clozapine and Metabolic-Diseases

Clozapine is the first second generation antipsychotic with different receptor profile of action. Clozapine is the most efficacious drug for the treatment of psychotic disorder and is the drug of choice in treatment resistant schizophrenia. Clozapine is used in elderly patients infrequently owing to its adverse effects profile and tolerability. There is paucity of literature with respect to clozapine use in late life. In this narrative review, we discuss clozapine use in elderly and challenges associated with its use.

Topics: Aged; Aging; Agranulocytosis; Antipsychotic Agents; Cardiovascular Diseases; Clozapine; Cognitive Dysfunction; Humans; Metabolic Diseases; Schizophrenia; Seizures

There is strong evidence from randomized controlled trials (RCTs) that second-generation antipsychotic (SGA) medications are associated with metabolic adverse events. However, with the recent increases in the use of SGAs worldwide and frequent off-label use, it is unclear whether these associations are generalizable to populations beyond those included in RCTs.. This review aims to characterize the impact of SGAs on the population through a systematic review of population-based studies of SGA users. Studies could examine the use of any SGA medication and any comparator group. Studies also needed to include at least one metabolic outcome such as type 2 diabetes mellitus, dyslipidemia, obesity, hypertension, or metabolic syndrome.. A systematic search process was used to identify studies for inclusion in this review. Included studies had to be population-based studies of users of any SGA medication with at least one reported metabolic outcome. Study quality was also assessed using the AMSTAR tool, and evidence was synthesized by both metabolic outcome and specific SGA medication.. In total, 15 studies were included in this review. Type 2 diabetes mellitus was the most frequently reported outcome; clozapine and olanzapine were most strongly associated with type 2 diabetes mellitus. Evidence was mixed for a moderate association between type 2 diabetes mellitus and risperidone or quetiapine. Few studies examined other metabolic outcomes, and therefore it is difficult to estimate the true effect in the population.. Population-based evidence for other SGAs and metabolic outcomes was limited. However, clozapine and olanzapine were consistently more strongly associated with metabolic adverse events than were other SGAs currently available.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Humans; Metabolic Diseases; Olanzapine; Randomized Controlled Trials as Topic; Research Design

Clozapine is the most effective antipsychotic medication for treatment-refractory schizophrenia and is also approved for suicidality in schizophrenia patients. However, it can cause significant medical morbidity and requires intensive medical monitoring once prescribed. Perhaps due to lack of familiarity with its use, it is underused in clinical practice and its initiation often delayed. This article reviews the literature on clozapine in order to measure its potential effectiveness against its adverse effects and ultimately aims to serve as a useful summary for clinicians in their everyday prescribing.

Topics: Antipsychotic Agents; Clozapine; Drug Monitoring; Heart Diseases; Hematologic Diseases; Humans; Metabolic Diseases; Practice Guidelines as Topic; Practice Patterns, Physicians'; Quality of Life; Schizophrenia; Suicide Prevention; Venous Thromboembolism; Weight Gain

Less than half of patients with schizophrenia obtain full response to antipsychotic drugs and, while clozapine represents the treatment of choice for refractory psychosis, a significant number of individuals remain only partially responsive. Despite a need for augmentation in this subpopulation, to date clear choices have not been forthcoming. Because clozapine, along with the majority of second-generation agents (SGAs), are linked to metabolic disturbances, augmentation strategies that do not further exacerbate these side effects are needed. Topiramate, unlike other anticonvulsants used for augmentation purposes, has been associated with weight loss. This article reviews the safety and efficacy of topiramate in treatment-refractory schizophrenia, including effects on metabolic disturbances, which burden this population. While current evidence specifically examining improvements in psychopathology demonstrates small to moderate benefits with topiramate augmentation, a growing body of evidence suggests that topiramate may have beneficial effects on antipsychotic-induced weight gain. We conclude that topiramate's metabolic profile, taken together with a current lack of evidence supporting a particular augmentation strategy, argues for further well-controlled studies examining its potential as an augmentation strategy in schizophrenia.

Topics: Anticonvulsants; Antipsychotic Agents; Clozapine; Drug Therapy, Combination; Fructose; gamma-Aminobutyric Acid; Glutamic Acid; Humans; Metabolic Diseases; Neuropsychological Tests; Schizophrenia; Schizophrenic Psychology; Topiramate; Weight Gain

Clozapine is often referred to as the gold standard for the treatment of schizophrenia and yet has also been described as the most underutilized treatment for schizophrenia supported by solid evidence-based medicine. In 2008, it was used to treat only 4.4% of patients with schizophrenia in the U.S., which is ~10-20% of those with approved indications for clozapine for which there is no alternative of equal efficacy. Its use is much higher in Scandinavian countries and China. The primary indications for clozapine are: 1) treatment-resistant schizophrenia or schizoaffective disorder, defined as persistent moderate to severe delusions or hallucinations despite two or more clinical trials with other antipsychotic drugs; and, 2) patients with schizophrenia or schizoaffective disorder who are at high risk for suicide. Concerns over a number of safety considerations are responsible for much of the underutilization of clozapine: 1) agranulocytosis; 2) metabolic side effects; and, 3) myocarditis. These side effects can be detected, prevented, minimized and treated, but there will be a very small number of fatalities. Nevertheless, clozapine has been found in two large epidemiologic studies to have the lowest mortality of any antipsychotic drug, mainly due to its very large effect to reduce the risk for suicide. Other reasons for limited use of clozapine include the extra effort entailed in monitoring white blood cell counts to detect granulocytopenia or agranulocytosis and, possibly, minimal efforts to market it now that it is largely generic. Awareness of the benefits and risks of clozapine is essential for increasing the use of this lifesaving agent.

Topics: Agranulocytosis; Antipsychotic Agents; Clozapine; Humans; Metabolic Diseases; Myocarditis; Risk Factors; Schizophrenia

The recognition, management, and if possible prevention, of major cardiovascular, central nervous system, haematological, and metabolic adverse effects, including diabetes mellitus and weight gain, of antipsychotics and some other drugs used to treat mental illness is a topic of much debate. However, a wide range of other adverse effects, some of which may be life-threatening, may also be encountered. Side-effects reviewed here include: gastrointestinal-associated effects (constipation, hypersalivation, oropharyngeal lesions, nasal congestion, nausea, nocturnal enuresis, and urinary retention), metabolic effects (obesity, insulin resistance, dyslipidemia, impaired glucose tolerance, and hypertension), neuromuscular effects (extrapyramidal side effects, myoclonus, and neuroleptic malignant syndrome, and pleurothotonus), thermoregulatory effects, effects on the liver, pancreas, and kidney, sexual side effects, and effects on skin and bone. Metabolic factors affecting the incidence of adverse effects to clozapine especially are also discussed. The increasing use of atypical (second generation) antipsychotics and indeed of selective serotonin reuptake inhibitors has led to a greater appreciation of not only the benefits of these drugs, but also of the spectrum of toxicity that may occur in clinical practice. The adverse effects of antipsychotics are a major factor in promoting poor adherence to, and even discontinuation of, antipsychotic treatment on the one hand, and increasing the risk of cardiovascular and metabolic disease on the other. As such they merit recognition and either harm minimization strategies (use of the minimum effective dose, or use of lower doses of combinations of antipsychotics), or in extreme cases discontinuation of the offending drug(s).

Topics: Animals; Antipsychotic Agents; Body Temperature Regulation; Bone Diseases; Clozapine; Digestive System Diseases; Dose-Response Relationship, Drug; Humans; Metabolic Diseases; Neuromuscular Diseases; Risk Assessment; Risk Factors; Sexual Dysfunction, Physiological; Skin Diseases

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Anti-Allergic Agents; Anti-Inflammatory Agents, Non-Steroidal; Antidepressive Agents; Antihypertensive Agents; Antipsychotic Agents; Chemistry, Pharmaceutical; Dopamine D2 Receptor Antagonists; Drug Design; Humans; Ligands; Metabolic Diseases; Peroxisome Proliferator-Activated Receptors; Receptors, Histamine H1; Selective Serotonin Reuptake Inhibitors

Topics: Adult; Aged; Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Female; Glucose; Humans; Male; Metabolic Diseases; Middle Aged; Olanzapine; Pirenzepine; Quetiapine Fumarate; Risperidone

Clozapine (CLZ) is the most effective drug for treatment-resistant schizophrenia but is associated with many side effects, including glycometabolism disorders. Immunological mechanisms may be involved in the development of clozapine side effects. Research relating the immunomodulatory effects of clozapine and its early markers to clinically relevant adverse events is needed to reduce the harmful side effects of clozapine. This study aimed to investigate the role of proinflammatory cytokines in clozapine-associated glycometabolism disorders.. We measured the effect of a range of doses of clozapine on glycometabolism-related parameters and proinflammatory cytokines levels in mice peripheral blood. We also examined the differences between these indicators in the peripheral blood of clozapine-treated schizophrenia patients and healthy controls. Furthermore, we detected proinflammatory cytokines expression in mice pancreatic tissue.. Following clozapine administration, glucagon significantly decreased in mouse serum, and proinflammatory cytokine IL-β levels markedly increased. Clozapine reliably increased proinflammatory cytokines (IL-1β, IL-6, and TNF-α) expression in murine pancreatic tissue. Compared with healthy controls, clozapine-treated patients' BMI, blood glucose, and proinflammatory cytokines (IL-1β, IL-6, and TNF-α) increased significantly. In clozapine-treated patients, a higher clozapine daily dosage was associated with higher levels of the proinflammatory cytokines IL-1β and IL-6, and a significant positive correlation was observed between blood glucose levels and the proinflammatory cytokines IL-6 and TNF-α.. Findings from animal experiments and clinical trials have shown clear evidence that clozapine has a regulatory effect on immune-related proinflammatory cytokines and influences glycometabolism indicators.

Topics: Adult; Animals; Antipsychotic Agents; Blood Glucose; Clozapine; Cytokines; Humans; Inflammation Mediators; Male; Metabolic Diseases; Mice; Mice, Inbred C57BL; Middle Aged; Schizophrenia; Tumor Necrosis Factor-alpha

Numerous studies have demonstrated that fluvoxamine has considerable pharmacokinetic and pharmacodynamic interactions with clozapine. We conducted a 12-week, randomized, double-blind, placebo-controlled study to evaluate the effects of fluvoxamine on metabolic parameters and psychopathology in clozapine-treated patients with schizophrenia.. We recruited 85 patients who received a DSM-IV diagnosis of schizophrenia. Eligible patients were randomized to receive fluvoxamine 50mg/day plus clozapine 100mg/day or clozapine 300mg/day. We studied metabolic parameters, psychopathology, and drug levels at baseline and 4, 8, and 12weeks after the intervention. Plasma levels of clozapine, norclozapine, clozapine N-oxide, and fluvoxamine were determined using high-performance liquid chromatography with ultraviolet detection.. No significant difference was observed in baseline characteristics between the two groups. Clozapine-fluvoxamine combined treatment significantly attenuated the increments in body weight, insulin resistance, and levels of insulin, glucose, and triglycerides compared with clozapine monotherapy. Both groups exhibited significant improvements in their Positive and Negative Syndrome Scale (PANSS) total and negative scores. The combined treatment group showed significant reduction in the PANSS general psychopathology scores compared with the monotherapy group. No difference was observed in the plasma clozapine level between the two groups. The monotherapy group showed higher levels of norclozapine and clozapine N-oxide than the combined group.. Compared with clozapine monotherapy, treatment with adjunctive fluvoxamine with clozapine for 12weeks can alleviate body weight gain and metabolic abnormalities in patients with schizophrenia, without sacrificing the clinical effect. Clinicians should interpret these findings cautiously considering the short duration of this study. The study was registered at www.clinicaltrials.gov (NCT01401491).

Topics: Antipsychotic Agents; Antisocial Personality Disorder; Body Weight; Clozapine; Double-Blind Method; Drug Therapy, Combination; Female; Fluvoxamine; Follow-Up Studies; Humans; Leukocytes; Male; Metabolic Diseases; Psychiatric Status Rating Scales; Schizophrenia; Selective Serotonin Reuptake Inhibitors; Time Factors; Treatment Outcome

Obesity-related genetic variants, including TMEM18 (rs6548238), SH2B1 (rs7498665), and GNPDA2 (rs10938397), have been shown to be associated with obesity in the general population. Our study aimed to test whether these genetic variants are associated with metabolic profiles and metformin treatment response in clozapine-treated schizophrenic patients. We recruited 107 clozapine-treated patients who were genotyped and measured their metabolic profiles. Fifty-five subjects, who had at least 1 metabolic abnormality in a range of measures, were subsequently randomized to a 24-week trial of metformin (n = 28) or placebo (n = 27). We examined the associations between TMEM18, SH2B1, GNPDA2 genetic variants and metabolic profiles at baseline in all patients and metabolic changes in the trial groups. We found a significant association between SH2B1 and blood pressure at baseline in all patients. In the metformin group, TMEM18 minor allele carriers had a greater reduction in insulin levels (P = 0.04). A significantly higher proportion of TMEM18 and GNPDA2 minor allele carriers (60% and 40%) lost more than 7% of their body weight after metformin treatment as compared with their homozygous counterparts (21.7% and 15.4%, P = 0.02 and 0.004, respectively).There were trends toward favorable metabolic changes in minor allele carrier groups. In the placebo group, no association between genetic variants and changes in metabolic profiles was found. In conclusion, the study results suggest that these genes might be associated with metabolic abnormalities and response to metformin in clozapine-treated patients with schizophrenia.

Topics: Adaptor Proteins, Signal Transducing; Adult; Aldose-Ketose Isomerases; Alleles; Antipsychotic Agents; Clozapine; Double-Blind Method; Female; Genetic Predisposition to Disease; Genetic Variation; Genotype; Humans; Male; Membrane Proteins; Metabolic Diseases; Metformin; Middle Aged; Obesity; Schizophrenia

This study was undertaken to examine if patients exhibit more pronounced metabolic abnormalities after 8-year treatment with clozapine or olanzapine than before, and also to investigate whether there exist any differences between long-term clozapine and olanzapine therapies regarding metabolic side- effects.. Fifty psychiatric outpatients diagnosed with schizophrenia or schizoaffective disorder and on treatment with clozapine or olanzapine were studied during 8 years. Fasting blood or serum samples for glucose, lipids, prolactin and antipsychotic drug concentrations were analyzed. In addition, body mass index was calculated.. More patients treated with olanzapine compared with those treated with clozapine ended with their medication, in most cases because of diabetes mellitus and/or hyperlipidemia, during the 8-year follow-up. Also more patients treated with olanzapine compared with those treated with clozapine developed manifest diabetes mellitus during the 8-year period. Prolactin levels were higher in the patients treated with olanzapine compared with in those treated with clozapine at study start, but there were no differences in the other parameters between the treatment groups at study start. In the patients remaining on their medication all 8 years, the glucose level increased over time in the clozapine group, but not in the olanzapine group, whereas body mass index and lipids were unchanged over time in both treatment groups.. Our findings point to that both olanzapine and clozapine long-term treatments cause development of hyperglycemia and/or hyperlipidemia. Furthermore, olanzapine long-term treatment seems to more often lead to development of manifest diabetes mellitus than long-term treatment with clozapine.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Clozapine; Diabetes Mellitus, Type 2; Female; Humans; Hyperglycemia; Hyperlipidemias; Male; Metabolic Diseases; Middle Aged; Olanzapine; Psychotic Disorders; Schizophrenia

Sedation is a common side effect of clozapine treatment and may exacerbate metabolic consequences of poor diet and exercise habits that are common in patients with schizophrenia. Modafinil has been proposed as a treatment for clozapine-induced sedation and metabolic abnormalities.. To estimate the effect sizes and person-to-person variation in anthropometric measures, glucose and lipid metabolism, and diet on modafinil treatment for future randomized control trials.. A double-blind, placebo-controlled, flexible-dosed 8-week pilot trial was conducted, adding modafinil up to 300 mg/day to stabilized schizophrenia outpatients receiving clozapine. Blood pressure, weight, BMI, laboratory assays, and dietary intake were tracked to monitor changes in metabolic markers.. Thirty-five participants were randomly assigned to treatment with study drug or placebo and were included in the analysis. Modafinil did not improve blood pressure, weight, BMI, glucose or lipid metabolism compared to placebo. Modafinil was well tolerated and did not worsen psychosis.. Results of this pilot trial do not support routine use of modafinil to counteract increased weight and metabolic diseases in patients taking clozapine. However, the effects of modafinil on weight and insulin regulation warrant further investigation with effect sizes of 0.4 to 0.6.

Topics: Adult; Analysis of Variance; Benzhydryl Compounds; Blood Glucose; Blood Pressure; Body Weight; Clozapine; Double-Blind Method; Female; Follow-Up Studies; Humans; Lipid Metabolism; Male; Metabolic Diseases; Middle Aged; Modafinil; Neuroprotective Agents; Retrospective Studies; Schizophrenia; Time Factors

The role of leptin in atypical antipsychotic-induced metabolic dysfunction was explored by assessing the anthropometric and metabolic profile and the response to metformin (MET) of clozapine- (CLZ) treated schizophrenia patients according to their single nucleotide polymorphisms (SNPs) in the leptin promoter (LEP2548/GA) and leptin receptor (LEPR Q223R) genes.. Phase 1. Body mass index (BMI), waist circumference, serum glucose, HbA1C, lipids, leptin, cortisol, insulin resistance index (HOMA-IR), metabolic syndrome and the frequencies of SNPs were assessed in 56 CLZ-treated patients (78.6% males). Phase 2. Fifty two phase 1 subjects were randomly assigned to MET XR (n=23) (1000 mg/day) or placebo (n=29) for 14 weeks. Changes in anthropometric and biochemical variables were compared between the SNPs.. Phase 1. The QQ group displayed the lowest triglyceride levels (p<0.05). No other significant difference was observed. Phase 2. Change in anthropometric variables did not differ between the genotypes in any treatment group. After MET, glucose levels significantly increased in the GG group (p<0.05), whereas the HOMA-IR and the low density cholesterol significantly decreased in the QQ- but not in the (QR+RR) group (p<0.05). No differences were observed after placebo.. BW response to CLZ was not related to LEP- and LEPR-SNPs. The GG and (QR+RR) genotypes showed an unexpectedly opposite and blunted response to MET administration respectively.

Topics: Adult; Antipsychotic Agents; Blood Glucose; Body Mass Index; Clozapine; Double-Blind Method; Female; Genotype; Humans; Hydrocortisone; Hypoglycemic Agents; Insulin Resistance; Leptin; Male; Metabolic Diseases; Metformin; Middle Aged; Pharmacogenetics; Polymorphism, Single Nucleotide; Receptors, Leptin; Schizophrenia; Venezuela

Psychotropic drugs may be associated with metabolic disorders, often but not only triggered by weight gain. Disorders include dysglycemia and diabetes, atherogenic dyslipidemia and metabolic syndrome. Overall, metabolic risk is lower with antidepressants than with antipsychotics. Among antidepressants, metabolic disorders may occur with both selective serotonin reuptake inhibitors and tricyclics, but with some between-molecule differences in each pharmacological family. Among antipsychotics, the risk is higher with second-generation (atypical) than first-generation agents. Higher risk was reported with clozapine and olanzapine, and lower risk with risperidone and aripiprazole. Weight gain is associated with increased insulin resistance, but impaired insulin secretion was also reported with clozapine and olanzapine. Metabolic disorders may be attenuated by the medication withdrawal and replacement by another safer drug. Besides deleterious effects of medications, the psychiatric population is also exposed to bad lifestyle habits (unhealthy diet and sedentary life), which also increase the risk of metabolic disorders. Management should first reinforce lifestyle measures. If this proves insufficient, specific drugs may be considered to tackle the metabolic disorder on a strategy similar to that applied in the general population.

Topics: Clozapine; Humans; Metabolic Diseases; Metabolic Syndrome; Olanzapine; Psychotropic Drugs

Patients with schizophrenia using antipsychotics often develop metabolic side effects, especially with clozapine. Previous studies indicated that antipsychotics could activate the pathway of the sterol regulatory element-binding protein (SREBP). The sterol regulatory element binding transcription factor 2 (SREBF2) gene mainly regulates the cholesterol biosynthetic gene. Therefore, we hypothesized that the SREBF2 gene would be a candidate gene for interindividual variation in drug-induced metabolic syndrome (MetS). In this genetic case-control study, we examined the SREBF2 gene polymorphisms in the risk of MetS patients treated with clozapine.. Ten single nucleotide polymorphisms (SNPs) of SREBF2 were genotyped in a CHB (Han Chinese in Beijing, China) population, a sample of 621 schizophrenia patients treated with clozapine. Patients were evaluated for metabolic parameters and screened for the MetS criteria.. The incidence of MetS among all subjects was 41.8% (260/621). Two markers of SREBF2 were associated with MetS induced by clozapine after False Discovery Rate (FDR) correction (rs1052717, corrected Pallele=0.010, corrected Pgenotype=0.022; and rs2267443, corrected Pgenotype=0.015). Patients who received clozapine and carried the A-allele of rs2267443 or rs1052717 had an increased risk of MetS (rs2267443, odds ratio (OR)=1.67, 95% confidence interval (CI): 1.20-2.34; and rs1052717, OR=1.81, 95% CI: 1.15-1.98), adjusted by logistic regression for clinical characteristics.. The results suggest that the genetic polymorphisms of SREBF2 gene may be associated with MetS in patients treated with clozapine.

Topics: Adult; Antipsychotic Agents; Case-Control Studies; Clozapine; Female; Genetic Association Studies; Humans; Logistic Models; Male; Metabolic Diseases; Middle Aged; Polymorphism, Single Nucleotide; Schizophrenia; Sterol Regulatory Element Binding Protein 2

The efficacy of clozapine for the treatment of schizophrenia has been demonstrated. However, a range of adverse events have been associated with its use. To date, there remains a paucity of data regarding the prevalence of clozapine-induced cardiovascular (CV) and parameters associated with the development of metabolic syndrome, alongside associated risk factors for their development.. An observational, clinical cohort study design of 355 clozapine patients who were enrolled in the Barwon Health Clozapine Program at Geelong Hospital, Victoria, Australia, between 2008-12. Medical records were accessed retrospectively. Multivariate logistic regression was used to determine associations with adverse event(s).. Older age of commencement with clozapine was consistently associated with increased risk of CV abnormalities, with the exception of tachycardia where older age was protective (Odds Ratio [OR]: 0.97; 95% Confidence Intervals [CI]: 0.95, 0.99). Males had significantly greater odds of most metabolic disturbances with the exception of being obese (BMI: ≥30 OR: 0.45; 95% CIs: 0.24, 0.85). Older age of commencement was a significantly associated variable with High- Density Lipoprotein-cholesterol (OR: 1.03; 95% CIs: 1.01, 1.07) and fasting glucose (OR:1.04; 95% CIs: 1.02, 1.07). An increase in BMI was consistently and significantly associated with all metabolic events.. Male patients who are obese at any point during treatment and older at treatment commencement may be the most vulnerable to adverse CV and metabolic events. While future studies using a matched case-control design may be required to verify these findings, we recommend that treating clinicians consider these risks when assessing patient suitability to clozapine therapy.

Topics: Adult; Age Factors; Aged; Antipsychotic Agents; Blood Glucose; Cardiovascular Diseases; Cholesterol, HDL; Clozapine; Cohort Studies; Female; Humans; Male; Metabolic Diseases; Middle Aged; Prevalence; Retrospective Studies; Risk Factors; Schizophrenia; Sex Factors; Substance-Related Disorders; Victoria

Clozapine, an evidence-based treatment of refractory schizophrenia, is associated with increased weight gain and metabolic dysregulation compared with most antipsychotics in short-term clinical trials. However, there are limited data describing comparative long-term metabolic risks. In this report, we examined whether short-term differences persist with long-term exposure to clozapine.. The data of all patients in a university-based clinic with a psychotic illness or a mood disorder with psychotic features, based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision diagnosis, and treated with an antipsychotic in calendar year 2012 were examined. A total of 307 patients met the criteria; 96 patients were treated with clozapine and the remaining 211 patients were treated with 1 or more non-clozapine antipsychotics. Body mass index, type 2 diabetes, hypertension, dyslipidemia, and obesity were compared.. The mean duration of the clozapine treatment was 7.6 years (range, 2 months to 21 y). On all metabolic measures, there were no statistically significant differences between the clozapine and non-clozapine groups (mean body mass index, 31 vs 32; type 2 diabetes, 17% vs 18%; dyslipidemia, 35% vs 38%; hypertension, 32% vs 39%; and obesity, 48% vs 54%). Removing the olanzapine-treated patients (n = 51) from the non-clozapine group did not change the findings.. In this university-based clinic sample with a large number of clozapine-treated patients, we found no evidence of increased risk in any individual measure for those receiving clozapine. Although speculative, the relative contribution of the increased short-term metabolic risk associated with clozapine may be diminished over time because multiple other variables likely also impact metabolic risk during the life span. Although speculative, the relative contribution of the increased short-term metabolic risk associated with clozapine may be diminished over time due to the accumulated impact of other variables that also impact metabolic risk across the life span.

Topics: Adult; Aged; Antipsychotic Agents; Clozapine; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Electronic Health Records; Female; Humans; Male; Metabolic Diseases; Middle Aged; Obesity; Psychotic Disorders; Schizophrenia; Weight Gain; Young Adult

Topics: Adult; Aged; Alanine; Antipsychotic Agents; Blood Glucose; Clozapine; Enzyme-Linked Immunosorbent Assay; Female; Gene Frequency; Genotype; Humans; Hypoglycemic Agents; Insulin; Leptin; Male; Metabolic Diseases; Metformin; Middle Aged; Polymorphism, Genetic; PPAR gamma; Proline

We studied the development of metabolic disorders related to tissue hypoxia in 54 patients with acute severe asaleptin intoxication complicated by acute respiratory insfficiency of mixed genesis. We also estimated the role of a substrate antihypoxant cytoflavin in the correction of these disorders and clinical features of acute intoxication. Cyroflavin was shown to accelerate normalization of metabolic disorders which in turn improves clinical symptoms of severe forms of acute asaleptin intoxication.

Topics: Acute Disease; Adult; Antipsychotic Agents; Clozapine; Drug Combinations; Female; Flavin Mononucleotide; Humans; Hypoxia; Inosine Diphosphate; Male; Metabolic Diseases; Middle Aged; Niacinamide; Respiratory Insufficiency; Severity of Illness Index; Succinates; Young Adult

Few studies on the association between atypical antipsychotic drug (AAP) administration and metabolic dysfunction have concurrently evaluated the general population (GP), other psychotropic drug treatments and drug-free psychiatric patients.. We assessed the frequency of the metabolic syndrome (MS) according to the National Cholesterol Education Program criteria (NCEP) and its constituting variables in a GP sample (n=271) and in patients receiving, for at least three consecutive months, antiepileptic drugs (n=93), olanzapine (n=162), clozapine (n=105), typical antipsychotics (n=117), other AAP (n=58), other psychotropic drugs (n=185), and drug-free individuals (n=636). Subjects were clinically classified as schizophrenia, bipolar or other axis I disorders (DSM-IV-RT), and as first-degree relatives of each diagnostic group.. The MS was detected in 26.6% of the GP (95% confidence interval: 21.5-31.8). No diagnostic or treatment group had a significantly higher age-adjusted frequency than the GP (p>0.05). Treatment duration did not significantly affect the results. However, significant differences were observed in the frequency of abnormal MS constituting variables in comparison to the GP. For example, schizophrenia patients and their relatives, bipolar subjects and olanzapine- and clozapine-treated patients had higher abnormal waist circumference values. In addition, bipolar patients and their relatives and subjects treated with olanzapine and other AAPs had higher frequencies of abnormal glucose levels. Neither schizophrenia nor bipolar patients in the diagnostic categories nor the olanzapine or the clozapine groups displayed higher proportions of abnormal triglycerides, high density cholesterol or blood pressure levels than the GP.. While we did not demonstrate an increased frequency of the MS in AAP-treated subjects, our results confirm that specific metabolic variables must be monitored in psychiatric patients. Besides they stress the importance, in epidemiological studies, of concurrently comparing the figures recorded in AAP-treated patients with those obtained in the local GP, other drug treatment groups and drug-free subjects when referring to the magnitude of the metabolic effects of specific antipsychotic agents.

Topics: Adult; Age Factors; Aged; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Body Mass Index; Cholesterol; Clozapine; Community Health Planning; Confidence Intervals; Family; Female; Humans; Male; Mental Disorders; Metabolic Diseases; Middle Aged; Olanzapine; Retrospective Studies; Treatment Outcome; Venezuela; Young Adult

Topics: Adult; Aluminum Hydroxide; Antacids; Antipsychotic Agents; Clozapine; Humans; Male; Metabolic Diseases; Psychotic Disorders

The receptor binding affinities of the three drug candidates 1 (SLV310), 2 (SLV313), and 3 (SLV314) were positioned against the results from nine (a)typical antipsychotic drugs. The receptor binding data from sixteen monoaminergic receptors served as the input in a principal component analysis (PCA). The PCA outcome revealed a unique binding profile of 1, 2, and 3 as compared with the reference compounds 4-8 and 10-12. The weight gain inducing antipsychotics 6-8 clustered in the PCA by scoring strongly negative for factor 1. The hyperprolactinaemia related antipsychotics 4, 5, 10, and 12 clustered by their negative scores for factor 2.

Topics: Antipsychotic Agents; Basal Ganglia Diseases; Benzoxazines; Biogenic Monoamines; Humans; Hyperprolactinemia; Indoles; Metabolic Diseases; Phthalimides; Piperazines; Principal Component Analysis; Pyridines; Radioligand Assay; Receptors, Biogenic Amine; Weight Gain