Abnormal Involuntary Movement Scale Research Articles

A Randomized Controlled Trial of Risperidone and Olanzapine for Schizophrenic Patients With Neuroleptic-Induced Tardive Dyskinesia

To compare the efficacy of risperidone and olanzapine in schizophrenic patients with tardive dyskinesia on treatment with first-generation antipsychotics. We conducted a 24-week, rater-blinded, flexible-dose study. Sixty patients with DSM-IV schizophrenia (n = 58) or schizoaffective disorder (n = 2) met the DSM-IV research criteria for neuroleptic-induced tardive dyskinesia and were randomly assigned to a risperidone or olanzapine group. The primary outcome was a comparison of the change in the total scores on the Abnormal Involuntary Movement Scale (AIMS) from baseline to study end point between the groups. The study was conducted from July 2000 to June 2004. The mean ± SD doses of risperidone and olanzapine from baseline to study end point were 1.9 ± 0.7 to 4.1 ± 1.4 mg/d and 8.1 ± 2.0 to 12.6 ± 5.4 mg/d, respectively. There were no statistically significant differences in demographic data, severity of tardive dyskinesia, or psychotic symptoms between risperidone and olanzapine groups at baseline assessment. Both groups showed significant improvement in mean ± SD AIMS total scores (risperidone: −7.4 ± 6.9, P < .0001; olanzapine: −6.2 ± 8.0, P = .0002). However, there was a more statistically significant change in the slope of AIMS total scores in the risperidone group than in the olanzapine group (P = .0001). Our findings demonstrated that olanzapine may not have better potential for tardive dyskinesia improvement than risperidone did. Double-blinded, fixed dose studies with a larger sample size on schizophrenic patients with tardive dyskinesia from different ethnic groups are needed to confirm the results of our study. clinicaltrials.gov Identifier NCT00621998

Objective measurement of dyskinesia in Parkinson's disease using a force plate

Clinical investigation of levodopa-induced dyskinesia (LID) in Parkinson's disease (PD) is limited because of lack of objective measurements and no consensus on use of a standard measuring tool. Currently, clinical trials use subject-completed diaries of dyskinesia throughout the day or investigator-administered clinical rating scales. An objective and valid method of measuring LID would reduce bias, variability, and decrease the time and number needed in trials of potential anti-dyskinetic agents. We have investigated using a force plate under standing subjects, which records movement of the center of pressure (CoP) to quantify LID over a levodopa (L-dopa) cycle. Twenty-two PD subjects (15 with LID, 7 without LID) admitted to an inpatient research facility had their PD meds withheld overnight, followed by a 2 hours intravenous L-dopa infusion the next day. The root mean squared of the velocity in the anterior-posterior direction (RMSV) derived from an analysis of the CoP, and, the modified Abnormal Involuntary Movement Scale (mAIMS) were performed repeatedly for 6 hours, initially as subjects were OFF before the infusion, through infusion until OFF again. There was a high correlation between the area under the curve (AUC) of the mAIMS and the RMSV within and between subjects. As a measure of LID, RMSV had excellent validity and reliability between subjects, and using a force plate was feasible. Sensitivity to changes in LID was initially demonstrated but should be repeated. Thus, CoP recordings on a force plate can objectively quantify LID in PD and may be very useful in clinical trials or other investigations of dyskinesia.

Ziprasidone Treatment of Refractory Generalized Anxiety Disorder

This 8-week, randomized, double-blind, placebo-controlled, flexible-dose trial assessed the efficacy, safety, and tolerability of ziprasidone in adults with treatment-resistant generalized anxiety disorder (GAD). Seventy-three subjects with treatment-resistant GAD were recruited, and 62 were randomized to either ziprasidone or placebo treatment at a ratio of 2:1 using a flexible dosing strategy (20-80 mg daily). Randomization was stratified into 2 subtypes of patients, those in whom the study drug was used as augmentation and those who have stopped their ineffective medications before entering the present trial (nonaugmented group). The subjects' clinical status was monitored weekly throughout the course of the study and included the Hamilton Anxiety Scale (primary outcome measure), the Clinical Global Impression Improvement and Severity of Illness scales, the Hamilton Depression Scale, the Sheehan Disability Scale, the Hospital Anxiety and Depression Scale, and the Abnormal Involuntary Movements Scale. Sixty-two patients were randomized to ziprasidone (n = 41) or placebo (n = 21). The dropout rate was 24%, consisting of 2 placebo patients and 13 ziprasidone patients. There was no statistically significant difference in the Hamilton Anxiety Scale score reduction between the drug and placebo groups. However, statistical trends were observed for an augmentation-study medication interaction effect, with ziprasidone patients producing more improvement in the nonaugmented than in the augmented group. This study provides pilot data for an augmentation-study medication interaction effect with ziprasidone patients producing more improvement in the nonaugmented than in the augmented group. Based on the data obtained in this trial and the subsequent power analyses, a future double-blind placebo-controlled trial should include at least 150 treatment-resistant GAD nonaugmented patients randomized to ziprasidone and placebo in a 1:1 ratio.

Association of the manganese superoxide dismutase gene Ala–9Val polymorphism with clinical phenotypes and tardive dyskinesia in schizophrenic patients

Objective Several recent studies that have investigated the genetic association between the manganese superoxide dismutase ( MnSOD) gene Ala–9Val single-nucleotide polymorphism (SNP) and tardive dyskinesia (TD) have produced conflicting results. This study was to investigate whether this SNP was associated with clinical phenotypes and antipsychotic-induced tardive dyskinesia (TD) in schizophrenia in a genetically homogeneous Han Chinese inpatient population. Methods Genotyping was performed for the MnSOD gene Ala–9Val SNP in Chinese schizophrenia patients with ( n = 176) and without TD ( n = 346). The severity of TD was assessed using the abnormal involuntary movement scale (AIMS), and psychopathology using the Positive and Negative Syndrome Scale (PANSS). Results The frequencies of genotypes and alleles did not differ significantly between schizophrenic patients with and without TD (both p > 0.05). Also, there was no significant difference in the AIMS total score between the Val/Val and Ala allele carrier groups ( p > 0.05). However, the PANSS negative symptom subscore was significantly higher in patients with Val/Val genotype (21.8 ± 7.3) than those with Ala alleles (20.1 ± 7.7) ( t = 2.32, p = 0.03). Conclusion While the MnSOD gene Ala–9Val polymorphism did not play a major role in the susceptibility to TD in schizophrenic patients, it might be associated with negative symptoms of schizophrenia.

L‐DOPA‐induced dopamine efflux in the striatum and the substantia nigra in a rat model of Parkinson’s disease: temporal and quantitative relationship to the expression of dyskinesia

L-DOPA-induced dyskinesia in Parkinson's disease is associated with large increases in brain dopamine (DA) levels following drug dosing, but the precise significance of this phenomenon is not understood. Here we compare DA efflux and metabolism in the striatum and the substantia nigra in dyskinetic and non-dyskinetic animals following a standard dose of L-DOPA. Rats with 6-hydroxydopamine lesions were treated chronically with L-DOPA, monitored on the abnormal involuntary movements scale, and then subjected to intracerebral microdialysis under freely-moving conditions. Following s.c. L-DOPA injection, peak extracellular DA levels in both striatum and substantia nigra were about twice as large in dyskinetic animals compared to non-dyskinetic rats. This effect was not attributable to differences in DOPA levels or DA metabolism. The larger DA efflux in dyskinetic animals was blunted by 5-HT1A/5-HT1B receptor agonists and tetrodotoxin infusion, reflecting release from serotonin neurons. Striatal levels of serotonin and its main metabolite, 5-hydroxyindolacetic acid were indeed elevated in dyskinetic animals compared to non-dyskinetic rats, indicating a larger serotonergic innervation density in the former group. High DA release was, however, not sufficient to explain dyskinesia. The 'abnormal involuntary movements output' per unit concentration of striatal extracellular DA was indeed much larger in dyskinetic animals compared to non-dyskinetic cases at most time points examined. The present results indicate that both a high DA release post-L-DOPA administration and an increased responsiveness to DA must coexist for a full expression of dyskinesia.

Incidence of Tardive Dyskinesia With Atypical Versus Conventional Antipsychotic Medications

Most previous studies of the incidence of tardive dyskinesia with atypical antipsychotics compared with conventional antipsychotics have not had tardive dyskinesia as their primary focus. The current study aimed to compare the incidence of tardive dyskinesia with atypical vs conventional antipsychotics using methods similar to those from a previous prospective cohort study at our site in the 1980s. Three hundred fifty-two initially tardive dyskinesia-free psychiatric outpatients (diagnosed at baseline using the Structured Clinical Interview for DSM-IV) were examined for a new diagnosis of tardive dyskinesia (using the Abnormal Involuntary Movement Scale and Glazer-Morgenstern criteria) every 6 months for up to 4 years at a community mental health center. At baseline, subjects were receiving conventional antipsychotics only (23%), atypicals only (64%), or both (14%). Only 26 subjects had never received conventional antipsychotics. Baseline evaluations were conducted from November 2000 through May 2003. Follow-ups were conducted through February 2005. Compared with subjects treated with conventional antipsychotics alone since the previous visit, the adjusted tardive dyskinesia incidence rate-ratio for subjects treated with atypical antipsychotics alone was 0.68 (95% CI, 0.29-1.64). The incidence and prevalence of tardive dyskinesia was similar to previous findings at this site in the 1980s. The incidence of tardive dyskinesia with recent exposure to atypical antipsychotics alone was more similar to that for conventional antipsychotics than in most previous studies. Despite high penetration of atypical antipsychotics into clinical practice, the incidence and prevalence of tardive dyskinesia appeared relatively unchanged since the 1980s. Clinicians should continue to monitor for tardive dyskinesia, and researchers should continue to pursue efforts to treat or prevent it.

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A Case of Severe Toluene Withdrawal Syndrome Treated With Clonazepam

Back to table of contents Previous article Next article LETTERFull AccessA Case of Severe Toluene Withdrawal Syndrome Treated With ClonazepamAnastasios V. Kouzoupis M.D.George Konstantakopoulos M.D.Panagiotis Oulis M.D., Ph.D.,Nikolaos Kalfakis M.D.Sokratis G. Papageorgiou M.D.,Anastasios V. Kouzoupis M.D.Search for more papers by this authorGeorge Konstantakopoulos M.D.Search for more papers by this authorPanagiotis Oulis M.D., Ph.D.Search for more papers by this author,Nikolaos Kalfakis M.D.Search for more papers by this authorSokratis G. Papageorgiou M.D.Search for more papers by this author,Published Online:1 Jan 2010https://doi.org/10.1176/jnp.2010.22.1.123.e16AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Inhalant abuse is a not uncommon substance abuse disorder that affects mainly adolescents and young adults. 1 Although withdrawal syndrome has been reported in up to 11% of inhalant abusers, the data on its clinical manifestations and treatment are still limited. 1 , 2 To the best of our knowledge, there has been no report on the use of clonazepam in the treatment of solvent withdrawal syndrome. Case ReportWe report the case of a 22-year-old man, a chronic toluene abuser since the age of 13, without any comorbid psychiatric disorder or history of other substance abuse. He received toluene holding a rag saturated in paint thinner to his face for many hours daily and all night long, while he was sleeping. During the last 2 years, he presented with parkinsonism and ataxia affecting his overall personal and social functioning, whereas abstinence resulted twice in withdrawal syndrome with anxiety, insomnia, irritability, and aggressive behavior, which lasted approximately 2 days and resolved after the resumption of toluene abuse. Toluene abuse was perforce discontinued when the patient was incarcerated for violent behavior against his brother. Three days later, he was admitted to our hospital with severe tremor, hypertonia, abasia, ataxia, cognitive impairment—disturbances of orientation, memory and concentration—anxiety, insomnia, and irritability. His scores on the Abnormal Involuntary Movement Scale (AIMS) and on the Mini-Mental State Examination (MMSE) were 29 and 12, respectively. The findings of the laboratory workup were normal with the exception of his MRI scan, which revealed mild cerebral and cerebellar atrophy as well as low signal in the basal ganglia. We prescribed clonazepam titrated to 2 mg/day. Within a week, the patient’s anxiety, insomnia, and irritability remitted completely, whereas his motor symptoms and cognitive functioning gradually improved. Two weeks later he could walk without support. His score on the AIMS dropped to 15, whereas his MMSE score increased to 25.Discussion This case report illustrates the severe symptoms after withdrawal from chronic heavy solvent abuse and the therapeutic difficulties due to the possible serious brain damage caused by toluene. MRI abnormalities in chronic toluene abuse and their clinical correlates have already been reported. 3 In our case, brain damage resulted in parkinsonism, ataxia, and mild cognitive impairment, whereas toluene withdrawal was followed by an exacerbation of these symptoms as well as anxiety, insomnia and irritability. The use of clonazepam was consequently indicated because of its anxiolytic, sedative, myorelaxant, and antiparkinsonian properties. Chronic exposure to toluene may induce enhancement of NMDA glutamatergic neurotransmission coupled with reduced GABAergic activity. These alterations may result in increased behavioral activity during withdrawal from chronic toluene exposure. 4 Consequently, clonazepam, a high-potency benzodiazepine which acts as a GABA A receptor agonist—enhancing thus GABAergic neurotransmission—may ameliorate the withdrawal symptoms of chronic toluene abuse. Moreover, clonazepam may also inhibit NMDA glutamatergic activity through the functional interaction between glutamatergic and GABAergic systems. 5Although anecdotal, the data of our case suggest that clonazepam might be efficacious as monotherapy in the treatment of toluene withdrawal syndrome.First Department of Psychiatry, Athens University Medical School, Eginition Hospital, Athens, GreeceDepartment of Neurology, Athens University Medical School, Eginition Hospital

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.

P03-316 - Gender differences in the extrapyramidal side effects of antipsychotic medication

IntroductionThe pathophysiology of extrapyramidal side effects of typical antipsychotic drugs and the role of gender as a risk factor is poorly understood.ObjectivesTo elucidate the role of gender and the oestrogen hypothesis in extrapyramidal side effect severity.AimsTo investigate gender differences in side effects of antipsychotic drugs and explore the role of oestrogen levels in side effect severity.Methods25 women and 23 men with a diagnosis of schizophrenia were examined for side effects using the Extrapyramidal Side Effects Rating Scale (ESRS), the Simpson Angus Rating Scale for Extrapyramidal Side Effects and the Abnormal Involuntary Movements Scale (AIMS).ResultsHigher antipsychotic doses and use of anticholinergics were noted in males.Women had higher ESRS scores and Simpson Angus scores. Men had higher mean scores for AIMS and the Barnes Akathisia Rating Scale. Age was significantly correlated with scores on ESRS, AIMS and Simpson Angus Rating Scale. There was a highly significant correlation between ESRS score and absence of a regular menstrual cycle. No association with age or antipsychotic dose was found between the groups. Women without a regular cycle scored significantly higher on Simpson Angus Rating Scale. Women with regular cycles scored significantly higher on Barnes Akathisia Rating Scale. There was no difference in AIMS score between the groups. No significant difference was found on any measure between women who were in the high and low oestrogen phases of the cycle.ConclusionsGender, age and the presence of a menstrual cycle should be considered when prescribing antipsychotic medication.

P03-385 - Aripiprazole in the treatment of risperidone associated tardive dyskinesia

ObjectivesTardive dyskinesia(TD) is a syndrome characterized by repetitive involuntary movements, usually involving mouth, face and tongue and sometimes the extremities. Atypical antipsychotics are of significantly lower risk for causing tardive dyskinesia, about one-fifth comparing with first generation antipsychotics. Furthermore, there is growing evidence that they may have a therapeutic effect on TD. We present a case that demonstrated a marked improvement in risperidone-induced TD following treatment with aripiprazole.MethodMr. A is a 21-year-old single male with a DSM-IV-TR diagnosis of schizophrenia, of approximately 2 years duration. He was mainly maintained on risperidone 4-6 mg/day during this time. Upon his admittance to our clinic, he was suffering auditory hallucinations, persecutory delusions, social withdrawal and he was noticed to have had some involuntary mouth movements. The patient scored three out of four (moderate) on the ‘lips and peri-oral area’ subcategory of the- Abnormal Involuntary Movement Scale (AIMS). A cranial CT scan was unremarkable and there was no past history or family history of neuro-psychiatric disorders. He was started on aripiprazole 15 miligrams per day.ResultsWithin two weeks a marked improvement was seen in his psychotic symptoms and he scored 2 on the AIMS. Two months after starting aripiprazole, he was free of psychotic symptoms and dyskinetic movements.ConclusionAltough atypical antipsychotics are known to be associated with lower risk of developing tardive dyskinesia, psychiatrists should be aware of these rare conditions. Aripiprazole, as a partial dopamine agonist, might be an alternate pharmacotherapy in threating psychosis and atypical antipsychotic-induced TD.

Gabapentin adjunctive to risperidone or olanzapine in partially responsive schizophrenia: an open-label pilot study

BackgroundThere is a great need in the treatment of schizophrenia for a drug, or drug combinations, to improve clinical response with fewer serious side effects. The objective of this study was to explore the therapeutic effects and tolerability of the anticonvulsant gabapentin as an adjunctive in the treatment of patients with partially responsive schizophrenia.MethodsTen consenting patients with a confirmed Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision diagnosis of schizophrenia were identified. All patients failed at least one 12-week treatment trial with risperidone or olanzapine. Gabapentin was added to ongoing antipsychotic treatment with olanzapine or risperidone for eight weeks. The primary outcome measure was the Positive and Negative Syndrome Scale (PANSS). Other scales included the Calgary Depression Scale (CDSS) and the Abnormal Involuntary Movement Scale (AIMS). Repeated-measures multivariate analysis of variance was utilized to examine changes in outcome measures over time with adjunctive treatment with gabapentin.ResultsThere was a significant drop in the PANSS and CDSS scores at endpoint (week 8). There were no significant differences between the two treatment groups with regard to changes in all outcome measures or in AIMS score. The adjunctive treatments were well tolerated and side effects were transient.ConclusionGabapentin could be used successfully as an adjunct to novel antipsychotics in partially responsive schizophrenia. However, large controlled studies are needed to examine the effectiveness of gabapentin in psychotic disorders.

PW01-20 - Adjunctive aripiprazole in patients with major depressive disorder: pooled safety and tolerability data from three short-term studies

ObjectivesThe safety and tolerability of aripiprazole as adjunctive treatment was examined in patients with major depressive disorder (MDD) without psychotic features who had a major depressive episode and who did not respond adequately to standard antidepressant therapy (ADT).MethodsData from three identical short-term, double-blind, placebo-controlled studies (CN138139, CN138163, CN138165) were pooled. After a prospective phase with placebo plus ADT, patients without adequate response entered a 6-week, double-blind phase with placebo or aripiprazole plus ADT. Safety endpoints included death, serious adverse events (SAEs), treatment-emergent adverse events (AEs), Simpson-Angus Scale (SAS), Barnes Akathisia Global Clinical Assessment, Abnormal Involuntary Movement Scale (AIMS), clinical laboratory tests, vital signs and electrocardiograms.ResultsIn total, 538 patients were randomized to adjunctive placebo and 547 to adjunctive aripiprazole. AEs with an incidence ≥5% and at least twice the rate of placebo were akathisia (adjunctive aripiprazole, 22.7%; adjunctive placebo, 4.1%), restlessness (12.4% vs 2.2%), fatigue (8.6% vs 4.3%), insomnia (8.2% vs 3.2%), vision blurred (6.2% vs 1.5%), somnolence (5.9% vs 2.6%), and constipation (4.9% vs 2.4%). AEs that had a treatment difference of ≥2% included akathisia, somnolence, sedation, dizziness, disturbance in attention, extrapyramidal disorder, restlessness, insomnia, constipation, dyspepsia, fatigue, feeling jittery, vision blurred, weight increased, and dyspnea. SAEs occurred in 0.7% of patients in each treatment group. There were no deaths during the studies.ConclusionsIn this pooled analysis of patients with MDD and an inadequate response to ADT, adjunctive aripiprazole showed consistently high study completion rates and low discontinuation rates resulting from adverse events.

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.

A candidate gene study of tardive dyskinesia in the CATIE schizophrenia trial

Tardive dyskinesia (TD) is a movement disorder characterized by involuntary oro-facial, limb, and truncal movements. As a genetic basis for inter-individual variation is assumed, there have been a sizeable number of candidate gene studies. All subjects met diagnostic criteria for schizophrenia and were randomized to receive antipsychotic medications as participants in the Clinical Antipsychotic Trials of Intervention Effectiveness project (CATIE). TD was assessed via the Abnormal Involuntary Movement Scale at regular intervals. Probable TD was defined as meeting Schooler-Kane criteria at any scheduled CATIE visit (207/710 subjects, 29.2%). A total of 128 candidate genes were studied in 710 subjects-2,580 SNPs in 118 candidate genes selected from the literature (e.g., dopamine, serotonin, glutamate, and GABA pathways) and composite genotypes for 10 drug-metabolizing enzymes. No single marker or haplotype association reached statistical significance after adjustment for multiple comparisons. Thus, we found no support for either novel or prior associations from the literature.

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.

Increased S100B serum levels in schizophrenic patients with tardive dyskinesia: Association with dyskinetic movements

Several studies show that calcium-binding protein S100B is increased in schizophrenia and may be involved in the pathogenesis of tardive dyskinesia (TD). We therefore compared serum S100B levels in normal controls ( n = 60), schizophrenic patients with ( n = 32) and without TD ( n = 50). Assessments included the abnormal involuntary movement scale (AIMS) and the positive and negative syndrome scale (PANSS). Serum S100B levels were measured by enzyme-linked immunosorbent assay (ELISA). The results indicated that patients with TD had higher serum S100B levels than normals and those without TD. Serum S100B levels were positively correlated with AIMS scores in patients with TD. These data suggest that increased S100B levels may be related to neuro-degeneration, associated with TD pathophysiology.

No influence of FAT polymorphisms in response to aripiprazole

The aim of this study was to investigate possible influences of a set of markers in the FAT gene (rs2306987, rs2306990, rs2637777 and rs2304865) on efficacy and tolerability of aripiprazole in the treatment of schizophrenic patients. Efficacy was assessed at baseline and weeks 1, 2, 4, 6, 8 and 12 using the Clinical Global Impression Severity and Improvement scale (CGI-S; CGI-I), the Brief Psychiatric Rating Scale and the Schedule for the Assessment of Negative Symptoms scale. Side effects were evaluated by means of the Simpson-Angus Scale for Extrapyramidal Symptoms, the Barnes Akathisia Scale and the Abnormal Involuntary Movement Scale. Multivariate analyses were employed to test possible influences of single nucleotide polymorphisms on clinical and safety variables. Analysis of haplotypes was also performed. No relevant association between FAT variants and clinical or safety scores was observed. Haplotype analysis did not reveal any significant association with clinical and safety scores at any time as well. Our data suggest no association between investigated alleles and genotypes in FAT and response to aripiprazole. However, because several limitations characterize the present study, further investigations on larger studies are required.

Genomewide Association Study of Movement-Related Adverse Antipsychotic Effects

Understanding individual differences in the development of extrapyramidal side effects (EPS) as a response to antipsychotic therapy is essential to individualize treatment. We performed genomewide association studies to search for genetic susceptibility to EPS. Our sample consisted of 738 schizophrenia patients, genotyped for 492K single nucleotide polymorphisms (SNPs). We studied three quantitative measures of antipsychotic adverse drug reactions-the Simpson-Angus Scale (SAS) for Parkinsonism, the Barnes Akathisia Rating Scale, and the Abnormal Involuntary Movement Scale (AIMS)-as well as a clinical diagnosis of probable tardive dyskinesia. Two SNPs for SAS, rs17022444 and rs2126709 with p = 1.2 x 10(-10) and p = 3.8 x 10(-7), respectively, and one for AIMS, rs7669317 with p = 7.7 x 10(-8), reached genomewide significance (Q value < .1). rs17022444 and rs7669317 were located in intergenic regions and rs2126709 was located in ZNF202 on 11q24. Fourteen additional signals were potentially interesting (Q value < .5). The ZNF202 is a transcriptional repressor controlling, among other genes, PLP1, which is the major protein in myelin. Mutations in PLP1 cause Pelizaeus-Merzbacher disease, which has Parkinsonism as an occurring symptom. Altered mRNA expression of PLP1 is associated with schizophrenia. Although our findings require replication and validation, this study demonstrates the potential of genomewide association studies to discover genes and pathways that mediate adverse effects of antipsychotics.

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, 16-Week Study of Adjunctive Aripiprazole for Schizophrenia or Schizoaffective Disorder Inadequately Treated With Quetiapine or Risperidone Monotherapy

Combining antipsychotics is common practice in the treatment of schizophrenia. This study investigated aripiprazole adjunctive to risperidone or quetiapine for treating schizophrenia and schizoaffective disorder. In this multicenter, double-blind, 16-week, placebo-controlled study conducted at 43 American sites from July 2006 to October 2007, patients with chronic, stable schizophrenia or schizoaffective disorder diagnosed with DSM-IV-TR were randomly assigned to receive aripiprazole (2-15 mg/d) or placebo in addition to a stable regimen of quetiapine (400-800 mg/d) or risperidone (4-8 mg/d). The primary outcome measure was the mean change from baseline to endpoint (week 16, last observation carried forward) in the Positive and Negative Syndrome Scale (PANSS) total score. 323 subjects being treated with either risperidone (n = 177) or quetiapine (n = 146) were randomly assigned to receive adjunctive aripiprazole (n = 168) or placebo (n = 155). Baseline characteristics were similar (mean PANSS total score: aripiprazole, 74.5; placebo, 75.9) except for history of suicide attempts (aripiprazole, 27%; placebo, 40%). Nearly 70% of subjects in each arm completed the trial. Adjunctive aripiprazole and placebo groups were similar in the mean change from baseline to endpoint in the PANSS total score (aripiprazole, -8.8; placebo, -8.9; P = .942). The incidence of treatment-emergent adverse events was similar between groups. Mean changes in Simpson-Angus Scale, Abnormal Involuntary Movement Scale, and Barnes Akathisia Rating Scale scores were not statistically significantly different. Adjunctive aripiprazole was associated with statistically significantly greater decreases in mean serum prolactin levels from baseline than was adjunctive placebo (-12.6 ng/mL for aripiprazole vs -2.2 ng/mL for placebo; P < .001), an effect that was seen in the risperidone subgroup (-18.7 ng/mL vs -1.9 ng/mL; P < .001) but not in the quetiapine subgroup (-3.01 ng/mL vs +0.15 ng/mL; P = .104). The addition of aripiprazole to risperidone or quetiapine was not associated with improvement in psychiatric symptoms but was generally safe and well tolerated. Further research is warranted to explore whether antipsychotic combination therapy offers benefits to particular patient populations-for example, in cases of hyperprolactinemia. clinicaltrials.gov Identifier: NCT00325689.