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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 Cochrane Database of Systematic... Nov 2023A panic attack is a discrete period of fear or anxiety that has a rapid onset and reaches a peak within 10 minutes. The main symptoms involve bodily systems, such as... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A panic attack is a discrete period of fear or anxiety that has a rapid onset and reaches a peak within 10 minutes. The main symptoms involve bodily systems, such as racing heart, chest pain, sweating, shaking, dizziness, flushing, churning stomach, faintness and breathlessness. Other recognised panic attack symptoms involve fearful cognitions, such as the fear of collapse, going mad or dying, and derealisation (the sensation that the world is unreal). Panic disorder is common in the general population with a prevalence of 1% to 4%. The treatment of panic disorder includes psychological and pharmacological interventions, including antidepressants and benzodiazepines.
OBJECTIVES
To compare, via network meta-analysis, individual drugs (antidepressants and benzodiazepines) or placebo in terms of efficacy and acceptability in the acute treatment of panic disorder, with or without agoraphobia. To rank individual active drugs for panic disorder (antidepressants, benzodiazepines and placebo) according to their effectiveness and acceptability. To rank drug classes for panic disorder (selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), mono-amine oxidase inhibitors (MAOIs) and benzodiazepines (BDZs) and placebo) according to their effectiveness and acceptability. To explore heterogeneity and inconsistency between direct and indirect evidence in a network meta-analysis.
SEARCH METHODS
We searched the Cochrane Common Mental Disorders Specialised Register, CENTRAL, CDSR, MEDLINE, Ovid Embase and PsycINFO to 26 May 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of people aged 18 years or older of either sex and any ethnicity with clinically diagnosed panic disorder, with or without agoraphobia. We included trials that compared the effectiveness of antidepressants and benzodiazepines with each other or with a placebo.
DATA COLLECTION AND ANALYSIS
Two authors independently screened titles/abstracts and full texts, extracted data and assessed risk of bias. We analysed dichotomous data and continuous data as risk ratios (RRs), mean differences (MD) or standardised mean differences (SMD): response to treatment (i.e. substantial improvement from baseline as defined by the original investigators: dichotomous outcome), total number of dropouts due to any reason (as a proxy measure of treatment acceptability: dichotomous outcome), remission (i.e. satisfactory end state as defined by global judgement of the original investigators: dichotomous outcome), panic symptom scales and global judgement (continuous outcome), frequency of panic attacks (as recorded, for example, by a panic diary; continuous outcome), agoraphobia (dichotomous outcome). We assessed the certainty of evidence using threshold analyses.
MAIN RESULTS
Overall, we included 70 trials in this review. Sample sizes ranged between 5 and 445 participants in each arm, and the total sample size per study ranged from 10 to 1168. Thirty-five studies included sample sizes of over 100 participants. There is evidence from 48 RCTs (N = 10,118) that most medications are more effective in the response outcome than placebo. In particular, diazepam, alprazolam, clonazepam, paroxetine, venlafaxine, clomipramine, fluoxetine and adinazolam showed the strongest effect, with diazepam, alprazolam and clonazepam ranking as the most effective. We found heterogeneity in most of the comparisons, but our threshold analyses suggest that this is unlikely to impact the findings of the network meta-analysis. Results from 64 RCTs (N = 12,310) suggest that most medications are associated with either a reduced or similar risk of dropouts to placebo. Alprazolam and diazepam were associated with a lower dropout rate compared to placebo and were ranked as the most tolerated of all the medications examined. Thirty-two RCTs (N = 8569) were included in the remission outcome. Most medications were more effective than placebo, namely desipramine, fluoxetine, clonazepam, diazepam, fluvoxamine, imipramine, venlafaxine and paroxetine, and their effects were clinically meaningful. Amongst these medications, desipramine and alprazolam were ranked highest. Thirty-five RCTs (N = 8826) are included in the continuous outcome reduction in panic scale scores. Brofaromine, clonazepam and reboxetine had the strongest reductions in panic symptoms compared to placebo, but results were based on either one trial or very small trials. Forty-one RCTs (N = 7853) are included in the frequency of panic attack outcome. Only clonazepam and alprazolam showed a strong reduction in the frequency of panic attacks compared to placebo, and were ranked highest. Twenty-six RCTs (N = 7044) provided data for agoraphobia. The strongest reductions in agoraphobia symptoms were found for citalopram, reboxetine, escitalopram, clomipramine and diazepam, compared to placebo. For the pooled intervention classes, we examined the two primary outcomes (response and dropout). The classes of medication were: SSRIs, SNRIs, TCAs, MAOIs and BDZs. For the response outcome, all classes of medications examined were more effective than placebo. TCAs as a class ranked as the most effective, followed by BDZs and MAOIs. SSRIs as a class ranked fifth on average, while SNRIs were ranked lowest. When we compared classes of medication with each other for the response outcome, we found no difference between classes. Comparisons between MAOIs and TCAs and between BDZs and TCAs also suggested no differences between these medications, but the results were imprecise. For the dropout outcome, BDZs were the only class associated with a lower dropout compared to placebo and were ranked first in terms of tolerability. The other classes did not show any difference in dropouts compared to placebo. In terms of ranking, TCAs are on average second to BDZs, followed by SNRIs, then by SSRIs and lastly by MAOIs. BDZs were associated with lower dropout rates compared to SSRIs, SNRIs and TCAs. The quality of the studies comparing antidepressants with placebo was moderate, while the quality of the studies comparing BDZs with placebo and antidepressants was low.
AUTHORS' CONCLUSIONS
In terms of efficacy, SSRIs, SNRIs (venlafaxine), TCAs, MAOIs and BDZs may be effective, with little difference between classes. However, it is important to note that the reliability of these findings may be limited due to the overall low quality of the studies, with all having unclear or high risk of bias across multiple domains. Within classes, some differences emerged. For example, amongst the SSRIs paroxetine and fluoxetine seem to have stronger evidence of efficacy than sertraline. Benzodiazepines appear to have a small but significant advantage in terms of tolerability (incidence of dropouts) over other classes.
Topics: Adult; Humans; Panic Disorder; Selective Serotonin Reuptake Inhibitors; Paroxetine; Fluoxetine; Venlafaxine Hydrochloride; Serotonin and Noradrenaline Reuptake Inhibitors; Alprazolam; Clomipramine; Reboxetine; Clonazepam; Desipramine; Network Meta-Analysis; Antidepressive Agents; Antidepressive Agents, Tricyclic; Benzodiazepines; Diazepam
PubMed: 38014714
DOI: 10.1002/14651858.CD012729.pub3 -
European Neuropsychopharmacology : the... Feb 2024Major depressive disorder (MDD) is a highly prevalent psychiatric disorder, but chances for remission largely decrease with each failed treatment attempt. It is...
Major depressive disorder (MDD) is a highly prevalent psychiatric disorder, but chances for remission largely decrease with each failed treatment attempt. It is therefore desirable to assign a given patient to the most promising individual treatment option as early as possible. We used a polygenic score (PGS) informed electroencephalography (EEG) data-driven approach to identify potential predictors for MDD treatment outcome. Post-hoc we conducted exploratory analyses in order to understand the results in depth. First, an EEG independent component analysis produced 54 functional brain networks in a large heterogeneous cohort of psychiatric patients (n = 4,045; 5-84 yrs.). Next, the network that was associated to PGS for antidepressant-response (PRS-AR) in an independent sample (n = 722) was selected: an age-related posterior alpha network that explained >60 % of EEG variance, and was highly stable over recording time. Translational analyses were performed in two other independent datasets to examine if the network was predictive of psychopharmacotherapy (n = 535) and/or repetitive transcranial magnetic stimulation (rTMS) and concomitant psychotherapy (PT; n = 186) outcome. The network predicted remission to venlafaxine (p = 0.015), resulting in a normalized positive predicted value (nPPV) of 138 %, and rTMS + PT - but in opposite direction for women (p = 0.002) relative to men (p = 0.018) - yielding a nPPV of 131 %. Blinded out-of-sample validations for venlafaxine (n = 29) and rTMS + PT (n = 36) confirmed the findings for venlafaxine, while results for rTMS + PT could not be replicated. These data suggest the existence of a relatively stable EEG posterior alpha aging network related to PGS-AR that has potential as MDD treatment predictor.
Topics: Male; Humans; Female; Venlafaxine Hydrochloride; Transcranial Magnetic Stimulation; Depressive Disorder, Major; Prefrontal Cortex; Antidepressive Agents; Treatment Outcome; Aging
PubMed: 38000196
DOI: 10.1016/j.euroneuro.2023.11.002 -
Journal of Clinical PsychopharmacologySince insomnia and depression are interrelated, improved sleep early in antidepressant pharmacotherapy may predict a positive treatment outcome. We investigated whether... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Since insomnia and depression are interrelated, improved sleep early in antidepressant pharmacotherapy may predict a positive treatment outcome. We investigated whether early insomnia improvement (EII) predicted treatment outcome in psychotic depression (PD) and examined if there was an interaction effect between EII and treatment type to assess if findings were treatment-specific.
METHODS
This study is a secondary analysis of a randomized trial comparing 7 weeks treatment with the antidepressants venlafaxine, imipramine and venlafaxine plus the antipsychotic quetiapine in PD ( n = 114). Early insomnia improvement, defined as ≥20% reduced insomnia after 2 weeks, was assessed by the Hamilton Rating Scale for Depression (HAM-D-17). Associations between EII and treatment outcome were examined using logistic regressions. Subsequently, we added interaction terms between EII and treatment type to assess interaction effects. The predictive value of EII was compared with early response on overall depression (≥20% reduced HAM-D-17 score after 2 weeks).
RESULTS
EII was associated with response (odds ratio [OR], 7.9; 95% confidence interval [CI], 2.7-23.4; P = <0.001), remission of depression (OR, 6.1; 95% CI, 1.6-22.3; P = 0.009), and remission of psychosis (OR, 4.1; 95% CI, 1.6-10.9; P = 0.004). We found no interaction effects between EII and treatment type on depression outcome. Early insomnia improvement and early response on overall depression had a comparable predictive ability for treatment outcome.
CONCLUSIONS
Early insomnia improvement was associated with a positive outcome in pharmacotherapy of PD, regardless of the medication type. Future studies are needed to confirm our findings and to examine the generalizability of EII as predictor in treatment of depression.
Topics: Humans; Antidepressive Agents; Depression; Depressive Disorder, Major; Psychotic Disorders; Sleep; Sleep Initiation and Maintenance Disorders; Treatment Outcome; Venlafaxine Hydrochloride
PubMed: 37930199
DOI: 10.1097/JCP.0000000000001756 -
The Journal of Emergency Medicine Jan 2024
Topics: Humans; Venlafaxine Hydrochloride; Antidepressive Agents; Seizures; Drug Overdose; Electrocardiography
PubMed: 37891066
DOI: 10.1016/j.jemermed.2023.07.003 -
The Science of the Total Environment Jan 2024Exposure to single molecules under laboratory conditions has led to a better understanding of the mechanisms of action (MeOAs) and effects of pharmaceutical active... (Review)
Review
Mixture effects of pharmaceuticals carbamazepine, diclofenac and venlafaxine on Mytilus galloprovincialis mussel probed by metabolomics and proteogenomics combined approach.
Exposure to single molecules under laboratory conditions has led to a better understanding of the mechanisms of action (MeOAs) and effects of pharmaceutical active compounds (PhACs) on non-target organisms. However, not taking the co-occurrence of contaminants in the environment and their possible interactions into account may lead to underestimation of their impacts. In this study, we combined untargeted metabolomics and proteogenomics approaches to assess the mixture effects of diclofenac, carbamazepine and venlafaxine on marine mussels (Mytilus galloprovincialis). Our multi-omics approach and data fusion strategy highlighted how such xenobiotic cocktails induce important cellular changes that can be harmful to marine bivalves. This response is mainly characterized by energy metabolism disruption, fatty acid degradation, protein synthesis and degradation, and the induction of endoplasmic reticulum stress and oxidative stress. The known MeOAs and molecular signatures of PhACs were taken into consideration to gain insight into the mixture effects, thereby revealing a potential additive effect. Multi-omics approaches on mussels as sentinels offer a comprehensive overview of molecular and cellular responses triggered by exposure to contaminant mixtures, even at environmental concentrations.
Topics: Animals; Mytilus; Diclofenac; Venlafaxine Hydrochloride; Proteogenomics; Water Pollutants, Chemical; Carbamazepine; Benzodiazepines; Pharmaceutical Preparations
PubMed: 37879482
DOI: 10.1016/j.scitotenv.2023.168015 -
The Science of the Total Environment Jan 2024Several studies have shown that plants can absorb various micropollutants. The behavior of micropollutants from wastewater treatment plant resources was comprehensively...
Several studies have shown that plants can absorb various micropollutants. The behavior of micropollutants from wastewater treatment plant resources was comprehensively investigated in raised beds in which either a mixture of vegetables or maize was grown. The beds were either irrigated with treated wastewater or enriched with sewage sludge or composted sewage sludge. Over the year, samples of wastewater, water drained from the beds, soils and plants were analyzed. Of the seventy-five analyzed substances, fifty-four, thirty-three and twenty-seven were quantified in wastewater, sewage sludge, and composted sludge, respectively. Alarmingly, approximately 20 % of the compounds from wastewater were also detected in the solutions leached from the beds irrigated with wastewater (e.g., gabapentin, tramadol, sertraline, carbamazepine, its metabolites, and benzotriazoles). In addition, a gradual increase in the content of four substances (telmisartan, venlafaxine, carbamazepine, citalopram) was recorded in these beds. The compounds from both biosolids used for soil enrichment tended to remain in the soils (e.g., telmisartan, venlafaxine, sertraline, its metabolite, citalopram, and its metabolite). Only four compounds (sertraline and three benzotriazoles) leached from these beds. Uptake of some chemicals (e.g., gabapentin, tramadol, carbamazepine and its metabolite, and venlafaxine and its metabolite) and their accumulation in plant tissues was observed mainly in vegetables grown on beds irrigated with wastewater. However, daily consumption values for edible plant parts and individual compounds did not indicate a direct threat to human health. Results of this innovative study show possible risks associated with the use of these resources in agriculture. Of particular concern is the possible micropollutants percolation towards groundwater, including those for which high sorption and thus low mobility in the soil environment is expected, such as sertraline. Soil and crop contamination cannot be neglected either.
Topics: Humans; Wastewater; Sewage; Soil; Water; Citalopram; Gabapentin; Sertraline; Telmisartan; Tramadol; Venlafaxine Hydrochloride; Soil Pollutants; Vegetables; Carbamazepine
PubMed: 37866592
DOI: 10.1016/j.scitotenv.2023.167965 -
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 -
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 -
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