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Frontiers in Pharmacology 2023We compared and ranked the efficacy and tolerability of multiple prophylactic treatments for vestibular migraine (VM), including β-blockers, calcium channel blockers,...
We compared and ranked the efficacy and tolerability of multiple prophylactic treatments for vestibular migraine (VM), including β-blockers, calcium channel blockers, antiseizure medications, and antidepressants such as tricyclics and serotonin-noradrenaline reuptake inhibitors. PubMed, Web of Science, Embase, and Cochrane Center for Clinical Trials were systematically searched for relevant randomized clinical trials (RCTs) from March 2023 to May 2023. Studies on the efficacy and tolerability of prophylactic treatments for VM were included. Efficacy was measured using the average vertigo frequency per month and dizziness handicap inventory (DHI) improvement after 3-6 months of treatment. Tolerability was measured by the number of patients reporting at least one adverse event (AE). Network meta-analyses were performed according to a Bayesian framework and a random-effects model based on odds ratios or mean differences (MDs) and 95% confidence intervals (CIs). A sequence of ranking probability was calculated according to the surface under the cumulative ranking (SUCRA) curve. This network meta-analysis was previously registered with PROSPERO (CRD42023422258). Five RCTs comprising 334 patients were analyzed by synthesizing the published evidence. Considering the examined prophylactic therapies, there is significant evidence that valproate acid (VPA) is superior to placebo or abortive treatment alone (MD = -4.12, 95% CI = -8.09, -0.15) in reducing the frequency of vertigo. Flunarizine (MD = 20.00, 95% CI = 10.90, 29.10), valproate acid (MD = 18.88, 95% CI = 10.42, 27.34), and venlafaxine (MD = 11.48, 95% CI = 9.84, 13.12) were significantly more effective than placebo or abortive treatment in reducing DHI. VPA most strongly reduced the frequency of vertigo according to SUCRA, but it ranked third-to-last in tolerability. Flunarizine ranked best in DHI improvement but worst in tolerability. Metoprolol ranked worst for efficacy but best for tolerability. VPA and flunarizine reduced the frequency of vertigo and improved DHI, but they had unfavorable tolerability. The effects of metoprolol on vertigo require further study. Given the low certainty and limited sample, additional head-to-head RCTs are warranted to further confirm efficacy. https://www.crd.york.ac.uk/PROSPERO/; Identifier CRD42023422258.
PubMed: 38186654
DOI: 10.3389/fphar.2023.1332973 -
BMJ Open Dec 2023Investigate risk for falls, fractures and syncope in older adult patients treated with nortriptyline compared with paroxetine and alternative medications.
Adverse drug events associated with nortriptyline compared with paroxetine and alternative medications in an older adult population: a retrospective cohort study in Southern California.
OBJECTIVE
Investigate risk for falls, fractures and syncope in older adult patients treated with nortriptyline compared with paroxetine and alternative medications.
DESIGN
Retrospective cohort study.
SETTING
The electronic medical record and prescription drug database of a large integrated healthcare system in Southern California.
PARTICIPANTS
Ambulatory patients, age ≥65 years diagnosed with depression, anxiety disorder or peripheral neuropathy, dispensed one or more of ten study medications between 1 January 2008 and 31 December 2018.
MAIN OUTCOME MEASURES
HR for falls, fractures and syncope with exposure to study medications adjusted for patient demographic variables and comorbidities.
RESULTS
Among 195 207 subjects, 19 305 falls, 15 088 fractures and 11 313 episodes of syncope were observed during the study period. Compared with the reference medication, nortriptyline, the adjusted HRs (aHRs) for falls were statistically significantly greater for: paroxetine (aHR 1.48, 95% CI 1.39 to 1.57), amitriptyline (1.20, 95% CI 1.08 to 1.33), venlafaxine (1.44, 95% CI 1.34 to 1.56), duloxetine (1.25, 95% CI 1.12 to 1.40), fluoxetine (1.51, 95% CI 1.44 to 1.59), sertraline (1.53, 95% CI 1.44 to 1.62), citalopram (1.61, 95% CI 1.52 to 1.71) and escitalopram (1.37, 95% CI 1.21 to 1.54), but not gabapentin (0.95, 95% CI 0.89 to 1.02). For fractures, compared with nortriptyline, aHRs were significantly greater for: paroxetine, venlafaxine, duloxetine, fluoxetine, sertraline, citalopram, escitalopram and gabapentin, with aHRs ranging from 1.30 for gabapentin to 1.82 for escitalopram; risk was statistically similar for amitriptyline. For syncope, the aHRs were significantly greater for: paroxetine, venlafaxine, fluoxetine, sertraline and citalopram, with aHRs ranging from 1.19 for fluoxetine and paroxetine up to 1.30 for citalopram and sertraline; risk was similar for amitriptyline, duloxetine, escitalopram and gabapentin.
CONCLUSIONS
Compared with therapeutic alternatives, nortriptyline was found to represent a lower risk for falls, fractures and syncope, versus comparator medications, except for a few instances that had equivalent risk. The risk for these adverse events from paroxetine was comparable to the alternative medications.
Topics: Humans; Aged; Paroxetine; Nortriptyline; Citalopram; Fluoxetine; Sertraline; Venlafaxine Hydrochloride; Amitriptyline; Duloxetine Hydrochloride; Retrospective Studies; Escitalopram; Gabapentin; Drug-Related Side Effects and Adverse Reactions; Syncope
PubMed: 38154883
DOI: 10.1136/bmjopen-2023-076028 -
The Science of the Total Environment Feb 2024Plastic pollution is an increasing environmental concern. Pollutants such as microplastics (< 5 mm) and pharmaceuticals often co-exist in the aquatic environment. The...
Plastic pollution is an increasing environmental concern. Pollutants such as microplastics (< 5 mm) and pharmaceuticals often co-exist in the aquatic environment. The current study aimed to elucidate the interaction of pharmaceuticals with microplastics and ascertain how the process of photo-oxidation of microplastics affected the adsorption of the pharmaceuticals. To this end, a mixture containing ibuprofen, carbamazepine, fluoxetine, venlafaxine and ofloxacin (16 μmol L each) was placed in contact with one of six either virgin or aged microplastic types. The virgin microplastics were acquired commercially and artificially aged in the laboratory. Polypropylene, polyethylene, polyethylene terephthalate, polyamide, polystyrene, and polyvinyl chloride microparticles at two sizes described as small (D < 35 μm) and large (D 95-157 μm) were evaluated. Results demonstrated that the study of virgin particles may underestimate the adsorption of micropollutants onto microplastics. For virgin particles, only small microparticles of polypropylene, polyethylene, polyvinyl chloride, and both sizes of polyamide adsorbed pharmaceuticals. Aging the microplastics increased significantly the adsorption of pharmaceuticals by microplastics. Fluoxetine adsorbed onto all aged microplastics, from 18 % (large polyethylene terephthalate) to 99 % (small polypropylene). The current investigation highlights the potential of microplastics to act as a vector for pharmaceuticals in freshwater, especially after aging.
Topics: Microplastics; Plastics; Polypropylenes; Polyethylene Terephthalates; Nylons; Adsorption; Polyvinyl Chloride; Fluoxetine; Water Pollutants, Chemical; Fresh Water; Polyethylene; Pharmaceutical Preparations
PubMed: 38141976
DOI: 10.1016/j.scitotenv.2023.169467 -
International Journal of Molecular... Dec 2023Anxious depression represents a subtype of major depressive disorder and is associated with increased suicidality, severity, chronicity and lower treatment response....
Anxious depression represents a subtype of major depressive disorder and is associated with increased suicidality, severity, chronicity and lower treatment response. Only a few studies have investigated the differences between anxious depressed (aMDD) and non-anxious depressed (naMDD) patients regarding treatment dosage, serum-concentration and drug-specific treatment response. In our naturalistic and prospective study, we investigated whether the effectiveness of therapy including antidepressants (SSRI, SNRI, NaSSA, tricyclics and combinations) in aMDD patients differs significantly from that in naMDD patients. In a sample of 346 patients, we calculated the anxiety somatization factor (ASF) and defined treatment response as a reduction (≥50%) in the Hamilton Depression Rating Scale (HDRS)-21 score after 7 weeks of pharmacological treatment. We did not observe an association between therapy response and the baseline ASF-scores, or differences in therapy outcomes between aMDD and naMDD patients. However, non-responders had higher ASF-scores, and at week 7 aMDD patients displayed a worse therapy outcome than naMDD patients. In subgroup analyses for different antidepressant drugs, venlafaxine-treated aMDD patients showed a significantly worse outcome at week 7. Future prospective, randomized-controlled studies should address the question of a worse therapy outcome in aMDD patients for different psychopharmaceuticals individually.
Topics: Humans; Depression; Depressive Disorder, Major; Prospective Studies; Treatment Outcome; Antidepressive Agents
PubMed: 38138957
DOI: 10.3390/ijms242417128 -
European Neuropsychopharmacology : the... Feb 2024EEG brain abnormalities, such as slowing and isolated epileptiform discharges (IEDs), has previously been associated with non-response to antidepressant treatment with...
EEG brain abnormalities, such as slowing and isolated epileptiform discharges (IEDs), has previously been associated with non-response to antidepressant treatment with escitalopram and venlafaxine, suggesting a potential need for treatment with anticonvulsant property in some patients. The current study aims to replicate the reported association of EEG abnormality and treatment outcomes in an open-label trial of escitalopram for major depressive disorder (MDD) and explore its relationship to mood and cognition. Pretreatment, 6 min eyes-closed resting-state 256-channel EEG was recorded in 91 patients with MDD (age 18-57) who were treated with 10-20 mg escitalopram for 12 weeks; patients could switch to duloxetine after four weeks. A certified clinical neurophysiologist rated the EEGs. IED and EEG slowing was seen in 13.2%, and in 6.6% there were findings with unclear significance (i.e., Wicket spikes and theta activity). We saw no group-difference in remission or response rates after 8 and 12 weeks of treatment or switching to duloxetine. Patients with EEG abnormalities had higher pretreatment mood disturbances driven by greater anger (p=.039) and poorer verbal memory (p=.012). However, EEG abnormality was not associated with improved mood or verbal memory after treatment. Our findings should be interpreted in light of the rarity of EEG abnormalities and the sample size. While we cannot confirm that EEG abnormalities are associated with non-response to treatment, including escitalopram, abnormal EEG activity is associated with poor mood and verbal memory. The clinical utility of EEG abnormality in antidepressant treatment selection needs careful evaluation before deciding if useful for clinical implementation.
Topics: Humans; Adolescent; Young Adult; Adult; Middle Aged; Duloxetine Hydrochloride; Depressive Disorder, Major; Citalopram; Escitalopram; Antidepressive Agents; Electroencephalography; Treatment Outcome
PubMed: 38128462
DOI: 10.1016/j.euroneuro.2023.11.004 -
Journal of Pharmaceutical Policy and... Dec 2023The COVID-19 pandemic globally impacted healthcare provision. Prescribing changes in common medications can be used as a marker for new diagnoses. We describe how the...
INTRODUCTION
The COVID-19 pandemic globally impacted healthcare provision. Prescribing changes in common medications can be used as a marker for new diagnoses. We describe how the prescribing of specific psychotropics was impacted by the pandemic.
METHODS
Primary Care Prescribing data for different classes of drugs from March 2017 to February 2022 were considered. To capture the impact during periods of restricted access to health services for new diagnoses/existing conditions, repeat prescriptions/episodic prescribing were included with account taken of historical trends. The pre-pandemic prescriptions issued each month from March 2018 to February 2020 were linearly extrapolated forward to give an expected annual growth (EAG). The monthly average expected prescriptions for the pandemic period (March 2020-February 2022) were compared.
RESULTS
Physical health medications had lower monthly prescriptions during the pandemic, most markedly for antibiotics - 12.5% (EAG - 1.3%). Bronchodilator prescribing showed a marked increase in the early pandemic months from March 2020 of 5% (EAG 0.1%). Mental health medication prescribing increased above trend for hypnotics/anxiolytics by 0.2% (EAG - 2.3%), while antidepressants fell by - 0.2% (EAG 5.0%), with no net change for antipsychotics (EAG 2.8%), but a temporary increase in antipsychotic prescribing in the early pandemic period. For all the main antidepressants prescribed in England (Sertraline, Mirtazapine, Venlafaxine, Fluoxetine and Citalopram), prescribing actually decreased in the main pandemic period vs historical trend.
CONCLUSIONS
The increase in anxiolytic/hypnotic prescribing above trend links to pandemic effects on anxiety/worry. If anything, there was a slight fall in prescribing of the main antidepressants prescribed, which given prevailing circumstances at the time, suggests that access to services may have restricted access to timely assessment.
PubMed: 38124123
DOI: 10.1186/s40545-023-00655-9 -
Actas Espanolas de Psiquiatria Sep 2023Adherence to antidepressants is essential for good outcomes when treating depressive disorders.
Adherence to antidepressants is essential for good outcomes when treating depressive disorders.
Topics: Humans; Depressive Disorder, Major; Venlafaxine Hydrochloride; Patients
PubMed: 38117259
DOI: No ID Found -
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 -
Frontiers in Pharmacology 2023Non-adherence to antidepressants is associated with worse disease outcomes (morbidity and mortality) and correlates with higher healthcare resource utilization and...
Non-adherence to antidepressants is associated with worse disease outcomes (morbidity and mortality) and correlates with higher healthcare resource utilization and costs. A population-based registry study was conducted to assess non-adherence and to analyze the economic burden of treatment and from non-adherence to antidepressants in 2021. Non-adherence was measured by the Medication Possession Ratio and those below 80% were classified as non-adherent. In 2021, 246,718 patients (10.60% [95% CI: 10.48-10.72]) received antidepressants at a cost of €29 million. The median antidepressant cost per patient/year was €70.08€, ranging from €7.58 for amitriptyline to €396.66 for agomelatine. Out-of-pocket costs represented 6.09% of total expenditures, with a median copayment of €2.78 per patient. The 19.87% [95% CI 19.52-20.22)] of patients were non-adherent to antidepressants, costing €3.9 million (13.30% of total antidepressant costs). Non-adherence rates exceeded 20% for the tricyclic antidepressants, fluoxetine (23.53%), fluvoxamine (22.42%), and vortioxetine (20.58%). Venlafaxine (14.64%) and citalopram (14.88%) had the lowest non-adherence rates, of less than 15%. The median cost of non-adherent medications per patient/year was €18.96 and ranged from €2.50 (amitriptyline) to €133.42 (agomelatine). Reducing non-adherence to antidepressants is critical to improving clinical and economic outcomes. The implementation of interventions and standardized measures, including early detection indicators, is urgently needed. Antidepressants differ with regard to non-adherence and their cost, and this should be considered when prescribing this medication. The Medication Possession Ratio could be used by the healthcare provider and clinician to identify non-adherent patients for monitoring, and to take necessary corrective actions.
PubMed: 38035007
DOI: 10.3389/fphar.2023.1266034 -
Cureus Oct 2023Serotonin syndrome (SS) is an entity caused by interference with the serotonin metabolism and/or by medications that act as serotonin receptor agonists. The signs and...
Serotonin syndrome (SS) is an entity caused by interference with the serotonin metabolism and/or by medications that act as serotonin receptor agonists. The signs and symptoms are nonspecific, making the diagnosis challenging. Treatment depends on the severity of the manifestations. In mild to moderate cases, it typically resolves within the first 24 hours after initiating therapy and discontinuation of the serotoninergic medications. A 42-year-old woman with a previous history of depression was admitted to the hospital due to the voluntary ingestion of multiple tablets of escitalopram 10 mg and venlafaxine 75 mg. Physical examination showed a hyperthermic and diaphoretic patient. Tremor, agitation, bilateral ocular clonus, and spontaneous inferior limb clonus were also present. Hunter's criteria were applied, and the diagnosis of SS was assumed. Supportive and symptomatic treatments were initiated. The evolution was benign, with symptomatic remission in the first 24 hours. In the last decades, a large increase in the use of antidepressants was noted, and, as such, defining SS as rare is no longer appropriate. Delaying the treatment can dictate an increase in morbidity and mortality. It is important to highlight that the diagnosis is mainly clinical as diagnostic criteria may miss out on some cases. As such, clinical awareness of SS's multiplicity of presentations is of utmost importance.
PubMed: 38021488
DOI: 10.7759/cureus.47470