Oxypertine in tardive dyskinesia: a long-term controlled study

A 6-month, double-blind, placebo-controlled study of oxypertine in tardive dyskinesia is described. Results suggest that any beneficial effect noticed initially is not sustained. When this effect is compared with the time course of development of supersensitivity after neuroleptics as reported in the literature, it becomes apparent that the drug, despite its different mechanism of action, behaves like any other conventional neuroleptic. On the basis of the findings, the authors feel that all proposed anti-dyskinetic drugs should be subjected to longer, controlled trials to prove their clinical efficacy.     

Mild tardive dyskinesia: an 8-year follow-up study

The authors re-examined 20 patients who were found to exhibit mild tardive dyskinesia (TD) involving only one body area in 1980. Of these, 11 still showed TD of the same degree, whereas 4 had no TD and 5 aggravated TD. The authors conclude that mild TD involving one body area should be included in prevalence studies and that Schooler & Kane's definition of minimal manifestation of TD should be extended to include these patients.     

A 10-year follow-up study of tardive dyskinesia.

In a 10-year follow-up study of 44 patients with tardive dyskinesia (TD), the majority (22 or 50%) had no change in their TD severity, 9 (20%) had an improvement and 13 (30%) had a worsening of their TD. Little difference was noted in those patients whose medication was decreased (n = 12) and those whose medication remained unchanged (n = 32). Of the women, 26% showed improvement as compared with 11% of the men. Also, patients whose TD improved had lower present neuroleptic dose than those whose TD worsened. These two factors should be studied in larger patient cohorts.     

Treatment outcome with clozapine in tardive dyskinesia, neuroleptic sensitivity, and treatment-resistant psychosis

Thirty-eight chronically ill psychotic patients were treated with clozapine for indications of tardive dyskinesia, severe extrapyramidal side effects caused by other neuroleptics, or treatment-resistant psychosis. Fifty-five percent of all patients and 40% of schizophrenics improved with clozapine. Abnormal involuntary movements were suppressed during treatment and, with 1 exception, returned to baseline levels after clozapine was discontinued. Our results support the conclusion that clozapine's efficacy in refractory cases and its lack of neurological side effects make it a unique neuroleptic with advantages over conventional antipsychotic agents. The drug appears to be safe when treatment is accompanied by frequent clinical and hematologic monitoring.     

Treatment of tardive dyskinesia with donepezil: a pilot study

BACKGROUND: Tardive dyskinesia (TD) remains a significant clinical problem for which there is no uniformly effective treatment. Earlier trials with acetylcholine precursors may have been disappointing because of underlying damage to striatal cholinergic neurons in patients with TD. In contrast, new cholinesterase inhibitors, developed for the treatment of dementia, may improve TD by directly increasing cholinergic synaptic transmission. METHOD: We conducted an 8-week open-label trial of donepezil in the treatment of TD. Ten patients with schizophrenia or schizoaffective disorder who received stable doses of antipsychotics and met DSM-IV criteria for TD were treated with donepezil, 5 to 10 mg/day, for 6 weeks after a 2-week baseline period. Changes in total Abnormal Involuntary Movement Scale (AIMS) scores measured every 2 weeks were assessed for significance. Patients were also assessed using the Brief Psychiatric Rating Scale, the Mini-Mental State Examination, the Barnes Akathisia Scale, and the Simpson-Angus Scale. RESULTS: Total AIMS scores decreased significantly (p = .0009), with no changes in other measures. Nine patients showed a positive response. Improvement was greatest in orofacial and upper extremity movements. No significant interactions were noted between the total AIMS scores and age (p > .29), duration of TD (p > .38), or duration of antipsychotic treatment (p > .14). CONCLUSION: Donepezil appeared to be effective in suppressing TD in this pilot study. However, placebo-controlled, double-blind studies are necessary before donepezil can be recommended as a treatment for TD.     

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。     

Treatment of tardive dyskinesia with ceruletide: a double-blind, placebo-controlled study.

The effectiveness of a once-weekly i.m. injection of ceruletide (0.8 microgram/kg) in suppressing the symptoms of neuroleptic-induced tardive dyskinesia (TD) was evaluated in a double-blind, placebo-controlled, matched-pairs study. Global evaluation of the severity of TD symptoms over the 8-week study period revealed a significant improvement with ceruletide as compared with placebo. Analysis of the therapeutic response to ceruletide over the course of treatment revealed a slow, but long-lasting improvement of TD symptoms. Side effects, which were mild and transient, consisted mainly of nausea and epigastric discomfort. The incidence of side effects did not differ between the ceruletide- and placebo-treated groups. Ceruletide appears to be a novel and practical treatment that can substantially alleviate the symptoms of dyskinesia.     

An assessment of emergent tardive dyskinesia and existing dyskinesia in patients receiving long-acting, injectable risperidone: results from a long-term study

INTRODUCTION: Treatment-emergent tardive dyskinesia (TD) can be a serious side effect of antipsychotic treatment. Atypical antipsychotics are associated with a lower risk for TD than are conventional agents. A long-acting atypical antipsychotic, with more stable blood levels and lower peak blood levels than an oral formulation, may provide differential benefit regarding side effects, including movement disorders. This analysis assessed TD by defined research criteria in patients receiving long-acting, injectable risperidone. METHODS: Clinically stable subjects with schizophrenia or schizoaffective disorder participated in a 50-week, open-label trial of long-acting, injectable risperidone. TD was studied by defined research criteria (Schooler, N.R., Kane, J.M., 1982. Research diagnosis for tardive dyskinesia. Arch. Gen. Psychiatry. 39, 486-487; Americal Psychiatric Association, 2000. Diagnostic and Statistical Manual of Mental Disorders, fourth ed. American Psychiatric Association, Washington, DC). The severity of dyskinesia and other movement disorders were rated by the Extrapyramidal Symptom Rating Scale (ESRS). RESULTS: ESRS dyskinesia data were available for 662 patients. Five of 530 subjects without dyskinesia at baseline (0.94%) met the predefined criteria for emergent persistent TD during therapy. Based on either exposure to study medication or Kaplan-Meier analysis, the 1-year rate was 1.19%. Among the 132 subjects with dyskinesia at baseline, the mean score on the ESRS physician's exam for dyskinesia improved significantly at endpoint (-2.77; P<0.0001), regardless of anticholinergic drug use. (P=0.243 for patients with versus without anticholinergic drug use.) CONCLUSIONS: In this open-label study, treatment with long-acting risperidone was associated with a low rate of emergent persistent TD. Significant improvement in existing dyskinesias was noted. The TD rate reported here is consistent with other reports of atypical antipsychotics and substantially lower than with conventional antipsychotics.     

Reversibility of long-term tardive dyskinesia associated with antiparkinsonian medication: a case report

The author describes the case of a patient who received neuroleptics and antiparkinsonian medications for more than 7 years and whose tardive dyskinesia symptoms disappeared after trihexyphenidyl was discontinued. The case appears to support the hypothesis that there is a threshold effect of antiparkinsonian agents on tardive dyskinesia.     

Non-adherence with long-term prophylaxis: a 6-year naturalistic follow-up study of affectively ill patients

In a retrospective 6-year follow-up, we assessed the reasons for and the frequency and consequences of non-adherence in 76 affectively ill patients receiving lithium prophylaxis in two lithium clinics. Thirty-eight bipolar (50%), 21 unipolar (27.6%) and 17 schizoaffective patients (22.4%) diagnosed according to DSM-III-R, were investigated with a specialized follow-up documentation. Of the patients 53.9% discontinued prophylaxis at some time; 43.2% of the discontinuations occurred during the first 6 months. In contrast to other studies the main reason reported for non-adherence was resistance against long-term treatment. According to the Lithium Attitudes Questionnaire non-adherent patients showed significantly less acceptance of the prophylaxis in general, of the effectiveness of lithium and of the severity of their illness than adherent patients. In a multivariate analysis of various parameters, only the negative attitude to prophylaxis correlated significantly with non-adherence. Significant correlation was found between treatment outcome and duration of initial prophylaxis. During the 6-year follow-up only the adherent patients showed a significant reduction of the number and duration of admissions. Our findings confirmed non-adherence as a major problem in the effectiveness of lithium prophylaxis. The authors recommend prospective investigations of attitudes and the impact of psychoeducation on long-term adherence.     

Sleep symptoms and long-term outcome in adolescents with major depressive disorder: a naturalistic follow-up study

European Child & Adolescent Psychiatry - Sleep abnormalities in major depressive disorder (MDD) have been suggested to represent a vulnerability trait, which might predispose the individual to...     

A prospective,naturalistic follow-up study of treatment outcomes with clonazepam in rapid eye movement sleep behavior disorder

BackgroundRapid eye movement sleep behavior disorder (RBD) is characterized by prominent dream-enacting behaviors, often resulting in sleep-related injuries.ObjectivesThis study aimed to prospectively examine the treatment response of people with RBD treated with clonazepam, by quantitatively delineating the characteristic changes in the clinical and polysomnographic features, and to explore the factors associated with this response.MethodsPatients diagnosed with idiopathic RBD (iRBD) were consecutively recruited and invited to complete clinical and polysomnographic (PSG) assessments and self-administered questionnaires (including the modified REM Sleep Behavior Questionnaire, RBDQ-3M) before and after the initiation of treatment with clonazepam.ResultsThirty-nine iRBD patients (male: 74.4%, mean age at diagnosis: 68.3 ± 7.8 years) were recruited with a follow-up duration of 28.8 ± 13.3 months. Clonazepam was offered as the first-line treatment (starting dose: 0.43 ± 0.16 mg, range: 0.125–1.00; dose at follow-up: 0.98 ± 0.63 mg, range: 0.125–3). Treatment response, as defined by a complete elimination of sleep-related injuries and potentially injurious behaviors to self and/or to bed partner, at follow-up was reported in 66.7% of the overall study subjects. Frequency of disturbing dreams with violent and frightening content and vigorous behavioral RBD symptoms was significantly reduced, while residual nocturnal symptoms and an increase in REM-related EMG activities were observed at follow-up. Less optimal treatment outcomes were found to be associated with the presence of comorbid obstructive sleep apnea and earlier onset of RBD.ConclusionsClonazepam differentially changes dream affect and content, as well as reduces vigorous verbal and motor behaviors. Residual RBD symptoms are common, despite treatment. Other more effective alternative or adjunctive interventions are needed for better clinical management of RBD.     

Duloxetine-related tardive dystonia and tardive dyskinesia: a case report

Tardive dyskinesia and tardive dystonia are caused by dopamine receptor blocking agents, mostly antipsychotics and sometimes antidepressants or calcium channel blockers. Duloxetine-related tardive syndrome is rarely reported in the literature. We report one case of tardive dystonia and tardive dyskinesia occurring in a 58-year-old female with major depressive disorder, who developed distressing oral dyskinesia, mandibular dystonia with trismus and dystonia over left neck after treatment of duloxetine (30–60 mg per day) for 18 months. Despite discontinuation of duloxetine, she only obtained partial remission. Even though this association has been rarely reported, duloxetine may pose a potential risk of inducing tardive syndrome. Clinicians should cautiously detect early signs of movement abnormality when prescribing antidepressants.     

Risk factors for tardive dystonia: a case-control comparison with tardive dyskinesia

The objective of this study was to determine the putative risk factors for the development of tardive dystonia (TDt) in contrast with tardive dyskinesia (TD). Fifteen TDt patients seen in the Movement Disorders Clinic were compared with 2 groups of 15 TD controls each. The first control group was drawn from the Clinic and matched with the TDt cases for severity, using degree of dysfunction as the matching variable. The second control group comprised mild TD cases drawn from a separate study of drug-induced movement disorders in chronic schizophrenia and were matched for age and sex with the TDt cases. A number of demographic, treatment-related, diagnosis-related and historical variables suggested in the literature were examined. Most risk factors for TDt that have been suggested by previous studies were not supported. The first control group was significantly older than the TDt cases. The TDt patients had a more frequent past history of acute drug-induced dystonia and of postural tremor prior to the onset of the mental illness, although only the former reached statistical significance. The results suggested that TDt and TD do not differ in most putative risk factors, although the small sample size increases the likelihood of a type II error. It is inconclusive on the role of young age and male sex as risk factors. TDt cases may, however, be individuals vulnerable to the development of dystonia, with neuroleptics probably bringing out such a vulnerability. This finding needs to be examined in larger studies.     

Sustained improvement in tardive dyskinesia with diazepam: Indirect evidence for corticolimbic involvement

A rater-bind, ABA's design study of 21 cases indicates that diazepam significantly improves tardive dyskinesia and that some of the improvement persists for an extended period after diazepam is withdrawn. Since benzodiazepine receptors and sites of action seem to be mainly in the neocortex (especially frontal), limbic cortex, and deep limbs nuclei, and these structures provide most of the input into the nigrostriatopallidal system that probably regulates its role in voluntary movement, it may be suggested that impaired corticolimbic control of basal ganglia may be a factor in the pathogenesis of tardive dyskinesia.