Clinical and Biochemical Effects of Calcium-Hopantenate on Neuroleptics-Induced Tardive Dyskinesia

Abstract: Calcium-hopantenate (HOP A), a derivative of GABA, was administered to 9 psychiatric patients with neuroleptics-induced tardive dyskinesia. In a clinical study, involuntary movements have improved significantly after a 4–8-week medication. Although there was no correlation between the cerebrospinal fluid (CSF) levels of HOPA, GABA, HVA or clinical response, the CSF HOPA levels significantly correlated with changes in the CSF GABA levels. These results suggest that HOPA alleviates the symptoms of tardive dyskinesia being mediated by the central GABAergic mechanisms.     

Clinical Variants of Tardive Dyskinesia in Japan

Abstract: Involuntary movement disorders were investigated in a psychiatric hospital in Japan. The prevalence of tardive dyskinesia was 9.9 % and four clinical variants of tardive dyskinesia could be classified. Of the 716 patients, tardive dystonia was identified in 15 cases, tardive akathisia in one, respiratory dyskinesia in two and rabbit syndrome in 17. The existence of tardive forms for acute dystonic reactions and akathisia suggests that any type of acute extrapyramidal symptoms can have a tardive form.     

CSF Monoamine Metabolism in Patients with Tardive Dyskinesia: Effect of Oxypertine and Hydroxyzine Pamoate

Abstract: Cerebrospinal fluid (CSF) HVA, MHPG, 5-HIAA, cAMP and cGMP concentrations were measured in schizophrenic patients with tardive dyskinesia before and after a three-week administration of oxypertine (n = 4), hydroxyzine pamoate (n = 4) or placebo (n = 4). The oxypertine administration resulted in a reduction of the CSF HVA concentration and an elevation of the MHPG and cAMP concentrations, associated with a clinical improvement in tardive dyskinesia. The hydroxyzine administration reduced the CSF 5-HIAA concentration in all the patients and the CSF HVA concentration in two of four patients with a clinical improvement. A reduction in the CSF HVA concentration associated with possible therapeutic effects of oxypertine or hydroxyzine may suggest the normalization of a hyperdopaminergic state. Discussions were held that functional disorders of not only the dopaminergic system but the norepinephrinergic and serotoninergic systems may relate to the pathogenesis of tardive dyskinesia.     

Brain Atrophy and Intellectual Impairment in Tardive Dyskinesia

Abstract: Fourteen chronic schizophrenic patients with tardive dyskinesia (TD) and 13 without TD were given psychological tests and CT scans. The low density rate (LDR), i.e., the ratio of the X-ray absorption (corresponding nearly to that of cerebrospinal fluid) of a brain lesion to the X-ray absorption of the whole brain, was used as an index of brain atrophy (HN-method). The LDR of the left hemisphere of the TD patients was significantly higher than that of non-TD patients in the basal nucleus and lateral ventricle, and the LDR of the right hemisphere for the TD patients was significantly higher than that of non-TD patients in the basal nucleus. The Hasegawa Dementia Rating Scale (HDRS) and Bender-Gestalt Test (BGT) for the TD patients were significantly lower than those for the non-TD patients. Our study revealed that brain atrophy was greater in TD than in non-TD patients and tended to be more pronounced in the left hemisphere, and that the degree of intellectual impairment was greater in the TD patients than in the non-TD group. The results suggest that schizophrenic brains with TD tend to be more easily damaged than those without TD, that this tendency predominates on the left side, and that intellectual impairment in TD is related to brain atrophy.     

Tardive dystonia and severe tardive dyskinesia. A comparison of risk factors and prognosis

Nine tardive dystonia cases were compared with 13 tardive dyskinesia cases selected for the severity and persistence of their involuntary movements. Both groups were neurological referrals from an identical source. While advanced age and female preponderance were prominent features in tardive dyskinesia, onset in most tardive dystonia cases occurred in young adulthood, and the sex distribution showed a slight majority of males. Other differences in the dystonia group included gait abnormalities in four cases, lower tolerance of neuroleptic discontinuance, with the reappearance of psychoses, and a poorer prognosis for reversibility after follow-up. In fact, none of the dystonia patients reversed as opposed to seven of the tardive dyskinesia patients. In order to identify the full spectrum of tardive dystonia and exclude any referral bias, systematic epidemiological studies on psychiatric populations should include young adults of both sexes.     

Tardive dyskinesia and positive symptoms of schizophrenia.

Positive symptoms and movement disorders were rated in 44 schizophrenic inpatients. A significant negative correlation was demonstrated between tardive dyskinesia and positive symptoms. Possible explanatory mechanisms are discussed.     

Tardive dyskinesia and other movement disorders secondary to aripiprazole

The objective of this report is to draw attention to tardive dyskinesia (TD) caused by aripiprazole, a third generation antipsychotic. TD has been traditionally attributed to typical (first‐generation) antipsychotics, but other dopamine receptor blocking drugs and atypical (second‐ and third‐generation) neuroleptics are emerging as an important cause of TD. We reviewed the medical records of patients with TD seen at the Baylor College of Medicine Movement Disorders Clinic between 2002 and 2010 to identify patients with TD associated with aripiprazole. Among 236 patients with TD seen over the specified period, 8 (3.4%) were found to have aripiprazole‐associated TD. In 5 patients, TD occurred after exclusive exposure to aripiprazole. The mean age at onset was 55.8 ± 14.8 years with a female predominance. The average duration of treatment with aripiprazole was 18.4 ± 26.4 months. Oro‐bucco‐lingual stereotypy was seen in all patients. In most patients, TD did not spontaneously improve after stopping aripiprazole. Of the 5 patients treated with tetrabenazine, 4 improved during follow‐up. Although aripiprazole, a third generation antipsychotic, has been promoted to have a low risk of TD, the drug accounts for about 3.5% of patients with TD evaluated in a movement disorders clinic. This largest reported series draws attention to the growing incidence of TD and other drug‐induced movement disorders associated with “atypical antipsychotics.” © 2010 Movement Disorder Society     

Tardive dyskinesia in the mentally retarded: comparison of prevalence, risk factors and topography with a schizophrenic population.

Thirty mentally retarded patients treated with neuroleptics for aberrant behavior were compared with 30 neuroleptic-treated schizophrenics for the presence, topography and risk factors associated with tardive dyskinesia (TD). In the total sample (n = 60), female sex, schizophrenic diagnosis and increasing age were associated with TD. The length of neuroleptic treatment and current neuroleptic dose were not significantly associated with TD. The only topographical difference in TD presentation was that the mentally retarded group had significantly more tongue involvement.     

Tardive dyskinesia and deficit schizophrenia

Telfer S, Shivashankar S, Krishnadas R, McCreadie RG, Kirkpatrick B. Tardive dyskinesia and deficit schizophrenia. Objective: Despite comparable antipsychotic exposure, some patients experience involuntary movements yet others do not. Negative symptoms have been associated with tardive dyskinesia (TD), but it is not certain whether this is an association with primary negative symptoms or the effects of medications. The aim of the present study was to determine whether patients with deficit schizophrenia (who have primary negative symptoms) are more likely to experience TD than those with non‐deficit schizophrenia. Method: In 2006, all the people with a clinical diagnosis of schizophrenia in Nithsdale, Southwest Scotland, were identified using the ‘key informant’ method. These patients were categorized into those with and without the deficit syndrome and assessed for the presence of TD. Patients were also assessed for akathisia and extrapyramidal side effects. Results: Of the 131 people assessed, 31 were categorized as having deficit schizophrenia (23.7%) and 100 people (76.3%) as non‐deficit. There was no difference between the two groups with regard to age, antipsychotic exposure, and duration of illness. There was a significant association between deficit features and TD with an odds ratio = 2.97 [95% CI 1.128–6.88, P = 0.009]. Conclusion: Our findings support the proposal that the pathological process underlying deficit schizophrenia can predispose to the development of TD.     

迟发性运动障碍患者血清铁调素、铁蛋白水平的研究

目的:探讨伴有迟发性运动障碍(TD)的精神分裂症患者血清铁调素(Hep)、铁蛋白(Fn)水平,以及铁代谢状况与TD的关系。方法:采用酶免疫法及化学发光法测定30例伴TD的精神分裂症患者(TD组)、41例不伴TD的精神分裂症患者(非TD组)及41名正常人(正常对照组)血清Hep、Fn水平;用异常不自主运动量表(AIMS)评估患者TD的严重程度及其与血清Hep、Fn水平的相关性。结果:TD组血清Hep水平低于非TD组及正常对照组(Z=-2.99,Z=-3.62;P均0.01),非TD组与正常对照组之间Hep水平差异无统计学意义(Z=1.22,P0.05);TD组血清Fn水平高于非TD组及正常对照组(Z=2.00,Z=2.39;P均0.05),非TD组与正常对照组之间Fn水平差异无统计学意义(Z=-0.70,P0.05)。TD组血清Hep水平与Fn水平呈负相关(r=-0.396,P0.05),AIMS评分与血清Hep及Fn水平无相关性(r=-0.052,r=0.14;P均0.05)。结论:TD患者存在铁代谢蛋白异常,铁代谢障碍可能参与了TD的病理生理过程。     

Tardive dyskinesia in a chronically institutionalized population of elderly schizophrenic patients: prevalence and association with cognitive impairment

Background. Chronically hospitalized geriatric inpatients with schizophrenia are at particular risk for both tardive dyskinesia (TD) and cognitive impairment but have been insufficiently studied in this regard. Similarly, the relationship between TD and cognitive impairment has not been adequately addressed in this population. Objectives. (1) To determine the prevalence of TD in a cohort of chronically institutionalized schizophrenic geriatric inpatients. (2) To examine the relationship between the manifestations of TD in various body regions and several potentially related variables including current pharmacological regimen, age, age at first hospitalization and cognitive status. Method. TD was assessed by the Modified Simpson Dyskinesia Scale and cognitive status by the Mini-Mental State Examination (MMSE). The relationship between manifestations of TD and other variables was examined by t-tests, ANOVA, MANOVA and correlational analysis. Results. The prevalence of TD was 60%. Prevalence increased with age but was not related to current antipsychotic or anticholinergic regimen. Mean MMSE score did not differ between groups of patients with and without TD as defined by the criteria of Schooler and Kane (1982); however, the mean MMSE score was significantly (p<0·004) lower in subjects with orofacial TD as defined by Waddington and Youssef (1996), and the difference was not entirely accounted for by the older age of the latter group. Conclusions. TD and cognitive impairment both increase with age. However, TD alone does not account for the severity of cognitive impairment in this population. The present study provides further support for the hypothesis that the correlation between TD and cognitive impairment holds primarily for the orofacial manifestations of TD. © 1998 John Wiley & Sons, Ltd.     

Tardive dyskinesia with ziprasidone and citalopram use in an elderly female patient

Tardive dyskinesia (TD) is occasionally an irreversible condition caused by antipsychotic treatment. Second-generation antipsychotics are considered to have less extrapyramidal effects, including causing TD. Herein, we present a case of TD following ziprasidone use. A 67 year-old woman started to hear voices and 'see' people speaking to her, especially while praying. She presented to our clinic with anxiety, anhedonia, dysphoria, and auditory hallucinations. She was admitted with a diagnosis of depressive disorder with psychotic features. Citalopram 20 mg/day and ziprasidone 40 mg b.i.d. were started. After her symptoms had been relieved, the patient was was discharged and with monthly follow up. At her first visit 1 month after discharge, orofacial dyskinesia was found on physical examination. Ziprasidone may be associated with TD, even in someone who has never been exposed to a traditional neuroleptic. However, concomittant treatment with a serotonin reuptake inhibitor in the present case may have favored the appearance of TD.     

No Association between PAWR Gene Polymorphisms and Tardive Dyskinesia in Schizophrenia Patients

Tardive dyskinesia (TD) is a hyperkinetic movement disorder associated with the prolonged use of antipsychotic drugs. Since prostate apoptosis response 4 (Par-4) is a key ligand of the dopamine D2 receptor, the Par-4 gene (PAWR) is a good candidate gene to study in the context of TD susceptibility. We examined the association between PAWR gene polymorphisms and TD. Three single nucleotide polymorphisms of PAWR were selected for the analysis: rs7979987, rs4842318, and rs17005769. Two hundred and eighty unrelated Korean schizophrenic patients participated in this study (105 TD and 175 non-TD patients). Genotype/allele-wise and haplotype-wise analyses were performed. There were no significant differences in genotype and allele frequencies between the two groups. Haplotype analysis also did not reveal a difference between the two groups. Within the limitations imposed by the size of the clinical sample, these findings suggest that PAWR gene variants do not significantly contribute to an increased risk of TD.     

Quality of life in schizophrenia: relationship to sociodemographic factors,symptomatology and tardive dyskinesia

The influence of sociodemographic, clinical and treatment factors on the quality of life of patients with schizophrenia has yet to be fully defined. We evaluated the quality of life of patients with schizophrenia who were attending a catchment area rehabilitation centre, in order to establish its clinical correlates. These patients had a poor to moderate quality of life which was inversely related to negative symptom severity, illness duration, the cumulative length of previous hospitalization and patient age. Patients residing in hostels or group homes had a poorer quality of life than those living independently or with their family. The presence of tardive dyskinesia was associated with a poorer quality of life. This association merits further invesigation.     

Tardive dyskinesia in children treated with atypical antipsychotic medications.

Recent years have witnessed increased antipsychotic treatment of children despite limited long‐term safety data in children. In this study, motor side effects associated with the use of antipsychotic drugs in children were examined in a sample of pediatric psychiatric patients. Child and adolescent psychiatric patients receiving antipsychotics (most were on atypicals) for 6 months or longer (n = 118) were compared with antipsychotic‐naïve patients (n = 80) with similar age, sex ratio, and diagnoses. Only 19% of patients on antipsychotics had ever experienced psychotic symptoms. Eleven children (9%) on antipsychotics exhibited dyskinesia, when compared with 0 in the naïve group (P = 0.003, Fisher's exact test). Nine of 62 African–American children (15%) on antipsychotics exhibited dyskinesia, when compared with only 4% (2 of 52) of European–American children (P = 0.003, Fisher's exact test). Children treated with antipsychotic drugs might experience a significant risk of dyskinesia even when treated only with atypical antipsychotics. Ethnicity might also be a risk factor for dyskinesia in children. Side‐effect profile of the atypical antipsychotic drugs in children may be much different than that in adults. © 2007 Movement Disorder Society     

Serum-soluble interleukin-2 receptors in neuroleptic-naive schizophrenic subjects and in medicated schizophrenic subjects with and without tardive dyskinesia

There is a growing body of literature suggesting that some schizophrenic subjects have evidence of immune activation. One marker that has been consistently elevated in studies is the serum-soluble interleukin-2 receptor (SIL-2R). This article reports the results of 2 experiments: the first compares concentrations of serum SIL-2R in neuroleptic-naive schizophrenic patients and matched controls, and the second study contrasts serum SIL-2R concentrations in medicated schizophrenic subjects with and without tardive dyskinesia. Serum SIL-2R concentrations were elevated in neuroleptic-naive schizophrenic subjects as compared with controls (1705.7 (SD 1124.2) U/ml vs 739.8 (SD 325.5) U/ml). Medicated subjects with tardive dyskinesia had increased serum SIL-2R levels (2385.5 (SD 1822.0) U/ml) compared with medicated subjects without tardive dyskinesia (1259.6 (SD 1365.3) U/ml). Thus, elevations in serum SIL-2R levels are present prior to neuroleptic treatment, and there may be an association between serum SIL-2Rs and tardive dyskinesia.     

Tardive dyskinesia in schizophrenics. Prevalence, distribution and relationship to neurological "soft" signs in Nigerian patients

The prevalence of tardive dyskinesia (TD) in 70 Nigerian schizophrenics was 37%. Age was related to the presence of TD in males but not in females. Significantly more females had TD in the lower extremities. Comparison of patients with TD and those without revealed no significant differences with regard to the presence of neurological "soft" signs.     

Tardive dyskinesia (syndrome): Current concept and modern approaches to its management

Tardive dyskinesia is a serious, disabling and potentially permanent, neurological hyperkinetic movement disorder that occurs after months or years of taking psychotropic drugs. The pathophysiology of tardive dyskinesia is complex, multifactorial and still not fully understood. A number of drugs were tried for the management of this motor disturbance, yet until now no effective and standard treatment has been found. It is very disappointing to realize that the introduction of antipsychotics from the second generation has not significantly decreased the prevalence and incidence of tardive dyskinesia. Therefore, the management of this motor disturbance remains an actual topic as well as a challenge for clinicians. This review summarizes recent relevant publications concerning the treatment of tardive dyskinesia.     

Electroconvulsive Therapy in a Patient with Mania, Parkinsonism, and Tardive Dyskinesia

The authors describe a patient in whom ECT was associated with recovery from a manic episode, improvement in coexistent parkinsonism, and a marked change in the anatomic distribution of dyskinetic movements.