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Li A.-N.,Beijing Key Laboratory of Mental Disorders | Dong F.,Beijing Key Laboratory of Mental Disorders | He J.-L.,Beijing Key Laboratory of Mental Disorders | Shang D.-W.,Guangzhou University | And 4 more authors.
Pharmacopsychiatry | Year: 2015

Introduction: The prescribing of clozapine in China is common because of its outstanding efficacy and low price. There have been many cases of clozapine overdose in China. However, studies about the pharmacokinetics after overdose in the Chinese have rarely been reported. Population pharmacokinetics (PopPK) can analyze sparse data, and it is appropriate to compute clozapine pharmacokinetics after overdose. Methods: There were 47 clozapine overdose cases. We constructed a single-compartment first-order elimination PopPK model. We also considered some covariates that can influence the pharmacokinetics parameters. Results: 21 cases were included in the analysis. When the reported toxic dosage was 3 740 mg, the elimination rate constant of the population was 0.0258(h−1). The elimination half-life was 26.9 h. The coefficient of random variation was 17%. Discussion: PopPK can solve the problem of sparse data after overdose. The area under the concentration-time curve after clozapine overdose exhibited the “two peaks phenomenon.” The reported toxic dosage could impact clozapine elimination after overdose. Delayed absorption of clozapine is the best explanation for this finding. Copyright © 2015, Georg Thieme Verlag KG. All rights reserved. Source

Liu C.-H.,Beijing Key Laboratory of Mental Disorders | Liu C.-H.,Capital Medical University | Ma X.,Beijing Key Laboratory of Mental Disorders | Ma X.,Capital Medical University | And 12 more authors.
Brain Research | Year: 2015

Of major depression patients, 29-66% show only partial remission on a single antidepressant trial. Such patients are characterized by residual depressive symptoms such as anhedonia, psychic anxiety, sleep disturbance, and cognitive dysfunction. Despite having a tremendous impact on outcomes such as future relapse, morbidity, and mortality, the neural mechanisms of partially remitted depression remain unclear. Using the amplitude of low-frequency fluctuations (ALFF) approach, we investigated the intrinsic neural oscillation alterations during resting state in partially remitted depression. A total of 23 partially remitted depression patients and 68 healthy controls underwent magnetic resonance imaging for functional imaging. We compared ALFF differences between groups as well as correlations between clinical measurements and ALFF in the brain regions showing significant group differences. Compared with healthy controls, partially remitted depression patients showed increased ALFF in the left ventral anterior insula, bilateral posterior insula, and bilateral supramarginal gyrus, and decreased ALFF in the left calcarine gyrus. A trend positive correlation between the number of depressive episodes and ALFF values was found in the right posterior insula in the partially remitted depression group. In addition, the ALFF in the right supramarginal gyrus were negatively correlated with Hamilton Depression Rating Scale scores. Consistent with the emerging theory of the role of the salience network in sensing the changes of homeostasis that contributes to partially remitted depression, the current findings suggest that the increased intrinsic neural oscillation of the insula is related to the refractoriness to treatment and may be an imaging marker for predicting future depression recurrence. © 2014 Elsevier B.V. Source

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