Effects of Clozapine on Neurocognitive Functions in Schizophrenia: A Naturalistic Comparison to Non-clozapine Antipsychotics.

OBJECTIVE: While clozapine is recognized as the most effective antipsychotic for individuals with treatment-resistant schizophrenia, its effects on neurocognition remain unclear. This study aimed to compare the neurocognitive effects of clozapine treatment to those of non-clozapine antipsychotics in patients with schizophrenia and to examine the role of anticholinergic burden on cognitive impairments. DESIGN: This was a naturalistic study. Cross-sectional data were drawn from participants with chronic schizophrenia in two clinical trials assessing cognition. Cognition was evaluated using the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB). Anticholinergic burden was calculated for each medication using the Anticholinergic Cognitive Burden (ACB) scoring system. We stratified the participants treated with non-clozapine antipsychotics into high ACB score versus low ACB score groups. RESULTS: One hundred and seventy participants were enrolled and treated with clozapine (n=58) or non-clozapine antipsychotics (n=112). We observed no significant differences in the MCCB T-scores between the clozapine and the total non-clozapine groups for the cognitive composite score and the seven domain scores. However, the non-clozapine high ACB group showed significant impairments in processing speed and attention/vigilance, in contrast to the non-clozapine low ACB group (p<0.05). CONCLUSION: Our results show that cognitive effects of clozapine might be no different from other antipsychotics. Negative effects on neurocognition in participants treated with antipsychotics with a high ACB score were related to their total ACB score.

Transcranial direct-current stimulation in ultra-treatment-resistant schizophrenia.

BACKGROUND: Transcranial direct-current stimulation (tDCS), a non-invasive neurostimulation treatment, has been reported in a number of sham-controlled studies to show significant improvements in treatment-resistant auditory hallucinations in schizophrenia patients, primarily in ambulatory and higher-functioning patients, but little is known of the effects of tDCS on hospitalized, low-functioning inpatients. OBJECTIVE/HYPOTHESIS: The purpose of this study was to examine the efficacy and safety of tDCS for auditory hallucinations in hospitalized ultra-treatment-resistant schizophrenia (TRS) and to evaluate the effects of tDCS on cognitive functions. We hypothesized that treatment non-response reported in previous tDCS studies may have been due to the insufficient duration of direct-current stimulation. METHODS: Inpatient participants with DSM-V schizophrenia, long-standing treatment-resistance, and auditory verbal hallucinations (AVH) participated in this 4-week sham-controlled, randomized trial. Assessments included the Positive and Negative Syndrome Scale (PANSS) and MATRICS Consensus Cognitive Battery (MCCB) at baseline and endpoint (at the end of Week 4), and the Auditory Hallucinations Rating Scale (AHRS) administered at baseline, endpoint, and weekly throughout the study. Participants were randomized to receive active vs. sham tDCS treatments twice daily for 4 weeks. RESULTS: Twenty-eight participants were enrolled (tDCS, n = 15; control, n = 13) and 21 participants completed all 4 weeks of the trial. Results showed a significant reduction for the auditory hallucination total score (p ≤ 0.05). We found a 21.9% decrease in AHRS Total Score for the tDCS group and a 12.6% decrease in AHRS Total Score for the control group. Significant reductions in frequency, number of voices over time, length of auditory hallucinations, and overall psychopathology were also observed for the tDCS group. When assessing cognitive functioning, only Working Memory showed improvement for the tDCS group. CONCLUSION: Although there was only a small improvement noted in auditory hallucination scores for the tDCS group, this improvement was meaningful when compared to no standard treatment of the control group. While this makes the interpretation of clinical significance debatable, it does confirm that tDCS combined with pharmacological intervention can provide clinical gains over pharmacological intervention alone. Therefore, tDCS treatment appears to be effective not only for ambulatory, higher-functioning patients, but also for patients with ultra-treatment-resistant schizophrenia.

The relationship of cognitive improvement after cognitive remediation with social functioning in patients with schizophrenia and severe cognitive deficits.

BACKGROUND: This study aims to examine the effects of change in neurocognition on functional outcomes and to examine predictors of change in social functions following a 12-week course of cognitive remediation in patients with schizophrenia and schizoaffective disorder with severe cognitive impairments. METHOD: Level of social functioning was assessed using a performance based measure of functional capacity (PSP) in patients prior to and after the completion of 12-week cognitive remediation treatment (CRT). Participants completed a neuropsychological battery (MCCB-MATRICS) and clinical measures at both time points. RESULTS: 63 subjects with a mean age of 41.4 (SD=12.2) and with 12.2years of education (SD=2.4) were enrolled. There were significant improvements in overall PSP score from baseline to endpoint (p=0.021) as well as in PSP domain A (socially useful activities) (p≤0.001), domain B (personal and social relationships) (p=0.009), and domain D (disturbing and aggressive behaviors) (p=0.003). There was a significant improvement in the composite MCCB score (p=0.020) and the Working Memory (p<0.046). Stepwise logistic regression yielded a significant association for baseline Visual Learning (Wald=6.537, p=0.011, OR=1.195), Speed of Processing (Wald=4.112, p=0.043, OR=0.850) and level of PANSS positive symptoms (Wald=4.087, p=0.043, OR=0.739) with PSP overall improvement. CONCLUSIONS: Faster speed of processing, better visual and verbal learning and less prominent positive symptoms were associated with greater functional improvement after a systematic cognitive intervention within a rehabilitative setting.

A six month randomized controlled trial of long acting injectable risperidone 50 and 100mg in treatment resistant schizophrenia.

It has been suggested that atypical antipsychotic drugs (A-APDs) other than clozapine may be effective to improve positive symptoms in some patients with treatment resistant schizophrenia (TRS), if both the dose is higher, and the duration of the trial longer, than those which have been ineffective in non-TRS (NTRS) patients. This hypothesis was tested with long acting injectable risperidone (Risperdal Consta®, RLAI). One hundred sixty TRS patients selected for persistent moderate-severe delusions or hallucinations, or both, were randomized to RLAI, 50 or 100mg biweekly, in a six month, outpatient, double-blind, multicenter trial. We hypothesized that RLAI, 100mg, would be more effective than RLAI, 50mg. However, both doses produced clinically significant and equivalent improvement in PANSS Total, Positive, and Negative subscale scores, as well as key cognitive, global and functional measures, with increasing response during the course of the study, confirming the value of longer clinical trial duration for patients with TRS, but not superiority of the higher dose. The overall response rate was comparable to that previously reported for clozapine and high dose olanzapine, another A-APD, in TRS. Both doses of RLAI were equally well tolerated, producing minimal extrapyramidal side effects and few drop outs. Plasma levels of the active moiety, risperidone+9-hydroxyrisperidone, during treatment with RLAI 100mg, were comparable to those for 6-8 mg/day oral risperidone, which have not been effective in TRS. Further study of RLAI, ≥ 50-100mg biweekly, should compare it with clozapine and oral risperidone in TRS, with duration of treatment ≥ six months.

Pomaglumetad methionil: no significant difference as an adjunctive treatment for patients with prominent negative symptoms of schizophrenia compared to placebo.

This study tested whether treatment with pomaglumetad methionil (LY2140023 monohydrate), a metabotropic glutamate receptor 2/3 agonist compared with placebo (PBO), when added to a fixed-dose second-generation antipsychotic (SGA) demonstrated significantly greater reduction of negative symptoms, as assessed by the 16-item Negative Symptom Assessment scale (NSA-16), in patients with schizophrenia. This parallel-group, 16-week study enrolled adults with schizophrenia who were receiving standard of care (SOC) therapy, which included ≥3months treatment with one of four SGAs: aripiprazole, olanzapine, risperidone, or quetiapine. Patients received either 20mg of twice daily LY2140023 monohydrate (LY2140023) or concurrent PBO SGA. The primary efficacy measure was change from baseline to final visit in NSA-16 total score. Secondary measures included additional measures of efficacy, cognition, and assessments of safety. Of 352 patients screened, 167 were randomly assigned to treatment, and 110 patients completed the study. Patients treated with LY2140023 and SOC failed to demonstrate a statistically significant improvement over patients treated with PBO and SOC on NSA-16 total score at endpoint or at any point during the study (all p>0.131). Changes in secondary efficacy measures were not significantly different between groups at endpoint. With the exception of vomiting which was greater in the LY2140023 group, there were no statistically significant differences in safety and tolerability measures. This study found no benefit of adjunctive LY2140023 versus PBO for negative symptoms in patients with schizophrenia receiving treatment with SOC. LY2140023 was generally well-tolerated in these patients.

Therapeutic antibiotic use patterns in dogs: observations from a veterinary teaching hospital.

OBJECTIVES: To describe therapeutic antibiotic use patterns in dogs at a small animal teaching hospital. METHODS: A retrospective case analysis of randomly sampled antibiotic prescriptions in dogs from May 20, 2008 to May 20, 2009, deemed to be for therapeutic use, was performed. Records were reviewed to determine if there was documentation of confirmed, suspected or no evidence of infection. The five most frequently prescribed antibiotics were identified and analysed for their distribution in these categories. RESULTS: In 17% of therapeutic antibiotic prescriptions there was confirmed infection, in 45% suspected infection, and in 38% there was no documented evidence of infection. Amoxicillin-clavulanate was the most frequently prescribed antibiotic, followed by cefazolin/cephalexin, enrofloxacin, ampicillin/amoxicillin and doxycycline. Doxycycline was the most frequently prescribed with no documented evidence of infection, and amoxicillin-clavulanate was the most frequently prescribed with either confirmed or suspected evidence of infection. DISCUSSION: Clinicians use a variety of tools when deciding whether or not to prescribe an antibiotic and which antibiotic to use. As in human medicine, there is likely overuse and inappropriate use of antibiotics in veterinary medicine. Veterinarians should engage in discussions regarding clinically applicable guidelines for appropriate antibiotic use.

Long-acting injectable antipsychotics: focus on olanzapine pamoate.

Medication non-adherence in patients with schizophrenia continues to be a significant problem and threatens successful treatment outcomes. Medication non-adherence is often associated with negative consequences, including symptom exacerbation, more frequent emergency room visits, re-hospitalizations and relapse. Long-acting injectable (LAI) forms of antipsychotics allow for rapid identification of non-adherence, obviate the need for the patient to take the medication on a daily basis and increase adherence to some significant degree. Eli Lilly has developed a long-acting depot formulation of olanzapine, olanzapine pamoate, which has recently been approved by the FDA for the US market, and which will be reviewed here. Olanzapine LAI appears to be an effective antipsychotic at dosages of 210 mg every 2 weeks, 300 mg every 2 weeks and 405 mg every 4 weeks in patients with acute schizophrenia, and at 150 mg every 2 weeks, 300 mg every 2 weeks and at 405 mg every 4 weeks for the maintenance treatment of stable patients. Oral supplementation appears not to be needed, particularly not at the onset of treatment with the LAI as is necessary with risperidone LAI. Its efficacy is in general comparable to the efficacy seen with oral olanzapine at a corresponding dose. The side effect profile is also comparable to the side effects observed with oral olanzapine, including lower rates of extrapyramidal symptoms, prolactin elevation and cardiovascular side effects, but significant metabolic effects. The latter include significant weight gain, lipid abnormalities and glucose dysregulation. While the injection site adverse events are overall mild, the most significant serious adverse event is the post-injection delirium sedation syndrome (PDSS). While rare, this syndrome results from inadvertent intravascular injection of olanzapine LAI and can cause a range of olanzapine overdose-type of symptoms. Olanzapine LAI needs therefore to be administered by trained personnel in settings where a post-injection observation period for at least 3 hours by medical personnel is available. The overall use of olanzapine LAI will probably be limited by the possibility of a PDSS event. Patients who have a history of good response to oral olanzapine and are in need of assured medication administration may present a good indication for its use, provided that the appropriate mental health delivery setting is available.

Schizophrenia with impulsive and aggressive behaviors.

Impulsive and aggressive behaviors are important clinical challenges in the treatment of patients with schizophrenia. They occur both in the acute phase as well as in the chronic phase of the disorder and call for differentiated treatment interventions. It is important to always first consider behavioral and nonpharmacological interventions. High levels of structure and organization together with a nonconfrontational approach may be very successful interventions. In terms of acute pharmacological interventions, clinicians now have a broad spectrum of intramuscular antipsychotic compounds available with rapid onset of action and relatively little sedation. There is a need for new compounds with a more acceptable tolerability profile for the long-term treatment of these important syndromes.

N-desmethylclozapine: is there evidence for its antipsychotic potential?

OBJECTIVE: N-Desmethylclozapine (NDMC), one of clozapine's major metabolites, has become a recent focus of study for both its antipsychotic and metabolic effects. The aim of this review is to examine NDMC's biological activity in the context of the pathophysiology of schizophrenia and to critically evaluate the few recent preclinical and clinical studies of NDMC's potential antipsychotic effects to predict its therapeutic potential. RESULTS: We review the complex interaction between clozapine and NDMC at relevant receptor sites, notably at M1 sites where NDMC acts as an agonist and clozapine acts as an antagonist, and at D2 and D3 receptor sites, where NDMC acts as a partial agonist and clozapine as an inverse agonist. In terms of its antipsychotic potential, there is some support that higher NDMC/clozapine concentration ratios may be associated with symptom improvement; however, there are little data on NDMC alone as having specific potential antipsychotic effects. At best, NDMC shows efficacy only at very high doses in preclinical studies, particularly based on its muscarinic M1 agonism with a potential as a procognitive compound. Regarding metabolic effects, it seems that NDMC may be associated with more metabolic side effects than the parent compound clozapine, which may therefore reduce its overall tolerability profile. CONCLUSION: Although there is some suggestion based on animal data that NDMC may have a somewhat different biological profile than clozapine, clinical data on its antipsychotic efficacy are scant at this point. This makes it necessary to test NDMC alone compared with established antipsychotic compounds in clinical trials to elucidate its effects on schizophrenia symptoms, clinical outcome, and physiologic/metabolic side effects.

Schizophrenia: measurements of psychopathology.

A key problem in schizophrenia research is how to assess the effects of treatment interventions given the spectrum of schizophrenia symptoms and patients' functioning. Measuring symptoms is complex, because these symptoms cover a wide variety of psychopathologic domains. The commonly recognized domains are the positive, negative, cognitive, excitement, and depression domains. This article critically reviews some of the available assessment tools of these domains together with other associated syndromes. The instruments discussed cover the broad range of psychopathology found in patients who have schizophrenia.

Transcultural differences in suicide attempters: analysis on a high-risk population of patients with schizophrenia or schizoaffective disorder.

The aim of the study was to investigate transcultural differences between schizophrenia spectrum disorder patients who did or did not attempt suicide. DSM-IV schizophrenia (N=609) or schizoaffective disorder (N=371) patients who participated in the multicentre International Suicide Prevention Trial (InterSePT) were studied. Patients were sub-divided into 5 groups according to the different geographical regions of recruitment: North America (NA), Europe (EUR), East Europe (EEUR), South Africa (SAf), and South America (SA). The main lifetime clinical variables were compared, within each group, between attempters and non-attempters. The presence of comorbid substance abuse disorder and smoking was associated with suicide attempts in all the geographical groups considered (NA: chi(1)(2)=7.575, p<0.01 and chi(1)(2)=69.549, p<0.0001; EUR: chi(1)(2)=55.068, p<0.0001, and chi(1)(2)=48.431, p<0.0001; EEUR: chi(1)(2)=164.628, p<0.000, and chi(1)(2)=5.127, p<0.01; SA: chi(1)(2)=30.204, p<0.0001 and chi(1)(2)=11.710, p=0.001) except for SAf. For the other clinical variables various differences were found across the different groups. Variables related to suicide behavior were similar across the five groups investigated, with differences only in the age at the first suicide attempt (earlier in the NA sample) and the number of lifetime suicide attempts (higher in the NA sample). Results from this study show that, while some suicide-related clinical characteristics in schizophrenia patients are consistent worldwide suggesting the influence of stable biological traits, other variables may vary across different geographical areas suggesting environmental influences.

Pharmacological treatment strategies for schizophrenia.

The pharmacological choices for the treatment of schizophrenia have been greatly expanded with the availability of the atypical compounds clozapine (Clozaril, Novartis), risperidone (Risperdal, Janssen-Cilag), olanzapine (Zyprexa, Eli Lilly & Co.), quetiapine (Seroquel, AstraZeneca), ziprasidone (Geodon, Pfizer Inc.) and aripiprazole (Abilify, Otsuka Pharmaceutical Co. Ltd). In this article, the effects of the newer antipsychotics and their side effects are reviewed. Key issues in acute and maintenance treatment, often lifelong, will be reviewed. Side-effect management to ensure adherence to an optimal treatment regimen will be discussed. Coexisting syndromes must be treated in concordance with the patient's clinical presentation. For treatment-resistant patients, atypical compounds are generally more effective than their typical counterparts but medication augmentation strategies are frequently recommended. Finally, the results of recent meta-analyses comparing the effects of atypical versus typical compounds will be critically reviewed and remaining gaps in the current pharmacotherapy of schizophrenia will be explored.

The InterSePT scale for suicidal thinking reliability and validity.

BACKGROUND: The InterSePT Scale for Suicidal Thinking (ISST) is a 12-item instrument for the assessment of current suicidal ideation in patients with schizophrenia and schizoaffective disorders. We report the psychometric characteristics of this new scale based on two studies. METHOD: In Study 1, 22 inpatients with schizophrenia and schizoaffective disorders, who had recently attempted suicide or engaged in suicidal ideation, were rated by three trained independent raters to examine interrater reliability. In Study 2, a total of 980 patients with schizophrenia or schizoaffective disorder with a history of suicidal ideation in the past 36 months were enrolled in a 2-year industry-sponsored suicide prevention study. At baseline, these patients were administered the ISST and the Clinical Global Impression Scale for Severity of Suicidality (CGI-SS) by the Principal Investigator (PI) and by a blinded rater (BR), who also administered the Positive and Negative Symptom Scale (PANSS), the Calgary Depression Scale (CDS), and the Scale of Functioning (SOF). Indices of internal reliability, construct and discriminant validity were examined. RESULTS: The intraclass correlation coefficient (ICC) for the total ISST score for the 22 subjects in Study 1 was 0.90 and mean weighted item kappa coefficients ranged from 0.66 to 0.92. In Study 2, internal reliability (Cronbach alpha) was high, ranging from 0.86 to 0.89 for the individual items, and the overall Cronbach alpha coefficient for all items was 0.88. The ISST (PI) total score was highly correlated with the CGI-SS by the blind rater (r = 0.61, p < 0.0001). ISST total scores significantly differentiated the different levels of CGI-SS (F = 519.2; p < 0.0001). Results of construct and discriminant validity analyses are also presented. CONCLUSION: The ISST is a reliable and valid instrument for the assessment of current suicidal thinking in patients with schizophrenia and schizoaffective disorder by both clinicians and researchers.

Clozapine treatment for suicidality in schizophrenia: International Suicide Prevention Trial (InterSePT).

BACKGROUND: Approximately 50% of patients with schizophrenia or schizoaffective disorder attempt suicide, and approximately 10% die of suicide. Study results suggest that clozapine therapy significantly reduces suicidal behavior in these patients. METHODS: A multicenter, randomized, international, 2-year study comparing the risk for suicidal behavior in patients treated with clozapine vs olanzapine was conducted in 980 patients with schizophrenia or schizoaffective disorder, 26.8% of whom were refractory to previous treatment, who were considered at high risk for suicide because of previous suicide attempts or current suicidal ideation. To equalize clinical contact across treatments, all patients were seen weekly for 6 months and then biweekly for 18 months. Subsequent to randomization, unmasked clinicians at each site could make any interventions necessary to prevent the occurrence of suicide attempts. Suicidal behavior was assessed at each visit. Primary end points included suicide attempts (including those that led to death), hospitalizations to prevent suicide, and a rating of "much worsening of suicidality" from baseline. Masked raters, including an independent suicide monitoring board, determined when end point criteria were achieved. RESULTS: Suicidal behavior was significantly less in patients treated with clozapine vs olanzapine (hazard ratio, 0.76; 95% confidence interval, 0.58-0.97; P =.03). Fewer clozapine-treated patients attempted suicide (34 vs 55; P =.03), required hospitalizations (82 vs 107; P =.05) or rescue interventions (118 vs 155; P =.01) to prevent suicide, or required concomitant treatment with antidepressants (221 vs 258; P =.01) or anxiolytics or soporifics (301 vs 331; P =.03). Overall, few of these high-risk patients died of suicide during the study (5 clozapine vs 3 olanzapine-treated patients; P =.73). CONCLUSIONS: Clozapine therapy demonstrated superiority to olanzapine therapy in preventing suicide attempts in patients with schizophrenia and schizoaffective disorder at high risk for suicide. Use of clozapine in this population should lead to a significant reduction in suicidal behavior.

Effects of clozapine, olanzapine, risperidone, and haloperidol on hostility among patients with schizophrenia.

OBJECTIVE: This study compared the specific antiaggressive effects of clozapine with those of olanzapine, risperidone, and haloperidol. METHODS: A total of 157 inpatients with schizophrenia or schizoaffective disorder and a history of suboptimal treatment response were randomly assigned to receive clozapine, olanzapine, risperidone, or haloperidol in a double-blind 14-week trial. The trial was divided into two periods: eight weeks during which the dosage was escalated and then fixed, and six weeks during which variable dosages were used. The hostility item of the Positive and Negative Syndrome Scale (PANSS) was the principal outcome measure. Covariates included the items that reflect positive symptoms of schizophrenia (delusions, suspiciousness or feelings of persecution, grandiosity, unusual thought content, conceptual disorganization, and hallucinations) and the sedation item of the Nurses Observation Scale for Inpatient Evaluation (NOSIE). RESULTS: Patients differed in their treatment response as measured by the hostility item of the PANSS. The scores of patients taking clozapine indicated significantly greater improvement than those of patients taking haloperidol or risperidone. The effect on hostility appeared to be independent of the antipsychotic effect of clozapine on other PANSS items that reflect delusional thinking, a formal thought disorder, or hallucinations and independent of sedation as measured by the NOSIE. Neither risperidone nor olanzapine showed superiority to haloperidol. CONCLUSION: Clozapine has a relative advantage over other antipsychotics as a specific antihostility agent.

Performance of recommended screening tests for undiagnosed diabetes and dysglycemia.

OBJECTIVE: To evaluate the performance, in settings typical of opportunistic and community screening programs, of screening tests currently recommended by the American Diabetes Association (ADA) for detecting undiagnosed diabetes. RESEARCH DESIGN AND METHODS: Volunteers aged > or =20 years without previously diagnosed diabetes (n = 1,471) completed a brief questionnaire and underwent recording of postprandial time and measurement of capillary blood glucose (CBG) with a portable sensor. Participants subsequently underwent a 75-g oral glucose tolerance test; fasting serum glucose (FSG) and 2-h postload serum glucose (2-h SG) concentrations were measured. The screening tests we studied included the ADA risk assessment questionnaire, the recommended CBG cut point of 140 mg/dl, and an alternative CBG cut point of 120 mg/dl. Each screening test was evaluated against several diagnostic criteria for diabetes (FSG > or =126 mg/dl, 2-h SG > or =200 mg/dl, or either) and dysglycemia (FSG > or =110 mg/dl, 2-h SG > or =140 mg/dl, or either). RESULTS: Among all participants, 10.7% had undiagnosed diabetes (FSG > or =126 or 2-h SG > or =200 mg/dl), 52.1% had a positive result on the questionnaire, 9.5% had CBG > or =140 mg/dl, and 18.4% had CBG > or =120 mg/dl. The questionnaire was 72-78% sensitive and 50-51% specific for the three diabetes diagnostic criteria; CBG > or =140 mg/dl was 56-65% sensitive and 95-96% specific, and CBG > or =120 mg/dl was 75-84% sensitive and 86-90% specific. CBG > or =120 mg/dl was 44-62% sensitive and 89-90% specific for dysglycemia. CONCLUSIONS: Low specificity may limit the usefulness of the ADA questionnaire. Lowering the cut point for a casual CBG test (e.g., to 120 mg/dl) may improve sensitivity and still provide adequate specificity.

Hyperglycemia associated with the use of atypical antipsychotics.

The available literature suggests that patients with schizophrenia are at risk for diabetes mellitus and taking antipsychotic medication further increases the chance of developing non-insulin-dependent hyperglycemia. Case reports, chart reviews, and some results from clinical drug trials implicate a relationship between glucose levels and treatment with clozapine or olanzapine in patients with schizophrenia, although a few cases of hyperglycemia have also been reported in patients taking risperidone and quetiapine. These studies indicate that hyperglycemia is not dose dependent, is reversible on cessation of treatment with clozapine or olanzapine, and reappears on reintroduction of these therapies. The postulated underlying mechanisms involved in this process in patients with schizophrenia include (1) a decreased sensitivity to insulin that is independent of atypical medication, (2) an increased insulin resistance related to atypical medications, (3) the effects of atypical medications on serotonin receptors, and (4) overuse of insulin due to weight gain. These mechanisms are discussed in detail, and recommendations for the administration of atypical antipsychotics are offered. Overweight, ethnicity, family or personal history of diabetes mellitus or hypertension, and weight gain during the course of treatment have all been identified as risk factors in the development of hyperglycemia in patients with schizophrenia. However, it is difficult to statistically assess the true incidence of diabetes within each type of antipsychotic medication group with the exclusive dependence on available case studies and without proper epidemiologic research.

The role of state public health agencies in genetics and disease prevention: results of a national survey.

OBJECTIVES: The onset and severity of the clinical expression of most diseases that are of public health importance are influenced by genetic predisposition. The ability to assess human genetic predisposition for many diseases is increasing rapidly. Therefore, state public health agencies should be incorporating new developments in genetics and disease prevention into their core functions of assessment, policy development, and assurance. The authors assessed the status of this process. METHODS: The Council of State and Territorial Epidemiologists (CSTE) surveyed states about projects and concerns related to genetics and public health activities. Respondents were the Health Officer, the Maternal and Child Health/Genetics Program Director, the Chronic Disease Program Director, and the Laboratory Director. Where applicable, responses were categorized into assessment, policy development, and assurance functions. RESULTS: Thirty-eight (76%) state health departments responded. Ongoing genetics activities were assurance (82%), assessment (17%), and policy development (2%). In contrast, Health Officers responded that future genetics activities would be distributed differently: assurance, 41%; assessment, 36%; and policy development, 23%. Future assurance activities would be largely educational. Topics of interest and recently initiated activities in genetics were primarily assessment functions. Funding was the greatest concern, followed by lack of proven disease prevention measures and outcomes data. CONCLUSIONS: State health departments recognize a need to realign their activities to meet future developments in genetics. Lack of adequate resources, proven disease prevention measures, and outcomes data are potential barriers. Public health agencies need to develop a strategic plan to meet the opportunities associated with the development and implementation of genetic tests and procedures.