Although enhanced appetite and weight gain are potential side effects of treatment with antipsychotic agents, particularly olanzapine and clozapine, the mechanisms underlying these side effects are poorly understood. Leptin and ghrelin were recently identified as hormones that play crucial roles in the regulation of energy balance and glucose metabolism. To elucidate relationships between weight change and plasma levels of ghrelin and leptin, we investigated the circulating ghrelin and leptin levels and body weight during olanzapine treatment. Twenty-four patients with schizophrenia were examined during 6-month administration of olanzapine. Ghrelin, leptin, weight and body mass index (BMI) were measured before and after 2, 4, 8, 12, 16, and 24 weeks of olanzapine treatment. The concentration of glucose and various lipid metabolic parameters were measured at baseline and at 24 weeks. Significant increases in weight, BMI and leptin were observed at week 24. On the other hand, the serum levels of ghrelin decreased significantly after olanzapine treatment. In addition, the level of ghrelin was negatively correlated with the leptin level, BMI and weight. The leptin level was positively correlated with both BMI and weight. Ghrelin is associated with metabolic changes, in combination with leptin, during olanzapine treatment. However, further large-scale and longitudinal studies are warranted to elucidate the metabolic changes involving ghrelin, leptin and insulin during treatment with antipsychotics.
Antipsychotic Agents/*adverse effects ; Benzodiazepines/*adverse effects ; Body Mass Index ; Body Weight/*drug effects ; Ghrelin/*blood ; Humans ; Leptin/*blood ; Male ; Schizophrenia/blood/*drug therapy

Complete atrioventricular (AV) block is frequently regarded as a cause of informed syncopal attacks, even though the escape rhythm is maintained. Torsade de pointes (TdP) may be a significant complication of AV block associated with QT prolongation. Here, we report the case of a 42-year-old female who was referred to our hospital due to recurrent seizure-like attacks while taking anti-convulsant drugs at a psychiatric hospital. TdP with a long QT interval (corrected QT = 0.591 seconds) was observed on an electrocardiogram (ECG) taken in the emergency department. The patient's drug history revealed olanzapine as the suspicious agent. Even after the medication was stopped, however, the QT interval remained within an abnormal range and multiple episodes of TdP and related seizure-like symptoms were found via ECG monitoring. A permanent pacemaker was thus implanted, and the ventricular rate was set at over 80 beats/min. There was no recurrence of tachyarrhythmia or other symptoms.
Adult ; Atrioventricular Block/*complications ; Benzodiazepines/adverse effects ; Electrocardiography ; Epilepsy/*etiology ; Female ; Humans ; Pacemaker, Artificial ; Torsades de Pointes/*etiology/therapy

Aged ; Aged, 80 and over ; Analgesics, Opioid ; adverse effects ; Benzodiazepines ; adverse effects ; Cognitive Dysfunction ; chemically induced ; mortality ; Female ; Humans ; Male ; Postoperative Complications ; Randomized Controlled Trials as Topic ; Risk Factors

OBJECTIVE: To investigate the effect of ziprasidone and olanzapine on glucose and lipid metabolism in first-episode schizophrenia. METHODS: A total of 260 schizophrenics were assigned randomly to receive ziprasidone or olanzapine for 6 weeks. The weight was measured at baseline, week 2, 4 and 6. Fasting blood glucose (FBS), fasting insulin, high-density lipoprotein (HDL), total-cholesterol (TC) and triglycerides (TG) were measured at baseline and the end of 6-week treatment. Low-density lipoprotein (LDL) was measured in some patients at baseline and the end of 6-week treatment. Body mass index (BMI) and insulin resistance index (IRI) were counted. RESULTS: A total of 245 patients completed the trial, including 121 ziprasidone patients and 124 olanzapine patients. The average dose was 137.5 mg/d for ziprasidone and 19.5 mg/d for olanzapine. Patients treated with olanzapine had higher weight gain than those treated with ziprasidone [(4.55±3.37) kg vs (-0.83±2.05) kg, P<0.001]. After the treatment, FBS, fasting insulin, HDL, TC, TG, LDL and IRI levels were significantly increased in the olanzapine group (all P values<0.001 ). However, in the ziprasidone group, FBS decreased significantly and HDL and TG levels increased significantly after the 6-week treatment (all P values<0.05). The mean changes of FBS, fasting insulin, TC, TG, LDL and IRI were significantly different in the two groups (all P values<0.001). CONCLUSION Ziprasidone has less glucose and lipid metabolic effect for first-episode schizophrenia patients in short-term treatment. However, olanzapine induces weight gain and dysfunction of glucose and lipid metabolism significantly, which is associated with increased risk of complications. When the doctors choose antipsychotics in the clinic, they should consider the side effects of the medication.
Adolescent ; Adult ; Benzodiazepines ; adverse effects ; therapeutic use ; Blood Glucose ; drug effects ; Female ; Humans ; Lipid Metabolism ; drug effects ; Male ; Middle Aged ; Olanzapine ; Piperazines ; adverse effects ; therapeutic use ; Schizophrenia ; drug therapy ; Thiazoles ; adverse effects ; therapeutic use ; Young Adult

OBJECTIVETo evaluate the effect of neonatal perioperative anesthetic exposure in complex cardiac surgery on neurodevelopmental outcomes in preschool children.

METHODSGeneral clinical data and data concerning anesthetic exposure were collected from 89 infants undergoing complex cardiac surgery at Sichuan People' Hospital. The cohort was followed for neurodevelopment till preschool age (48-72 months) and assessed with Wechsler Preschool and Primary Scale of Intelligence-III, Beery-Buktenica Developmental Test of Visual Motor Integration (VMI-V), and General Adaptive Composite (GAC) of the Adaptive Behavior Assessment System-II.

RESULTSSeventy-one children were enrolled into the final analysis. Multiple linear regression found days on benzodiazepines (beta;=-0.49, P=0.005) and cumulative dose of benzodiazepines (β=-0.10, P=0.023) were associated with the full-scale IQ in these preschool children. Days on benzodiazepines (beta;=-0.39, P=0.009) and on chloral hydrate (beta;=-1.19, P=0.020) were associated with lower performance intelligence quotient (PIQ) at the preschool age. Cumulative dose of benzodiazepine exposure (beta;=-0.008, P=0.012) was associated with lower VMI scores. No correlations of other sedation/analgesia variables were found with the full-scale IQ, PIQ, Verbal IQ, VMI, or GAC scores.

CONCLUSIONWe found a significant association of days on benzodiazepines, cumulative dose of benzodiazepines, and days on chloral hydrate in neonatal cardiac surgery with neurodevelopmental outcomes at the preschool age, suggesting the need of minimizing anesthetic exposure during a neonatal cardiac surgery to improve the children's neurodevelopmental outcomes.

Anesthetics ; administration & dosage ; adverse effects ; Benzodiazepines ; administration & dosage ; adverse effects ; Cardiac Surgical Procedures ; Child ; Child Development ; drug effects ; Child, Preschool ; Chloral Hydrate ; administration & dosage ; adverse effects ; Humans ; Infant, Newborn ; Linear Models ; Multivariate Analysis ; Perioperative Period

OBJECTIVE: To determine the association between perioperative anesthetic exposure and neurodevelopmental status at age 1 year old baby underwent complex cardiac surgery.
 METHODS: One hundred and fifteen infants were selected from Sichuan People's Hospital. A cohort study was conducted on neonates who underwent complex cardiac surgery. The babies were performed brain MRI before the operation and 7 days after the operation, and 12-month neurodevelopmental testing was carried out with Bayley Scales of Infant and Toddler Development (the third Edition, Bayley-III). Doses of volatile anesthetics (VAA), benzodiazepines, and opioids were determined during the 12 months. The association between peri-operative anesthetic exposure and 12-month neurodevelopmental status were analyzed.
 RESULTS: A total of 92 infants were enrolled for the final analysis. Their Bayley-III scores of cognitive, language, and movement were as follows: 104.2 ± 14.7, 85.6 ± 11.3, and 86.9 ± 13.5, respectively. MRI results showed that 17 infants showed pre-operative brain injury and 25 infants showed new post-operative injury. After performing the analysis of stepwise multivariable linear regression, MRI showed the factors affecting neurodevelopment of newborn include the new post-operative injury, higher VAA exposure, fentanyl dose, benzodiazepine dose, ICU length of stay, pre-operative mean regional cerebral oxygen saturation (rSO₂), and abnormal chromosomes.
 CONCLUSION VAA exposure and ICU length of stay are associated with poor neurodevelopmental scores at 12 months of age. Further studies need to identify the potential modifiable factors in the peri-operative care of neonates to improve neurodevelopmental outcomes.
Anesthetics ; adverse effects ; Benzodiazepines ; adverse effects ; Cardiac Surgical Procedures ; Child Development ; drug effects ; Cohort Studies ; Fentanyl ; adverse effects ; Humans ; Infant ; Infant, Newborn ; Length of Stay ; Linear Models ; Magnetic Resonance Imaging ; Neuroimaging

We report an elderly patient who developed severe delirium and extrapyramidal signs after initiation of lithium-olanzapine combination. On hospital admission, serum levels of lithium were found to be 3.0 mM/L which were far above toxic level. Immediate discontinuation of both drugs resulted in complete resolution of most of the symptoms except for perioral dyskinesia which persisted for three more months. We critically discussed the differential diagnosis of lithium intoxication and assessed confounding factors which induce delirium and extrapyramidal signs related with combination therapy of lithium and olanzapine.
Antipsychotic Agents/adverse effects/therapeutic use ; Basal Ganglia Diseases/*chemically induced ; Benzodiazepines/adverse effects/therapeutic use ; Bipolar Disorder/drug therapy ; Delirium/*chemically induced ; Drug Therapy, Combination ; Female ; Humans ; Lithium/*adverse effects/therapeutic use ; Middle Aged

Adenoma ; complications ; pathology ; Adult ; Antipsychotic Agents ; adverse effects ; therapeutic use ; Aripiprazole ; Benzodiazepines ; adverse effects ; therapeutic use ; Bromocriptine ; adverse effects ; therapeutic use ; Dopamine Antagonists ; adverse effects ; therapeutic use ; Female ; Hormone Antagonists ; adverse effects ; therapeutic use ; Humans ; Hyperprolactinemia ; complications ; etiology ; Piperazines ; adverse effects ; therapeutic use ; Pituitary Neoplasms ; complications ; pathology ; Quinolones ; adverse effects ; therapeutic use ; Risperidone ; adverse effects ; therapeutic use ; Schizophrenia ; drug therapy ; etiology ; pathology ; Serotonin Antagonists ; adverse effects ; therapeutic use ; Trifluoperazine ; adverse effects ; therapeutic use

OBJECTIVES: To evaluate the risk of fractures related with zolpidem in elderly insomnia patients. METHODS: Health claims data on the entire South Korean elderly population from January 2005 to June 2006 were extracted from the Health Insurance Review and Assessment Service database. We applied a case-crossover design. Cases were defined as insomnia patients who had a fracture diagnosis. We set the hazard period of 1 day length prior to the fracture date and four control periods of the same length at 5, 10, 15, and 20 weeks prior to the fracture date. Time independent confounding factors such as age, gender, lifestyle, cognitive function level, mobility, socioeconomic status, residential environment, and comorbidity could be controlled using the casecrossover design. Time dependent confounding factors, especially co-medication of patients during the study period, were adjusted by conditional logistic regression analysis. The odds ratios and their 95% confidence intervals (CIs) were estimated for the risk of fracture related to zolpidem. RESULTS: One thousand five hundred and eight cases of fracture were detected in insomnia patients during the study period. In our data, the use of zolpidem increased the risk of fracture significantly (adjusted odds ratio [aOR], 1.72; 95% CI, 1.37 to 2.16). However, the association between benzodiazepine hypnotics and the risk of fracture was not statistically significant (aOR, 1.00; 95% CI, 0.83 to 1.21). Likewise, the results were not statistically significant in stratified analysis with each benzodiazepine generic subgroup. CONCLUSIONS: Zolpidem could increase the risk of fracture in elderly insomnia patients. Therefore zolpidem should be prescribed carefully and the elderly should be provided with sufficient patient education.
Aged ; Aged, 80 and over ; Benzodiazepines/adverse effects/therapeutic use ; Cross-Over Studies ; Female ; Fractures, Bone/chemically induced/*epidemiology ; Humans ; Hypnotics and Sedatives/adverse effects/therapeutic use ; Male ; Odds Ratio ; Pyridines/*adverse effects/*therapeutic use ; Republic of Korea/epidemiology ; Risk Assessment ; Risk Factors ; Sleep Initiation and Maintenance Disorders/*drug therapy

The treatment of benzodiazepine withdrawal is difficult, and the search continues for substances that can reduce craving and the risk of relapse. Here, we report three cases of benzodiazepine addicts with histories of unsuccessful withdrawal attempts who experienced marked reductions in craving and improved relapse prognoses under add-on administration of agomelatine. These cases demonstrate a possible area of use for the antidepressant agomelatine in the treatment of benzodiazepine withdrawal and addiction. The extent to which this effect is due to the anti-craving effects of agomelatine, or its profile of receptor activation, should be further investigated in larger clinical and experimental studies.
Acetamides ; therapeutic use ; Adult ; Antidepressive Agents ; therapeutic use ; Behavior, Addictive ; Benzodiazepines ; adverse effects ; Female ; Follow-Up Studies ; Humans ; Hypnotics and Sedatives ; adverse effects ; Lorazepam ; adverse effects ; Male ; Middle Aged ; Substance Withdrawal Syndrome ; drug therapy ; Substance-Related Disorders ; drug therapy ; Time Factors ; Treatment Outcome