Generation Antipsychotic Medications Research Articles

Improving Metabolic Syndrome Screening on Patients on Second Generation Antipsychotic Medication

AimThis quality improvement project aims at stressing the importance of screening for metabolic syndrome (MS) on patients with serious mental illness (SMI) managed with second generation antipsychotic (SGA) medication. MethodOne hundred charts of patients who were on SGA (n=100) were randomly selected from more than 1000 charts for the purpose of this project with (n=50) charts for pre-intervention and (n=50) charts for post intervention. A chi-square test of independence was calculated comparing the frequency of labs and vital done in pre-intervention and post-intervention period. ResultsA significant interaction was found [χ2(2)=32.67, p<.001] indicating that providers were more likely to order labs in postintervention (62%) than in pre-intervention (22%). No significant relationship was found for vital signs [χ2(1)=.542, p>.05]. The use of the screening and monitoring tool showed that gaps exist in the screening for MS among patients on SGA. Implication to practiceAdvanced health nurse practitioners are well placed to take the lead in screening, monitoring, and implementing the necessary measures to address MS among patients with serious mental illness.

AMDA Conference Keynoter Urges Critical Thinking About Drug Choices

AMDA Conference Keynoter Urges Critical Thinking About Drug Choices

Comparison of Resource use and Health Care Costs in New Initiators of Long-Acting Injectable (Lai) and Oral Second Generation Antipsychotics.

To measure health care utilization and costs among new initiators of LAI and oral second generation antipsychotics with schizophrenia or bipolar disorder. A large database of a commercially insured US population was used to index patients on their first treatment between 1/1/2011 and 12/31/2011. Patients were required to have ≥ 12 months pre-index and ≥ 12 months post-index, were new users of a second generation antipsychotic, and diagnosed with schizophrenia or bipolar disorder during their pre-index period. LAI and oral patients were matched 1: 3 using propensity scores. Mean differences in annual resource use and costs were compared across groups in an unadjusted difference-in-difference analysis: [ (LAI post - LAI pre) - (Oral post - Oral pre) ]. Initial selection identified 250 LAI and 8,356 oral treatment patients. Matching resulted in balanced cohorts of 204 LAI and 612 oral initiators. Annual hospitalizations and ER visits from pre-index to post-index was significantly lower in LAI initiators compared to oral initiators. Mean annual hospitalizations per LAI patient reduced from 1.09 to 0.51 (p < 0.0001) while that of the oral cohort reduced from 0.53 to 0.39 (p = 0.0011). This resulted in a net reduction of 0.45 annual hospitalizations per patient in the LAI cohort, using the oral cohort as a reference (p < 0.0001). Mean annual ER visits reduced from 1.72 to 1.03 per LAI patient compared to no change in the oral cohort, resulting in a net difference of 0.72 ER visits between the two groups (p <0.0001). The unadjusted difference-in-difference analysis showed a relative reduction in total health care costs of $4,997 in the LAI cohort compared to the oral cohort. Initiating treatment with an LAI resulted in greater reductions in hospitalizations and ER visits compared to oral second generation antipsychotic medications in patients with schizophrenia or bipolar disease.

Validation of the Glasgow Antipsychotic Side-Effect Scale (GASS) in Greece

The aim of the present study was to evaluate the linguistic adaptation and psychometric validation into the Greek language of the GASS scale for the assessment of side effects in patients treated with second generation antipsychotic medication. The GASS scale takes 5 minutes to complete (21 items for men and women) and contains self-explanatory questions in everyday plain English while providing a structured systematic method of reviewing antipsychotic side effects. The translation and cultural adaptation of the questionnaire was performed according to international standards. Internal consistency using the Cronbach α coefficient and test-retest reliability using the intraclass correlation coefficient (ICC) was used to assess the reliability of the instrument. Patient's sample consisted of 80 participants with a mean age of 42.6 years. Internal consistency and intraclass correlation coefficient were adequate (Cronbach α = 0.79 and ICC = 0.96). The test-retest percent agreement for the aforementioned categories was 95.9. Agreement was satisfactory according to Kappa coefficient which was equal to 0.78 (p<0.001).The Greek validation of the GASS scale shows appropriate feasibility, reliability, and discriminative performance as a patient-reported outcome to be used for the assessment of the impact of side effects on patients with schizophrenia.

Diet and exercise effects on aerobic fitness and body composition in seriously mentally ill adults

Low exercise capacity and high obesity levels are the main characteristics of people with serious mental illness (SMI). We conducted a pilot study on the effects of a 3-month exercise and dietary intervention on the aerobic capacity and body composition of obese adults with SMI taking Olanzapine, a second generation antipsychotic medication known to induce weight increments. Fifty adults with SMI (15 males and 35 females) followed a 3-month weight loss intervention programme based on exercise and diet. Pre- and post-intervention, a submaximal O2 exercise test was performed in order to assess O2max anthropometric and body composition measurements were also performed. All participants were obese (body mass index (BMI): 33.61 ± 0.91 kg/m2). Pre- and post-intervention, a submaximal O2 exercise test on the treadmill was performed in order to assess O2max anthropometric and body composition measurements were also performed. Significant reductions in body weight, BMI, body fat and waist circumference were found from pre to post (p < 0.01). O2max was significantly improved in both genders (males: pre: 30.63 ± 2.06 vs. post: 33.19 ± 1.77 ml.kg−1 min−1, females: pre: 25.93 ± 1.01 vs. post: 29.51 ± 1.06 ml.kg−1 min−1, p < 0.01). A significant correlation was found between the change in O2max and the change in body weight and BMI (p < 0.05). Multiple regression analysis revealed that the relative change in O2max explained approximately 26% of the variance in the changes for both BMI (p = 0.07) and body weight (p = 0.06). A treatment of exercise and diet improves the aerobic capacity and body composition of obese adults with SMI, despite the use of Olanzapine.

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Introduction: to compare the cost-effectiveness of the oral second generation anti psychotic medication Quetiapine with that of the intravenous centrally acting sedative Dexmedetomidine in the treatment of intensive care unit (ICU) delirium. We hypothesized that Quetiapine, when the oral route is accessible, is as effective as Dexmedetomidine in the treatment of ICU delirium, and is cheaper. Methods: In a single center retrospective medical record review, a total of 70 patients diagnosed with ICU delirium through the Confusion Assessment Method (CAM-ICU) scale between July 1,2010 and December 31,2012 and treated with either Quetiapine per os (35 patients) or intravenous Dexmedetomidine (35 patients), plus or minus Haldol, were included. The cost was assessed directly via the drug cost to pharmacy, the efficacy was related to resolution of delirium, ICU and hospital length of stay (LOS). Results: Deidentified data were collected on demographics, admission diagnosis, Acute Physiology and Chronic Health Evaluation II score, chronic health conditions, ICU and hospital LOS, ventilation duration, use of benzodiazepine drugs, outcome, and cost of the studied drugs. Baseline characteristics were similar between the 2 groups, the admission diagnosis did not differ significantly. The average dose of Dexmedetomidine was 0.92 mcg/kg/hr (0.2–1.5) v/s 65 mg/day (25–200) for Quetiapine. Haldol was used equally (5 patients in each group, average of 20 mg/patient); the Quetiapine group spent less days in the ICU and the hospital but the difference did not reach statistical significance (8.32 (2–35) v/s 11.35 (3–43), p=0.11) and 12.08 (4–35) v/s 14.67 (3–43), p=0.12 respectively). The days spent on the ventilator did not reach statistical significance (7.6 (1–35) for the Dexmedetomidine group v/s 4.6 (1–18), p=0.57). benzodiazepine drips or PRN doses were not used in any of the groups. 4 Patients expired in the Dexmedetomidine group v/s 7 in the other group (p=0.3). The delirium resolved in all the patients with a mean of 2.67 days (1–21) in the Dexmedetomidine group and 3.14 days (1–10) in the Quetiapine group (p=0.23). Quetiapine was used on an average of 6.35 days (1–25) v/s 2.94 (1–6) days for Dexmedetomidine. Dexmedetomidine average cost to pharmacy was 2013 USD per patient v/s 4.625 USD per patient for Quetiapine. Conclusions: Quetiapine is as effective as dexmedetomidine in treating ICU delirium and is at least 435 times less expensive.

Low dosage of aripiprazole induced neuroleptic malignant syndrome after interaction with other neuroleptic drugs

Aripiprazole is a 2nd generation antipsychotic medication, atypical neuroleptic used for treatment of schizophrenia improving symptoms such as hallucinations, delusions, and disorganized thinking. A potentially fatal symptom complex sometimes referred to as neuroleptic malignant syndrome (NMS) has been reported in association with administration of antipsychotic drugs, including aripiprazole. Rare cases of NMS occurred during aripiprazole treatment in the worldwide clinical database. The disease is characterized by a distinctive clinical syndrome of mental status change, rigidity, fever, and dysautonomia. We report on a 63-year old woman with depression syndrome who developed neuroleptic malignant syndrome after twelve days of aripripazole 5 mg per day. Our case is added to the small number already described and suggests the need for caution when aripripazole is added to increase the effect of other antipsychotics.

Les rechutes : causes et conséquences

Relapse after a first episode of schizophrenia is the recurrence of acute symptoms after a period of partial or complete remission. Due to its variable aspects, there is no operational definition of relapse able to modelise the outcome of schizophrenia and measure how the treatment modifies the disease. Follow-up studies based on proxys such as hospital admission revealed that 7 of 10 patients relapsed after a first episode of schizophrenia. The effectiveness of antipsychotic medications on relapse prevention has been widely demonstrated. Recent studies claim for the advantages of atypical over first generation antipsychotic medication. Non-adherence to antipsychotic represents with addictions the main causes of relapse long before some non-consensual factors such as premorbid functioning, duration of untreated psychosis and associated personality disorders. The consequences of relapse are multiple, psychological, biological and social. Pharmaco-clinical studies have demonstrated that the treatment response decreases with each relapse. Relapse, even the first one, will contribute to worsen the outcome of the disease and reduce the capacity in general functionning. Accepting the idea of continuing treatment is a complex decision in which the psychiatrist plays a central role besides patients and their families. The development of integrated actions on modifiable risk factors such as psychosocial support, addictive comorbidities, access to care and the therapeutic alliance should be promoted. Relapse prevention is a major goal of the treatment of first-episode schizophrenia. It is based on adherence to the maintenance treatment, identification of prodromes, family active information and patient therapeutical education.

Modafinil improves antipsychotic-induced parkinsonism but not excessive daytime sleepiness, psychiatric symptoms or cognition in schizophrenia and schizoaffective disorder: A randomized, double-blind, placebo-controlled study

ObjectiveTo examine the efficacy and safety of modafinil on parkinsonism and excessive daytime sleepiness (EDS), as well as on negative symptoms and cognitive abilities in patients with schizophrenia or schizoaffective disorder (DSM-IV criteria) in a randomized double-blind placebo-controlled 8-week study. MethodsTwenty-four male patients, who were aged 20–63years and on stable dose of second generation antipsychotic medications and with a negative symptom score of ≥20 on the Positive and Negative Syndrome Scale (PANSS), were randomized into either the modafinil (n=12) or placebo (n=12) group. The modafinil group received flexible does of modafinil 50–200mg/day. Primary measurements were the Simpson-Angus Scale (SAS) for extrapyramidal side effects (EPS), the Epworth Sleepiness Scale (ESS), the PANSS and a neuropsychological (NP) test battery. Data were collected on Days 0, 14, 28, 42 and 56 for rating scales, and on Days 0, 28 and 56 for NP tests. ResultsMixed model analyses showed a significant group-x-time interaction for total SAS scores (P<0.006), with scores decreasing in the modafinil group but remaining the same in the placebo group. There were no significant group-x-time interactions for scores of ESS (total), PANSS (total, positive and negative), and NP tests (composite and domains) (all P's>0.5). No significant adverse events were observed. ConclusionThe data suggest that modafinil was a safe adjunctive treatment which improved parkinsonian symptoms and signs in patients with schizophrenia or schizoaffective disorder. Further studies in larger samples and with longer study time are needed to test/confirm the beneficial effects of modafinil on motor function.

Hyperglycaemia in patients treated with second generation antipsychotics.

The association of second generation antipsychotic medications and hyperglycaemia has been reported for Caucasian populations but is unknown for asian patients who unfortunately are predisposed to diabetes. We report the findings from a health quality improvement project which tracked patients with schizophrenia and schizoaffective disorder newly started on second generation antipsychotics. 266 patients were newly started on second generation antipsychotics in a 2 year period. Amongst the baseline parameters monitored was the fasting plasma glucose levels. Repeat testing was done at 4 weeks, 12 weeks and 12 months. 14 patients were excluded form the analysis as they had diabetes at the start of treatment with second generation antipsychotics. Hyperglycaemia was found in 88 patients (34.9%). 68 (77.3%) of these patients experienced the Hyperglycaemia at 12 weeks, 3 patients (3.4%) at 4 weeks and 17 patients (19.3%) at 12 months. Fasting plasma glucose levels were highest at 4 weeks. Despite the limitations of the project, the one third prevalence of hyperglycaemia amongst patients newly started on second generation antipsychotics is a cause for concern and suggests the need for further extensive follow-up and assessment of the problem.

Drug treatments for schizophrenia: pragmatism in trial design shows lack of progress in drug design

Aims. The introduction of second generation antipsychotic (SGA) medication over a decade ago led to changes in prescribing practices; these drugs have eclipsed their predecessors as treatments for schizophrenia. However, the metabolic side effects of these newer antipsychotics have been marked and there are increasing concerns as to whether these novel drugs really are superior to their predecessors in terms of the balance between risks and benefits. In this article, we review the literature regarding comparisons between first generation antipsychotic (FGA) and SGA in terms of clinical effectiveness. Methods. Large (n>150) randomized-controlled trials (RCTs) comparing the effectiveness (efficacy and side effects) of FGA and SGA medications other than clozapine were reviewed, as were meta-analyses that included smaller studies. Results. The superiority in efficacy and reduced extrapyramidal side effects (EPSE) of SGAs is modest, especially when compared with low-dose FGAs. However, the high risk of weight gain and other metabolic disturbances associated with certain SGAs such as olanzapine is markedly higher than the risk with FGAs at the doses used in the trials. Conclusions. The efficacy profiles of various FGAs and SGAs are relatively similar, but their side effects vary between and within classes. Overall, large pragmatic trials of clinical effectiveness indicate that the care used in prescribing and managing drug treatments to ensure tolerability may be more important than the class of drug used.

Improving metabolic parameters of antipsychotic child treatment (IMPACT) study: rationale, design, and methods.

BackgroundYouth with serious mental illness may experience improved psychiatric stability with second generation antipsychotic (SGA) medication treatment, but unfortunately may also experience unhealthy weight gain adverse events. Research on weight loss strategies for youth who require ongoing antipsychotic treatment is quite limited. The purpose of this paper is to present the design, methods, and rationale of the Improving Metabolic Parameters in Antipsychotic Child Treatment (IMPACT) study, a federally funded, randomized trial comparing two pharmacologic strategies against a control condition to manage SGA-related weight gain.MethodsThe design and methodology considerations of the IMPACT trial are described and embedded in a description of health risks associated with antipsychotic-related weight gain and the limitations of currently available research.ResultsThe IMPACT study is a 4-site, six month, randomized, open-label, clinical trial of overweight/obese youth ages 8–19 years with pediatric schizophrenia-spectrum and bipolar-spectrum disorders, psychotic or non-psychotic major depressive disorder, or irritability associated with autistic disorder. Youth who have experienced clinically significant weight gain during antipsychotic treatment in the past 3 years are randomized to either (1) switch antipsychotic plus healthy lifestyle education (HLE); (2) add metformin plus HLE; or (3) HLE with no medication change. The primary aim is to compare weight change (body mass index z-scores) for each pharmacologic intervention with the control condition. Key secondary assessments include percentage body fat, insulin resistance, lipid profile, psychiatric symptom stability (monitored independently by the pharmacotherapist and a blinded evaluator), and all-cause and specific cause discontinuation. This study is ongoing, and the targeted sample size is 132 youth.ConclusionAntipsychotic-related weight gain is an important public health issue for youth requiring ongoing antipsychotic treatment to maintain psychiatric stability. The IMPACT study provides a model for pediatric research on adverse event management using state-of-the art methods. The results of this study will provide needed data on risks and benefits of two pharmacologic interventions that are already being used in pediatric clinical settings but that have not yet been compared directly in randomized trials.Trial registrationClinical Trials.gov NCT00806234

Neurobiology and Effectiveness of Antipsychotic Drugs in Resistant Obsessive-Compulsive Disorder: A Systematic Review

A systematic review of the literature was conducted using PRISMA criteria. The paradigm search was “obsessive compulsive disorder and antipsychotic agents”. Medline, Cochrane and Web of science databases were explored without date or language restriction. Case reports, open label studies and randomized double-blind controlled trials were included in the qualitative review. Unlike the classical serotonergic hypothesis, OCD may result from striatal dopaminergic hyperactivity, modulated in some patients by an underlying serotonergic hypo activity. In the treatment of resistant OCD, most studies report the effectiveness of first-generation antipsychotic (haloperidol, amisulpride) and some second-generation antipsychotics (risperidone, olanzapine, aripiprazole, quetiapine) in combination with an SSRI. Moreover, in case reports, recrudescence or onset of OCD symptoms in patients with schizophrenia have been described in a switch from first generation antipsychotic medication to olanzapine, risperidone, aripiprazole or clozapine, but not within a switch to amisulpride or quetiapine.

Fatal Diabetic Ketoacidosis and Antipsychotic Medication

Hyperglycemia and new onset diabetes have been described with certain antipsychotic medications and some of the initial presentations are fatal diabetic ketoacidosis (DKA). We report 17 deaths due to DKA in psychiatric patients treated with second generation antipsychotic medications. Death certificates and toxicology data were searched for DKA and hyperglycemia. We reviewed the medical examiner records which included the autopsy, toxicology, police, and medical examiner investigators' reports. The decedents ranged in age from 32 to 57years (average 48years). There were 15 men and two women. The immediate cause of death was DKA in all. The psychiatric disorders included: 10 schizophrenia, three bipolar/schizophrenia, two bipolar, and two major depression. The most frequent atypical antipsychotic medications found were quetiapine and olanzapine followed by risperidone. In 16 deaths, we considered the medication as primary or contributory to the cause of death.

Metabolic Syndrome: Relative Risk Associated with Post-Traumatic Stress Disorder (PTSD) Severity and Antipsychotic Medication Use

In recent years, numerous lines of converging evidence have revealed an association between post-traumatic stress disorder (PTSD) and impaired physical health outcomes, including cardiovascular disease and metabolic syndrome. Although these findings have been interpreted as indicating a direct association of PTSD with metabolic syndrome and obesity, previous studies have not addressed the important confound of antipsychotic drug usage in this population. Second generation antipsychotic medications themselves are associated with metabolic syndrome and obesity, and it is unclear whether the common utilization of these drugs in PTSD may account for some if not all of the observed metabolic problems. The present study examined the relative contributions of PTSD severity and use of antipsychotic medications to risk of metabolic syndrome among veterans. Cross-sectional clinical data, including five factors representing metabolic syndrome, psychiatric diagnoses, and medications were gathered from 253 veterans enrolling in mental health services. We used a logistic regression model to measure the relative association of antipsychotic medication use and PTSD severity on risk of metabolic syndrome. We found that antipsychotic medication usage was not uniquely associated with elevated risk of metabolic syndrome (Wald = 0.30, ns) when PTSD severity and other sociodemographic, psychiatric, and behavioral variables were accounted for. Furthermore, PTSD severity continued to be a significant and unique predictor of risk for metabolic syndrome (Wald = 4.04, p < 0.05). These findings suggest that chronic and moderately severe PTSD, independent of antipsychotic medications, is associated with increased risk of metabolic syndrome.

A randomized controlled trial undertaken to test a nurse‐led weight management and exercise intervention designed for people with serious mental illness who take second generation antipsychotics

AimTo test the effect of a nurse-led intervention on weight gain in people with serious mental illness prescribed and taking second generation antipsychotic medication.BackgroundWeight gain and obesity has reached epidemic proportions in the general population with the prevalence of Metabolic Syndrome reaching 20–25% of the global population. People with serious mental illness are at even higher risk, particularly those taking second generation antipsychotic medication.DesignAn experimental randomized controlled trial was undertaken.MethodThe control group received a 12-week healthy lifestyle booklet. In addition to the booklet, the intervention group received weekly nutrition and exercise education, exercise sessions, and nurse support. Participants (n = 101) were assessed at baseline and 12 weeks. Data were collected between March 2008–December 2010. Seven outcome measures were used: body measurements included girth (cm), weight (kg), height (cm), and body mass index (kg/m2); questionnaires included the medication compliance questionnaire, the Drug Attitude Inventory, the Liverpool University Neuroleptic Side Effect Rating Scale, and the Medical Outcomes Study Short Form 36. Differences in primary outcome measures between baseline and 12 weeks follow-up were compared between intervention and control groups using standard bi-variate statistical tests. The study was conducted between 2008–2010.ResultsThe analysis of outcome measures for the control group (n = 50) and intervention group (n = 51) was not statistically significant. There was a mean weight change of −0·74 kg at 12 weeks for the intervention group (n = 51), while the control group (n = 50) had a mean weight change of −0·17 kg at 12 weeks.ConclusionThe results were not statistically significant.

CA4-05: Electronic Health Record Phenotyping to Define Rate of Extreme Weight Gain Associated with the Use of 2nd/3rd Generation Antipsychotic Medications

Background/AimsWeight gain is an undesirable side effect of treatment with 2nd/3rd generation antipsychotic drugs which may have genetic determinants. A number of candidate genes have been analyzed but no genome-wide association studies (GWAS) have yet been reported. The purpose of this study was to determine the rate of extreme weight gain (EWG) among adult users of 2nd/3rd generation antipsychotic medications for future GWAS.MethodsA standardized dataset was extracted on antipsychotic medications users at Group Health and Geisinger Health System from 2004–2010 that included demographics, enrollment, vitals, and pharmacy data. Electronic health record search algorithms were used to identify adult subjects with body weight increases of 15%+ within one year of the initiation of new 2nd/3rd generation antipsychotic drugs. To adjudicate the association of EWG with drug treatment, SAS was used to plot and visually inspect a single graph for each episode that encompassed all weight measurements, antipsychotic orders/fills, pregnancy- and cancer-related visits, and steroid and insulin orders/fills over time. The rate of EWG was then compared among the common types of antipsychotic medications.ResultsThere were 7128 episodes of antipsychotic use that qualified for analysis (5251 patients). The most common medication types were quetiapine (n=2543), risperidone (n=1817), aripiprazole (n=1315), olanzapine (n=971), and ziprasidone (n=413). The least common medications were clozapine (n=37), olanzapine/fluoxetine (n=23), and paliperidone (n=9). EWG was identified for 275 of the 7128 episodes (3.86 per 100 episodes). EWG was significantly different among common medication types (p-value<0.0001). EWG was highest for olanzapine (5.46 per 100 episodes, 95% CI=[4.77, 6.24]), followed by quetiapine (3.93 per 100 episodes, 95% CI=[3.25, 4.75]), risperidone (3.58 per 100 episodes, 95% CI=[3.14, 4.07]), and aripiprazole (3.50 per 100 episodes, 95% CI=[2.65, 4.62]). For ziprasidone, EWG was 2–3 fold lower (1.69 per 100 episodes, 95% CI=[1.46, 1.96]). EWG was not significantly different between Geisinger and Group Health (4.43 per 100 episodes versus 3.65 per 100 episodes, p=0.157).DiscussionRates of EWG differed significantly by type of 2nd/3rd generation antipsychotic medication, which was consistent in two geographically diverse populations. Future GWAS may help determine if genetic determinants of EWG are drug specific.

Case reports of atypical (second generation) antipsychotic overdose in adolescents

Introduction Atypical (second generation) antipsychotics are increasingly being used in psychiatry, due to better efficacy and side effect profile. Reports of intentional overdose with these drugs in adolescents are rare. Cardiovascular toxicity was common with first generation (older) antipsychotic medications, but less common with second generation antipsychotic medications. Aim To describe various presentations and cardiovascular system effects of atypical antipsychotic overdose in adolescents. Methods Retrospective study of case notes of adolescents admitted to paediatric ward with atypical antipsychotic overdose. Description We report three adolescents who presented to our hospital during a single month with an overdose of atypical antipsychotics, which had been prescribed to family members or friends. 1)15 year old male presented with agitation, dystonia, constricted pupils and a GCS fluctuating between 6 to 11. ECG showed sinus tachycardia, ST depression and tall T-waves. History of Olanzapine overdose was revealed retrospectively (Olanzapine level - 373 mcg/ml). 2)15 year old female with a history of Clozapine overdose presented with a GCS of 8 along with hyper-salivation. She had tachycardia, hypotension and prolonged QTc interval. 3)13 year old girl with Quetiapine overdose presented with a GCS of 14 and prolonged QTc interval on ECG. Results All patients needed High Dependency Care to monitor for potential cardio-respiratory problems. Their baseline blood tests were normal. They responded well to supportive treatment and made a full recovery. Summary All 3 adolescents with atypical antipsychotic overdose presented with depressed consciousness and ECG changes. Other signs included agitation and pupillary constriction with Olanzapine (mimicking Opioid overdose) and hyper-salivation with Clozapine. All had normal blood tests and made a complete recovery within 48 hours. Conclusions With increasing access to atypical antipsychotics, overdose with these medications should be considered in the differential diagnosis of children presenting with unexplained sedation and electrocardiographic changes. Olanzapine should be thought in addition to opioid and alpha 2 adrenergic agonists overdose in patients with depressed mental status and miosis.

Are neurocognitive, clinical and social dysfunctions in schizotaxia reversible pharmacologically? Results from the Changsha study

The Changsha study identifies adult, non-psychotic relatives of patients with schizophrenia who show deficits in neurocognitive, social, clinical and other dimensions, and who meet provisional criteria for a liability syndrome for schizophrenia (‘schizotaxia’). In this study, we investigated whether negative symptoms, neurocognitive deficits, or other measures of clinical and social function in subjects who met our research criteria for schizotaxia were amenable to pharmacological remediation with a low dose (2.0mg) of risperidone, a second generation antipsychotic medication. One hundred eighty nine relatives were assessed at the Mental Health Institute, Second Xiangya Hospital of Central South University, Changsha (Hunan Province, China), between 12/06 and 12/08. Eighty six of these individuals met modified criteria for schizotaxia, and 36 agreed to enter a 6-week, double-blind, placebo-controlled protocol. ANCOVAs using age and gender as covariates showed significant improvement in the risperidone group (n=20) on neurocognitive function (Wisconsin Card Sorting Test Total Errors and Perseverative Errors) and on a self-report measure of social function (Social Adjustment Scale), compared to the placebo-control group (n=16). Effect sizes were small to medium. Notably, risperidone effect sizes were larger (medium to large) in a subset of subjects (risperidone=15; placebo=10) whose membership in the schizotaxic group was supported empirically by cluster analysis. Negative symptoms did not change significantly in either analysis. The results are generally consistent with previous open-label investigations of risperidone administration in subjects with schizotaxia, and provide evidence that some neurocognitive and clinical problems are amenable to remediation in non-psychotic relatives of people with schizophrenia.

Applied monitoring for tardive dyskinesia and other extrapyramidal side effects

While the rate of tardive dyskinesia (TD) and other extrapyramidal side effects (EPSE) is lower with second generation antipsychotic medications compared to first generation antipsychotic medications, these side effects remain of clinical concern. This paper reviews the basis for the continued concern and the importance of secondary prevention, or early detection, within the primary-secondary-tertiary prevention model. The importance of standardized assessment instruments, education, and training is reviewed. Given the widespread use of antipsychotic drugs, the fact that antipsychotic drugs are the standard of care for several psychiatric conditions (with little indication that the magic bullet is on the immediate horizon to replace current antipsychotic drugs) applied monitoring and the early detection of TD and EPSE takes on added importance.