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BMC Medical Informatics and Decision... Oct 2022Dementia is a group of symptoms that largely affects older people. The majority of patients face behavioural and psychological symptoms (BPSD) during the course of their...
BACKGROUND
Dementia is a group of symptoms that largely affects older people. The majority of patients face behavioural and psychological symptoms (BPSD) during the course of their illness. Alzheimer's disease (AD) and vascular dementia (VaD) are two of the most prevalent types of dementia. Available medications provide symptomatic benefits and provide relief from BPSD and associated health issues. However, it is unclear how specific dementia, antidepressant, antipsychotic, antianxiety, and mood stabiliser drugs, used in the treatment of depression and dementia subtypes are prescribed in hospital admission, during hospital stay, and at the time of discharge. To address this, we apply multi-dimensional data analytical approaches to understand drug prescribing practices within hospitals in England and Wales.
METHODS
We made use of the UK National Audit of Dementia (NAD) dataset and pre-processed the dataset. We evaluated the pairwise Pearson correlation of the dataset and selected key data features which are highly correlated with dementia subtypes. After that, we selected drug prescribing behaviours (e.g. specific medications at the time of admission, during the hospital stay, and upon discharge), drugs and disorders. Then to shed light on the relations across multiple features or dimensions, we carried out multiple regression analyses, considering the number of dementia, antidepressant, antipsychotic, antianxiety, mood stabiliser, and antiepileptic/anticonvulsant drug prescriptions as dependent variables, and the prescription of other drugs, number of patients with dementia subtypes (AD/VaD), and depression as independent variables.
RESULTS
In terms of antidepressant drugs prescribed in hospital admission, during stay and discharge, the number of sertraline and venlafaxine prescriptions were associated with the number of VaD patients whilst the number of mirtazapine prescriptions was associated with frontotemporal dementia patients. During admission, the number of lamotrigine prescriptions was associated with frontotemporal dementia patients, and with the number of valproate and dosulepin prescriptions. During discharge, the number of mirtazapine prescriptions was associated with the number of donepezil prescriptions in conjunction with frontotemporal dementia patients. Finally, the number of prescriptions of donepezil/memantine at admission, during hospital stay and at discharge exhibited positive association with AD patients.
CONCLUSION
Our analyses reveal a complex, multifaceted set of interactions among prescribed drug types, dementia subtypes, and depression.
Topics: Aged; Anticonvulsants; Antidepressive Agents; Antipsychotic Agents; Depression; Donepezil; Dothiepin; Frontotemporal Dementia; Hospitals; Humans; Lamotrigine; Memantine; Mirtazapine; NAD; Sertraline; Valproic Acid; Venlafaxine Hydrochloride; Wales
PubMed: 36207697
DOI: 10.1186/s12911-022-01892-9 -
Drug Design, Development and Therapy 2020The purpose of the present study was to investigate the effects of vonoprazan on the pharmacokinetics of venlafaxine in vitro and in vivo.
PURPOSE
The purpose of the present study was to investigate the effects of vonoprazan on the pharmacokinetics of venlafaxine in vitro and in vivo.
METHODS
The mechanism underlying the inhibitory effect of vonoprazan on venlafaxine was investigated using rat liver microsomes. In vitro, the inhibition was evaluated by determining the production of O-desmethylvenlafaxine. Eighteen male Sprague-Dawley rats were randomly divided into three groups: control group, vonoprazan (5 mg/kg) group, and vonoprazan (20 mg/kg) group. A single dose of 20 mg/kg venlafaxine was administrated to rats orally without or with vonoprazan. Plasma was prepared from blood samples collected via the tail vein at different time points and concentrations of venlafaxine and its metabolite, O-desmethylvenlafaxine, were determined by ultra-performance liquid chromatography-tandem mass spectrometry.
RESULTS
We observed that vonoprazan could significantly decrease the amount of O-desmethylvenlafaxine (IC = 5.544 μM). Vonoprazan inhibited the metabolism of venlafaxine by a mixed inhibition, combining competitive and non-competitive inhibitory mechanisms. Compared with that in the control group (without vonoprazan), the pharmacokinetic parameters of venlafaxine and its metabolite, O-desmethylvenlafaxine, were significantly increased in both 5 and 20 mg/kg vonoprazan groups, with an increase in MR.
CONCLUSION
Vonoprazan significantly alters the pharmacokinetics of venlafaxine in vitro and in vivo. Further investigations should be conducted to check these effects in humans. Therapeutic drug monitoring of venlafaxine in individuals undergoing venlafaxine maintenance therapy is recommended when vonoprazan is used concomitantly.
Topics: Administration, Oral; Animals; Chromatography, High Pressure Liquid; Desvenlafaxine Succinate; Male; Microsomes, Liver; Pyrroles; Rats; Rats, Sprague-Dawley; Sulfonamides; Tandem Mass Spectrometry; Venlafaxine Hydrochloride
PubMed: 33204067
DOI: 10.2147/DDDT.S276704 -
PLoS Medicine Nov 2021The prevalence of depression and the exposure to antidepressants are high among women of reproductive age and during pregnancy. Duloxetine is a selective...
BACKGROUND
The prevalence of depression and the exposure to antidepressants are high among women of reproductive age and during pregnancy. Duloxetine is a selective serotonin-norepinephrine reuptake inhibitor (SNRI) approved in the United States and Europe in 2004 for the treatment of depression. Fetal safety of duloxetine is not well established. The present study evaluates the association of exposure to duloxetine during pregnancy and the risk of major and minor congenital malformations and the risk of stillbirths.
METHODS AND FINDINGS
A population-based observational study was conducted based on data from registers in Sweden and Denmark. All registered births and stillbirths in the medical birth registers between 2004 and 2016 were included. Malformation diagnoses were identified up to 1 year after birth. Logistic regression analyses were used. Potential confounding was addressed through multiple regression, propensity score (PS) matching, and sensitivity analyses. Confounder variables included sociodemographic information (income, education, age, year of birth, and country), comorbidity and comedication, previous psychiatric contacts, and birth-related information (smoking during pregnancy and previous spontaneous abortions and stillbirths). Duloxetine-exposed women were compared with 4 comparators: (1) duloxetine-nonexposed women; (2) selective serotonin reuptake inhibitor (SSRI)-exposed women; (3) venlafaxine-exposed women; and (4) women exposed to duloxetine prior to, but not during, pregnancy. Exposure was defined as redemption of a prescription during the first trimester and throughout pregnancy for the analyses of malformations and stillbirths, respectively. Outcomes were major and minor malformations and stillbirths gathered from the national patient registers. The cohorts consisted of more than 2 million births with 1,512 duloxetine-exposed pregnancies. No increased risk for major malformations, minor malformations, or stillbirth was found across comparison groups in adjusted and PS-matched analyses. Duloxetine-exposed versus duloxetine-nonexposed PS-matched analyses showed odds ratio (OR) 0.98 (95% confidence interval [CI] 0.74 to 1.30, p = 0.909) for major malformations, OR 1.09 (95% CI 0.82 to 1.45, p = 0.570) for minor malformation, and 1.18 (95% CI 0.43 to 3.19, p = 0.749) for stillbirths. For the individual malformation subtypes, some findings were statistically significant but were associated with large statistical uncertainty due to the extremely small number of events. The main limitations for the study were that the indication for duloxetine and a direct measurement of depression severity were not available to include as covariates.
CONCLUSIONS
Based on this observational register-based nationwide study with data from Sweden and Denmark, no increased risk of major or minor congenital malformations or stillbirth was associated with exposure to duloxetine during pregnancy.
Topics: Abnormalities, Drug-Induced; Adolescent; Adult; Cohort Studies; Congenital Abnormalities; Denmark; Duloxetine Hydrochloride; Female; Humans; Maternal Exposure; Middle Aged; Pregnancy; Risk Factors; Stillbirth; Sweden; Young Adult
PubMed: 34807906
DOI: 10.1371/journal.pmed.1003851 -
BMJ (Clinical Research Ed.) Feb 2020To evaluate the risk of adverse maternal and infant outcomes following in utero exposure to duloxetine.
OBJECTIVE
To evaluate the risk of adverse maternal and infant outcomes following in utero exposure to duloxetine.
DESIGN
Cohort study nested in the Medicaid Analytic eXtract for 2004-13.
SETTING
Publicly insured pregnancies in the United States.
PARTICIPANTS
Pregnant women 18 to 55 years of age and their liveborn infants.
INTERVENTIONS
Duloxetine exposure during the etiologically relevant time window, compared with no exposure to duloxetine, exposure to selective serotonin reuptake inhibitors, exposure to venlafaxine, and exposure to duloxetine before but not during pregnancy.
MAIN OUTCOME MEASURES
Congenital malformations overall, cardiac malformations, preterm birth, small for gestational age infant, pre-eclampsia, and postpartum hemorrhage.
RESULTS
Cohort sizes ranged from 1.3 to 4.1 million, depending on the outcome. The number of women exposed to duloxetine varied by cohort and exposure contrast and was around 2500-3000 for early pregnancy exposure and 900-950 for late pregnancy exposure. The base risk per 1000 unexposed women was 36.6 (95% confidence interval 36.3 to 36.9) for congenital malformations overall, 13.7 (13.5 to 13.9) for cardiovascular malformations, 107.8 (107.3 to 108.3) for preterm birth, 20.4 (20.1 to 20.6) for small for gestational age infant, 33.6 (33.3 to 33.9) for pre-eclampsia, and 23.3 (23.1 to 23.4) for postpartum hemorrhage. After adjustment for measured potential confounding variables, all baseline characteristics were well balanced for all exposure contrasts. In propensity score adjusted analyses versus unexposed pregnancies, the relative risk was 1.11 (95% confidence interval 0.93 to 1.33) for congenital malformations overall and 1.29 (0.99 to 1.68) for cardiovascular malformations. For preterm birth, the relative risk was 1.01 (0.92 to 1.10) for early exposure and 1.19 (1.04 to 1.37) for late exposure. For small for gestational age infants the relative risks were 1.14 (0.92 to 1.41) and 1.20 (0.83 to 1.72) for early and late pregnancy exposure, respectively, and for pre-eclampsia they were 1.12 (0.96 to 1.31) and 1.04 (0.80 to 1.35). The relative risk for postpartum hemorrhage was 1.53 (1.08 to 2.18). Results from sensitivity analyses were generally consistent with the findings from the main analyses.
CONCLUSIONS
On the basis of the evidence available to date, duloxetine is unlikely to be a major teratogen but may be associated with an increased risk of postpartum hemorrhage and a small increased risk of cardiac malformations. While continuing to monitor the safety of duloxetine as data accumulate over time, these potential small increases in risk of relatively uncommon outcomes must be weighed against the benefits of treating depression and pain during pregnancy in a given patient.
TRIAL REGISTRATION
EUPAS 15946.
Topics: Abnormalities, Drug-Induced; Adolescent; Adult; Cohort Studies; Duloxetine Hydrochloride; Female; Heart Defects, Congenital; Humans; Infant, Small for Gestational Age; Middle Aged; Postpartum Hemorrhage; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Premature Birth; Prenatal Exposure Delayed Effects; Serotonin and Noradrenaline Reuptake Inhibitors; United States; Young Adult
PubMed: 32075794
DOI: 10.1136/bmj.m237 -
Neuropsychobiology 2023Currently, major depressive disorder (MDD) treatment plans are based on trial-and-error, and remission rates remain low. A strategy to replace trial-and-error and... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Currently, major depressive disorder (MDD) treatment plans are based on trial-and-error, and remission rates remain low. A strategy to replace trial-and-error and increase remission rates could be treatment stratification. We explored the heartbeat-evoked potential (HEP) as a biomarker for treatment stratification to either antidepressant medication or rTMS treatment.
METHODS
Two datasets were analyzed: (1) the International Study to Predict Optimized Treatment in Depression (iSPOT-D; n = 1,008 MDD patients, randomized to escitalopram, sertraline, or venlafaxine, and n = 336 healthy controls) and (2) a multi-site, open-label rTMS study (n = 196). The primary outcome measure was remission. Cardiac field artifacts were removed from the baseline EEG using independent component analysis (ICA). The HEP-peak was detected in a bandwidth of 20 ms around 8 ms and 270 ms (N8, N270) after the R-peak of the electrocardiogram signal. Differences between remitters and non-remitters were statistically assessed by repeated-measures ANOVAs for electrodes Fp1, Cz, and Oz.
RESULTS
In the venlafaxine subgroup, remitters showed a lower HEP around the N8 peak than non-remitters on electrode site Cz (p = 0.004; d = 0.497). The rTMS group showed a non-significant difference in the opposite direction (d = -0.051). Retrospective stratification to one of the treatments based on the HEP resulted in enhanced treatment outcome prediction for venlafaxine (+22.98%) and rTMS (+10.66%).
CONCLUSION
These data suggest that the HEP could be used as a stratification biomarker between venlafaxine and rTMS; however, future out-of-sample replication is warranted.
Topics: Humans; Venlafaxine Hydrochloride; Depressive Disorder, Major; Citalopram; Heart Rate; Retrospective Studies; Evoked Potentials; Treatment Outcome; Biomarkers
PubMed: 36927872
DOI: 10.1159/000529308 -
Chemosphere Aug 2021Antidepressants in coastal waters may affect ontogeny of predatory behaviour in cuttlefish, which may, as a result, affect growth of newly-hatched cuttlefish. We...
Antidepressants in coastal waters may affect ontogeny of predatory behaviour in cuttlefish, which may, as a result, affect growth of newly-hatched cuttlefish. We investigated the effects of two of the most prescribed antidepressants, fluoxetine (FLX) and venlafaxine (VEN) in environmentally realistic concentrations on the predatory behaviour of hatchlings of Sepia officinalis. Newly-hatched cuttlefish were exposed from 1 h (i.e., day 1) to 5 days after hatching to either FLX alone (5 ng·L) or combined with VEN (2.5 ng·L or 5 ng·L each) to simulate an environmentally realistic exposure scenario. Their predatory behaviour was analysed through several parameters: prey detection, feeding motivation and success in catching the prey. All parameters improved in control animals over the first five days. The combination of FLX and VEN at 5 ng·L each altered the predatory behaviour of the hatchlings by increasing the latency before attacking the prey, i.e., reducing feeding motivation, as well as by reducing the number of successful attacks. The changes in predatory behaviour tended to reduce food intake and affected growth significantly at 28 days post-hatching. Exposures to either FLX at 5 ng·L or FLX and VEN in mixture at 2.5 ng·L each tended to produce similar effects, even though they were not statistically significant. It is likely that the antidepressants affect maturation of the predatory behaviour and/or learning processes associated with the development of this behaviour. The slightest delay in maturation processes may have detrimental consequences for growth and population fitness.
Topics: Animals; Decapodiformes; Fluoxetine; Predatory Behavior; Venlafaxine Hydrochloride; Water Pollutants, Chemical
PubMed: 33794438
DOI: 10.1016/j.chemosphere.2021.130169 -
The Journal of Clinical Psychiatry Oct 2020Fluoxetine, paroxetine, sertraline, topiramate, and venlafaxine have previously shown efficacy for posttraumatic stress disorder (PTSD). One prior study using US... (Comparative Study)
Comparative Study
OBJECTIVE
Fluoxetine, paroxetine, sertraline, topiramate, and venlafaxine have previously shown efficacy for posttraumatic stress disorder (PTSD). One prior study using US Department of Veterans Affairs (VA) medical records data to compare these agents found no differences in symptom reduction in clinical practice. The current study addresses several weaknesses in that study, including limited standardization of treatment duration, inability to account for prior treatment receipt, use of an outdated symptomatic assessment for PTSD, and lack of functional outcome.
METHODS
A total of 834 VA outpatients were identified with DSM-5 clinical diagnoses of PTSD between October 2016 and March 2018 who initiated one of the medications and met prespecified criteria for treatment duration and dose, combined with baseline and endpoint DSM-5 PTSD Checklist (PCL-5) measurements. Twelve-week acute-phase changes in PCL-5 score and remission of PTSD symptoms were compared among patients receiving the different medications, as was use of acute psychiatric services in the subsequent 6-month continuation phase.
RESULTS
In the acute phase, patients improved by a mean of 6.8-10.1 points on the PCL-5 and 0.0%-10.9% achieved remission of PTSD symptoms. Those taking venlafaxine were significantly more likely to achieve remission (P = .008 vs fluoxetine and P < .0001 vs paroxetine, sertraline, and topiramate). In the continuation phase, there were no differences in acute psychiatric care use between medications. Those who continued their medication were less likely to use acute psychiatric services (HR = 0.55; P = .03).
CONCLUSIONS
There may be an advantage to venlafaxine over other agents in achieving acute-phase remission for DSM-5 PTSD in routine clinical practice, but this finding requires further study. Regardless of the agent chosen, medication cessation during the continuation phase is associated with a higher risk of acute psychiatric care use.
Topics: Acute Disease; Adult; Carbonic Anhydrase Inhibitors; Female; Fluoxetine; Humans; Male; Medication Adherence; Outcome Assessment, Health Care; Paroxetine; Remission Induction; Selective Serotonin Reuptake Inhibitors; Serotonin and Noradrenaline Reuptake Inhibitors; Sertraline; Stress Disorders, Post-Traumatic; Topiramate; United States; United States Department of Veterans Affairs; Venlafaxine Hydrochloride
PubMed: 33049805
DOI: 10.4088/JCP.20m13244 -
International Journal of Molecular... May 2024Depression is emerging as the predominant psychiatric disorder globally. Despite the wide availability of antidepressants, up to 30% of patients exhibit poor response to...
Depression is emerging as the predominant psychiatric disorder globally. Despite the wide availability of antidepressants, up to 30% of patients exhibit poor response to treatment, falling into the category of treatment-resistant depression (TRD). This underscores the need for the exploration of novel therapeutic options. Our work aims to study the effect of chronic administration of the pyridoindole derivative SMe1EC2M3, a triple reuptake inhibitor, and the combination of zoletil and venlafaxine under conditions of stress induced by a 4-week chronic mild stress (CMS) procedure in Wistar-Kyoto male rats as an animal model of TRD. Therefore, we investigated the possible effect of the selected compounds in four experimental groups, i.e., stress + vehicle, stress + venlafaxine, stress + zoletil + venlafaxine and stress + SMe1EC2M3. The following variables were assessed: anhedonia in sucrose preference test (SPT), spontaneous locomotion and exploration in open field test (OF), anxiety-like behavior in elevated plus maze test (EPM), motivation and depressive-like behavior in forced swim test (FST) and nociception in tail flick test. We also evaluated cognition, particularly recognition memory, in the novel object recognition test (NOR). Sucrose preference was significantly increased in the SMe1EC2M3 group ( < 0.05) in comparison with the venlafaxine animals. In the OF, we observed a significantly higher number of entries into both the central and peripheral zones in the venlafaxine ( < 0.05 central zone; ≤ 0.05 periphery zone) and SMe1EC2M3 ( < 0.05 central zone; < 0.05 periphery zone) groups compared to the venlafaxine + zoletil group. SMe1EC2M3 was able to significantly increase the time of climbing in FST ( < 0.05) in comparison with the venlafaxine and control groups. The NOR test revealed a significantly higher discrimination ratio in the SMe1EC2M3 group ( < 0.05) compared to the control and venlafaxine groups. Analyses of the tail flick test showed a significant increase in reaction time to painful stimuli in the SMe1EC2M3 group ( < 0.05) in comparison to both the control and venlafaxine groups. Our findings suggest that SMe1EC2M3 has the potential to ameliorate some behavioral changes associated with TRD, and the venlafaxine + zoletil combination treatment was not a promising treatment alternative in the animal model of TRD.
Topics: Animals; Rats; Male; Disease Models, Animal; Antidepressive Agents; Venlafaxine Hydrochloride; Depression; Behavior, Animal; Depressive Disorder, Treatment-Resistant; Rats, Inbred WKY; Stress, Psychological; Anxiety; Indoles; Anhedonia
PubMed: 38791304
DOI: 10.3390/ijms25105265 -
Neuropsychopharmacology Reports Mar 2024To update the major depressive disorder (MDD) treatment guidelines of the Japanese Society of Mood Disorders, we conducted a systematic review and pairwise meta-analysis... (Meta-Analysis)
Meta-Analysis
AIM
To update the major depressive disorder (MDD) treatment guidelines of the Japanese Society of Mood Disorders, we conducted a systematic review and pairwise meta-analysis of double-blind, randomized, placebo-controlled trials of available antidepressants in Japan for older adults with MDD.
METHODS
Outcome measures included response rate (primary), improvement in depressive symptom scale score, remission rate, all-cause discontinuation, discontinuation due to adverse events, and at least one adverse event. A random-effects model was used to calculate the risk ratio (RR) and standardized mean difference (SMD) with a 95% confidence interval (95% CI).
RESULTS
Nine double-blind, randomized, placebo-controlled trials (n = 2145) were identified. No study has been conducted in Japan. Our meta-analysis included the following antidepressants: duloxetine, escitalopram, imipramine, sertraline, venlafaxine, and vortioxetine. Antidepressants have significantly higher response rates than placebo (RR [95% CI] = 1.38 [1.04, 1.83], p = 0.02). Antidepressants outperformed placebo in terms of improving depressive symptom scale score (SMD [95% CI] = -0.62 [-0.92, -0.33], p < 0.0001). However, antidepressants were associated with a higher discontinuation rate due to adverse events (RR [95% CI] = 1.94 [1.30, 2.88], p = 0.001) and a higher incidence of at least one adverse event (RR [95% CI] = 1.11 [1.02, 1.21], p = 0.02) compared to placebo. The groups did not differ significantly in terms of remission rate or all-cause discontinuation.
CONCLUSIONS
Our meta-analysis concluded that treatment with antidepressants available in Japan is only weakly recommended for moderate to severe MDD in older adults.
Topics: Humans; Aged; Depressive Disorder, Major; Japan; Antidepressive Agents; Duloxetine Hydrochloride; Venlafaxine Hydrochloride; Randomized Controlled Trials as Topic
PubMed: 38318955
DOI: 10.1002/npr2.12422 -
International Clinical... May 2020This double-blind, randomized study evaluated the efficacy and safety of trazodone OAD (once-a-day) in comparison with venlafaxine XR (extended-release) in 324 patients... (Comparative Study)
Comparative Study Randomized Controlled Trial
A randomized, double-blind study comparing the efficacy and safety of trazodone once-a-day and venlafaxine extended-release for the treatment of patients with major depressive disorder.
This double-blind, randomized study evaluated the efficacy and safety of trazodone OAD (once-a-day) in comparison with venlafaxine XR (extended-release) in 324 patients (166 trazodone and 158 venlafaxine) with major depressive disorder (MDD). The primary efficacy endpoint was the mean change from baseline in the 17-item Hamilton Depression Rating Scale (HAM-D) at week 8. Both treatments were effective in reducing the HAM-D-17 total score at week 8 vs. baseline (intent-to-treat: trazodone -12.9, venlafaxine -14.7; per protocol: trazodone -15.4, venlafaxine -16.4). Patients in the venlafaxine group achieved better results after 8 weeks, whereas the trazodone group achieved a statistically significant reduction in HAM-D-17 following only 7 days of treatment. The most frequent adverse events (AEs) were dizziness and somnolence in the trazodone group, and nausea and headache in the venlafaxine group. Most AEs were mild-to-moderate in severity. This study confirmed that both venlafaxine XR and trazodone OAD may represent a valid treatment option for patients with MDD.
Topics: Adolescent; Adult; Aged; Antidepressive Agents, Second-Generation; Delayed-Action Preparations; Depressive Disorder, Major; Double-Blind Method; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Trazodone; Venlafaxine Hydrochloride; Young Adult
PubMed: 31972628
DOI: 10.1097/YIC.0000000000000304