Ziprasidone is widely used in the treatment of psychiatric disorders. Despite its prevalence, there is a notable lack of population pharmacokinetics (PPK) studies on ziprasidone in serum, both domestically and internationally. This study aimed to comprehensively investigate the various factors influencing the PPK characteristics of Ziprasidone, thereby providing a scientific basis for personalized treatment strategies in clinical settings. This is a retrospective study. A non-linear mixed-effects modeling method was used for data analysis, with the ziprasidone PPK model established using the Phoenix NLME 8.1 software. Model evaluation employed goodness-of-fit plots, visual predictive checks, and Bootstrap methods to ensure reliability and accuracy. To further validate the model\'s applicability, data from an additional 30 patients meeting the same inclusion criteria but not included in the final model were collected for external validation. Simulations were performed to explore the personalized dosage regimens. This retrospective analysis collected 547 drug concentration data points from 185 psychiatric disorder patients, along with related medical records. The data included detailed demographic information (such as age, gender, weight), dosing regimens, laboratory test results, and concomitant medication details. In the final model, Ka was fixed at 0.5 h-1 based on literature, and the population typical values for ziprasidone clearance (CL) and volume of distribution (V) were 18.74 L/h and 110.24 L, respectively. Co-administration of lorazepam and valproic acid significantly influenced the clearance of ziprasidone. Moreover, the model evaluation indicated good stability and predictive accuracy. A simple to use dosage regimen table was derived based on the results of simulations. This study successfully established and validated a PPK model for ziprasidone in Chinese patients with psychiatric disorders. The model provides a scientific reference for individualized dosing of ziprasidone and holds the potential to optimize treatment strategies, thereby enhancing therapeutic efficacy and safety.

OBJECTIVE: To observe the efficacy of acupuncture for reducing the south to reinforce the north on executive function, sleep structure and sleep quality in patients with chronic insomnia disorder of heart-kidney disharmony.
METHODS: A total of 100 patients with chronic insomnia disorder of heart-kidney disharmony were randomized into an acupuncture group (50 cases, 1 case dropped out) and a western medication group (50 cases, 2 cases dropped out). Acupuncture for reducing the south to reinforce the north was applied at Baihui (GV 20) and bilateral Shenmen (HT 7), Sanyinjiao (SP 6), Shenmai (BL 62), Zhaohai (KI 6), Xinshu (BL 15), Shenshu (BL 23) in the acupuncture group, once a day, 5 days a week. Lorazepam tablet was given orally in the western medication group, 0.5-1 mg a time, once a day. Both groups were treated for 4 weeks. The Stroop color-word test (SCWT) indexes (the time consuming and the correct number of card A, B, C and the Stroop interference effect [SIE]), sleep structure indexes (total sleep time [TST], sleep latency [SL], wake after sleep onset [WASO], sleep efficiency [SE], non-rapid eye movement period 1 [N1], non-rapid eye movement period 2 [N2], non-rapid eye movement period 3 [N3], rapid eye movement period [REM]) and Pittsburgh sleep quality index (PSQI) score were observed before and after treatment in the two groups.
RESULTS: After treatment, the time consuming of card B and C, the time consuming and the correct number of SIE, SL, WASO, N1, N2, as well as the sub-item scores and total score of PSQI were decreased (P<0.05, P<0.01), the correct number of card A, B and C, TST, SE, N3 and REM were increased (P<0.01) compared with those before treatment in the acupuncture group; the time consuming of card C and SIE, the correct number of card A and SIE, TST, SE, REM were increased (P<0.05, P<0.01), SL, WASO, N1, as well as the sub-item scores of sleep quality, sleep latency, sleep duration, sleep efficiency, daytime function and total score of PSQI were decreased (P<0.01) compared with those before treatment in the western medication group. After treatment, in the acupuncture group, the time consuming of card C, the time consuming and the correct number of SIE, N1, N2, as well as the sub-item scores of sleep quality, sleep dysfunction, daytime function and total score of PSQI were lower than those in the western medication group (P<0.01), the correct number of card B and C, N3, REM were higher than those in the western medication group (P<0.01).
CONCLUSIONS: Acupuncture for reducing the south to reinforce the north can improve the executive function of patients with chronic insomnia disorder of heart-kidney disharmony, adjust the sleep structure, and improve the night sleep quality and daytime body function.
目的: 观察泻南补北法针刺对心肾不交型慢性失眠障碍患者执行功能、睡眠结构及睡眠质量的影响。方法: 将100例心肾不交型慢性失眠障碍患者随机分为针刺组（50例，脱落1例）和西药组（50例，脱落2例）。针刺组施泻南补北法针刺（穴取百会及双侧神门、三阴交、申脉、照海、心俞、肾俞，每日1次，每周5 d），西药组予口服劳拉西泮片（每次0.5~1 mg，每日1次），两组均治疗4周。分别于治疗前后观察两组患者Stroop色词测验（SCWT）指标［卡片A、B、C耗时数和正确数，Stroop干扰量（SIE）耗时数和正确数］、睡眠结构指标［总睡眠时间（TST）、睡眠潜伏期（SL）、入睡后清醒时间（WASO）、睡眠效率（SE）、非快速眼球运动1期（N1）、非快速眼球运动2期（N2）、非快速眼球运动3期（N3）、快速眼球运动期（REM）］及匹兹堡睡眠质量指数（PSQI）评分。结果: 治疗后，针刺组卡片B耗时数、卡片C耗时数、SIE耗时数、SIE正确数、SL、WASO、N1、N2、PSQI各项评分及总分较治疗前减少（P<0.05，P<0.01），卡片A正确数、卡片B正确数、卡片C正确数、TST、SE、N3、REM较治疗前增加（P<0.01）；西药组卡片C耗时数、SIE耗时数、卡片A正确数、SIE正确数、TST、SE、REM较治疗前增加（P<0.05，P<0.01），SL、WASO、N1较治疗前减少（P<0.01），PSQI睡眠质量、入睡时间、睡眠时间、睡眠效率、日间功能评分及总分较治疗前减少（P<0.01）。治疗后，针刺组卡片C耗时数、SIE耗时数、SIE正确数、N1、N2低于西药组（P<0.01），PSQI睡眠质量、睡眠障碍、日间功能评分及总分低于西药组（P<0.01），卡片B正确数、卡片C正确数、N3、REM高于西药组（P<0.01）。结论: 泻南补北法针刺可改善心肾不交型慢性失眠障碍患者的执行功能，调节其睡眠结构，并提高其夜间睡眠质量、日间机体功能。.

Psychotropic medications are one of the most prescribed pharmaceuticals in the world. Given their frequent detection and ecotoxicity to the no-target organism, the emission of these medications into environments has gradually draw attention. The study developed a sensitive and reliable analytic method to simultaneously investigate 47 psychotropic medications in four matrices: wastewater, surface water, activated sludge, and sediment by ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS). These 47 target analytes include 24 antidepressants, 17 antianxiety drugs, 5 anticonvulsants, and 1 relevant hormone. Solid phase extraction (SPE) was employed to extract analytes from water-phase samples. Ultrasonic Solvent Extraction method with Enhanced Matrix Removal clean-up (USE-EMR) was utilized to extract target compounds from solid-phase samples, which requires more straightforward and convenient procedures than previous methods. The extraction recoveries of all analytes ranged from 80 % to 120 % in these four sample matrices. In this study, The limit of quantitation for 47 psychotropic medications were 0.15 ng/L (estazolam) to 2.27 ng/L (lorazepam), 0.08 ng/L (desvenlafaxine) to 2 ng/L (mianserin), 0.22 ng/g (dry weight, dw) (nordiazepam) to 3.65 ng/g (dw) (lorazepam), and 0.07 ng/g (dw) (carbamazepine) to 2.85 ng/g (lorazepam), in wastewater, surface water, sludge, and sediment, respectively. In addition, the developed method was employed to analyse actual samples in two wastewater treatment plants and their receiving rivers. Carbamazepine, escitalopram, clozapine, desvenlafaxine, diazepam, lamotrigine, sertraline, temazepam, and venlafaxine were nearly ubiquitous in all matrices. Moreover, this study indicated that the inadequate removal efficiencies of psychotropic medications in wastewater treatment plants (WWTPs) had resulted in a persistent discharge of these contaminants from human sources into environments.

It is challenging to manage schizophrenic catatonia and comorbid chronic intestinal pseudo-obstruction (CIPO). The pathology of catatonia is unclear. There are few reports or research on this issue. In this case, we present a middle-aged woman diagnosed with schizophrenia with catatonic features and comorbid CIPO. In the treatment process, modified electroconvulsive therapy (mECT) improved her stupor and CIPO partially. Lorazepam alleviated her stupor and CIPO completely. It is the first report describing complete remission with lorazepam in patient suffering from comorbid schizophrenic catatonia and CIPO, which may benefit the exploration of pathophysiology and treatment of comorbidity of schizophrenia with catatonia and CIPO.

Polypharmacy increases the risk of potential drug-drug interactions (pDDIs). This retrospective analysis was conducted to detect pDDIs and adverse drug reactions (ADRs) among older adults with psychiatric disorder, and identify pDDIs with clinical significance.
A retrospective analysis was carried out based on the medical records of older adults with psychiatric disorders. Data on demographic characteristics, substance abuse, medical history, and medications were extracted. The Lexi-Interact online database was used to detect pDDIs. The minimal clinically important difference (MCID) was set as the change in the Treatment Emergent Symptom Scale (TESS) score between admission and discharge. The median and interquartile ranges were used for continuous variables, and frequencies were calculated for dichotomous variables. Poisson regression was implemented to determine the factors influencing the number of ADR types. The influencing factors of each ADR and the clinical significance of the severity of the ADR were analysed using binary logistic regression. P < 0.05 was considered statistically significant.
A total of 308 older adults were enrolled, 171 (55.52%) of whom had at least 1 pDDI. Thirty-six types of pDDIs that should be avoided were found, and the most frequent pDDI was the coadministration of lorazepam and olanzapine (55.5%). A total of 26 ADRs induced by pDDIs were identified, and the most common ADR was constipation (26.05%). There was a 9.4 and 10.3% increase in the number of ADR types for each extra medical diagnosis and for each extra drug, respectively. There was a 120% increase in the number of ADR types for older adults hospitalized for 18-28 days compared with those hospitalized for 3-17 days. There was an 11.1% decrease in the number of ADR types for each extra readmission. The length of hospitalization was a risk factor for abnormal liver function (P < 0.05). The use of a large number of drugs was a risk factor for gastric distress (P < 0.05) and dizziness and fainting (P < 0.05). None of the four pDDIs, including coadministrations of olanzapine and lorazepam, quetiapine and potassium chloride, quetiapine and escitalopram, and olanzapine and clonazepam, showed clinical significance of ADR severity (P > 0.05).
pDDIs are prevalent in older adults, and the rate is increasing. However, many pDDIs may have no clinical significance in terms of ADR severity. Further research on assessing pDDIs, and possible measures to prevent serious ADRs induced by DDIs is needed to reduce the clinical significance of pDDIs.

暂无摘要。

Delirium is a very common condition associated with significant morbidity, mortality, and costs. Current critical care guidelines recommend first and foremost the use of nonpharmacological strategies in both the prevention and treatment of delirium. Pharmacological interventions may augment these approaches and they are currently used widely in clinical practice to manage the symptoms of delirium. Benzodiazepines are currently used in clinical practice to treat behavioural disturbances associated with delirium but current guidelines do not recommend their use for this indication. The use of these medicines is controversial because there is uncertainty about whether they are effective for patients or have the potential to harm them.
To assess the effectiveness and safety of benzodiazepines in the treatment of delirium (excluding delirium related to withdrawal from alcohol or benzodiazepines) in any healthcare settings other than intensive care units (ICU).
We searched ALOIS: the Cochrane Dementia and Cognitive Improvement Group\'s Specialized Register up to 10 April 2019. ALOIS contains records of clinical trials identified from monthly searches of a number of major healthcare databases (including MEDLINE, Embase, PsycINFO, CINAHL, LILACS), numerous trial registries (including national, international and pharmaceutical registries), and grey literature sources.
We included randomised controlled trials (RCTs) conducted in healthcare settings that ranged from nursing homes and long-term care facilities to any hospital setting except for ICUs, involving adult patients with delirium excluding those with delirium related to alcohol or benzodiazepine withdrawal. Included RCTs had to assess the effect of benzodiazepines, at any dose and given by any route, compared with placebo or another drug intended to treat delirium.
Two review authors independently assessed study eligibility, extracted data, and assessed the risk of bias of included studies. We decided whether or not to pool data on the basis of clinical heterogeneity between studies. We used GRADE (Grades of Recommendation, Assessment, Development and Evaluation) methods to assess the quality of evidence.
We identified only two trials that satisfied the selection criteria. We did not pool the data because of the substantial clinical differences between the trials. In one trial, participants (n = 58) were patients in an acute palliative care unit with advanced cancer who had a mean age of 64 years. All of the participants had delirium, were treated with haloperidol, and were randomised to receive either lorazepam or placebo in combination with it. Due to very serious imprecision, all evidence was of low certainty. We were unable to determine whether there were clinically important differences in the severity of delirium (mean difference (MD) 2.10, 95% CI -0.96 to 5.16; n = 50), length of hospital admission (MD 0.00, 95% CI -3.45 to 3.45; n = 58), mortality from all causes (risk ratio (RR) 0.33, 95% CI 0.04 to 3.02; participants = 58) or any of a number of adverse events. Important effects could not be confirmed or excluded. The study authors did not report the length of the delirium episode. In the other trial, participants (n = 30) were patients in general medical wards with acquired immune deficiency syndrome (AIDS) who had a mean age of 39.2 years. Investigators compared three drug treatments: all participants had delirium, and were randomised to receive lorazepam, chlorpromazine, or haloperidol. Very low-certainty evidence was identified, and we could not determine whether lorazepam differed from either of the other treatments in the effect on severity of delirium, any adverse event, or mortality from all causes. The study authors did not report the length of the delirium episode or the length of hospital admission.
There is no enough evidence to determine whether benzodiazepines are effective when used to treat patients with delirium who are cared for in non-ICU settings. The available evidence does not support their routine use for this indication. Because of the scarcity of data from randomised controlled trials, further research is required to determine whether or not there is a role for benzodiazepines in the treatment of delirium in non-ICU settings.

Although several pharmacological interventions for delirium have been investigated, their overall benefit and safety remain unclear.
To evaluate evidence regarding pharmacological interventions for delirium treatment and prevention.
PubMed, Embase, ProQuest, ScienceDirect, Cochrane Central, Web of Science, ClinicalKey, and ClinicalTrials.gov from inception to May 17, 2018.
Randomized clinical trials (RCTs) examining pharmacological interventions for delirium treatment and prevention.
To extract data according to a predetermined list of interests, the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines were applied, and all meta-analytic procedures were conducted using a random-effects model.
The primary outcomes were treatment response in patients with delirium and the incidence of delirium in patients at risk of delirium.
A total of 58 RCTs were included, in which 20 RCTs with 1435 participants (mean age, 63.5 years; 65.1% male) compared the outcomes of treatment and 38 RCTs with 8168 participants (mean age, 70.2 years; 53.4% male) examined the prevention of delirium. A network meta-analysis demonstrated that haloperidol plus lorazepam provided the best response rate for delirium treatment (odds ratio [OR], 28.13; 95% CI, 2.38-333.08) compared with placebo/control. For delirium prevention, the ramelteon, olanzapine, risperidone, and dexmedetomidine hydrochloride groups had significantly lower delirium occurrence rates than placebo/control (OR, 0.07; 95% CI, 0.01-0.66 for ramelteon; OR, 0.25; 95% CI, 0.09-0.69 for olanzapine; OR, 0.27; 95% CI, 0.07-0.99 for risperidone; and OR, 0.50; 95% CI, 0.31-0.80 for dexmedetomidine hydrochloride). None of the pharmacological treatments were significantly associated with a higher risk of all-cause mortality compared with placebo/control.
This network meta-analysis demonstrated that haloperidol plus lorazepam might be the best treatment and ramelteon the best preventive medicine for delirium. None of the pharmacological interventions for treatment or prophylaxis increased the all-cause mortality.

The pharmacokinetic (PK) parameters of many drugs are altered as a consequence of the pathophysiological changes associated with critical illness. The critically ill population presents challenges when titrating infusions of sedatives and analgesics to maintain optimal sedation and pain levels. This systematic review examined the PK data in critically ill adult patients with prolonged infusions (>24 hours) of commonly used sedatives and analgesics to highlight possible altered PK parameters compared with noncritically ill patients.
A literature search of PK studies was performed by using MEDLINE (1946-December 2017) and EMBASE (1910-December 2017); we identified further studies by citation tracking (Web of Science) and checked references of retrieved studies and review articles. All studies were included that were published in English, Chinese, or German; conducted in critically ill adult patients receiving lorazepam, midazolam, propofol, dexmedetomidine, sufentanil, alfentanil, remifentanil, morphine, or fentanyl infusion for ≥24 hours; and reported PK parameters. When appropriate, we conducted a meta-analysis on volume of distribution at steady state (Vdss) (liters), clearance (Cl) (liters per hour), and elimination t1/2 (hours) by using a DerSimonian-Laird random effects model to estimate the summary mean and 95% CIs. Results were compared with commonly reported PK ranges in 70-kg noncritically ill patients.
Thirty-three randomized controlled trials and prospective cohort studies were identified involving 1803 adult critically ill patients with 35 drug treatment arms: fifteen midazolam (n = 906) studies, three dexmedetomidine (n = 561), nine propofol (n = 165), four lorazepam (n = 86), one morphine (n = 20), two remifentanil (n = 55), and one sufentanil (n = 10). Each study showed large variations in Vdss, Cl, and elimination t1/2 within and between individual participants. High clinical and methodical heterogeneity between the dexmedetomidine studies prevented the direct comparison of PK parameters between critically ill and noncritically ill patients. Use of midazolam, propofol, and lorazepam in critically ill patients was associated with at least a 2- to 4-fold increase in Vdss compared with noncritically ill patients; Cl decreased ∼2-fold for midazolam and 10-fold for morphine. Critically ill patients receiving prolonged infusions of midazolam, propofol, remifentanil, and sufentanil had at least 2-fold longer elimination or terminal t1/2 than noncritically ill patients.
These findings show a marked difference in many PK parameters from those reported for noncritically ill patients. Initiatives to improve the delivery of prolonged sedatives and analgesic infusions should be informed by PK parameters (Vdss, context-sensitive t1/2, and elimination t1/2) and data derived from critically ill patients.

Compounds with selectivity for GABAA receptor subtypes may differ significantly from nonselective benzodiazepines in their dopaminergic effects in vivo. To explore the exact role of the GABAA receptor subtypes in the regulation of prolactin secretion and the differential effects of selective and nonselective GABA receptor modulators, the effects of the nonselective benzodiazepine lorazepam, as well as two novel α2 /α3 subunit-selective GABAA receptor modulators AZD7325 and AZD6280, on prolactin levels were measured in healthy male volunteers. Following administration of lorazepam at 2 mg doses and AZD6280 at 10 mg and 40 mg doses, prolactin levels increased significantly compared with placebo (difference 42.0%, 19.8%, and 32.8%, respectively), suggesting that the α2 and/or α3 receptor subtypes are involved in GABAergic modulation of prolactin secretion, although possible roles of the α1 and α5 receptor subtypes are not excluded. The increases in prolactin levels after administration of AZD7325 at 2 mg and 10 mg doses (difference 7.6% and 10.5%, respectively) did not reach statistical significance, suggesting that doses of AZD7325 or intrinsic efficacy at the α2 and α3 receptor subtypes may have been too low.