. This is especially important in patients with mood disorders who can be managed using alternative drug classes and can achieve early and full resolution of the movement disorder without the need for antidyskinetic medications. • Differentiation of tardive dyskinesia from tardive dystonia and tardive akathisia is important as they may have different prognoses and treatment. This can be achieved both by expert clinical assessment and the use of scales that capture nuances in tardive syndromes • Newer antipsychotics such as lurasidone are increasingly used in mood disorders with good efficacy but there is limited data on the risks of tardive syndromes in this population. Further work is necessary to characterize which factors are most associated with early onset tardive syndromes. Tardive syndromes (TS) are a group of movement disorders that typically occur following chronic exposure to Dopamine D2 receptor antagonists. Rarely, these syndromes may occur in less than six months following the initiation of a causative medication. Owing to Lurasidone's recent introduction to the North American market, there is limited literature on its association with tardive syndromes. We describe three cases with mood disorder prospectively and systematically followed for tardive syndromes on Lurasidone and present a literature review of existing data on tardive syndromes associated with Lurasidone in patients with mood disorders. These three cases all developed TS before three months. A single previously published case series included cases of early-onset tardive syndromes following lurasidone use. This is an open case series in a single academic practice focused on mood disorders. There is limited data in the literature for comparison. Lurasidone's common use in patients with vulnerabilities to developing tardive syndromes, such as those with mood disorders, may be an area for clinical concern. Clinicians should strongly consider earlier screening for tardive syndromes in patients with appropriate risk factors.

Long-term effects of pallidal deep brain stimulation in tardive dystonia: a follow-up of 5–14 years

IntroductionPallidal DBS is an established treatment for severe isolated dystonia. However, its use in disabling and treatment-refractory tardive syndromes (TS) including tardive dyskinesia and tardive dystonia (TD) is less well investigated and long-term data remain sparse. This observational study evaluates long-term effects of deep brain stimulation (DBS) of the globus pallidus internus (GPi) in patients with medically refractory TS.MethodsWe retrospectively analyzed a cohort of seven TD patients with bilateral GPi-DBS. Involuntary movements, dystonia and disability were rated at long-term follow-up (LT-FU) after a mean of 122 ± 33.2 SD months (range 63–171 months) and compared to baseline (BL), short-term (ST-FU; mean 6 ± 2.0 SD months) and 4-year follow-up (4y-FU; mean 45 ± 12.3 SD months) using the Abnormal Involuntary Movement Scale (AIMS) and the Burke–Fahn–Marsden Dystonia Rating Scale (BFMDRS), respectively. Quality of life and mood were evaluated using the SF36 and Beck Depression Index (BDI) questionnaires, respectively.ResultsAt LT-FU patients had improved by 73% ± 14.2 SD in involuntary movements and 90% ± 1.0 SD in dystonia. Mood had improved significantly whereas quality of life remained unchanged compared to baseline. No serious long-lasting stimulation-related adverse events (AEs) were observed. Three patients of this cohort presented without active stimulation and ongoing symptom relief at long-term follow-up after 3–10 years of continuous DBS.ConclusionPallidal DBS is a safe and effective long-term TD treatment. Even more interesting, three of our patients could stop stimulation after several years of DBS without serious relapse. Larger studies need to explore the phenomenon of ongoing symptom relief after DBS cessation.

Brain Calcifications in Complex Sexual Aneuploidy.

Brain Calcifications in Complex Sexual Aneuploidy.

5.4 MANAGEMENT OF DRUG-INDUCED MOVEMENT DISORDERS (DIMDS): A CHILD NEUROLOGIST’S PERSPECTIVE

Common drug-induced movement disorders (DIMDs) in children vary widely and include hyperkinetic and hypokinetic syndromes. Based on time course, they can be acute, chronic, tardive, and withdrawal. They can be emergent (eg, acute dystonic reaction) or even threatening (ie, neuroleptic malignant syndrome and serotonin syndrome). They can be chronic and disabling (eg, tardive syndromes, tremors). Therefore, it is very important for providers to be familiar with the recognition and treatment of DIMDs.

5.3 PSYCHOTROPIC MEDICATIONS RELATED TO CAUSING MOVEMENT DISORDERS IN PEDIATRICS: A CHILD AND ADOLESCENT PSYCHIATRIST’S NIGHTMARE

Common drug-induced movement disorders (DIMDs) in children vary widely and include hyperkinetic and hypokinetic syndromes. Based on time course, they can be acute, chronic, tardive, and withdrawal DIMDs. They can be emergent (eg, acute dystonic reaction) or even threatening (ie, neuroleptic malignant syndrome and serotonin syndrome), and can be chronic and disabling (eg, tardive syndromes, tremors). Therefore, it is very important for providers to be familiar with the recognition and treatment of DIMDs.

Prescription of Anticholinergics in Tardive Syndromes: A "Dual Center" Survey among Psychiatrists.

Methods We assessed the attitude of two groups of psychiatrists (practicing in Italy and Thailand) towards the prescription of anticholinergics by a short online survey consisting of four questions. A total of one hundred questionnaires were sent out (50 in Italy and 50 in Thailand), and 42 psychiatrists responded to the survey. Results When comparing the two cohorts, the difference, both for age and years of practice, was statistically significant (p < 0.00001 and p < 0.0001, respectively), with Thai psychiatrists being younger and with less time in practice as specialists. The results from the survey showed that the prescription of anticholinergic drugs at the beginning of the antipsychotic treatment was used by 5 psychiatrists (20.0%) of the Italian cohort and by 1 (5.9%) of the Thai cohort. Regarding the Italian psychiatrists who did not prescribe anticholinergics concomitantly with neuroleptics, we found that 5 (25.0%) of them had prescribed anticholinergics in the past but had abandoned this practice, while 15 (93.7%) of the Thai psychiatrists who did not prescribe anticholinergics at the moment of the survey answered that they had prescribed these drugs in the past. Conclusion According to this preliminary survey, the practice to use anticholinergics as a treatment for tardive syndromes is still relatively common, particularly in psychiatrists of the older generation, but seemingly in decline over the years.

Tardive syndrome: An update and mini-review from the perspective of phenomenology.

Tardive syndrome (TS) is a group of movement disorders caused by the long-term use of dopamine receptor blocking agents. The phenotypic presentation of TS is diverse, ranging from the most well-characterized symptom of tardive dyskinesia to other symptoms, including dystonia, akathisia, myoclonus, parkinsonism, tremor, and tics. These tardive symptoms are distinct not only in their phenomenology but also in their clinical outcomes. However, our knowledge of the pathophysiology and management of TS is almost exclusively based on tardive dyskinesia. First-generation antipsychotics have a higher risk of inducing TS and have largely been replaced by second-generation antipsychotics with a lower risk of TS. However, patients with off-label use of second-generation antipsychotics are still at risk of developing TS. Thus, the management of TS remains a challenging and important issue for physicians. In this review, we update the information on the epidemiology, phenomenology, and treatment of TS from the perspective of the specific form of TS.

Management of Tardive Syndrome: Medications and Surgical Treatments.

Tardive syndrome (TS) is an iatrogenic, often persistent movement disorder caused by drugs that block dopamine receptors. It has a broad phenotype including movement (orobuccolingual stereotypy, dystonia, tics, and others) and nonmotor features (akathisia and pain). TS has garnered increased attention of late because of the Food and Drug Administration approval of the first therapeutic agents developed specifically for this purpose. This paper will begin with a discussion on pathogenesis, clinical features, and epidemiology. However, the main focus will be treatment options currently available for TS including a suggested algorithm based on current evidence. Recently, there have been significant advances in TS therapy, particularly with the development of 2 new vesicular monoamine transporter type 2 inhibitors for TS and with new data on the efficacy of deep brain stimulation. The discussion will start with switching antipsychotics and the use of clozapine monotherapy which, despite the lack of higher-level evidence, should be considered for the treatment of psychosis and TS. Anti-dyskinetic drugs are separated into 3 tiers: 1) vesicular monoamine transporter type 2 inhibitors, which have level A evidence, are approved for use in TS and are recommended first-choice agents; 2) drugs with lower level of evidence for efficacy including clonazepam, Ginkgo biloba, and amantadine; and 3) drugs that have the potential to be beneficial, but currently have insufficient evidence including levetiracetam, piracetam, vitamin B6, melatonin, baclofen, propranolol, zolpidem, and zonisamide. Finally, the roles of botulinum toxin and surgical therapy will be examined. Current therapies, though improved, are symptomatic. Next steps should focus on the prevention and reversal of the pathogenic process.

Expanding phenomenologic heterogeneity of tardive syndromes: Time for an updated assessment tool

Tardive syndromes (TDS) are a group of hyperkinetic and hypokinetic movement disorders that occurs after exposure to dopamine receptor blocking agents such as antipsychotic and antiemetic drugs. The Abnormal Involuntary Movement Scale (AIMS) is a widely used instrument that has become the standard for assessment of tardive dyskinesia (TDD), the most common form of TDS. However, the AIMS has a number of clinimetric limitations and was designed primarily to assess the anatomic distribution and severity of involuntary movements without regard to phenomenology. To build on recent advances in understanding and treatment of TDS, re-evaluation and revision of the AIMS that could aid both clinical practice and research may be worthwhile. Challenges, such as retaining the efficiency of the current AIMS, incorporating evaluation of impairment in daily activities, and re-training clinicians for a revised examination procedure and rating instrument, are very likely surmountable.

Long-Term Response to Clozapine and Its Clinical Correlates in the Treatment of Tardive Movement Syndromes: A Naturalistic Observational Study in Patients With Psychotic Disorders.

Given that switching to clozapine is an important treatment option for tardive movement syndrome (TMS), its effect and clinical correlates have not been fully explored yet. This study investigated the improvement of TMS after switching to clozapine and factors associated with the response in a naturalistic outpatient setting. Subjects were 35 patients with schizophrenia or bipolar disorder receiving only clozapine as an antipsychotic drug for more than 12 months. Their prior antipsychotics were switched to clozapine after the onset of tardive dyskinesia and/or tardive dystonia. Tardive movement syndrome and clinical characteristics were assessed through direct examination and review of hospital records. Offending antipsychotics administered at the time of TMS onset were second-generation antipsychotics in 88.6% of patients. Tardive movement syndrome symptoms were remitted in 65.7% of patients after switching to clozapine. Younger age, younger age at onset of TMS, and lower baseline Abnormal Involuntary Movement Scale score were significantly associated with remission of TMS. Female sex and good antipsychotic effects of clozapine showed a trend of association with better response. Clozapine seems to be an excellent treatment option for TMS in the era of second-generation antipsychotics, especially for younger patients with mild tardive dyskinesia. Clinical trials comparing the effect of switching antipsychotics to clozapine with add-on therapy of new drugs targeting TMS are difficult to design in ordinary clinical settings. Therefore, more naturalistic observational studies are warranted to identify predictors of TMS response to clozapine.

An Unusual Cause of Camptocormia

<strong>Background:</strong> Camptocormia is defined as forward flexion of the spine that manifests during walking and standing and disappears in recumbent position. The various etiologies include idiopathic Parkinson’s disease, multiple system atrophy, myopathies, degenerative joint disease, and drugs. <strong>Case Report:</strong> A 67-year-old diabetic female presented with bradykinesia and camptocormia that started 1 year prior to presentation. Evaluation revealed levosulpiride, a dopamine receptor blocker commonly used for dyspepsia, to be the culprit. <strong>Discussion:</strong> It is well known that dopamine receptor blockers cause parkinsonism and tardive syndromes. We report a rare and unusual presentation of camptocormia attributed to this commonly used gastrointestinal drug in the Asian population.

Setting the record straight: The nosology of tardive syndromes

We propose the use of the term tardive dyskinesia to refer to the original description of repetitive and complex oral-buccal-lingual (OBL) movements and the analogous repetitive movements of the limbs, trunk, or pelvis.The term tardive syndrome is an umbrella term to be used to refer to the spectrum of all persistent hyperkinetic, hypokinetic, and sensory phenomenologies resulting from chronic dopamine receptor blocking agent (DRBA) exposure. TD is a type of TS.The term tardive dystonia (TDyst) should be used when dystonia is the main feature of TS. Retrocollis and oromandibular dystonia appear to be the most common form of Tdyst. Tardive akathisia refers to the inability to remain still with an urge to move, giving the appearance of restlessness. In tardive tourettism, the patient has complex motor and phonic tics associated with premonitory urge and relief of tension after performing the tic behavior, thus resembling Tourette's syndrome. Tardive tremor is composed of mainly postural and kinetic tremors. It differs from the resting tremor seen in drug-induced parkinsonism. Tardive pain occurs in association with chronic use of DRBAs and involves the mouth, tongue, and genital region with no physical findings. In tardive parkinsonism, the patient has persistent parkinsonism even after discontinuation of the DRBA although this diagnosis is in question and may represent DRBA-uncovered idiopathic Parkinson's disease or coincident development of Parkinson's disease while taking DRBAs.

Changes in recruitment of motor cortex excitation and inhibition in patients with drug-induced tardive syndromes

It has recently been suggested that drug-induced tardive syndromes (TS) might be due to maladaptive plasticity, which increases motor excitability in cerebral cortex and basal ganglia. In order to test this hypothesis, we performed the first measurements of cortical excitability in TS. Motor cortex excitability was examined using transcranial magnetic stimulation (TMS) in 22 TS patients and compared with that in 20 age and sex-matched healthy individuals. Resting and active motor threshold (RMT, AMT) and input-output curves (I/O curves) assessed corticospinal excitability. The duration of the contralateral silent period (cSP) at a range of stimulation intensities and ipsilateral silent period (iSP) were used as measures of inhibition. There were no significant differences in RMT and AMT between patients and controls, although the input-output curves were significantly steeper in patients. The cSP (at different stimulus intensities) and iSP were both longer in the patients compared to the control group. However, most of this difference could be accounted for by increased recruitment of motor evoked potentials (MEPs) in patients. TS is characterized by hyperexcitability of corticospinal output that might contribute to the lack of selectivity in muscle recruitment and contribute to excess involuntary movement. The findings are opposite to those in naturally-occurring hyperkinesia such as Sydenham's and Huntington's chorea, suggesting a fundamental difference in the pathophysiology.

Repetitive transcranial magnetic stimulation for treatment of tardive syndromes: double randomized clinical trial.

Tardive syndromes (TDS) typically manifest 3 months or later after exposure to antipsychotic drugs, and unfortunately have no satisfactory medical treatment. We explored the possibility of using therapeutic repetitive transcranial magnetic stimulation (rTMS). Twenty-six patients were allocated to receive real or sham rTMS over the hand/arm area of motor cortex (M1). Each received a daily total of 2000 rTMS pulses (20Hz at 100% rMT: 1000 stimuli per hemisphere) for 10 consecutive days. Outcome was assessed using the Abnormal Involuntary Movement Scale (AIMS) and TMS measures of M1 excitability. Three patients in the sham group failed to complete the study. At baseline, there was no significant difference between the groups in age, sex distribution, duration of illness, AIMS score and drug treatment. rTMS improved symptoms in both groups. However, there was a greater reduction in the AIMS score of the real rTMS group compared with the sham group (real, 8.3 ± 1.7 points; sham 1.2 ± 3.3; repeated measure analysis ANOVA Time X Group interaction P = 0.001). The same trends were observed in the clinical subscales. Following treatment, MEP amplitudes at higher intensities (140, and 150%) increased more in the real treatment group than in the sham group. This is the first clinical trial study of bilateral hemispheric rTMS in patients with TDS and suggests that 20Hz rTMS might be a feasible treatment option in patients unresponsive to "first-line" treatment.Clinical trial registration ClinicalTrials.gov Identifier: NCT03145311.