Respiratory irregularity and tardive dyskinesia. A prevalence study

In a survey of 351 chronically hospitalized adult psychiatric patients, clinical evidence of irregular respiration compatible with respiratory tardive dyskinesia was present in eight subjects (2.3%). In four, audible involuntary respiratory noises were present. All patients with respiratory irregularities had a facio-bucco-lingual dyskinesia and in four the dyskinesia also involved extremities and/or other regions of the body. The prevalence of respiratory irregularities amongst patients with tardive dyskinesia was eight out of 108 (7.4%); none of the patients without tardive dyskinesia had respiratory irregularities. The prevalence of respiratory irregularities was significantly greater in patients with an organic mental disorder (11.1%) compared with those without (1.3%) (P less than 0.005). None of the patients complained of their respiratory symptoms and none had been diagnosed as having a respiratory dyskinesia prior to the survey. In two patients the symptoms were severe, leading in one case to prominent gasping, dysphagia, severe choking when eating, and episodes of aspiration pneumonia. In a second patient the noisy respiration was interpreted as attention-seeking and intimidating behaviour which led to rejection by the staff. In the remaining six patients respiratory symptoms were relatively minor.     

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.     

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.     

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.     

The association of tardive dyskinesia and pseudoparkinsonism

1. 1. A survey of 315 chronic inpatients for the presence of extrapyramidal side effects indicates that 58.7% of the patients had no evidence of extrapyramidal side effects, 28.6% had tardive dyskinesia (TD) alone, 8.9% had pseudoparkinsonism and 3.8% had a combination of both.

2. 2. Women seemed to exhibit more side effects.

3. 3. Aging was another factor associated with a higher risk for the appearance of extrapyramidal side effects.

4. 4. Affective disorder patients carried more risk than patients with schizophrenia.

5. 5. The low prevalence of the combined TD and pseudoparkinsonism may be related to several factors. The possible explanations are explored and discussed. These patients present a therapeutic dilemna.

Disappearance of tardive dyskinesia during catatonic stupor

A 61-year-old man diagnosed as having catatonic schizophrenia was treated with neuroleptics for many years. From 1983 he showed tardive dyskinesia on trunk and limbs as well as orofacial dyskinesia. In September 1985 he displayed a catatonic stupor several times. With the outbreak of the stupor the dyskinesia disappeared and vice varsa. This finding induces the hypothesis that the dopaminergic system is suppressed during catatonic stupor in such a way that tardive dyskinesia is no longer visible.     

糖尿病对迟发性运动障碍的影响

目的：比较迟发性运动障碍（TD）在有糖尿病与无糖尿病的精神障碍患者中的发生率。方法：对1 016例精神障碍患者进行时点调查,分为糖尿病组与非糖尿病组,采用异常不自主运动量表（AIMS）评定患者有无TD及严重程度。结果：TD的总发生率为10.93%。糖尿病组中TD的发生率为18.50%,非糖尿病组中TD的发生率为9.40%,两组比较差异有显著性（χ^2=11.72,P〈0.01）。糖尿病组中TD患者的AIMS平均为（7.97±1.35）分,非糖尿病组中AIMS平均（6.60±2.38）分,两组比较差异有显著性（t=3.79,P〈0.01）。结论：糖尿病可能是TD发生的1个重要易感因素。     

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.     

Levetiracetam in tardive dyskinesia: an open label study.

Levetiracetam (LEV), a novel antiepileptic drug, has demonstrated antidyskinetic effect in preclinical animal models of Parkinson's disease (PD) and in one open label study in PD patients with levodopa-induced dyskinesia. The acute antidyskinetic effects of LEV in patients with tardive dyskinesia were evaluated in an open label study. Eight patients received oral LEV (1,000 mg/day) for 1 month and blinded evaluations were performed at baseline and at the end of the treatment period. A significant reduction of the abnormal movements was recorded while psychiatric symptoms did not worsen and the adverse event profile was benign. LEV may be efficacious for the treatment of tardive dyskinesia and deserves further clinical testing.     

A statistical trial of subclassification for tardive dyskinesia

The authors applied a statistical method to subclassify tardive dyskinesia (TD) in 71 psychiatric patients. Based on two-step statistical procedures and findings reported previously, TD is considered to consist of 2 subgroups: a classical dyskinesic group and a dystonic group. Symptoms manifested in the former group are seen most frequently in the oral region while the latter group, which is usually called tardive dystonia, is manifested by movement disorders in the trunk and extremities, predominantly. Abnormal movements occurring in the facial region characterize a population whose members may belong to either group.     

Botulinum toxin as a treatment for tardive dyskinesia.

Two older female patients with a history of psychotic depression were treated with a combination of an antipsychotic and an antidepressant. Both developed persistent tardive dyskinesia with severe tongue protrusion. Botulinum toxin was injected into the genioglossal area and the embarrassing tongue protrusion practically disappeared. Both patients chose to continue taking botulinum toxin.     

Prevalence of tardive dyskinesia in samples of elderly people in Hong Kong

The prevalence of dyskinesia was studied in 4 samples of elderly Chinese people in Hong Kong – a psychogeriatric clinic, a mental hospital, a geriatric day hospital and a senior citizen centre. Research Diagnostic Criteria were used to identify cases of tardive dyskinesia. The overall prevalence of spontaneous dyskinesia was 2.4% and tardive dyskinesia was 25.9%. The rate of spontaneous dyskinesia differs across the study samples and is related to nervous system conditions associated with increased age. On the other hand, the rate of dyskinesia associated with antidepressants may not be significantly different from that of spontaneous dyskinesia.     

Thiethylperazine and tardive dyskinesia

Over a 14-month period in the outpatient department of a geriatric hospital, 7 female patients over 75 years of age were identified with tardive dyskinesia associated with the use of thiethylperazine. The indication for thiethylperazine treatment had been vertigo or dizziness. 3 of the patients also had symptoms related to cerebral arteriosclerosis and 2 had mild Parkinson's disease without levodopa therapy. None of them were markedly demented nor had chronic psychosis. Tardive dyskinesia appeared after a treatment period of 3 weeks to 6 years. These findings suggest that association of tardive dyskinesia with the use of thiethylperazine is not uncommon in geriatric outpatients.     

The catechol-O-methyl-transferase gene in tardive dyskinesia

Abstract

Tardive dyskinesia (TD) is a severe and potentially irreversible motor side effect linked to long-term antipsychotic exposure. Changes in dopamine neurotransmission have been implicated in the etiology of TD, and catechol-O-methyl-transferase (COMT) is an enzyme that metabolizes dopamine. Objectives. We investigated five single-nucleotide polymorphisms in addition to the functional Val158Met variant spanning the COMT gene for association with TD. Methods. We analyzed the six COMT single-nucleotide polymorphisms in a sample of schizophrenia/schizoaffective disorder patients (n=226; 196 Caucasians and 30 African Americans). Results. We found a significant association between the marker rs165599 in the 3′ untranslated region of COMT and TD (AA versus G-carrier: OR_AA=2.22, 95% CI:1.23–4.03; P=0.007). The association appeared to be originating from males. We did not find a significant association of the other five tested polymorphisms with TD in our samples. We performed a sex-stratified meta-analysis across all of the published studies (n=6 plus our own data) of COMT and TD, and found an association between ValVal genotype and TD in females (OR_ValVal=1.63, 95% CI: 1.09–2.45; P=0.019) but not in males. Conclusions. Overall, our results suggest that the COMT gene may have a minor but consistent role in TD, although sex-stratified studies with additional markers in larger clinical samples should be performed.     

Experimental tardive dyskinesia

In this work, we have attempted to reproduce dyskinesia similar to tardive dyskinesia by two methods. In the first experiment, we have administered to 6 macacca mulatta, haloperidol 0.25 mg/kg daily for six months. During that period we observed in all monkeys, after each dose: restelessness, akinesia and tremor. One monkey developed choreoathetoid movements, which were seen each day after the first month. They disappeared however upon cessation of the drug administration. Only one animal developed a bucco lingual dyskinesia after two months which was still present when they were sacrificed six month after the drug administration was discontinued. At that time, harmaline 3 mg/kg induced a postural tremor in all monkeys suggesting a lesion of the rubro-olivo-cerebello rubral loop. Histological analysis of the brains revealed no gross abnormality. In a second experiment, a left mid-brain electrolytic lesion was performed in twelve monkeys. One monkey, developed a contralateral tremor but five including the trembling one developed a buccolingual dyskinesia which has now lasted more than a year. This dyskinesia is present at rest but increased by dopaminergic agents and blocked by haloperidol. Histological analysis of the brain of one of the monkeys revealed a dorsal lesion involving the region of the nucleus parafascicularis thalami. The substantia nigra was spared.     

Effect of gamma-vinyl GABA in tardive dyskinesia

gamma-Vinyl GABA (gamma-aminobutyric acid), a drug that increases brain GABA via GABA transaminase inhibition, was evaluated in a blind, placebo-controlled trial in 10 patients with stable tardive dyskinesia. Drug effects during active treatment (2 to 6 g/day) and during pre- and posttreatment placebo periods were determined by scoring randomly sequenced videotapes of tardive dyskinesia and parkinsonian symptoms recorded weekly during standardized examinations. Tardive dyskinesia was significantly reduced, and correlated to increased parkinsonism. Eye blinking rates decreased, but psychiatric symptoms were unchanged during treatment.     

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.     

迟发性运动障碍与血清尿酸的关系

目的：观察伴迟发性运动障碍（TD）的精神分裂症患者血清尿酸变化,探索尿酸与TD的关系。方法：采用尿酸酶法测定23例TD患者、相匹配的23例非TD患者及24例正常对照的血清尿酸水平,使用异常不自主运动量表（AIMS）评定TD的严重程度。结果：TD组血清尿酸水平显著低于非TD组及对照组（P均〈0．01）,而非TD组与对照组之间血清尿酸水平无差异。TD组中AIMS评分与血清尿酸水平呈负相关（r=-0．435,P〈0．05）。结论：TD患者存在低血清尿酸水平并与TD的严重程度有关,尿酸可能参与了TD的病理生理过程。     

Calcium metabolism and abnormal involuntary movements (tardive dyskinesia) in psychosis

Serum calcium levels were measured in 25 chronically ill psychotic inpatients with involuntary movements, in comparison with 25 otherwise indistinguishable patients without such a syndrome. Those with involuntary movements were significantly more likely to have a serum calcium level below the normal range. These results are discussed in terms of the role of calcium in neuronal dysfunction, and in broader aspects of the general biological disadvantage that appears to characterize older patients with this movement disorder.     

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.