慢性精神分裂症迟发性运动障碍患者6年随访

目的:了解长期服用抗精神病药的慢性精神分裂症住院患者迟发性运动障碍(TD)的预后。方法:对以往诊断为TD的54例住院患者TD症状进行6年随访。结果:42.6%患者TD症状改善,35.2%患者症状不变,22.2%患者症状恶化。服用新型非典型抗精神病药者TD症状改善较明显。患者的年龄、性别、目前药物剂量、药物剂量的改变、首次用药年龄、累计服药时间及总病程对TD症状的改善无影响。结论:长期用药患者TD症状仍可有所改善,新型非典型抗精神病药物可能改善TD症状。     

Morbidity and mortality in tardive dyskinesia: associations in chronic schizophrenia

A population of 101 chronic schizophrenic inpatients were assessed for the presence or absence of tardive dyskinesia, and followed up 32 months later. At follow up, the mortality rates in 44 patients with and 57 patients without involuntary movements were 16% vs. 9% respectively; this difference widened when only the more prominent involuntary movements were considered. Of those surviving, patients with tardive dyskinesia were much more likely to contract an attack of respiratory tract infection, and to do so on multiple occasions, and tended to suffer from more cardiovascular disorders. They appeared more likely to show smoking-related pathology. Chronic schizophrenic patients with tardive dyskinesia constitute a more biologically disadvantaged group, suggesting a broader disease concept of the syndrome.     

Current topics in tardive dyskinesia in Japan

Abstract This article reviews current topics in tardive dyskinesia (TD), a movement disorder associated with the prolonged use of neuroleptic agents, especially therapeutic and preventive strategies which have been or are now being studied in Japan. Tardive dyskinesia has become a major problem in the clinical psychiatric field since the early 1970s in Japan, lagging behind Western countries by more than 10 years. The average prevalence rate of TD has been estimated as 7.7% in Japan, while it has been reported in the English literature at around 15 to 20%. Clinical trials of treatments for TD have been or are now being performed in Japan with a number of novel compounds, such as ceruletide, meclofenoxate, and rolipram; however, no effective treatment has yet been established and measures to prevent TD have therefore been emphasized. These include (i) the development of new antipsychotic drugs which are free from TD, (ii) the identification of risk factors from prospective longitudinal studies, and (iii) the investigation of genetic variations that could act as a marker to identify especially vulnerable patients within the whole population of patients who need neuroleptic therapy.     

Acculturation is associated with the prevalence of tardive dyskinesia and akathisia in community-treated patients with schizophrenia

Objective: Ethnicity is a risk factor for tardive dyskinesia (TD) and other antipsychotic drug‐induced movement disorders (ADIMD). It is unclear whether this association is mediated through genetic, environmental or cultural factors individually or in combination. This pilot study aimed to explore this interaction by determining if acculturation in migrant groups contributed to the prevalence of ADIMD. Method: Culturally diverse but relatively genetically homogeneous (white Caucasian) patients with schizophrenia (n = 40) treated at a single site were assessed for the presence of ADIMD and level of acculturation. Results: Higher levels of acculturation correlated with an increased prevalence of TD and akathisia but not Parkinsonism. The level of acculturation significantly predicted TD. Conclusion: This study identifies for the first time that acculturation significantly contributes to the prevalence of TD and akathisia but not Parkinsonism in culturally diverse migrant populations and must be accounted for when explaining ethnic variation in rates of ADIMD.     

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.     

迟发性运动障碍患者的血清铁指数研究

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指数(血清铁含量、铁结合力和铁蛋白)。方法:使用异常不自主运动量表(AIMS)评定有无TD及其严重程度。采用比色法和酶联免疫吸附法(ELISA)分别测定40例TD患者和相匹配的58例非TD患者血清铁指数。结果:TD组与非TD组间的血清铁含量、铁蛋白的比较无明显差异,而TD组的铁结合力显著低于非TD组(P<0.05)。在TD组,AIMS评分与铁蛋白的浓度有明显的相关关系(P<0.05)。重度TD组(AIMS≥5分)与非TD组相比,铁蛋白的差异有显著性(P<0.05)。结论:血清铁蛋白的水平可能与服用典型抗精神病药的男性精神分裂症患者的TD发生有关。     

Changes in negative symptoms and the risk of tardive dyskinesia: a longitudinal study. UK700 Group

OBJECTIVE: To examine whether the development of tardive dyskinesia (TD) is accompanied by a parallel process of worsening negative symptoms in a longitudinal study. METHOD: A sample of 708 psychotic patients were followed over a period of 2 years, using the Abnormal Involuntary Movement Scale and the Scale for the Assessment of Negative Symptoms (SANS). RESULTS: Of 361 individuals with no prior evidence of dyskinesia, 46 (13%) developed TD by year 2. Independent of the effects of male sex (odds ratio (OR)=2.18, 95% confidence interval: 1.00-4.74), age (OR per quartile group = 1.39, 95% CI: 1.01-1.90), duration of exposure to antipsychotic medication (OR = 2.35 per 8 months, 95% CI: 1.17-4.72) and average SANS score (OR per quartile group = 1.38, 95% CI: 0.99-1.93), worsening of negative symptoms over the 2 previous years was associated with TD onset (OR per quartile group = 1.46, 95% CI: 1.07-2.00). CONCLUSION: The development of TD is linked, independent of the effect of antipsychotics and older age, to an illness-related pathological process, characterized by worsening negative symptoms.     

The coding‐synonymous polymorphism rs1045280 (Ser280Ser) in β‐arrestin 2 (ARRB2) gene is associated with tardive dyskinesia in Chinese patients with schizophrenia

Background: Tardive dyskinesia (TD) is a severe and potentially irreversible adverse effect of long‐term antipsychotic treatment. Typical antipsychotics are commonly binding to the dopamine receptor D2 (DRD2), but the occurrence of antipsychotic‐induced TD is rather delayed; therefore, the development of TD may be associated with mediators or signalling complexes behind DRD2, such as β‐arrestin 2 (ARRB2), an important mediator between DRD2 and serine–threonine protein kinase (AKT) signal cascade. Methods: A case–control study to evaluate the association between rs1045280 (Ser280Ser) and antipsychotic‐induced TD was performed amongst 381 patients (TD/non‐TD = 228/153). Results: There was a significant difference in the genotype distribution between TD and non‐TD groups (P = 0.025); furthermore, the allelic analysis indicated that patients with T allele had increased risk of TD occurrence (OR_T = 1.58, 95% CI = 1.14–2.19, P = 0.007). Conclusions: To the best of our knowledge, this is the first study reporting a positive association between the SNP rs1045280 and TD in schizophrenic patients.     

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。     

Aripiprazole in the acute treatment of male patients with schizophrenia: effectiveness, acceptability, and risks in the inner-city hospital setting

Aripiprazole, a novel atypical antipsychotic that acts as a partial agonist at the dopamine D₂ receptors, has been reported to be effective in the treatment of chronic schizophrenia. However, the risks and benefits of using aripiprazole in the acute hospital setting to treat severe psychotic disorders are unclear. This naturalistic study assessed the effectiveness of aripiprazole monotherapy in a group of actively psychotic male patients (n = 10) with schizophrenia who were admitted to an inner-city acute psychiatric unit. Most patients (n = 7) responded to aripiprazole treatment, which was well tolerated and significantly ameliorated psychotic symptoms after 2–3 weeks. Patients who responded to it could be safely discharged on aripiprazole monotherapy. Side effects observed were mostly mild and transient, and included extrapyramidal symptoms (n = 1) and neutropenia (n = 1). Aripiprazole also remarkably attenuated dyskinetic movements in 1 patient with severe tardive dyskinesia, thereby suggesting that it may be useful in the treatment of other disorders that are also associated with dopamine dysfunction. Results showed that aripiprazole can be safely and effectively employed in the hospital setting to treat severely psychotic patients with schizophrenia, but further studies are required to establish the full range of adverse reactions and therapeutic indications associated with its use.     

Clinical effectiveness of the Kampo medicine kamishoyosan for adjunctive treatment of tardive dyskinesia in patients with schizophrenia: a 16-week open trial

The purpose of the present study was to evaluate the clinical effectiveness of kamishoyosan for antipsychotic-induced tardive dyskinesia, and to investigate the relationship between tardive dyskinesia and serum brain-derived neurotrophic factor (BDNF) levels. Sixty-nine schizophrenia patients were enrolled; of these, 49 presented with tardive dyskinesia while the remaining 20 patients showed no tardive dyskinesia. The tardive dyskinesia group was treated for 16 weeks with kamishoyosan and assessed using the abnormal involuntary movement scale. The abnormal involuntary movement scale scores in the tardive dyskinesia group were evaluated at baseline and after 4, 8, and 16 weeks of treatment. The BDNF levels of all subjects were measured at baseline in order to compare differences in serum BDNF levels between the tardive dyskinesia group and the non-tardive dyskinesia group, and to correlate the severity of tardive dyskinesia and serum BDNF in the tardive dyskinesia group. A meaningful reduction in total abnormal involuntary movement scale scores was observed in the tardive dyskinesia group treated with kamishoyosan at 4, 8, and 16 weeks of treatment (P < 0.01). No significant differences in serum BDNF levels were detected between the tardive dyskinesia group and the non-tardive dyskinesia group at baseline. Furthermore, no significant correlation was seen between the severity of tardive dyskinesia and serum BDNF levels. The present study suggests that kamishoyosan might be a promising adjunctive treatment for antipsychotic-induced tardive dyskinesia.     

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.     

The course of tardive dyskinesia in newly treated psychogeriatric patients.

The author reports on the course of tardive dyskinesia in 10 newly treated psychogeriatric patients. Of the 5 whose medication was discontinued, 3 improved; TD continued unchanged in the other 5 patients whose neuroleptics were not discontinued. The author recommends that neuroleptics be discontinued whenever possible in this patient population.     

Negative association between Catechol-O-methyltransferase (COMT) gene Val158Met polymorphism and persistent tardive dyskinesia in schizophrenia

Summary. Chronic administration of typical antipsychotic agents, which mainly act on the dopamine receptors, implicates a role of dopamine system on the susceptibility of tardive dyskinesia (TD). In the present study, the association between a functional Val158Met polymorphism of Catechol-O-methyltransferase (COMT) gene and TD occurrence and TD severity was investigated in 299 Chinese schizophrenic patients with long-term antipsychotic treatment (TD: 166, non-TD: 133). After adjusting the effects of confounding factors, there was no significant association between COMT genotype and TD occurrence (p=0.367). Among TD patients, we found no significant correlation between COMT genotypes and the total scores of abnormal involuntary movement scale (AIMS) (p=0.629). We concluded that this COMT polymorphism might not play a major role in the susceptibility of TD nor on the severity of TD.     

Epidemiology of tardive dyskinesia: Is risk declining with modern antipsychotics?

Second-generation antipsychotic drugs (APDs), including aripiprazole, clozapine, olanzapine, risperidone, quetiapine, and ziprasidone dominate outpatient and inpatient clinical practice, having largely displaced the older neuroleptics. Modern APDs have relatively low risk for acute extrapyramidal syndromes characteristic of older neuroleptics, particularly acute dystonia and Parkinsonism, with variable risks of akathisia and the rare neuroleptic malignant syndrome. Anticipated reduction in risk of tardive dyskinesia (TD) is less well documented. Nearly 50 years after initial reports on TD, it is appropriate to reexamine the epidemiology of this potentially severe late adverse effect of long-term APD treatment in light of current research and practice. We compared recent estimates of incidence and prevalence of TD identified with some modern APDs to the epidemiology of TD in the earlier neuroleptic era. Such comparisons are confounded by complex modern APD regimens, uncommon exposure limited to a single modern APD, effects of previous exposure to typical neuroleptics, and neurological assessments that are rarely prospective or systematic. Available evidence suggests that the risk of TD may be declining, but longitudinal studies of patients never treated with traditional neuroleptics and exposed to only a single modern APD are required to quantify TD risks with specific drugs. Long-term use of APDs should continue to be based on research-supported indications, with regular specific examination for emerging TD.     

Association analysis of a neural nitric oxide synthase gene polymorphism and antipsychotics-induced tardive dyskinesia in Chinese schizophrenic patients

Summary. Recent findings from rodent studies with chronic administration of antipsychotic drugs have indicated the role of neural nitric oxide synthase (NOS1) on the susceptibility of tardive dyskinesia (TD). In the present study, the association between a 3-untranslated region C267T (3-UTR C267T) polymorphism of the NOS1 gene and TD as well as TD severity was investigated in 251 Chinese schizophrenic patients with long-term antipsychotic treatment (TD: 128, non-TD: 123). After adjusting the effects of confounding factors, there was no significant association between NOS1 3-UTR C276T genotypes and TD occurrence (p=0.758). With in the TD group, we could not discover a significant correlation between NOS1 3-UTR C276T genotypes and the scores of abnormal involuntary movement scale (AIMS) (p=0.219 and 0.774). We concluded that the NOS1 3-UTR C276T polymorphism might not play a major role in the susceptibility of TD development, or on the severity of TD.     

血浆同型半胱氨酸与迟发性运动障碍的关系

目的:探讨血浆同型半胱氨酸(Hey)与迟发性运动障碍(TD)的关系.方法:对33例伴TD的精神分裂症患者(TD组)与33例不伴,TD的精神分裂症患者(非TD组)进行血浆Hey与血清维生素B12、叶酸水平检测.结果:TD组血浆Hey水平显著高于非TD组,而血清叶酸水平显著低于非TD组.两组血浆Hey水平均与血清维生素B1...     

Smoking and tardive dyskinesia in male patients with chronic schizophrenia

Interactions between smoking and movement disorders include the contrasting associations of more cigarette smoking with reductions in Parkinson's disease and increases in tardive dyskinesia (TD) symptoms. Here we examine the relationship between smoking and TD in a large sample of inpatients with schizophrenia. We used cross-sectional naturalistic methods to analyze the prevalence and severity of neuroleptic-induced TD in relation to cigarette smoking among 764 male chronic and medicated inpatients meeting DSM-IV criteria for schizophrenia. We administered a detailed questionnaire including general information, medical and psychological conditions, and smoking behaviors. We evaluated TD severity using the abnormal involuntary movement scale (AIMS) and psychopathology using the Positive and Negative Syndrome Scale (PANSS). The main statistical analyses used cross-tabulations for the prevalence of TD by smoking and multivariate regression analyses for continuous measures (AIMS and PANSS). We found that the prevalence of TD did not significantly differ between smokers (41% = 237/578) and non-smokers (37% = 69/186). Secondary outcomes showed a significant association between the AIMS total score and age, duration of illness and hospitalization times. Thus, smoking was not associated with TD in male Chinese schizophrenics, but consistent with previous reports, older patients with a longer duration of illness and more hospitalizations showed greater severity of TD.     

The prevalence of tardive dyskinesia after a nine month naturalistic randomized trial comparing olanzapine with conventional treatment for schizophrenia and related disorders

Aims of the study To assess the impact of olanzapine versus conventional neuroleptic therapy among subjects with schizophrenia on ratings of tardive dyskinesia (TD). Method The naturalistic study was conducted in three psychiatric hospitals in Brazil. Patients had a diagnosis of schizophrenia and related disorders (DSMIV) and with a BPRS score > 24. Patients were evaluated by means of the PANSS scale for symptomatology (Kay et al. 1986), the Clinical Global Impression, The UKU side effect rating scale (Lingjaerde et al. 1987), and the Tardive Dyskinesia AIMS scale (Guy et al. 1976). Patients were seen by the treating physician routinely while hospitalized and then monthly on an out-patient basis. All scale assessments were repeated after 9 months of discharge. Result The sample was comprised of 190 patients (99 in the olanzapine and 91 in the standard treatment), with a completion rate of 88.2 % for olanzapine and 84.9% for the conventional treatment (p=0.385, n. s.). The mean change from baseline in the PANSS total score favored olanzapine regarding negative symptoms (2.3, 95% C. I. 0.6–4.1, p < 0.001); and general psychopathology (4.0, 95% C.I. 0.8–7.2, p < 0.02) factors. TD was defined by applying Morgenstern & Glazer (1993) and Schooler & Kane (1982) criteria, on the basis of the AIMS scale. Both results favored olanzapine at the end of the follow-up (Morgenstern & Glazer: 25.6% versus 56.3%; Schooler & Kane: 16.3% versus 45.2 %). At the end of the follow-up, by using the overall rating of the AIMS scale, the presence of TD was 2.3% for olanzapine (2/87), and 16.7% (12/72) for the conventional treatment. Conclusions The results of this open label naturalistic trial showed that olanzapine had an impact on negative symptoms, decreased general psychopathology and reduced the risk of tardive dyskinesia.     

Tiapride in the treatment of tardive dyskinesia

The effect of Tiapride on dyskinesia was evaluated in 12 patients with tardive dyskinesia in a double-blind controlled cross-over trial. The effect was measured by a Doppler-radar device and by counting the number of involuntary movements from video-recordings. Besides these methods, subjective assessments were made on analogue scales by family, nurses and attendant doctors. The subjective evaluation appeared to be useless because of many inconsistent answers. The quantitative methods revealed a significant diminution of the involuntary movements in the Tiapride therapy period (P less than 0.01). It appears that tiapride is an effective drug in the treatment of tardive dyskinesia. No clinically important side-effects have been observed. The drug appeared not to induce parkinsonism.