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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including limited standardization of treatment duration, inability to account for prior treatment receipt, use of an outdated symptomatic assessment for PTSD, and lack of functional outcome.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 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 -
Harm Reduction Journal Dec 2023Perception of drug adulteration has increased in Mexico, but there is little research on adulterants and toxicity. The aim of this study was to identify drug composition...
BACKGROUND
Perception of drug adulteration has increased in Mexico, but there is little research on adulterants and toxicity. The aim of this study was to identify drug composition in an electronic music outdoor festival nearby Mexico City.
METHODS
The participants completed a questionnaire with demographic data, harm reduction strategies, drug-use patterns, history, and the drug they expected to find. We took a small sample of each substance and prepared it for drug checking. A two-section drug testing station was placed within the grounds of the festival. Interaction with participants occurred at the front part. Drug checking was conducted at the rear part. The service was free of charge, voluntary and confidential. Forty persons aged 22 to 48 years participated (mode = 28), of which 92.5% were male, most (82.5%) were single. Through the Substance Analysis Program of "ReverdeSer Collective," we conducted the testing with the attendants that provided 51 drug samples, following ethical and biosafety protocols. We used colorimetry, Fourier Transform Infrared Spectroscopy, and fentanyl immunoassay strips for sample analysis.
RESULTS
Substances of choice among attendants were psychostimulants (MDMA and other amphetamine-like drugs) and hallucinogens. Most samples contained what the users expected plus adulterants. Main adulterants were methylene-dioxy-ethyl-amphetamine, methylene-dioxy-propyl-amphetamine, hydroxyamphetamine, and the selective serotonin reuptake inhibitor venlafaxine. Fentanyl was present in 2 out of 4 cocaine samples and in 14 of the 22 confirmed MDMA samples.
CONCLUSIONS
Some of the adulterants found pose serious health risks, especially fentanyl, amphetamine-like substances, and venlafaxine. Therefore, it is urgent to monitor these adulterants at electronic music festivals and to implement prevention, treatment, and harm reduction public policies. Naloxone distribution and drug-assisted therapies should be part of government programs in Mexico.
Topics: Humans; Male; Female; Illicit Drugs; Fentanyl; Holidays; N-Methyl-3,4-methylenedioxyamphetamine; Mexico; Venlafaxine Hydrochloride; Amphetamine
PubMed: 38053148
DOI: 10.1186/s12954-023-00905-8 -
The Lancet. Psychiatry Jul 2019
Topics: Antidepressive Agents; Depressive Disorder, Major; Humans; Mirtazapine; Selective Serotonin Reuptake Inhibitors; Venlafaxine Hydrochloride
PubMed: 31178368
DOI: 10.1016/S2215-0366(19)30221-4 -
Journal of Cellular and Molecular... May 2020Recent human and animal studies indicate that oxidative and nitrosative stress may play a role in the aetiology and pathogenesis of depression. This study investigates...
Recent human and animal studies indicate that oxidative and nitrosative stress may play a role in the aetiology and pathogenesis of depression. This study investigates the effect of chronic administration of the serotonin-norepinephrine reuptake inhibitor, venlafaxine, on the expression and methylation status of SOD1, SOD2, GPx1, GPx4, CAT, NOS1 and NOS2 in the brain and blood of rats exposed to a chronic mild stress (CMS) model of depression. Separate groups of animals were exposed to CMS for 2 or 7 weeks; the second group received saline or venlafaxine (10 mg/kg/d, IP) for 5 weeks. After completion of both stress conditions and drug administration, the mRNA and protein expression of selected genes and the methylation status of their promoters were measured in peripheral mononuclear blood cells (PBMCs) and in brain structures (hippocampus, amygdala, hypothalamus, midbrain, cortex, basal ganglia) with the use of TaqMan Gene Expression Assay, Western blot and methylation-sensitive high-resolution melting techniques. CMS caused a decrease in sucrose consumption, and this effect was normalized by fluoxetine. In PBMCs, SOD1, SOD2 and NOS2 mRNA expression changed only after venlafaxine administration. In brain, CAT, Gpx1, Gpx4 and NOS1 gene expression changed following CMS or venlafaxine exposure, most prominently in the hippocampus, midbrain and basal ganglia. CMS increased the methylation of the Gpx1 promoter in PBMCs, the second Gpx4 promoter in midbrain and basal ganglia, and SOD1 and SOD2 in hippocampus. The CMS animals treated with venlafaxine displayed a significantly higher CAT level in midbrain and cerebral cortex. CMS caused an elevation of Gpx4 in the hippocampus, which was lowered in cerebral cortex by venlafaxine. The results indicate that CMS and venlafaxine administration affect the methylation of promoters of genes involved in oxidative and nitrosative stress. They also indicate that peripheral and central tissue differ in their response to stress or antidepressant treatments. It is possible that that apart from DNA methylation, a crucial role of expression level of genes may be played by other forms of epigenetic regulation, such as histone modification or microRNA interference. These findings provide strong evidence for thesis that analysis of the level of mRNA and protein expression as well as the status of promoter methylation can help in understanding the pathomechanisms of mental diseases, including depression, and the mechanisms of action of drugs effective in their therapy.
Topics: Animals; Brain; DNA Methylation; Disease Models, Animal; Epigenesis, Genetic; Gene Expression Profiling; Gene Expression Regulation; Male; Organ Specificity; Oxidative Stress; Rats; Stress, Psychological; Sucrose; Transcriptome; Venlafaxine Hydrochloride
PubMed: 32281745
DOI: 10.1111/jcmm.15231 -
CNS Neuroscience & Therapeutics Sep 2018Different mechanisms may be involved in the antinociceptive effects of oxycodone (opioid) and venlafaxine (serotonin-norepinephrine reuptake inhibitor), and the aim of... (Comparative Study)
Comparative Study Randomized Controlled Trial
AIM
Different mechanisms may be involved in the antinociceptive effects of oxycodone (opioid) and venlafaxine (serotonin-norepinephrine reuptake inhibitor), and the aim of this study was to investigate the effect of these drugs on brain functional connectivity.
METHODS
Resting state functional magnetic resonance imaging was acquired in 20 healthy volunteers before and after a 5-day treatment with oxycodone, venlafaxine, or placebo in a randomized, double-blind, crossover study. Functional connectivity analyses were performed between four predefined seeds (dorsal anterior cingulate cortex, rostral anterior cingulate cortex, posterior insula, and prefrontal cortex), and the whole brain.
RESULTS
The overall interpretation was that there were differences between the effects of oxycodone and venlafaxine on functional connectivity. Oxycodone mainly showed decreased functional connectivity between limbic structures and to supralimbic areas (all P < 0.05). Venlafaxine also showed decreased functional connectivity between limbic structures and to supralimbic areas, but increased functional connectivity to structures in the midbrain and brain stem was also found (all P < 0.05).
CONCLUSIONS
Oxycodone and venlafaxine showed differential effects on resting-state functional connectivity as compared to placebo. This supports that the two drugs exert different mechanisms, and that the drugs in combination may exert additive effects and could potentially improve pain therapy.
Topics: Adult; Analgesics, Opioid; Cerebral Cortex; Cross-Over Studies; Double-Blind Method; Humans; Magnetic Resonance Imaging; Male; Nerve Net; Oxycodone; Rest; Serotonin and Noradrenaline Reuptake Inhibitors; Venlafaxine Hydrochloride; Young Adult
PubMed: 29468854
DOI: 10.1111/cns.12827 -
Environmental Science and Pollution... Feb 2024The European Union requires environmental monitoring of the antidepressant drug venlafaxine. Advanced oxidation processes provide a remedy against the spread of...
The European Union requires environmental monitoring of the antidepressant drug venlafaxine. Advanced oxidation processes provide a remedy against the spread of micropollutants. In this study, the photoinduced and electrochemical decompositions of venlafaxine were investigated in terms of mechanism and efficacy using high-performance liquid chromatography coupled to high-resolution multifragmentation mass spectrometry. Kinetic analysis, structure elucidation, matrix variation, and radical scavenging indicated the dominance of a hydroxyl-mediated indirect mechanism during photodegradation and hydroxyl and direct electrochemical oxidation for electrochemical degradation. Oxidants, sulfate, and chloride ions acted as accelerants, which reduced venlafaxine half-lives from 62 to 25 min. Humic acid decelerated degradation during ultra-violet irradiation up to 50%, but accelerated during electrochemical oxidation up to 56%. In silico quantitative structure activity relationship analysis predicted decreased environmental hazard after advanced oxidation process treatment. In general, photoirradiation proved more efficient due to faster decomposition and slightly less toxic transformation products. Yet, matrix effects would have to be carefully evaluated when potential applications as a fourth purification stage were to be considered.
Topics: Venlafaxine Hydrochloride; Kinetics; Oxidants; Oxidation-Reduction; Hydroxyl Radical; Water Pollutants, Chemical
PubMed: 38252206
DOI: 10.1007/s11356-024-32018-5 -
Basic & Clinical Pharmacology &... Dec 2018Offset analgesia (OA) is a pain-modulating mechanism described as a disproportionately large decrease in pain intensity evoked by a discrete decrease in stimulus... (Randomized Controlled Trial)
Randomized Controlled Trial
Offset analgesia (OA) is a pain-modulating mechanism described as a disproportionately large decrease in pain intensity evoked by a discrete decrease in stimulus temperature. The role of the opioidergic, serotonergic and noradrenergic systems on OA remains unclear. The aim of this study was to evaluate whether OA is modulated by an opioid (oxycodone) and a serotonin and noradrenaline reuptake inhibitor (venlafaxine) in terms of psychophysical assessments. In this randomized, double-blinded, placebo-controlled cross-over study, 20 healthy male participants (mean age: 24.6 ± 2.5 years) received 10 mg oxycodone, 37.5 mg venlafaxine or placebo twice daily for 5 days in three periods. OA was induced by noxious thermal stimulation on the forearm at baseline and last day of treatment. A control session of constant stimulus intensity was included for comparison. OA magnitude was unaffected by oxycodone and venlafaxine (p = 0.20 and p = 0.90, respectively). Oxycodone affected the control paradigm where a decreased rating of pain intensity was observed compared to placebo (p = 0.001). OA could not be modulated by oxycodone or venlafaxine and may be a robust phenomenon in healthy volunteers and not suitable for exploring pharmacological mechanisms of analgesia in human beings.
Topics: Analgesia; Analgesics, Opioid; Cross-Over Studies; Double-Blind Method; Hot Temperature; Humans; Male; Oxycodone; Pain Measurement; Pain Perception; Serotonin and Noradrenaline Reuptake Inhibitors; Venlafaxine Hydrochloride; Young Adult
PubMed: 29938898
DOI: 10.1111/bcpt.13078 -
Asian Journal of Pharmaceutical Sciences Nov 2018The objective of this study is to design sustained-release tablets using matrix technology, which can well control the release of highly water-soluble drugs with good...
Tunable and sustained-release characteristics of venlafaxine hydrochloride from chitosan-carbomer matrix tablets based on in situ formed polyelectrolyte complex film coating.
The objective of this study is to design sustained-release tablets using matrix technology, which can well control the release of highly water-soluble drugs with good system robustness and simple preparation process. Taking venlafaxine hydrochloride (VH) as a drug model, the feasibility of using chitosan (CS), carbomer (CBM) combination system to achieve this goal was studied. Formulation and process variables influencing drug release from CS-CBM matrix tablets were investigated. It was found that CS-CBM combination system weakened the potential influence of CS, CBM material properties and gastric emptying time on drug release profile. Demonstrated by direct observation, differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR), in situ self-assembled polyelectrolyte complex (PEC) film was formed on the tablet surface during gastrointestinal tract transition, which contributed to the tunable and robust control of drug release. The sustained drug release behavior was further demonstrated in Beagle dogs, with level A and correlation (IVIVC) established successfully. In conclusion, CS-CBM matrix tablets are promising system to tune and control the release of highly water-soluble drugs with good system robustness.
PubMed: 32104430
DOI: 10.1016/j.ajps.2018.01.004 -
Basic & Clinical Pharmacology &... May 2021According to previous studies, R-(-)-venlafaxine (VEN) has higher enantioselectivity than S-(+)-VEN, and the plasma concentration of R-(-)-VEN varies depending on CYP2D6... (Observational Study)
Observational Study
According to previous studies, R-(-)-venlafaxine (VEN) has higher enantioselectivity than S-(+)-VEN, and the plasma concentration of R-(-)-VEN varies depending on CYP2D6 activity. Therefore, we examined the pharmacokinetic effects of CYP2D6*10 genotypes on the steady-state concentrations of the enantiomers of VEN. The individuals were 71 Japanese depressed patients treated with racemic VEN. The concentrations of the enantiomers of VEN and O-desmethylvenlafaxine (ODV) were measured. Polymerase chain reaction (PCR) was used to determine the CYP2D6*10 genotypes. The plasma concentrations of S-(+)-VEN were approximately 1.9-fold higher than those of R-(-)-VEN. The plasma concentrations of S-(+)-VEN and R-(-)-VEN seemed to be higher in individuals with two mutant alleles of CYP2D6*10, although no significant differences were found in the plasma levels of S-(+)-VEN and R-(-)-VEN between CYP2D6*10 genotypes. The number of mutant alleles of CYP2D6*10 was a significant factor associated with the R-(-)-ODV/R-(-)-VEN ratio (P = .004) in multiple regression analysis. This suggests that CYP2D6*10 mutations affect the metabolism of R-(-)-VEN and S-(+)-VEN. Further studies are needed to examine how these findings affect clinical practice.
Topics: Adult; Aged; Aged, 80 and over; Alleles; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP2D6; Depressive Disorder; Female; Humans; Japan; Male; Middle Aged; Pharmacogenomic Variants; Stereoisomerism; Venlafaxine Hydrochloride; Young Adult
PubMed: 33470005
DOI: 10.1111/bcpt.13560