Movement Scale Scores Research Articles

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

Arthrocentesis and stabilizing splint are the treatment of choice for acute intermittent closed lock in patients with bruxism

This study aimed to evaluate the long-term outcome of arthrocentesis and stabilizing splints for the treatment of acute closed lock in patients with bruxism. This study included 20 female patients who were divided into two equal groups and who underwent temporomandibular joint (TMJ) arthrocentesis. Patients in the first group wore a full coverage stabilizing splint following arthrocentesis. The second group underwent arthrocentesis only. The scores for preoperative maximal mouth opening (MMO), protrusive movement (PM), contra-lateral (CL) movement (CLM) and visual analogue scale (VAS) scores for pain and dysfunction were compared with the follow-up scores obtained by the questionnaire and clinical examination. Statistical evaluation of the baseline and follow-up data was made with the t-test. The follow-up period was 12 months. There was a significant ( P < 0.001) increase in the MMO, CL and PMs during the longer-term follow-up period for group 1, while there was a significant decrease ( P < 0.019) in these parameters for group 2. The pain and dysfunction levels at follow-up were significantly ( P < 0.001) lower than the preoperative values. Ninety percent of patients in group 2 showed pain and dysfunction scores that increased significantly ( P < 0.001) and ranged from moderate to severe. The overall success rate was 90% for group 1 and 30% for group 2. In conclusion, arthrocentesis and a stabilizing splint are the treatment of choice for acute closed lock of short duration in young patients with bruxism.

Drs. Nelson and Papakostas Reply

Drs. Nelson and Papakostas Reply

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.

The Early Effects of Tendon Transfers and Open Capsulorrhaphy on Glenohumeral Deformity in Brachial Plexus Birth Palsy

Persistent muscle imbalance and soft-tissue contractures can lead to progressive glenohumeral joint dysplasia in patients with brachial plexus birth palsy. The objective of the present investigation was to determine the effects of tendon transfers and open glenohumeral reduction on shoulder function and dysplasia in patients with preexisting joint deformity secondary to brachial plexus birth palsy. Twenty-three patients with preexisting glenohumeral deformity underwent latissimus dorsi and teres major tendon transfers to the rotator cuff with concomitant musculotendinous lengthening of the pectoralis major and/or subscapularis and open glenohumeral joint reduction for the treatment of internal rotation contracture and external rotation weakness. Shoulder function was assessed with use of the modified Mallet classification system and the Active Movement Scale. Glenoid version and humeral head subluxation were quantified radiographically, and glenohumeral deformity was appropriately graded. The mean duration of clinical and radiographic follow-up was thirty-one and twenty-five months, respectively. Clinically, all patients demonstrated improved global shoulder function, with the mean aggregate Mallet score improving from 10 points preoperatively to 18 points postoperatively (p < 0.01). The mean modified Mallet score for external rotation improved from 2 to 4 (p < 0.01). Similarly, the mean Active Movement Scale score for external rotation improved from 3 to 6 (p < 0.01). The mean Mallet hand-to-spine score improved from 1 to 2 (p < 0.01). The mean Active Movement Scale score for internal rotation remained constant at 6. Radiographically, the mean glenoid version improved from -39 degrees preoperatively to -18 degrees postoperatively (p < 0.01). The mean percentage of the humeral head anterior to the middle of the glenoid similarly improved from 13% to 38% (p < 0.01). The mean glenohumeral deformity score improved from 3 to 2 (p < 0.01). Nineteen (83%) of the twenty-three patients demonstrated glenohumeral remodeling; one patient had progressive worsening of glenohumeral deformity. Tendon transfers to the rotator cuff, combined with musculotendinous lengthenings and open reduction of the glenohumeral joint, improve global shoulder function and lead to glenohumeral joint remodeling in the majority of selected patients with mild-to-moderate preexisting glenohumeral dysplasia secondary to brachial plexus birth palsy. Future study of the long-term outcomes of these procedures will help to clarify the ultimate effect on glenohumeral joint function.

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.

Navigating the gray zone: a guideline for surgical decision making in obstetrical brachial plexus injuries

In the literature, the best recommendations are imprecise as to the timing and selection of infants with obstetrical brachial plexus injury (OBPI) for surgical intervention. There is a gray zone (GZ) in which the decision as to the benefits and risks of surgery versus no surgery is not clear. The authors propose to describe this category, and they have developed a guideline to assist surgical decision-making within this GZ. The authors first performed a critical review of the medical literature to determine the existence of a GZ in other clinical publications. In those reports, 47-89% of infants with OBPI fell within such a GZ. Complete recovery in those reported patients ranged from 9 to 59%. Using a prospective inception cohort design, all infants referred to the OBPI Clinic at McMaster Children's Hospital were systematically evaluated up to 3 years of age. The Active Movement Scale scores were compared for surgical and nonsurgical groups of infants in the GZ to identify any important trends that would guide surgical decision-making. In the authors' population of infants with OBPI, 81% fell within the GZ, of whom 44% achieved complete recovery. Mean scores differed significantly between surgery and no surgery groups in terms of total Active Movement Scale score and shoulder abduction and flexion at 6 months. Elbow flexion and external rotation differed at 3 months. There is compelling evidence that there is a group of infants with OBPI in whom the assessment of the risk/benefit ratio for surgical versus nonsurgical treatment is not evident. These infants reside within what the authors have called the GZ. Based on their results, a guideline was derived to assist clinicians working with infants with OBPI to navigate the GZ.

Final Results of Grafting versus Neurolysis in Obstetrical Brachial Plexus Palsy

The authors previously showed that neurolysis in obstetrical brachial plexus palsy resulted in improved function in some patients at 1 year's follow-up. In this study, the hypothesis that the long-term outcome of neuroma-in-continuity resection and nerve grafting yields better results than neurolysis was tested. Obstetrical brachial plexus palsy patients treated with primary nerve surgery with a minimum follow-up of 4 years were studied. Patients were classified as undergoing neurolysis (n = 16) or resection and grafting (n = 92) and separated into Erb's or total palsy groups. The Active Movement Scale was used for patient evaluation. Changes in Active Movement Scale scores were analyzed using the Wilcoxon signed rank test. Fifteen movements were tested, and the proportion of patients in each group with scores deemed functionally useful (6 or 7) was compared using McNemar's exact test. After 4 years' follow-up, Erb's palsy neurolysis patients showed no improvement in function. Conversely, Erb's palsy grafting patients had improved function in seven movements. Total palsy neurolysis patients showed no improvement in function, whereas grafted patients showed improved function in 11 of 15 movements. Early improvements in function produced by neurolysis in Erb's palsy were not sustained over time. Neuroma-in-continuity resection and nerve grafting for both Erb's and total palsy produced significant improvements in Active Movement Scores and in the proportion of patients demonstrating functionally useful scores. Neurolysis as a complete surgical treatment for obstetrical brachial plexus palsy should be abandoned in favor of neuroma resection and nerve grafting.

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.

The Early Effects of Tendon Transfers and Open Capsulorrhaphy on Glenohumeral Deformity in Brachial Plexus Birth Palsy

Persistent muscle imbalance and soft-tissue contractures can lead to progressive glenohumeral joint dysplasia in patients with brachial plexus birth palsy. The objective of the present investigation was to determine the effects of tendon transfers and open glenohumeral reduction on shoulder function and dysplasia in patients with preexisting joint deformity secondary to brachial plexus birth palsy. Twenty-three patients with preexisting glenohumeral deformity underwent latissimus dorsi and teres major tendon transfers to the rotator cuff with concomitant musculotendinous lengthening of the pectoralis major and/or subscapularis and open glenohumeral joint reduction for the treatment of internal rotation contracture and external rotation weakness. Shoulder function was assessed with use of the modified Mallet classification system and the Active Movement Scale. Glenoid version and humeral head subluxation were quantified radiographically, and glenohumeral deformity was appropriately graded. The mean duration of clinical and radiographic follow-up was thirty-one and twenty-five months, respectively. Clinically, all patients demonstrated improved global shoulder function, with the mean aggregate Mallet score improving from 10 points preoperatively to 18 points postoperatively (p < 0.01). The mean modified Mallet score for external rotation improved from 2 to 4 (p < 0.01). Similarly, the mean Active Movement Scale score for external rotation improved from 3 to 6 (p < 0.01). The mean Mallet hand-to-spine score improved from 1 to 2 (p < 0.01). The mean Active Movement Scale score for internal rotation remained constant at 6. Radiographically, the mean glenoid version improved from -39 degrees preoperatively to -18 degrees postoperatively (p < 0.01). The mean percentage of the humeral head anterior to the middle of the glenoid similarly improved from 13% to 38% (p < 0.01). The mean glenohumeral deformity score improved from 3 to 2 (p < 0.01). Nineteen (83%) of the twenty-three patients demonstrated glenohumeral remodeling; one patient had progressive worsening of glenohumeral deformity. Tendon transfers to the rotator cuff, combined with musculotendinous lengthenings and open reduction of the glenohumeral joint, improve global shoulder function and lead to glenohumeral joint remodeling in the majority of selected patients with mild-to-moderate preexisting glenohumeral dysplasia secondary to brachial plexus birth palsy. Future study of the long-term outcomes of these procedures will help to clarify the ultimate effect on glenohumeral joint function. Therapeutic Level IV. See Instructions to Authors for a complete description of levels of evidence.

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.

Ability for Basic Movement as an Early Predictor of Functioning Related to Activities of Daily Living in Stroke Patients

Background. Early functional outcomes for activities of daily living at an early stage after a stroke may enable clinicians to establish treatment-optimal training and goals. The objective of this study was to assess the relationship between the ability to perform basic movements at the bedside, which were measured using a new scale, the Ability for Basic Movement Scale, in the early stage after stroke and functional ability at discharge from the hospital. Methods . A total of 142 stroke patients participated in this prospective study. In addition to the Ability for Basic Movement Scale score, age, limb paresis as measured by the Brunnstrom stage, and functional ability as measured by the Barthel Index were also selected as predictor variables. Results . Pearson correlation coefficient analysis showed that the state of functional ability at discharge had significant positive correlations with total scores of the Ability for Basic Movement Scale and Brunnstrom stage at all stages of data collection. The results of linear stepwise regression analysis indicated that “turn over from supine position,” “remain sitting,” and “sit up” of the Ability for Basic Movement Scale at 10 days after onset, in addition to age at onset of stroke, the baseline Barthel Index, and the baseline Brunnstrom stage, were significant predictors (75.6%) of functional ability at discharge. Conclusions. This study provides evidence for the predictive value of the Ability for Basic Movement Scale with regard to functional ability in stroke patients.

No Association between Dopamine D4 Receptor Gene –521 C/T Polymorphism and Tardive Dyskinesia in Schizophrenia

Tardive dyskinesia (TD) is a long-term adverse effect of antipsychotics. We evaluated whether a candidate functional polymorphism of the dopamine D4 receptor (DRD4) gene is associated with drug-induced TD in 209 Korean schizophrenic patients with TD (n = 83) and without TD (n = 126) who were matched for antipsychotic drug exposure and other relevant variables. There was no significant association of the genotype and allele frequencies determined by the –521 C/T SNP of DRD4 between TD and non-TD patients. In addition, there was no significant difference in terms of total Abnormal Involuntary Movement Scale scores among the 3 genotype groups. Within the limitations imposed by the size of the clinical sample, these findings suggest that the DRD4 –521 C/T SNP does not contribute significantly to the risk for TD.

Outcomes for Latin American Versus White Patients Suffering From Acute Mania in a Randomized, Double-Blind Trial Comparing Olanzapine and Haloperidol

Data from a published double-blind randomized trial comparing olanzapine versus haloperidol in acute mania were used to address the response and tolerability of Latin American patients. Primary efficacy end point was the remission rate (Young Mania Rating Scale score <or=12 and Hamilton Depression Rating Scale score of <or=8). Patients were analyzed on an intent-to-treat basis. The mean modal doses (milligrams per day) were similar in Latin American (OL) (14.2; n = 51) and white (OC) (15.1; n = 120) patients treated with olanzapine, and in Latin American (HL) (7.1; n = 48) and white (HC) (8.5; n = 113) patients treated with haloperidol. At week 6, remission rates were similar among the OL and HL patients (64.7% vs. 68.8%) but were higher in the OC than in HC (49.2% vs. 32.7%; P = 0.012). Significantly more HL than OL patients experienced extrapyramidal symptoms such as akathisia and tremor. Tremor was significantly higher in HL than in HC patients, whereas a significant increase in the Barnes Akathisia Scale and Abnormal Involuntary Movement Scale scores was observed in HC versus HL. Somnolence and weight gain were significantly higher in OL than in OC patients, and more OL and OC patients experienced weight gain in comparison with the HL and HC groups, respectively. The incidence of nonfasting glucose levels above normal levels did not statistically differ between groups. In conclusion, in contrast to our findings among white patients, the Latin American patients who have acute mania did not differ in overall response to olanzapine or haloperidol. The pattern of adverse events differed between treatment groups. Prospective clinical trials in Latin American bipolar populations are justified.

Treatment of Tardive Dyskinesia With Galantamine

Recent evidence suggests that tar-dive dyskinesia may result from antipsychotic-induced damage to striatal cholinergic neurons. To test whether cholinesterase inhibitors compensate for diminished cholinergic activity, we conducted a 30-week randomized, double-blind, placebo-controlled crossover trial of galantamine in patients with tardive dyskinesia. Patients with tardive dyskinesia were recruited between June 2001 and June 2004. After a 2-week baseline period, 35 male schizophrenia patients, on stable doses of antipsychotics, were randomly assigned to receive galantamine (8-24 mg) or placebo for two 12-week phases separated by a 4-week washout period. Patients were evaluated every 2 weeks for changes in extrapyramidal symptoms and before and after each treatment for effects on psychiatric symptoms and cognition. Galantamine reduced mean total Abnormal Involuntary Movement Scale (AIMS) scores more than placebo, but this difference was not statistically significant (p = .08). However, patients initially randomly assigned to galantamine showed a reversal of AIMS scores after switching to placebo. Simpson-Angus Scale ratings of parkinsonism were significantly higher with galantamine than placebo (p = .0005) and correlated with age. There were no significant differences between groups in akathisia, cognition, or psychiatric symptoms. More patients dropped out while receiving galantamine, but this outcome did not significantly influence the results. In contrast to previous reports, reductions in tardive dyskinesia associated with galantamine were not statistically significant compared with placebo in this trial. However, galantamine was associated with a modest rebound in dyskinesia scores after discontinuation and clinically minor but statistically higher ratings of parkinsonism. These findings support the need for further investigations of cholinergic mechanisms underlying tardive dyskinesia and extrapyramidal effects of cholinesterase inhibitors when used in combination with antipsychotics in susceptible patients. ClinicalTrials.gov identifier NCT00164242.

Levetiracetam in Tardive Dyskinesia

The aim of this study was to evaluate the effect of levetiracetam on tardive dyskinesia (TD), which is known to be a major limitation of chronic antipsychotic drug therapy, particularly with conventional antipsychotics. Sixteen patients suffering from chronic psychosis with TD were enrolled consecutively. Levetiracetam was given in gradually increasing doses, starting with 125 twice a day until the best clinical benefit was achieved (mean dosage, 2,290 mg; range, 1,000-3,000 mg). Tardive dyskinesia was assessed using the Abnormal Involuntary Movement Scale at baseline and after 1 month and 3 months of treatment with levetiracetam. Compared with baseline, there was a significant improvement in the Abnormal Involuntary Movement Scale score after 1 month still present after 3 months (P < 0.001). All patients well tolerated levetiracetam, except one who dropped out of the trial after the first 2 weeks owing to excessive drowsiness. The results of this open-label observational study suggest that levetiracetam is a well-tolerated drug and effectively controls TD.