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Psychopharmacology Feb 2024The selective serotonin and norepinephrine reuptake inhibitor venlafaxine is among the most prescribed antidepressant drugs worldwide and, according to guidelines, its... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The selective serotonin and norepinephrine reuptake inhibitor venlafaxine is among the most prescribed antidepressant drugs worldwide and, according to guidelines, its dose titration should be guided by drug-level monitoring of its active moiety (AM) which consists of venlafaxine (VEN) plus active metabolite O-desmethylvenlafaxine (ODV). This indication of therapeutic drug monitoring (TDM), however, assumes a clear concentration/effect relationship for a drug, which for VEN has not been systematically explored yet.
OBJECTIVES
We performed a systematic review and meta-analysis to investigate the relationship between blood levels, efficacy, and adverse reactions in order to suggest an optimal target concentration range for VEN oral formulations for the treatment of depression.
METHODS
Four databases (MEDLINE (PubMed), PsycINFO, Web of Science Core Collection, and Cochrane Library) were systematically searched in March 2022 for relevant articles according to a previously published protocol. Reviewers independently screened references and performed data extraction and critical appraisal.
RESULTS
High-quality randomized controlled trials investigating concentration/efficacy relationships and studies using a placebo lead-in phase were not found. Sixty-eight articles, consisting mostly of naturalistic TDM studies or small noncontrolled studies, met the eligibility criteria. Of them, five cohort studies reported a positive correlation between blood levels and antidepressant effects after VEN treatment. Our meta-analyses showed (i) higher AM and (ii) higher ODV concentrations in patients responding to VEN treatment when compared to non-responders (n = 360, k = 5). AM concentration-dependent occurrence of tremor was reported in one study. We found a linear relationship between daily dose and AM concentration within guideline recommended doses (75-225 mg/day). The population-based concentration ranges (25-75% interquartile) among 11 studies (n = 3200) using flexible dosing were (i) 225-450 ng/ml for the AM and (ii) 144-302 ng/ml for ODV. One PET study reported an occupancy of 80% serotonin transporters for ODV serum levels above 85 ng/ml. Based on our findings, we propose a therapeutic reference range for AM of 140-600 ng/ml.
CONCLUSION
VEN TDM within a range of 140 to 600 ng/ml (AM) will increase the probability of response in nonresponders. A titration within the proposed reference range is recommended in case of non-response at lower drug concentrations as a consequence of VEN's dual mechanism of action via combined serotonin and norepinephrine reuptake inhibition. Drug titration towards higher concentrations will, however, increase the risk for ADRs, in particular with supratherapeutic drug concentrations.
Topics: Humans; Antidepressive Agents; Depression; Desvenlafaxine Succinate; Norepinephrine; Reference Values; Serotonin; Venlafaxine Hydrochloride
PubMed: 37857898
DOI: 10.1007/s00213-023-06484-7 -
The American Journal of Psychiatry Jan 2024The authors investigated the clinical outcomes of commonly used antidepressants among older adults who initiated first-time antidepressants for depression by analyzing...
OBJECTIVE
The authors investigated the clinical outcomes of commonly used antidepressants among older adults who initiated first-time antidepressants for depression by analyzing the 1-year risk of selected clinically relevant outcomes.
METHODS
This cohort study used nationwide Danish registry data and included all older adults who redeemed a first-time (since 1995) antidepressant prescription with an indication of depression between 2006 and 2017. Only the 10 most frequently redeemed antidepressants were included in the analyses. Outcomes included discontinuation, switching, augmentation, psychiatric hospital contacts, suicide attempt or self-harm, fall-related injuries, cardiovascular events, and all-cause mortality. Incidence rate ratios (IRRs) and 95% confidence intervals were estimated using Poisson regression models, controlling for potential confounders.
RESULTS
The study sample included 93,883 older adults (mean age, 78.0 years, SD=7.5 years; 56% female). The most frequently prescribed antidepressants were selective serotonin reuptake inhibitors (citalopram, 47.04%; escitalopram, 11.81%; fluoxetine, 0.55%; paroxetine, 0.52%; sertraline, 11.17%), serotonin-norepinephrine reuptake inhibitors (duloxetine, 0.71%; venlafaxine, 1.54%), a tricyclic antidepressant (amitriptyline, 1.86%), and two atypical antidepressants (mianserin, 1.93%; mirtazapine, 22.87%). Compared with users of sertraline (the reference drug in this analysis, as Danish guidelines recommend it as the first-choice treatment for depression), users of most of the other nine antidepressants had a significantly higher risk of discontinuation (e.g., mirtazapine: IRR=1.55, 95% CI=1.50-1.61; venlafaxine: IRR=1.22, 95% CI=1.12-1.32), switching (amitriptyline: IRR=1.45, 95% CI=1.15-1.81; venlafaxine: IRR=1.47, 95% CI=1.20-1.80), augmentation, cardiovascular events, and mortality. Overall, mirtazapine and venlafaxine users had the most adverse outcomes compared with sertraline users. These results remained consistent in analyses stratified by sex and age (≤75 years vs. >75 years).
CONCLUSIONS
This real-world evidence suggests that clinical outcomes may vary among initiators of commonly used antidepressants in older adults, which may inform benefit-risk evaluation at treatment initiation, and highlights the importance of careful selection of antidepressant treatment.
Topics: Female; Humans; Aged; Male; Venlafaxine Hydrochloride; Sertraline; Depression; Cohort Studies; Mirtazapine; Amitriptyline; Antidepressive Agents; Selective Serotonin Reuptake Inhibitors; Cardiovascular Diseases; Denmark
PubMed: 37849303
DOI: 10.1176/appi.ajp.20230356 -
Journal of Chromatography. A Nov 2023An eco-friendly dispersive liquid-liquid microextraction mediated with a reverse micelle and coupled to an HPLC-DAD was developed for the simultaneous determination of...
A reverse micelle-mediated dispersive liquid-liquid microextraction coupled to high-performance liquid chromatography for the simultaneous determination of agomelatine and venlafaxine in pharmaceuticals and human plasma.
An eco-friendly dispersive liquid-liquid microextraction mediated with a reverse micelle and coupled to an HPLC-DAD was developed for the simultaneous determination of venlafaxine and agomelatine in dosage forms and human plasma. All the parameters affecting the extraction efficiencies of both drugs were investigated and optimized. Under the optimal conditions, an effective analytes' preconcentration with enrichment factors (EFs) up to 72 was achieved. The linearity of the method was established over the concentration range of 0.50-70.0 and 3.0-100.0 ng/mL for venlafaxine and agomelatine, respectively with good correlation coefficients > 0.998. The method exhibited low detection limits in the range of 0.15-0.89 ng/mL and excellent precisions expressed in %RSD < 3% with average recoveries between 95.0 to 101.0%. The proposed method was employed to analyze the targeted analytes in dosage forms and human plasma samples with favorable characteristics like excellent enrichment, high sensitivity, great accuracy, and high precision. Finally, the greenness of the developed method was assessed using three distinct metric tools, confirming the greenness of the proposed method. The findings of this research could have more general implications for the extraction of other analytes from various matrices.
Topics: Humans; Liquid Phase Microextraction; Micelles; Chromatography, High Pressure Liquid; Venlafaxine Hydrochloride; Limit of Detection
PubMed: 37832460
DOI: 10.1016/j.chroma.2023.464441 -
Clinical NeuropharmacologyIn persons with narcolepsy type 1, sudden withdrawal of antidepressants can cause status cataplecticus. We describe a 77-year-old female patient with long-standing... (Review)
Review
In persons with narcolepsy type 1, sudden withdrawal of antidepressants can cause status cataplecticus. We describe a 77-year-old female patient with long-standing history of narcolepsy type 1 complaining of recurrent short sudden episodes of whole-body paralysis, with preserved consciousness and memory. Episodes started an hour after her family invited her to celebrate Mother's Day. One week prior, patient had abruptly discontinued duloxetine. Cataplectic episodes resolved within 24 hours after resumption of duloxetine and treatment of hypokalemia. Status cataplecticus has been reported after withdrawal of venlafaxine, fluoxetine, and clomipramine. This is the first report of status cataplecticus due to duloxetine withdrawal. We review the pathophysiology of antidepressant withdrawal-induced status cataplecticus. In persons with narcolepsy type 1, physicians discontinuing any antidepressant should counsel on adverse effects of antidepressant withdrawal and reduce the dose in tapering manner.
Topics: Female; Humans; Aged; Duloxetine Hydrochloride; Cataplexy; Narcolepsy; Antidepressive Agents; Venlafaxine Hydrochloride
PubMed: 37748003
DOI: 10.1097/WNF.0000000000000563 -
Current Therapeutic Research, Clinical... 2023Intranasal administration is among the most effective alternatives to deliver drugs directly to the brain and prevent first-pass metabolism. Venlafaxine-loaded liposomes...
BACKGROUND
Intranasal administration is among the most effective alternatives to deliver drugs directly to the brain and prevent first-pass metabolism. Venlafaxine-loaded liposomes are biocompatible carriers that enhance transport qualities over the nasal mucosa.
OBJECTIVE
This research aimed to develop, formulate, characterize, and observe the prepared formulation.
METHODS
The formulation was developed using the thin-film hydration technique. The response surface plot interrelationship between three independent variables are lipid, cholesterol and polymer and four dependent variables such as particle size, percentage entrapment efficiency, and percentage drug release were ascertained using the Box-Behnken design.
RESULTS
The drug-release chitosan-coated liposomes were reported to have a particle size distribution, entanglement efficiency, and 84%, respectively, of 191 ± 34.71 nm, 94 ± 2.71% and 94 ± 2.71%. According to investigations, liposomes as a delivery system for the nasal route provided a more sustained drug release than the oral dosing form.
CONCLUSIONS
The intranasal administration of venlafaxine liposomal vesicles effectively enhanced the absolute bioavailability, retention time, and brain delivery of venlafaxine.
PubMed: 37727460
DOI: 10.1016/j.curtheres.2023.100714 -
International Journal of Pharmaceutics Oct 2023Corn processing industries generate an extensive fibrous byproduct consisting of corn fiber gum (CFG) and residual starch (S). The present study hypothesized that CFG...
Corn processing industries generate an extensive fibrous byproduct consisting of corn fiber gum (CFG) and residual starch (S). The present study hypothesized that CFG and S could be isolated as a single crosslinked conjugate. The isolated CFG-S conjugate was acidic, with a pKa value of 11.49, and a swelling index of 99.60%. Henderson-Hasselbalch equation predicted negligible ionization throughout the gastrointestinal pH range. The DSC thermogram highlights glass transition and temperature-specific structure stabilization through the exothermic crystallization domain. FTIR, SEM & XRD confirmed the structural conjugation and integrity of the conjugate. Tablets containing Venlafaxine hydrochloride as a model drug were prepared using CFG-S (14 and 57%) as excipient by wet granulation method. Percentage cumulative drug release with low concentration was up to 99.67175 ± 0.09 % in 5 h whereas with high concentration, it was extended to 12 h (P < 0.05). Korsemayer-Peppas release exponent indicates zero order (R2 = 0.9935) kinetics with super case-II anomalous transport showing diffusion and erosion as drug release mechanisms. The results confirmed that CFG-S isolate could act as a good binding agent at low concentrations and release extending cross-linked matrix former at a higher concentration for release retardant excipient.
Topics: Excipients; Zea mays; Starch; Tablets
PubMed: 37696343
DOI: 10.1016/j.ijpharm.2023.123401 -
Journal of Chromatography. A Oct 2023In this work, carboxymethylated maltodextrin (Cm-MD) was successfully synthesized as an efficient anionic chiral selector and applied for the enantiomer separation of...
In this work, carboxymethylated maltodextrin (Cm-MD) was successfully synthesized as an efficient anionic chiral selector and applied for the enantiomer separation of some basic drugs including tramadol, venlafaxine, verapamil, hydroxyzine, citalopram, fluoxetine, and amlodipine by capillary electrophoresis (CE). The synthesized chiral selector was characterized by the nuclear magnetic resonance and Fourier transform infrared spectrophotometry. Under the optimized Cm-MD modified CE conditions (background electrolyte: phosphate buffer (pH 5.0, 50 mM) containing 5% (w/v) Cm-MD; applied voltage: 20 kV; and capillary column temperature: 25 °C), successful enantiomer separation of all studied chiral drugs were observed. By comparison of Cm-MD and MD for enantiomer separation of the model drugs, it was revealed that Cm-MD exhibits a higher resolution in comparison to the MD modified CE. This enhanced resolution could be attributed to the electrostatic interactions between the cationic drugs and anionic Cm-MD and opposite direction mobility of the host-guest complex relative to the chiral analyte. The optimized Cm-MD modified CE method was successfully used for the assay of the enantiomers of citalopram and venlafaxine in commercial tablets. The proposed method showed the linear range of 5.0-150.0 mg/L and 10.0-150.0 mg/L for both enantiomers of citalopram and venlafaxine, respectively. The limits of quantification were 5.0 and 10.0 mg/L for the enantiomers of citalopram and venlafaxine, respectively. The limit of detection for all enantiomers was found to be < 3.0 mg/L. Intra- and inter-day RSDs (n = 4) were less than 9.7%. The relative errors were less than 9.4% for all enantiomers. The obtained results in this research show that Cm-MD as a new, efficient and inexpensive chiral selector can be used for enantiomer separation of basic drugs using the CE technique.
Topics: Citalopram; Venlafaxine Hydrochloride; Electrophoresis, Capillary; Amlodipine
PubMed: 37696127
DOI: 10.1016/j.chroma.2023.464335 -
CNS Drugs Sep 2023Although one of the major presentations of vestibular migraine is dizziness with/without unsteady gait, it is still classified as one of the migraine categories.... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Although one of the major presentations of vestibular migraine is dizziness with/without unsteady gait, it is still classified as one of the migraine categories. However, in contrast to ordinary migraine, vestibular migraine patients have distinct characteristics, and the detailed treatment strategy for vestibular migraine is different and more challenging than ordinary migraine treatment. Currently, there is no conclusive evidence regarding its management, including vestibular migraine prophylaxis.
AIM
The objective of this current network meta-analysis (NMA) was to compare the efficacy and acceptability of individual treatment strategies in patients with vestibular migraine.
METHODS
The PubMed, Embase, ScienceDirect, ProQuest, Web of Science, ClinicalKey, Cochrane Central, and ClinicalTrials.gov databases were systematically searched for randomized controlled trials (RCTs), with a final literature search date of 30 December 2022. Patients diagnosed with vestibular migraine were included. The PICO of the current study included (1) patients with vestibular migraine; (2) intervention: any active pharmacologic or non-pharmacologic intervention; (3) comparator: placebo-control, active control, or waiting list; and (4) outcome: changes in migraine frequency or severity. This NMA of RCTs of vestibular migraine treatment was conducted using a frequentist model. We arranged inconsistency and similarity tests to re-examine the assumption of NMA, and also conducted a subgroup analysis focusing on RCTs of pharmacological treatment for vestibular migraine management. The primary outcome was changes in the frequency of vestibular migraines, while the secondary outcomes were changes in vestibular migraine severity and acceptability. Acceptability was set as the dropout rate, which was defined as the participant leaving the study before the end of the trial for any reason. Two authors independently evaluated the risk of bias for each domain using the Cochrane risk-of-bias tool.
RESULTS
Seven randomized controlled trials (N = 828, mean age 37.6 years, 78.4% female) and seven active regimens were included. We determined that only valproic acid (standardized mean difference [SMD] -1.61, 95% confidence interval [CI] -2.69, -0.54), propranolol (SMD -1.36, 95% CI -2.55, -0.17), and venlafaxine (SMD -1.25, 95% CI -2.32, -0.18) were significantly associated with better improvement in vestibular migraine frequency than the placebo/control groups. Furthermore, among all the investigated pharmacologic/non-pharmacologic treatments, valproic acid yielded the greatest decrease in vestibular migraine frequency among all the interventions. In addition, most pharmacologic/non-pharmacologic treatments were associated with similar acceptability (i.e. dropout rate) as those of the placebo/control groups.
CONCLUSIONS
The current study provides evidence that only valproic acid, propranolol, and venlafaxine might be associated with beneficial efficacy in vestibular migraine treatment.
TRIAL REGISTRATION
CRD42023388343.
Topics: Adult; Female; Humans; Male; Migraine Disorders; Network Meta-Analysis; Propranolol; Valproic Acid; Venlafaxine Hydrochloride
PubMed: 37676473
DOI: 10.1007/s40263-023-01037-0 -
Drug Research Oct 2023Breast cancer is the most common cancer in women worldwide. Premature menopause and hot flashes are the main complications of breast cancer treatments. About 40 to 50... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Breast cancer is the most common cancer in women worldwide. Premature menopause and hot flashes are the main complications of breast cancer treatments. About 40 to 50 percent of breast cancer women who undergo chemotherapy are experiencing premature menopause symptoms, including hot flashes. Some endocrine therapies such as tamoxifen and aromatase inhibitors are associated with induction or aggravating hot flashes. Hot flashes are often debilitating and significantly impair daily functions. Therefore many therapeutic options have been studied so far for the management of this adverse effect. However, there are still some clinical challenges in managing hot flashes in patients with breast cancer.
OBJECTIVE
We aimed to evaluate and compare the efficacy of venlafaxine and citalopram on hot flashes in breast cancer women receiving tamoxifen.
DESIGN
We conducted a double-blind, placebo-controlled trial in forty-one, 35 to 65 years old female patients. The study lasted for four weeks, and the follow-up was for two months. Venlafaxine and citalopram treatments started with doses of 37.5 mg or 10 mg, respectively. Venlafaxine and citalopram dosages were increased in the second week to 75 and 20 mg, respectively. The study was conducted during the year 2017.
KEY RESULTS
The results indicated that the total efficacy was significantly different in groups receiving citalopram, venlafaxine, and placebo. Total efficacy in the placebo group, venlafaxine, and citalopram was 14.3, 53.8, and 64.3%, respectively (p=0.02). During the second week, the efficacy in groups receiving citalopram, venlafaxine, and placebo was 57.1, 53.8, and 14.3%, respectively (p=0.04). Generally, both citalopram and venlafaxine were well tolerated. The associated adverse effects were mild to moderate in both groups.
CONCLUSIONS
Although citalopram was associated with more adverse effects, including constipation, it was more effective in reducing the frequency of hot flashes when compared to venlafaxine or placebo.
Topics: Female; Humans; Adult; Middle Aged; Aged; Citalopram; Venlafaxine Hydrochloride; Hot Flashes; Selective Serotonin Reuptake Inhibitors; Breast Neoplasms; Menopause, Premature; Tamoxifen; Double-Blind Method; Treatment Outcome
PubMed: 37647930
DOI: 10.1055/a-2061-7020 -
Psychopharmacology Bulletin Aug 2023A growing body of evidence has recently suggested that taking venlafaxine during pregnancy may be linked to increased risk of certain congenital defects. The study aimed...
OBJECTIVES
A growing body of evidence has recently suggested that taking venlafaxine during pregnancy may be linked to increased risk of certain congenital defects. The study aimed to address the effects of venlafaxine use during pregnancy on the development of the brain in mice.
EXPERIMENTAL DESIGN
Fourteen female BALB/c mice were randomly divided into two equally-sized groups: venlafaxine-treated and control. After mating, pregnant mice of venlafaxine-treated group were orally received the venlafaxine 35 mg/kg/day throughout pregnancy, while pregnant control mice did not receive any treatment. All pups were killed on postnatal day 21 and brain images were quantified using ImageJ software. The mRNA expression levels of SHANK3, TUBB5 and DDC of genes in pups' brain tissue samples were evaluated using quantitative real-time PCR method.
PRINCIPAL OBSERVATIONS
The mean brain size of pups was significantly smaller in the venlafaxine-treated group than in the control group. Results showed that the mRNA expression levels of SHANK3 and TUBB5 was significantly downregulated in venlafaxine-treated mice compared to control group. Expression of DDC gene didn't showed significant differences between two groups.
CONCLUSIONS
These results provide evidence that use of venlafaxine during pregnancy may affect the brain development in mice and altered the expression of SHANK3 and TUBB5 genes in brain tissue.
Topics: Animals; Female; Mice; Pregnancy; Aromatic-L-Amino-Acid Decarboxylases; Brain; Nerve Tissue Proteins; RNA, Messenger; Venlafaxine Hydrochloride
PubMed: 37601086
DOI: No ID Found