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Psychiatria Polska Oct 2023The aim of the study was to review studies evaluating the pharmacodynamic properties of selective serotonin reuptake inhibitors (SSRIs) and their safety. SSRIs in...
The place of selective serotonin reuptake inhibitors (SSRIs) in the treatment of depressive disorders in children and adolescents. Recommendations of the Main Board of the Polish Psychiatric Association. Part 2 - pharmacological properties and safety of use.
The aim of the study was to review studies evaluating the pharmacodynamic properties of selective serotonin reuptake inhibitors (SSRIs) and their safety. SSRIs in patients <18 years of age sometimes have different pharmacokinetic parameters compared to adults, which has a significant impact on their effectiveness and tolerance. The concentration of fluoxetine, fluvoxamine or paroxetine is about 2 times higher in children compared to adolescents and adults, which should be taken into account at the stage of both drug introduction and setting target doses. In the event of significant problems with the selection of the drug and / or dose of the drug due to unsatisfactory efficacy and / or tolerance in a patient < 18 years of age, examination of the dominant polymorphism for the metabolism of a given isoenzyme may be very important. SSRIs are generally well tolerated in patients less than 18 years of age and the majority of adverse reactions (TEAEs) during treatment are mild or moderate. Most RCTs evaluating the efficacy of SSRIs in depression in patients <18 years of age rates of suicidal ideation or suicidal ideation during follow-up are comparable to placebo, suicide attempts are rare, and isolated cases occur in both the active treatment groups and the placebo arm. There was no statistically significant increased risk for antidepressants (including all SSRIs) or psychotherapy or combinations of antidepressants with psychotherapy (except venlafaxine). Only venlafaxine therapy was associated with an increased risk of suicidal behavior and/or ideation in short-term therapy compared to placebo.
Topics: Child; Adult; Humans; Adolescent; Selective Serotonin Reuptake Inhibitors; Venlafaxine Hydrochloride; Poland; Antidepressive Agents; Depressive Disorder
PubMed: 38345119
DOI: 10.12740/PP/171464 -
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 -
Environmental Science and Pollution... Feb 2024In this paper, we report a study concerning the quantification of new emerging pollutants in water as a request from the third European Watch List mechanism. The EU...
Determination of pollutants, antibiotics, and drugs in surface water in Italy as required by the third EU Water Framework Directive Watch List: method development, validation, and assessment.
In this paper, we report a study concerning the quantification of new emerging pollutants in water as a request from the third European Watch List mechanism. The EU Watch List compound was investigated by an internal method that was validated in terms of detection limits, linearities, accuracy, and precision in accordance with quality assurance criteria, and it was used to monitor several rivers from 11 Italian regions. The methodology developed was satisfactorily validated from 5 to 500 ng L for the emerging pollutants studied, and it was applied to different river waters sampled in Italy, revealing the presence of drugs and antibiotics. Rivers were monitored for 2 years by two different campaigns conducted in 2021 and 2022. A total of 19 emerging pollutants were investigated on 45 samples. The most detected analytes were O-desmethylvenlafaxine and venlafaxine. About azole compounds, sulfamethoxazole, fluconazole, and Miconazole were found. About antibiotics, ciprofloxacin and amoxicillin were found in three and one samples, respectively. Moreover, statistical analyses have found a significant correlation between O-desmethylvenlafaxine with venlafaxine, sulfamethoxazole with venlafaxine, and fluconazole with venlafaxine.
Topics: Water; Venlafaxine Hydrochloride; Desvenlafaxine Succinate; Water Pollutants, Chemical; Anti-Bacterial Agents; Fluconazole; Rivers; Italy; Sulfamethoxazole
PubMed: 38280169
DOI: 10.1007/s11356-024-32025-6 -
The Journal of Clinical Psychiatry Jan 2024
Topics: Humans; Suicide; Venlafaxine Hydrochloride
PubMed: 38270549
DOI: 10.4088/JCP.23cr14930 -
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 -
Environmental Science and Pollution... Feb 2024There is growing evidence of negative impacts of antidepressants on behavior of aquatic non-target organisms. Accurate environmental risk assessment requires an...
There is growing evidence of negative impacts of antidepressants on behavior of aquatic non-target organisms. Accurate environmental risk assessment requires an understanding of whether antidepressants with similar modes of action have consistent negative impacts. Here, we tested the effect of acute exposure to two antidepressants, fluoxetine and venlafaxine (0-50 µg/L), on the behavior of non-target organism, i.e., freshwater pond snail, Lymnaea stagnalis. As compounds interact with chemical cues in the aquatic ecosystems, we also tested whether the effects altered in the presence of bile extract containing 5α-cyprinol sulfate (5α-CPS), a characterized kairomone of a natural predator, common carp (Cyprinus carpio). Behavior was studied using automated tracking and analysis of various locomotion parameters of L. stagnalis. Our results suggest that there are differences in the effects on locomotion upon exposure to venlafaxine and fluoxetine. We found strong evidence for a non-monotonic dose response on venlafaxine exposure, whereas fluoxetine only showed weak evidence of altered locomotion for a specific concentration. Combined exposure to compounds and 5α-CPS reduced the intensity of effects observed in the absence of 5α-CPS, possibly due to reduced bioavailability of the compounds. The results highlight the need for acknowledging different mechanisms of action among antidepressants while investigating their environmental risks. In addition, our results underline the importance of reporting non-significant effects and acknowledging individual variation in behavior for environmental risk assessment.
Topics: Animals; Lymnaea; Fluoxetine; Venlafaxine Hydrochloride; Carps; Ecosystem; Antidepressive Agents; Snails; Aquatic Organisms; Locomotion; Fresh Water; Water Pollutants, Chemical
PubMed: 38233708
DOI: 10.1007/s11356-024-31914-0 -
European Journal of Clinical... Mar 2024The aim of this study was to examine the age of onset for increased dose-adjusted serum concentrations (C/D ratio) of common antidepressant drugs and to explore the... (Observational Study)
Observational Study
PURPOSE
The aim of this study was to examine the age of onset for increased dose-adjusted serum concentrations (C/D ratio) of common antidepressant drugs and to explore the potential association with sex and CYP2C19/CYP2D6 genotype.
METHODS
Serum concentrations and prescribed daily doses for citalopram, escitalopram, sertraline, venlafaxine and mirtazapine, and CYP genotypes, were obtained from a therapeutic drug monitoring (TDM) service. Segmented linear regression analysis was used to examine the relationship between age and antidepressant log C/D ratio in (i) all individuals, (ii) men and women, and (iii) CYP2D6/CYP2C19 normal metabolizers (NMs) and CYP2D6/CYP2C19 intermediate or poor metabolizers (IMs/PMs).
RESULTS
A total of 34,777 individuals were included in the study; CYP genotype was available for 21.3%. An increase in C/D ratio started at 44‒55 years of age. Thereafter, the increase progressed more rapidly for citalopram and escitalopram than for venlafaxine and mirtazapine. A doubled C/D ratio was estimated to occur at 79 (citalopram), 81 (escitalopram), 86 (venlafaxine), and 90 years (mirtazapine). For sertraline, only modest changes in C/D ratio were observed. For escitalopram and venlafaxine, the observed increase in C/D ratio started earlier in women than in men. The results regarding CYP genotype were inconclusive.
CONCLUSION
The age-related increase in C/D ratio starts in middle-aged adults and progresses up to more than twofold higher C/D ratio in the oldest old. Sertraline seems to be less prone to age-related changes in C/D ratio than the other antidepressants.
Topics: Adult; Male; Middle Aged; Aged, 80 and over; Female; Humans; Citalopram; Sertraline; Venlafaxine Hydrochloride; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP2D6; Mirtazapine; Escitalopram; Age of Onset; Antidepressive Agents; Genotype
PubMed: 38197945
DOI: 10.1007/s00228-023-03611-3 -
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 -
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 -
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