How provider payment methods affect health expenditure of depressive patients? Empirical study from national claims data in China from 2013 to 2017.

BACKGROUND: This study aimed to investigate the associations between provider payment methods and expenditure of depressive patients, stratified by service types and hospital levels. METHODS: We used a 5 % random sample of urban claims data in China (2013-2017), collected by China Health Insurance Research Association. Provider payment methods (fee-for-services, global budget, capitation, case-based and per-diem payments) were the explanatory variables. A generalized linear model was fitted for the associations between provider payment methods and expenditure. All analyses were adjusted for patient"cioeconomic and health-related characteristics. RESULTS: In total, 64,615 depressive patient visits were included, 59,459 for outpatients and 5156 for inpatients. Female patients accounted for 63.00 %. The total and out-of-pocket (OOP) expenditure significantly differentiated by provider payments. Among outpatient services, when comparing with fee-for-services, capitation payment was associated with substantial marginal reduction in total and OOP expenditure (-$34.18, -$9.71) in primary institutes, yet increases ($27.26, $24.11) in secondary hospitals. Similarly, global budget was associated with lower total and OOP expenditure (-$13.51, -$1.61) in secondary hospitals, while higher total and OOP expenditure ($7.43, $32.27) in tertiary hospitals than fee-for-services. For inpatients, total and OOP expenditures under per-diem (-$857.65, -$283.48) and case-based payments (-$997.93, -$137.56) were remarkably smaller than those under fee-for-services in primary and secondary hospitals, respectively. Besides, case-base payment was only linked with the largest reduction in OOP expense (-$239.39) in inpatient services of tertiary hospitals. LIMITATION: Only urban claims data was included in this study, and investigations for rural population still warrant. And updated data are needed for future studies. CONCLUSIONS: There were varying correlations between provider payment methods and expenditure, which differed by service types and hospital levels. These findings provided empirical evidence for optimizing the mixed payment methods for depression in China.

A Chinese medicine called Danggui Longhui may be a new clinically relevant clozapine inducer: Two case reports identified by therapeutic drug monitoring.

BACKGROUND: Danggui Longhui is a traditional Chinese medicine made from the dried root of Angelica sinensis. It is used in psychiatric patients in China to reduce associated constipation. In a population pharmacokinetic model in olanzapine patients from Beijing Anding Hospital, we demonstrate that dangguilonghui tablets doubled olanzapine clearance, indicating the induction of olanzapine metabolism. Olanzapine metabolism is similar to clozapine metabolism. METHODS: Two cases of possible clozapine induction using dangguilonghui tablets 4 g/day were identified in Beijing Anding Hospital. Dividing the minimum therapeutic concentration of 350 ng/mL by the concentration-to-dose (C/D) ratio provides the minimum therapeutic dose. RESULTS: Case 1 was a female smoker on clozapine for 415 days. The mean of 6 clozapine C/D ratios associated with smoking provided a minimum therapeutic dose of 267 mg/day. There were 6 steady-state concentrations on the combination of valproic acid and dangguilonghui tablets, which provided a much higher minimum therapeutic dose of 833 mg/day. Four steady-state clozapine C/D ratios based on smoking and valproate after 4 months of carbamazepine 200 mg/day provided a minimum therapeutic dose of 603 mg/day. Case 2 was a female non-smoker on clozapine for 58 days. She had 3 clozapine C/D ratios on dangguilonghui tablets with a mean of 0.30 ng/mL providing a minimum therapeutic dose of 1167 mg/day. CONCLUSION: Future clinical studies with repeated measures need to replicate the possibility that dangguilonghui tablets are a moderate-to-strong inducer of clozapine metabolism as suggested by these two limited cases.

Which can Predict the Outcome of Antidepressants: Metabolic Genes or Pharmacodynamic Genes?

Drug therapy is the primary modality for depression; however, its outcome is often unpredictable, ranging from beneficial effects to serious adverse effects. Genetic variations in drug metabolizing enzymes and pharmacodynamic molecules are responsible for a considerable proportion of interindividual differences in the effectiveness and toxicity of antidepressants. For the improvement in the use of antidepressants, the focus is mainly on personalized treatment emphasizing interindividual differences in genes. This study provides a comprehensive review of the literature on the clinical applications of pharmacogenomics for antidepressant therapy. The polymorphisms of metabolizing enzymes (CYP2D6, CYP2C19, and others) governing the pharmacokinetic behavior of drugs are potential predictors of side effects or treatment failure with medications and there are good pharmacogenetic clinical recommendations for a wide selection of psychopharmacological agents based on functional diplotypes of CYP2C19 and CYP2D6. The relationship between pharmacodynamic genes, including FKBP5, SLC6A4, BDNF, ABCB1, HTR1A, and HTR2A, and clinical outcomes varies in different races. Receptors that are currently used as drug targets for antidepressant drugs are evolutionarily conserved to a higher extent than genes encoding drug metabolism, and the actionability of pharmacodynamic-related genotyping is currently still questionable. The limited availability of largescale, long-term clinical studies on different races and medications currently impedes the implementation of pharmacogenomics in antidepressant treatment. The use of pharmacokinetic and pharmacodynamic modeling, and therapeutic drug monitoring combined with genetic, somatic, dietary, and environmental factors represents a promising avenue for improving the precision and effectiveness of antidepressant therapy.

Two cases of high serum clozapine concentrations occurring during inflammation in Chinese patients.

Objective Serious infections or inflammations have been associated with serum clozapine concentration increases and sometimes with clozapine toxicity. Method These two cases describe Chinese patients (Case 1: a 57-year-old female nonsmoker with severe dermatitis and Case 2: a 47-year-old male nonsmoker with influenza and secondary infection). Results In both cases, the Drug Interaction Probability Scale established the presence of a probable drug-drug interaction. In both cases, the clozapine and the total clozapine concentration-to-dose ratios followed a temporal pattern (normal-high-normal), consistent with an inhibition of clozapine metabolism during peak inflammation. In the first case, the total clozapine concentration-to-dose ratio (8 with no/low inflammation: median of 3.10 and 2 at peak inflammation: median of 3.90) provided a significant difference (P = 0.044). In the second patient, because of the smaller sample size and reduced statistical power (4 with no infection: a median of 1.59 and 2 at peak infection: 3.46), the increase did not reach significance (P = 0.13). In the first case, the median baseline clozapine concentration-to-dose ratio increased by a factor of 1.45 from 2.00 to a peak of 2.89. To compensate for the inhibition of clozapine metabolism, the dose correction factor was 0.69 (1/1.45) or a decrease in dose of approximately one-third. In the second case, the median baseline clozapine concentration-to-dose ratio increased by a factor of 2.56 from 1.15 to a peak of 2.94. Conclusion This provided a dose correction factor of 0.40 (1/2.56) or approximately half the dose, similar to published cases in Caucasians with serious respiratory infections.