The effects of intranasal oxytocin on reward circuitry responses in children with autism spectrum disorder.

BACKGROUND: Intranasal oxytocin (OT) has been shown to improve social communication functioning of individuals with autism spectrum disorder (ASD) and, thus, has received considerable interest as a potential ASD therapeutic agent. Although preclinical research indicates that OT modulates the functional output of the mesocorticolimbic dopamine system that processes rewards, no clinical brain imaging study to date has examined the effects of OT on this system using a reward processing paradigm. To address this, we used an incentive delay task to examine the effects of a single dose of intranasal OT, versus placebo (PLC), on neural responses to social and nonsocial rewards in children with ASD. METHODS: In this placebo-controlled double-blind study, 28 children and adolescents with ASD (age: M = 13.43 years, SD = 2.36) completed two fMRI scans, one after intranasal OT administration and one after PLC administration. During both scanning sessions, participants completed social and nonsocial incentive delay tasks. Task-based neural activation and connectivity were examined to assess the impact of OT relative to PLC on mesocorticolimbic brain responses to social and nonsocial reward anticipation and outcomes. RESULTS: Central analyses compared the OT and PLC conditions. During nonsocial reward anticipation, there was greater activation in the right nucleus accumbens (NAcc), left anterior cingulate cortex (ACC), bilateral orbital frontal cortex (OFC), left superior frontal cortex, and right frontal pole (FP) during the OT condition relative to PLC. Alternatively, during social reward anticipation and outcomes, there were no significant increases in brain activation during the OT condition relative to PLC. A Treatment Group × Reward Condition interaction revealed relatively greater activation in the right NAcc, right caudate nucleus, left ACC, and right OFC during nonsocial relative to social reward anticipation during the OT condition relative to PLC. Additionally, these analyses revealed greater activation during nonsocial reward outcomes during the OT condition relative to PLC in the right OFC and left FP. Finally, functional connectivity analyses generally revealed changes in frontostriatal connections during the OT condition relative to PLC in response to nonsocial, but not social, rewards. CONCLUSIONS: The effects of intranasal OT administration on mesocorticolimbic brain systems that process rewards in ASD were observable primarily during the processing of nonsocial incentive salience stimuli. These findings have implications for understanding the effects of OT on neural systems that process rewards, as well as for experimental trials of novel ASD treatments developed to ameliorate social communication impairments in ASD.

Possible interaction of zopiclone and nefazodone.

OBJECTIVE: To describe a case in which concurrent treatment with nefazodone was associated with an elevation in the plasma concentration of zopiclone, possibly resulting in enhanced hypnosedative efficacy. CASE REPORT: An 86-year-old white woman was treated with nefazodone for depression. Zopiclone was also introduced for the management of insomnia, but she subsequently experienced morning drowsiness. The concentration of zopiclone in plasma was subsequently measured eight hours after administration on two occasions, during nefazodone therapy and after its withdrawal. After discontnuation of nefazodone, the plasma concentration of the S-enantiomer of zopiclone decreased from 107 to 16.9 ng/mL, while the R-enantiomer plasma concentration decreased from 20.6 to 1.45 ng/mL. DISCUSSION: Nefazodone is a relatively potent inhibitor of CYP3A4, a hepatic isoenzyme thought to play a major role in the metabolic elimination of zopiclone. The substantial decrease in the plasma zopiclone concentrations observed after withdrawal of nefazodone likely reflects a drug interaction. Despite the normally short elimination half-life of zopiclone, the residual sedation initially observed in this case suggests that the interaction may have clinical significance. CONCLUSIONS: The features observed in this case suggest the possibility of a drug-drug interaction between nefazodone and zopiclone. Further prospective investigation is required to elucidate the nature and magnitude of this effect.

A brief analysis of clinical pharmacy interventions undertaken in an Australian teaching hospital.

Selected clinical pharmacy interventions undertaken during a 30-day data capture period were analysed, seeking to gain a greater understanding of the nature of the drug-related problems involved. Pharmacists were asked to record only interventions that were of potentially major significance. A total of 67 interventions were submitted for analysis. In 28 cases (41.7% of the initial total) the intervention reports were excluded from further analysis after initial review. For the remaining 39 interventions, 20 patients (51%) were under the care of a medical unit, and cardiovascular/antithrombotic agents accounted for 17 reports (43.5%). The majority of interventions were implemented at the time of inpatient medication order review by the clinical pharmacist (n=25, 64%). The most common category of drug-related problem addressed in the interventions related to the prescription of inappropriately high doses of the correct drug for the patient (n=17, 43.6%). Deficiencies in technical knowledge accounted for less than 25% of all cases.

Characteristics of tranquilizer use among Australian Vietnam War veterans.

OBJECTIVE: To examine characteristics of tranquilizer use in a cohort of Australian Vietnam War veterans. DESIGN: Prospective analysis of medication use and assessment of social and clinical variables, including tranquilizer dependence. PATIENTS: Fifty-one Australian Vietnam War veterans were recruited from the department of psychiatry of an Australian teaching hospital. All subjects were men, with a mean +/- SD age of 52.2 +/- 3.3 years. MAIN OUTCOME MEASURES: A structured interview was used to obtain details of medical and psychiatric history, medication use, substance use, forensic history, and health service utilization data. Anxiety was assessed using the Hamilton Anxiety Rating Scale (Ham-A). A validated tranquilizer dependence rating scale was administered for each patient. RESULTS: Commonly used tranquilizers included diazepam (n = 19 patients) and zopiclone (26). Most patients (44) reported the use of one or more drugs for the purpose of nighttime sedation, while exclusive daytime use of tranquilizers for anxiolytic effect was uncommon. The median time spent in the hospital during the preceding year was 21.0 +/- 56.8 days. Symptoms of anxiety were prevalent, with a mean Ham-A score of 35.5 +/- 7.8. Screening criteria suggestive of tranquilizer dependence were met in 34 subjects. Health service utilization was correlated with tranquilizer intake and overall medication use. Tranquilizer dependence was independently associated with cigarette smoking (p = 0.039; odds ratio = 5.13, 95% CI 1.08 to 24.33). CONCLUSIONS: This study provides insight into the nature of tranquilizer use in an Australian population of Vietnam War veterans. The extensive use of these drugs suggests that further research and possibly intervention in this area is needed.

Patient-oriented strategies for the prevention of drug interactions.

Drug interactions are a common and serious problem arising from polypharmacy. Strategies to reduce the likelihood of the co-prescription of hazardous drug combinations are likely to enhance the quality of care provided for patients requiring polypharmacotherapy. Drugs for which patient-oriented information strategies may decrease the likelihood of drug interactions tend to be those of low therapeutic index. and have interaction potential with other drugs commonly prescribed or available without prescription.