Abnormal Involuntary Movement Scale Scores Research Articles

Withdrawing amantadine in dyskinetic patients with Parkinson disease

The AMANDYSK trial was designed to assess long-term efficacy of chronic treatment with amantadine in patients with Parkinson disease (PD) and levodopa-induced dyskinesia (LID). This was a 3-month, multicenter, randomized, double-blind, placebo-controlled, parallel-group, wash-out study conducted in 57 amantadine-treated (≥200 mg/d for ≥6 months) dyskinetic patients with PD. The primary outcome measure was the change from baseline in a Unified Parkinson's Disease Rating Scale (UPDRS) dyskinesia subscore (items 32 [duration] + 33 [severity]). Secondary outcomes included other LID measurements ("responders" analysis, premature dropout for LID, Abnormal Involuntary Movement Scale). Exploratory outcomes included time with troublesome dyskinesia as measured by diaries, UPDRS Motor Examination (part III) for motor symptoms of PD, and fatigue and apathy scores for nonmotor symptoms. UPDRS items 32 + 33 deteriorated more in patients switched to placebo ("discontinuing" group) (+1.7 ± 2.0 units; 95% confidence interval 0.9, 2.4) as compared with those maintained on amantadine ("continuing" group) (+0.2 ± 1.5 units; 95% confidence interval -0.4, 0.8; p = 0.003). Secondary outcomes confirmed this difference because there were significantly more responders, more dropouts for LID, greater increase in "ON" time with troublesome dyskinesia, and greater worsening of Abnormal Involuntary Movement Scale score in the discontinuing group. There were no between-group differences in the UPDRS Motor Examination, whereas apathy (as measured by caregivers) and fatigue scores tended to worsen more in patients randomized to placebo. Wash-out of amantadine in dyskinetic patients with PD significantly worsened LID. No significant effect was observed on motor parkinsonian symptoms, while exploratory outcomes suggested that amantadine might improve apathy and fatigue in such patients. This article provides Class II evidence that in patients with PD, withdrawing amantadine significantly aggravates LID in a median time of 7 days.

Bilateral pallidal stimulation for Wilson's disease

To report on the clinical efficacy of bilateral globus pallidus internus deep brain stimulation in a 29-year-old patient with severe generalized dystonia secondary to Wilson's disease. The primary outcome measure was the Burke-Fahn-Marsden Dystonia Scale motor severity score (blinded assessment) and the secondary outcome measures were the Abnormal Involuntary Movement Scale (blinded assessment) and the Zaritt Caregiver Burden Interview score, at 20-week postoperative follow up. There was a 14% improvement in the Burke-Fahn-Marsden Dystonia Scale motor severity score. Abnormal Involuntary Movement Scale score remained unchanged while the Zaritt Caregiver Burden Interview score improved by 44.4%. Bilateral globus pallidus deep brain stimulation can be effective in ameliorating dystonia and caregiver burden in Wilson's disease. Outcomes may depend on the stage of the disease at which the surgical procedure is completed. © 2013 Movement Disorder Society.

Orobuccolingual Dyskinesia After Long-Term Use of Black Cohosh and Ginseng

Back to table of contents Previous article Next article LettersFull AccessOrobuccolingual Dyskinesia After Long-Term Use of Black Cohosh and GinsengA. Sen, M.D.A. SenSearch for more papers by this author, M.D.Published Online:1 Oct 2013https://doi.org/10.1176/appi.neuropsych.12120395AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Black cohosh (BC), also known as Cimicifuga racemosa, is a frequently used herbal remedy for alleviating menopausal symptoms.1 Ginseng has been widely used as herbal medicine in eastern Asia.2 We report a on a patient who developed orobuccolingual dyskinesia (OBLD) while being treated with an herbal supplement containing BC and ginseng.Case ReportA 46-year-old woman was admitted to our hospital with a 3-month history of OBLD that interfered with her speech, tongue-biting, and eating difficulties. Her neurological examination was otherwise normal except for OBLD (Abnormal Involuntary Movement Scale Score [AIMSS]: 8). Her personal and family history were not relevant for neuropsychiatric disorders. The patient denied any exposure to dopamine-blocking drugs or other medications. She reported the use of a 2-tablet/day dose of a plant-based preparation containing 20 mg BC and 50 mg Panax ginseng to treat her menopausal symptoms for at least 15 months. The general physical examination, routine blood examinations, and comprehensive tests for movement disorders (also including genetic tests) were all normal. Her cranial computerized tomography, contrast-enhanced cranial magnetic resonance imaging, and cranial fluorodeoxyglucose positron emission tomography were also normal. The preparation was stopped. She improved substantially with a combination of baclofen 40 mg/day and clonazepame 2 mg/day (AIMSS: 2).CommentTo our knowledge, this is the first reported case of OBLD observed after the combined use of BC and ginseng. The action mechanisms, pharmacokinetics, and metabolites of BC have not been totally identified. Recent data have demonstrated that BC may have an effect on dopaminergic, serotoninergic, and GABAergic systems.1 It has been suggested that unknown dopaminergic compounds may contribute to the pharmacological activity of BC.3 More than 30 different ginsenosides, the main components responsible for the actions of ginseng, have been isolated and identified from ginseng.2 In spite of some in-vivo studies indicating that some ginsenosides can be neuroprotective to striatal neurons,4 the results from a recently-published in-vitro study were mixed. This study has shown that low doses of some ginsenosides exhibited striatal neuroprotective effects, whereas overdoses have caused striatal toxic effects.2 Wu et al.2 reported that there could only be a fine line between the neuroprotective and toxic effects of ginsenosides. The use of ginseng can cause complications when used in combination with other medications. Adverse effects, including nervousness and insomnia,2 have been reported from long-term use and high doses of ginseng; BC has been linked to liver, cardiovascular, CNS, and peripheral nervous system adverse events. It was reported that mono-preparation of BC is safe in the short term for otherwise-healthy menopausal women, and Huntley3 recommended limiting its use to 6 months.Estrogens have well-known neuroprotective activity. Postmenopausal estrogen deficiency leaves the dopaminergic system vulnerable to neurotoxicity.5We suggest that BC together with ginseng could be responsible for the OBLD. Previous use of BC together with ginseng should be investigated carefully in patients with OBLD. Further studies on basic pharmacological mechanisms of actions and toxicity of BC and ginsenosides are needed.Bakirkoy Research and Training Hospital for Psychiatry, Neurology, and Neurosurgery, Istanbul, TurkeyCorrespondence: e-mail: [email protected]comFinancial Disclosure Statement: The author has not received any financial support for this clinical/scientific note.References1 Cicek SS, Khom S, Taferner B, et al.: Bioactivity-guided isolation of GABA(A) receptor-modulating constituents from the rhizomes of Actaea racemosa. J Nat Prod 2010; 73:2024–2028Crossref, Medline, Google Scholar2 Wu J, Jeong HK, Bulin SE, et al.: Ginsenosides protect striatal neurons in a cellular model of Huntington’s disease. J Neurosci Res 2009; 87:1904–1912Crossref, Medline, Google Scholar3 Huntley A: The safety of black cohosh (Actaea racemosa, Cimicifuga racemosa). Expert Opin Drug Saf 2004; 3:615–623Crossref, Medline, Google Scholar4 Lian XY, Zhang Z, Stringer JL: Protective effects of ginseng components in a rodent model of neurodegeneration. Ann Neurol 2005; 57:642–648Crossref, Medline, Google Scholar5 Vegeto E, Benedusi V, Maggi A: Estrogen anti-inflammatory activity in brain: a therapeutic opportunity for menopause and neurodegenerative diseases. Front Neuroendocrinol 2008; 29:507–519Crossref, Medline, Google Scholar FiguresReferencesCited byDetailsCited ByEthnobotany, Phytochemistry, Traditional and Modern Uses of Actaea racemosa L. (Black cohosh): A Review17 April 2021Journal of Ethnopharmacology, Vol. 209Reactions Weekly, Vol. 1510, No. 1 Volume 25Issue 4 Fall 2013Pages E50-E50 Metrics PDF download History Published online 1 October 2013 Published in print 1 October 2013

D-serine adjuvant treatment alleviates behavioural and motor symptoms in Parkinson's disease

Parkinson's disease (PD) manifestations include motor symptoms and behavioural deficits that resemble schizophrenia negative symptoms. The N-methyl-D-aspartate subtype of glutamate receptor (NMDAR) represents a novel pharmacological target in PD. D-serine (DSR) allosterically modulates in-vivo NMDAR-mediated neurotransmission and has been shown to improve negative and antipsychotic drug-induced parkinsonian symptoms in schizophrenia patients. This pilot study assessed DSR effects in ten PD patients who completed a 6-wk double-blind, placebo-controlled, crossover adjuvant treatment trial with 30 mg/kg.d DSR. Primary outcome analyses consisted of separate repeated-measures multivariate analyses of variance for Unified Parkinson's Disease Rating Scale (UPDRS), Simpson-Angus Scale for Extrapyramidal Symptoms (SAS), Abnormal Involuntary Movement Scale (AIMS), and Positive and Negative Syndrome Scale (PANSS) scores. DSR treatment was well tolerated and resulted in increased DSR serum levels (p=0.001) and significantly reduced UPDRS (p=0.02), SAS (p=0.009) and PANSS (0.05) total scores. These preliminary findings suggest that DSR treatment may be beneficial in PD. Larger-sized studies with optimized DSR dosages are warranted.

Association Study between Tryptophan Hydroxylase 2 Gene -703G/T Polymorphism and Tardive Dyskinesia

Objectives : Tardive dyskinesia (TD) is a serious and sometimes irreversible adverse effect that may develop during long-term antipsychotics treatment. Previous studies have suggested that brain serotonergic systems are related to TD vulnerability and tryptophan hydroxylase (TPH) is the rate limiting enzyme in the biosynthesis of serotonin. This study aimed to investigate the association between TPH2 gene -703G/T polymorphism (rs4570625) and antipsychotic-induced TD in the Korean schizophre- nia patients. Methods : We investigated whether TPH2 gene -703G/T polymorphism is associated with antipsychotic-induced TD in 280 Ko- rean schizophrenia patients. The subjects with TD (n=105) and without TD (n=175) were matched for antipsychotic drug expo- sure and other relevant variables. Results : There was no significant difference in the distribution of genotypic (χ 2 =3.00, p=0.223) and allelic (χ 2 =0.19, p=0.661) frequencies between patients group with TD and without TD. There was no significant difference in total Abnormal Involuntary Movement Scale score (F=1.95, p=0.362) among the genotype groups, either. Conclusions : The present study does not support that TPH2 gene -703G/T polymorphism is involved in TD of the Korean schizophrenia subjects. (Korean J Schizophr Res 2012;15:34-38)

Postthalamic Stroke Dystonic Choreoathetosis Responsive to Tetrabenazine

To describe the case of a woman with poststroke choreoathetosis whose symptoms improved after treatment with tetrabenazine. A 48-year-old left-handed woman developed progressive involuntary dystonic choreoathetoid movements of her arm following a cerebrovascular event. Involuntary abnormal movements (IAMs) were treated with haloperidol, but they worsened 6 months later, also involving her mouth, tongue, and perioral area. Because of the suspected occurrence of drug-induced tardive dyskinesia, treatment was switched to tetrabenazine (titration up to 100 mg/daily), with rapid remission of the involuntary abnormal movements (Abnormal Involuntary Movement Scale score switching from 20 to 1). One month later, following discontinuation of tetrabenazine, the dystonic choreoathetoid movements rapidly reappeared. Subsequent rechallenge with tetrabenazine caused remission of her symptoms. Poststroke IAMs are rare, and lesions involving the basal ganglia and/or thalamus seem to be particularly implicated in such disorders. The exact pathogenic mechanism has not been clarified; however, it has been postulated that a central dopaminergic overactivity might play an important role in the IAM occurrence. Thus, antipsychotics are the main treatment option, but they are often associated with therapeutic failure or adverse effects, including extrapyramidal symptoms and metabolic complications. Interestingly, when our patient was treated with tetrabenazine for haloperidol-induced tardive dyskinesia, she demonstrated substantial improvement in the dystonic choreoathetoid movements of her left upper limb. The improved response of this case to tetrabenazine monotherapy suggests that tetrabenazine may be a pharmacologic alternative for patients with poststroke choreoathetosis that is intolerant or unresponsive to antipsychotic agents. Further studies are needed to better define the risk versus benefit profile of tetrabenazine.

Prefrontal alterations in Parkinson's disease with levodopa‐induced dyskinesia during fMRI motor task

Levodopa-induced dyskinesia represents disabling complication of long-term therapy with dopaminergic drugs in treating Parkinson's disease (PD). Recently, our group demonstrated that PD patients with levodopa-induced dyskinesia were characterized by abnormal volumetric changes in the inferior prefrontal gyrus. In this study, the functional relevance of this structural abnormality was explored using functional magnetic resonance imaging. Ten dyskinetic PD patients and 10 nondyskinetic PD patients were studied in the OFF phase with functional magnetic resonance imaging while performing externally and internally triggered visuomotor tasks. Although neither group demonstrated behavioral differences during execution of motor tasks, magnetic resonance imaging analysis detected significant changes in target cortical regions. In particular, PD patients with levodopa-induced dyskinesia showed significant overactivity in the supplementary motor area and underactivity in the right inferior prefrontal gyrus during execution of both tasks when compared with PD patients without levodopa-induced dyskinesia. Moreover, these prefrontal functional alterations were significantly correlated with Abnormal Involuntary Movement Scale scores. This functional magnetic resonance imaging study together with our previous volumetric findings highlights the role of the prefrontal cortex in the neuronal mechanisms of dyskinesia.

Rapid Response of Disabling Tardive Dyskinesia to Amantadine

To the Editor: About 20% of patients treated with standard neuroleptic drugs are affected with tardive dyskinesia (TD), and approximately 5% are expected to develop TD with each year of neuroleptic treatment.1 The majority of patients with TD have a mild disorder, but about 5%–10% suffer impairment from the dyskinesia.2 The evidence in relation to the atypical antipsychotics suggests that these drugs present a significantly lower risk for TD in comparison to first-generation antipsychotics.3 Reports suggest that the risk of TD is lowest with clozapine, followed by quetiapine.4 The severity of TD and the absolute need for neuroleptic therapy often dictate the treatment approach. Although there is no currently effective treatment for TD, amantadine has been reported to be beneficial, possibly because of its glutamatergic effects.4,5 Herein, I report a patient with disabling TD due to quetiapine that responded rapidly to amantadine. To my knowledge, this report is the first description of rapid improvement of quetiapine-induced TD by amantadine. Case report. Ms A, a 57-year-old retired librarian, was hospitalized in the fall of 2009 with long-standing history of treatment-resistant DSM-IV-TR–defined major depressive disorder, recurrent, severe episode without psychotic features. For 6 weeks, she was treated with fluoxetine (60 mg/d), duloxetine (120 mg/d), quetiapine (400 mg/d), and clonazepam (2 mg/d) and underwent bilateral electroconvulsive treatment (ECT) once per week. At this hospitalization, her 17-item Hamilton Depression Rating Scale (HDRS)6 score was 40 and her Abnormal Involuntary Movement Scale (AIMS) score was 10.7 Her blood workup for the causes of refractory depression revealed no abnormalities. Ms A denied consent for ECT. She was switched from fluoxetine to paroxetine treatment (increased to 40 mg/d), and clonazepam was increased to 3 mg/d. Quetiapine was continued as an augmenting agent and was increased to 600 mg/d. She had no change in depressive symptoms and was noted to be more anxious and agitated during the following 4 weeks (HDRS score = 38 and AIMS score = 16). Therefore, paroxetine treatment was switched to mirtazapine treatment (increased to 45 mg/d) and duloxetine treatment was switched to venlafaxine extended release treatment (increased to 300 mg/d). The patient continued to worsen over the next 3 weeks. Gradually, varieties of repeated stereotypic abnormal movement became evident. She was noted to have dyskinetic blinking, frowning, lip smacking, puckering, chewing, jaw clenching, mouth opening, and facial grimacing movements. She also had stereotypic and involuntary movements of hands and toes. These movements would aggravate when she became more anxious and would disappear while she was sleeping. She was unable to interact because her speech was broken, repetitive, and nonfluent. Ms A became incapacitated to the extent that she was not able to communicate with others and take care of her daily routine activities. Her HDRS score was 38 and AIMS score increased to 41. At that time, findings of electroencephalogram and magnetic resonance imaging of the head with and without contrast were within normal limits. Clonazepam was increased to 5 mg/d, and vitamin E 1,600 units was added. The neurology department was consulted the following week when no change in her condition was noted. They stopped vitamin E and administered amantadine 400 mg/d in 4 divided doses. Within 3 days she started to improve, and her AIMS score reduced to 18 in 5 days. Clonazepam was decreased to 1 mg 2 times daily. Then, a gradual taper of quetiapine was started at the rate of 100 mg/wk. She agreed to ECT treatments and was discharged after 2 weeks, at which time her HDRS and AIMS scores were 15 and 14, respectively. During the office follow-up, quetiapine was completely stopped in the next 4 weeks. Amantadine was then tapered gradually to 100 mg/d without any worsening of TD. She has been stable for the last year, and her AIMS score at 1-year follow-up was 12. Tardive dyskinesia is the most serious consequence of long-term neuroleptic administration, and all known approaches to its treatment are relatively unsuccessful.5 Amantadine is a commonly used drug in neurology, but psychiatrists are generally less experienced with its use. There has been very little research on the use of amantadine in TD, and the patient population studied was on treatment with typical antipsychotics only.8–14 An 18-week, double-blind, crossover study by Angus et al14 demonstrated that amantadine is significantly better than placebo in the management of TD and that there is little risk of exacerbating psychosis. Using amantadine to treat TD has produced a rapid improvement in dyskinesia without emergence of psychosis even with prolonged administration. More studies are needed to prove the utility of amantadine in atypical antipsychotic–induced TD. Meanwhile, a trial of amantadine for a short period (1–2 weeks) in a patient with debilitating TD may be useful.

Extract ofGinkgo bilobaTreatment for Tardive Dyskinesia in Schizophrenia

Free radicals may be involved in the pathogenesis of tardive dyskinesia (TD). Extract of Ginkgo biloba (EGb) is a potent antioxidant possessing free radical-scavenging activities. The aim of the study was to evaluate the efficacy of EGb-761, a standardized extract given in capsule form, in treating TD in schizophrenia patients. Inpatients with DSM-IV-diagnosed schizophrenia and TD (n = 157) in a mainland China Veterans Affairs psychiatric hospital were randomly assigned to 12 weeks of treatment with either EGb-761, 240 mg/d (n = 78) or a placebo (n = 79) in a double-blind manner. Primary outcome measures were (1) change from baseline in the Abnormal Involuntary Movement Scale (AIMS) score and (2) proportion of patients with a ≥ 30% reduction in their AIMS total score at week 12. Secondary outcome measures included the Positive and Negative Syndrome Scale (PANSS) and cognitive performance as measured by the Continuous Performance Test-37 Version and the 3-card Stroop task. Patients were recruited for the study between December 2006 and May 2007. Of the 157 patients who were randomly assigned, 152 (96.8%) completed the study. EGb-761 treatment significantly decreased the AIMS total score in patients with TD compared to those who were given a placebo (2.13 ± 1.75 vs -0.10 ± 1.69; P < .0001), with 40 (51.3%) and 4 (5.1%) patients achieving response in the EGb-761 and placebo treatment groups, respectively. There were no between-group differences in the PANSS total score or cognitive measures from baseline to week 12. EGb-761 appears to be an effective treatment for reducing the symptoms of TD in schizophrenia patients, and improvement may be mediated through the well-known antioxidant activity of this extract. clinicaltrials.gov identifier: NCT00672373.

Treatment Outcomes of Patients With Tardive Dyskinesia and Chronic Schizophrenia

We compared the response to antipsychotic treatment between patients with and without tardive dyskinesia (TD) and examined the course of TD. This analysis compared 200 patients with DSM-IV-defined schizophrenia and TD and 997 patients without TD, all of whom were randomly assigned to receive one of 4 second-generation antipsychotics. The primary clinical outcome measure was time to all-cause treatment discontinuation, and the primary measure for evaluating the course of TD was change from baseline in Abnormal Involuntary Movement Scale (AIMS) score. Kaplan-Meier survival analysis and Cox proportional hazards regression models were used to compare treatment discontinuation between groups. Changes in Positive and Negative Syndrome Scale (PANSS) and neurocognitive scores were compared using mixed models and analysis of variance. Treatment differences between drugs in AIMS scores and all-cause discontinuation were examined for those with TD at baseline. Percentages of patients meeting criteria for TD postbaseline or showing changes in AIMS scores were evaluated with χ(2) tests. Data were collected from January 2001 to December 2004. Time to treatment discontinuation for any cause was not significantly different between the TD and non-TD groups (χ(2)(1) = 0.11, P = .743). Changes in PANSS scores were not significantly different (F(1,974) = 0.82, P = .366), but patients with TD showed less improvement in neurocognitive scores (F(1,359) = 6.53, P = .011). Among patients with TD, there were no significant differences between drugs in the decline in AIMS scores (F(3,151) = 0.32, P = .811); 55% met criteria for TD at 2 consecutive visits postbaseline, 76% met criteria for TD at some or all postbaseline visits, 24% did not meet criteria for TD at any subsequent visit, 32% showed a ≥ 50% decrease in AIMS score, and 7% showed a ≥ 50% increase in AIMS score. Schizophrenia patients with and without TD were similar in time to discontinuation of treatment for any cause and improvement in psychopathology, but differed in neurocognitive response. There were no significant differences between treatments in the course of TD, with most patients showing either persistence of or fluctuation in observable symptoms. clinicaltrials.gov Identifier: NCT00014001.

Amisulpride May Worsen Dyskinesia and Trigger New-Onset Dyskinetic Movements

Back to table of contents Previous article Next article LETTERFull AccessAmisulpride May Worsen Dyskinesia and Trigger New-Onset Dyskinetic MovementsDattatreya Namdeorao Mendhekar D.P.M., M.D.,Chittaranjan Andrade D.P.M., M.D.,Dattatreya Namdeorao Mendhekar D.P.M., M.D.Search for more papers by this author,Chittaranjan Andrade D.P.M., M.D.Search for more papers by this author,Published Online:1 Jul 2010https://doi.org/10.1176/jnp.2010.22.3.352.e24AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: There is surprisingly little literature on tardive dyskinesia with amisulpride. A PubMed search conducted on March 19, 2009, identified only three relevant case reports. 1 – 3 We report a patient whose existing tardive dyskinesia worsened and who developed new dyskinetic movements after treatment with amisulpride. We discuss distinct mechanisms whereby amisulpride may be associated with tardive dyskinesia. Case ReportMrs. A, a 72-year-old woman with DSM-IV schizophrenia, presented with a 3-year history of dyskinetic movements of the right forearm, wrist, and fingers. She had received trifluperazine, haloperidol, risperidone, and other antipsychotics in the past and had been receiving chlorpromazine, 300 mg/day, during the 3 years prior to the index presentation. Her Abnormal Involuntary Movement Scale (AIMS) score was 5. Her medical comorbidity included diabetes mellitus and hypertension, both of which were well controlled. There was no past or current history of substance use or neurological disorder, nor any family history of movement disorders. In order to address the dyskinesia, the dose of chlorpromazine was reduced to 100 mg/day. Two months later, whereas the tardive dyskinesia persisted and remained unchanged, positive symptoms of psychosis emerged.Amisulpride (350 mg/day) was added to the 100 mg/day of chlorpromazine. This resulted in moderate improvement in psychiatric symptomatology but, after about 10–12 weeks of combined therapy, the existing dyskinesia was noted to have worsened, and new choreoathetoid movements appeared in the buccal, jaw, and tongue areas, and in the left forearm, wrist, and fingers. Akathisia was also present. Her AIMS score was 14. Chlorpromazine was withdrawn. She was maintained with amisulpride, 350 mg/day, alone; however, 6 weeks later, there was no improvement in the dyskinetic movements. She was later lost to follow-up.Discussion Risk factors for tardive dyskinesia in our patient were old age, female gender, diabetes mellitus, and exposure to neuroleptic and other antipsychotic drugs. 4 Tardive dyskinesia in our patient had appeared during treatment with chlorpromazine and had persisted unchanged until amisulpride was introduced. The introduction of amisulpride was associated with worsening of the original tardive dyskinesia and development of new-onset tardive dyskinesia. Lowering of the chlorpromazine dose could have unmasked tardive dyskinesia in the oral regions and in the left hand, or the addition of amisulpride could have triggered the new-onset tardive dyskinesia. We favor the latter explanation because unmasking of tardive dyskinesia should have occurred shortly after the decrease in chlorpromazine dose; however, the new-onset tardive dyskinesia actually appeared after 3 months of combined therapy, implying a gradual-onset consequence of the amisulpride-chlorpromazine combination. All previous cases reported the development of tardive dyskinesia 8–24 months after the patients were started on amisulpride. Why was amisulpride associated with new-onset tardive dyskinesia? The dose of 350 mg/day appeared to be optimal to treat psychosis in this geriatric patient, 5 presumably by blocking dopamine postsynaptic receptors in the mesolimbic pathway; however, it is conceivable that it may not have been sufficiently high to block dopamine postsynaptic receptors in the nigrostriatal pathway, due to which the increased presynaptic release of dopamine may have increased postsynaptic dopaminergic neurotransmission in neurons already sensitized by prior exposure to neuroleptic drugs. This would have led to the emergence of new tardive dyskinesia and worsening of existing dyskinesia. Neuropsychiatry and Headache Clinic, Pratap Nagar Metro Pillar 129, Delhi-7 IndiaDepartment of Psychopharmacology, National Institute of Mental Health and Neurosciences, Bangalore, India

Drs. Nelson and Papakostas Reply

Drs. Nelson and Papakostas Reply

Association of the orphan nuclear receptor NR4A1 with tardive dyskinesia

Recent evidence has identified the NR4A1 (NUR77, NGFI-B) gene as a strong candidate for involvement in tardive dyskinesia (TD). We have investigated the association of six single nucleotide polymorphisms within the NR4A family of genes with TD in a sample of 171 patients with schizophrenia of Caucasian descent. The NR4A1 single nucleotide polymorphism (SNP) marker rs2603751 showed a nominal association with the risk of TD, as well as with the extent of TD based on the Abnormal Involuntary Movements Scale (AIMS) scores. The haplotype generated by the markers rs2603751 and rs2701124 also showed association with TD and, after adjustment for multiple testing, both the NR4A1 marker rs2603751 and the haplotype continued to show a trend toward association with TD. Although the results of this study are limited by a small sample size, it presents important pilot data and warrants further investigation of the involvement of NR4A1 variants in TD.

The clinical effectiveness and cost-effectiveness of testing for cytochrome P450 polymorphisms in patients with schizophrenia treated with antipsychotics: a systematic review and economic evaluation

To determine whether testing for cytochrome P450 (CYP) polymorphisms in adults entering antipsychotic treatment for schizophrenia leads to improvement in outcomes, is useful in medical, personal or public health decision-making, and is a cost-effective use of health-care resources. The following electronic databases were searched for relevant published literature: Cochrane Controlled Trials Register, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effectiveness, EMBASE, Health Technology Assessment database, ISI Web of Knowledge, MEDLINE, PsycINFO, NHS Economic Evaluation Database, Health Economic Evaluation Database, Cost-effectiveness Analysis (CEA) Registry and the Centre for Health Economics website. In addition, publicly available information on various genotyping tests was sought from the internet and advisory panel members. A systematic review of analytical validity, clinical validity and clinical utility of CYP testing was undertaken. Data were extracted into structured tables and narratively discussed, and meta-analysis was undertaken when possible. A review of economic evaluations of CYP testing in psychiatry and a review of economic models related to schizophrenia were also carried out. For analytical validity, 46 studies of a range of different genotyping tests for 11 different CYP polymorphisms (most commonly CYP2D6) were included. Sensitivity and specificity were high (99-100%). For clinical validity, 51 studies were found. In patients tested for CYP2D6, an association between genotype and tardive dyskinesia (including Abnormal Involuntary Movement Scale scores) was found. The only other significant finding linked the CYP2D6 genotype to parkinsonism. One small unpublished study met the inclusion criteria for clinical utility. One economic evaluation assessing the costs and benefits of CYP testing for prescribing antidepressants and 28 economic models of schizophrenia were identified; none was suitable for developing a model to examine the cost-effectiveness of CYP testing. Tests for determining genotypes appear to be accurate although not all aspects of analytical validity were reported. Given the absence of convincing evidence from clinical validity studies, the lack of clinical utility and economic studies, and the unsuitability of published schizophrenia models, no model was developed; instead key features and data requirements for economic modelling are presented. Recommendations for future research cover both aspects of research quality and data that will be required to inform the development of future economic models.

Community Integration and Associated Factors Among Older Adults With Schizophrenia

Community integration has been increasingly recognized as an important element in recovery. There is a paucity of data on community integration for older adults with schizophrenia. This study compared community integration for older persons with schizophrenia with their age peers in the community and examined factors associated with community integration in the schizophrenia group. The schizophrenia group consisted of 198 community-dwelling persons aged 55 and older who developed schizophrenia before age 45. A community comparison group (N=113) was recruited by randomly selected block groups. Wong and Solomon's 2002 conceptual framework was used to develop a 12-item community integration scale with four components: independence, psychological integration, physical integration, and social integration. Moos' ecosystem model was used to examine 15 personal and environmental factors associated with community integration. Compared with the general community group, the schizophrenia group had significantly lower total community integration scale scores and lower scores on each of the four components. Within the schizophrenia group, regression analysis showed that seven variables were significantly associated with community integration: being female, higher personal income, lower depressive symptoms, lower positive symptoms, lower Abnormal Involuntary Movement Scale score, higher CAGE lifetime scores, and greater control of one's life. The model was significant and explained 49% of the variance. The data confirmed that older persons with schizophrenia had a lower level of community integration than their age peers in the community and that the model for community integration can identify potentially ameliorable clinical and social variables that may be targets for intervention research.

Long-term effects of pallidal deep brain stimulation in tardive dystonia

High-frequency stimulation of the globus pallidus internus (GPi) is a highly effective therapy in primary dystonia. Recent reports have also demonstrated almost immediate improvement of motor symptoms in patients with tardive dystonia after pallidal deep brain stimulation (DBS). Here, we show the long-term effect of continuous bilateral GPi DBS in tardive dystonia on motor function, quality of life (QoL), and mood. Nine consecutive patients undergoing DBS for tardive dystonia were assessed during continuous DBS at 3 time points: 1 week, 3 to 6 months, and last follow-up at the mean of 41 (range 18-80) months after surgery using established and validated movement disorder and neuropsychological scales. Clinical assessment was performed by a neurologist not blinded to the stimulation settings. One week and 3 to 6 months after pallidal DBS, Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) motor scores were ameliorated by 56.4 +/- 26.7% and 74.1 +/- 15.8%, BFMDRS disability scores by 62.5 +/- 21.0% and 88.9 +/- 10.3%, and Abnormal Involuntary Movement Scale (AIMS) scores by 52.3 +/- 24.1% and 69.5 +/- 27.6%, respectively. At last follow-up, this improvement compared with the presurgical assessment was maintained as reflected by a reduction of BFMDRS motor scores by 83.0 +/- 12.2%, BFMDRS disability scores by 67.7 +/- 28.0%, and AIMS scores by 78.7 +/- 19.9%. QoL improved significantly in physical components, and there was a significant improvement in affective state. Furthermore, cognitive functions remained unchanged compared with presurgical status in the long-term follow-up. No permanent adverse effects were observed. Pallidal deep brain stimulation is a safe and effective long-term treatment in patients with medically refractory tardive dystonia.

No Evidence for Association between Tyrosine Hydroxylase Gene Val81Met Polymorphism and Susceptibility to Tardive Dyskinesia in Schizophrenia

ObjectiveTyrosine hydroxylase (TH) is the rate-limiting enzyme in dopamine biosynthesis. Because the TH Val81Met polymorphism is located in the amino-terminal regulatory domain of the tetrameric enzyme, it is a candidate marker for susceptibility to dopamine-related traits. We investigated the hypothesis that TH Val81Met polymorphism can influence susceptibility to tardive dyskinesia (TD) in schizophrenia.MethodsTH Val81Met polymorphism was analyzed by PCR-based methods in 83 schizophrenic patients with TD and 126 schizophrenic patients without TD, matched for antipsychotic drug exposure and other relevant variables.ResultsThere was no significant association of the genotype and allele frequencies determined by the TH Val81Met polymorphism between TD and non-TD patients. In addition, there was no significant difference in terms of total Abnormal Involuntary Movement Scale scores among the three genotype groups.ConclusionWithin the limitations imposed by the size of the clinical sample, these findings suggest that the Val81Met polymorphism of the TH gene does not contribute significantly to the risk for TD.

Amisulpride-Induced Tardive Dyskinesia and Possible Association of Dyskinesia with Hypothyroidism

Back to table of contents Previous article Next article LETTERFull AccessAmisulpride-Induced Tardive Dyskinesia and Possible Association of Dyskinesia with HypothyroidismDattatrya Namdeorao Mendhekar D.P.M., M.D.,Chittaranjan Andrade M.D.,Dattatrya Namdeorao Mendhekar D.P.M., M.D.Search for more papers by this author,Chittaranjan Andrade M.D.Search for more papers by this author,Published Online:1 Jan 2009AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Amisulpride, a second generation antipsychotic, is a substituted benzamide derivative that preferentially binds to dopamine D2/D3 receptors in limbic rather than striatal structures. The literature is sparse, with only two case reports of tardive dyskinesia associated with amisulpride. 1 , 2 We report a similar case and also highlight possible interaction of thyroid hormone and dopamine receptors in the emergence of tardive dyskinesia. Case ReportMr. S, a 24-year-old single male engineer, was diagnosed with schizophrenia 3 years ago according to ICD-10 criteria. He had good premorbid functioning, with no significant family or personal history of psychiatric and neurological illness. He exhibited predominantly negative symptoms as well as periods of paranoid symptoms. Mr. S consulted a psychiatrist for the first time 6 months after the onset of his illness. He was stabilized on olanzapine, up to 20 mg/day for 2 years, and was later switched to aripiprazole due to significant weight gain. After 4 months of optimal dose of aripiprazole (30 mg/day), however, there was no further improvement in his positive or negative symptomatology. Subsequently, Mr. S was started on amisulpride, 50 mg/day, titrated up to 400 mg/day over 10 weeks. After 15 weeks of amisulpride therapy, he developed dyskinetic finger movements in both hands, predominately involving his right thumb. Although he was aware of the movements, he had no difficulty in carrying out his daily routine activities. When asked to control it, he could suppress these movements only for a few seconds. There were no abnormal movements noticed in other parts of the body. His Abnormal Involuntary Movements Scale (AIMS) score was 9. In view of persistent weight gain and marked negative symptoms, a metabolic panel was obtained, including thyroid function tests. These showed elevated thyroid-stimulating hormone (8.3 mU /liter; normal range =0.4–5.0 mU/liter). Amisulpride was discontinued and it was replaced by clozapine, which was gradually titrated to 75 mg/day along with levothyroxine, 25 mg/day. All dyskinetic movements subsided after 6 weeks of this combined therapy. Subsequent thyroid profile also became normal, and he was continued on clozapine and levothyroxine.Discussion The appearance of dyskinesia while on amisulpride and the prompt resolution of dyskinesia after discontinuing amisulpride strongly suggests a case of amisulpride-induced tardive dyskinesia. There has been no information associating tardive dyskinesia and hypothyroidism in patients receiving amisulpride. Hypothyroidism has been associated with subsensitivity of strial dopamine receptors and thyroid hormones potentiate dopaminergic behavior. 3 A study carried out in rats treated with haloperidol revealed significant upregulation of dopamine receptors in hypothyroid rats compared with hyperthyroid rats. 4 Furthermore those psychotropic drugs which generally do not show the tendency to develop tardive dyskinesia such as clozapine, supiride, and nomifensine also exhibited tardive dyskinesia and associated hypothyroidism. 5 – 7 It is possible that thyroid dysfunction interacts with or has some influence on the dopaminergic system as far as emergence of tardive dyskinesia is concerned. This case raises the possibility of underreporting the association of tardive dyskinesia and hypothyroidism and demonstrates a need for further research to answer the queries about the risk factors between hypothyroidism and the emergence of tardive dyskinesia. Neuropsychiatry and Headache Clinic, Pratap Nagar Metro, Delhi, IndiaDepartment of Psychopharmacology, National Institute of Mental Health and Neurosciences, Bengalooru, IndiaReferences1 . Masdrakis VG, Papadimitriou GN, Papageorgiou C, et al: Development of tardive dyskinesia in a patient taking amisulpride. Prog Neuropsychopharmacol Biol Psychiatry 2007; 31:586–587Google Scholar2 . Fountoulakis KN, Panagiotidis P, Siamouli M, et al: Amisulpride-induced tardive dyskinesia. Schizophr Res 2006; 88:232–234Google Scholar3 . Goetz CG, Wriner WJ, Klawans HL: Treatment of chorea, in Disorders of Movements. Edited by Bareau A. Lancaster, England, MTP Press, 1989, pp 29–43Google Scholar4 . Crocker AD, Overstreet DH: Modification of the behavioral effects of haloperidol and dopamine receptor regulation by altered thyroid status. Psychopharmol 1984; 82:102–106Google Scholar5 . Mendhekar DN, Duggal HS: Clozapine induced tardive dyskinesia and hypothyroidism. J Neuropsychiatry Clin Neurosci 2006; 18:2Google Scholar6 . Sandyk R: Tardive dyskinesia induced by sulpride in a patient with hypothyroidism. Clin Neuropharmacol 1986; 9:100–101Google Scholar7 . Sandyk R, Gilman MA: Nomifensive exacerbates orofacial dyskinesia in hypothyroidism. Neurology 1985; 35:282Google Scholar FiguresReferencesCited byDetailsCited byThyroid dysfunction in Down's syndrome secondary to risperidone8 November 2022 | Progress in Neurology and Psychiatry, Vol. 26, No. 4Asian Journal of Psychiatry, Vol. 41Clinical Psychopharmacology and Neuroscience, Vol. 16, No. 2 Volume 21Issue 1 Winter, 2009Pages 104-105 Metrics PDF download History Published online 1 January 2009 Published in print 1 January 2009

Treatment of tardive dyskinesia with levetiracetam in a transplant patient

To describe successful treatment of tardive dyskinesia with levetiracetam. Tardive dyskinesia is a late-onset movement disorder caused by exposure to dopamine receptor blocking agents, most commonly neuroleptics. Metoclopramide is frequently used to treat gastrointestinal dysmotility. It has antidopaminergic properties, and is estimated to be responsible for two-thirds of drug-related movement disorders. Case report. A 68-year-old woman presented with a history of intestinal transplantation (12 years ago; short gut syndrome related to bowel resection for rectal carcinoma) and renal transplantation (1 year ago; diabetes). She developed involuntary movements with stereotypic oro-buccal-lingual dyskinesias and right-sided choreiform movements. Her Abnormal Involuntary Movement Scale score (AIMS) score was 27. She has been treated with metoclopramide for gastrointestinal dysmotility for more than 10 years and was diagnosed with tardive dyskinesia. Treatment with levetiracetam 250 mg orally b.i.d. led to a significant improvement of abnormal movements within a week. Her AIMS score decreased to 8. Tardive dyskinesia may be quite disabling and options include withdrawal of offending medication, or use of tetrabenazine or reserpine. Several reports also suggested improvement of tardive movement disorders with levetiracetam. In our patient, levetiracetam relieved symptoms of tardive dyskinesia and allowed continuous use of metoclopramide. Larger studies are needed to confirm its efficacy.

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.