-
Contact Dermatitis May 2024
Topics: Humans; Citalopram; Patch Tests; Dermatitis, Allergic Contact; Selective Serotonin Reuptake Inhibitors; Depression
PubMed: 38354423
DOI: 10.1111/cod.14504 -
Journal of Affective Disorders May 2024Selective serotonin reuptake inhibitors (SSRIs) are the first-line anti-depressants. Unfortunately, about 30 % depressed patients do not effectively respond to SSRIs....
OBJECTIVES
Selective serotonin reuptake inhibitors (SSRIs) are the first-line anti-depressants. Unfortunately, about 30 % depressed patients do not effectively respond to SSRIs. It is still unclear that the gastrointestinal characteristics of responders and non-responders, and the differences.
METHODS
Herein, we characterized gut microbiome and metabolome of depressed rats with differential responses to Paroxetine (PX) by 16S rRNA sequencing and H NMR-based metabolomics, respectively. On top of this, we constructed both inter- and inner-layer networks, intuitively showing the correlations among behavioral indicators, immune factors, intestinal bacteria, and differential metabolites.
RESULTS
Consequently, we found that depressed rats differently responded to PX, which could be divided into PX responsive (PX-R) and non-responsive (PX-N) groups. Firstly, the depressive behaviors of PX-R rats and PX-N rats significantly differed. Meanwhile, inflammatory balance was also characterized for depressed rats with different responses to PX. Overall, PX-R rats and PX-N rats exhibited differential gut microbiome and metabolome, including intestinal structures, intestinal functions, metabolic profiles, metabolites, and metabolic pathways.
LIMITATIONS
Metabolites that identified by metabolomics based on H NMR are not comprehensive enough.
CONCLUSIONS
Taken together, our study demonstrated that gut microbiome and metabolome, as well as related functions, are of significance in differential responses of depressed rats to PX, which might be novel insights in uncovering the mechanisms of differences in efficacies of antidepressants.
Topics: Humans; Rats; Animals; Paroxetine; Selective Serotonin Reuptake Inhibitors; RNA, Ribosomal, 16S; Metabolome; Metabolomics; Microbiota
PubMed: 38346646
DOI: 10.1016/j.jad.2024.02.017 -
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 -
Molecules (Basel, Switzerland) Jan 2024This article discusses a new method for monitoring drug concentrations in blood samples from patients with mood disorders. The method uses solid-phase microextraction to...
This article discusses a new method for monitoring drug concentrations in blood samples from patients with mood disorders. The method uses solid-phase microextraction to extract analytes directly from blood samples. It has been adapted to identify the most commonly used drugs in mood disorders, including amitriptyline, citalopram, fluoxetine, paroxetine, sertraline, trazodone, duloxetine, venlafaxine, lamotrigine, quetiapine, olanzapine, and mirtazapine. The analysis is carried out using high-performance liquid chromatography coupled with mass spectroscopy. The proposed DI-SPME/LC-MS method allows for a simple and quick screening analysis while minimizing the volume of the tested sample and solvent, in line with the principles of green analytical chemistry. The method was used to analyze 38 blood samples taken from patients with mood disorders, and drug concentrations were determined and compared with therapeutic and toxic dose ranges. This allowed for better control of the course of treatment.
Topics: Humans; Solid Phase Microextraction; Mood Disorders; Drug Monitoring; Immersion; Fluoxetine
PubMed: 38338419
DOI: 10.3390/molecules29030676 -
Journal of Clinical Medicine Jan 2024: Histamine intolerance manifests when there is an imbalance between the production of histamine and the body's capacity to metabolise it. Within the gastrointestinal...
Exploring the Relationship between Diamine Oxidase and Psychotropic Medications in Fibromyalgia Treatment, Finding No Reduction in Diamine Oxidase Levels and Activity except with Citalopram.
: Histamine intolerance manifests when there is an imbalance between the production of histamine and the body's capacity to metabolise it. Within the gastrointestinal tract, diamine oxidase (DAO) plays a pivotal role in breaking down ingested histamine. Insufficient levels of DAO have been linked to various diseases affecting the respiratory, cardiovascular, nervous, muscular, and digestive systems; some of these symptoms are evidenced in fibromyalgia syndrome. This underscores the crucial role of DAO in maintaining the histamine balance and highlights its association with diverse physiological systems and health conditions. The management of fibromyalgia commonly involves the use of psychotropic medications; however, their potential interactions with DAO remain not fully elucidated. : This study delved into the influence of various psychotropic medications on DAO activity through experiments. Additionally, we explored their impact on the human intestinal cell line Caco-2, examining alterations in DAO expression at both the mRNA and protein levels along with DAO activity. : Notably, the examined drugs-sertraline, pregabalin, paroxetine, alprazolam, and lorazepam-did not exhibit inhibitory effects on DAO activity or lead to reductions in DAO levels. In contrast, citalopram demonstrated a decrease in DAO activity in assays without influencing DAO levels and activity in human enterocytes. : These findings imply that a collaborative approach involving psychotropic medications and DAO enzyme supplementation for individuals with fibromyalgia and a DAO deficiency could offer potential benefits for healthcare professionals in their routine clinical practice.
PubMed: 38337486
DOI: 10.3390/jcm13030792 -
Urology Mar 2024To identify which medications are mostly associated with ejaculatory disorders through a disproportionality analysis.
OBJECTIVE
To identify which medications are mostly associated with ejaculatory disorders through a disproportionality analysis.
METHODS
The Food and Drug Administration Adverse Event Reporting System (FDA-FAERS) and the Eudra-Vigilance (EV) database were queried to identify medications more commonly associated to ejaculatory disorders from September 10, 2012 to June 1, 2023. Proportional Reported Ratios (PRRs) were computed for all the selected drugs.
RESULTS
Overall, 7404 reports of ejaculatory disorders reports were identified, and of these, 6854 cases (92.6%) were attributed to ten specific medications. On FDA-FAERS and EV databases, Paroxetine and Tamsulosin were the main responsible of delayed ejaculation (103/448 events, 23.0%) and retrograde ejaculation (366/1033 events, 35.4%), respectively. Finasteride was mostly related to painful ejaculation and ejaculation failure, with 150 events (7.8%) and 735 events (38.4%) respectively. Within the group of high-risk medications, Sildenafil presented higher risk of ejaculatory disorders than Tadalafil (PRR=5.85 (95%CI 5.09-6.78), P < .01).
CONCLUSION
Ten drugs were recognized to display significant reporting levels of ejaculatory disorders. Among them, Finasteride and Sildenafil were responsible for the most reports in FDA-FAERS and in EV databases, respectively. Physicians should thoroughly counsel patients treated with these drugs about the risk of ejaculatory disorders. Further integration into clinical trials is needed to enhance the applicability and significance of these results.
Topics: Male; United States; Humans; Finasteride; Sildenafil Citrate; United States Food and Drug Administration; Pharmacovigilance; Tamsulosin; Databases, Factual
PubMed: 38331221
DOI: 10.1016/j.urology.2023.12.021 -
Biological & Pharmaceutical Bulletin 2024Alzheimer's disease (AD) is accompanied by behavioral and psychological symptoms of dementia (BPSD), which is often alleviated by treatment with psychotropic drugs, such...
Alzheimer's disease (AD) is accompanied by behavioral and psychological symptoms of dementia (BPSD), which is often alleviated by treatment with psychotropic drugs, such as antidepressants, hypnotics, and anxiolytics. If these drugs also inhibit acetylcholinesterase (AChE) activity, they may contribute to the suppression of AD progression by increasing brain acetylcholine concentrations. We tested the potential inhibitory effects of 31 antidepressants, 21 hypnotics, and 12 anxiolytics on recombinant human AChE (rhAChE) activity. At a concentration of 10 M, 22 antidepressants, 19 hypnotics, and 11 anxiolytics inhibited rhAChE activity by <20%, whereas nine antidepressants (clomipramine, amoxapine, setiptiline, nefazodone, paroxetine, sertraline, citalopram, escitalopram, and mirtazapine), two hypnotics (triazolam and brotizolam), and one anxiolytic (buspirone) inhibited rhAChE activity by ≥20%. Brotizolam (≥10 M) exhibited stronger inhibition of rhAChE activity than the other drugs, with its pIC value being 4.57 ± 0.02. The pIC values of the other drugs were <4, and they showed inhibitory activities toward rhAChE at the following concentrations: ≥3 × 10 M (sertraline and buspirone), ≥10 M (amoxapine, nefazodone, paroxetine, citalopram, escitalopram, mirtazapine, and triazolam), and ≥3 × 10 M (clomipramine and setiptiline). Among these drugs, only nefazodone inhibited rhAChE activity within the blood concentration range achievable at clinical doses. Therefore, nefazodone may not only improve the depressive symptoms of BPSD through its antidepressant actions but also slow the progression of cognitive symptoms of AD through its AChE inhibitory actions.
Topics: Humans; Anti-Anxiety Agents; Acetylcholinesterase; Hypnotics and Sedatives; Sertraline; Clomipramine; Mirtazapine; Paroxetine; Citalopram; Escitalopram; Amoxapine; Buspirone; Triazolam; Antidepressive Agents
PubMed: 38296462
DOI: 10.1248/bpb.b23-00719 -
The Canadian Veterinary Journal = La... Feb 2024An 8-month-old spayed female golden retriever × standard poodle dog was presented for assessment because of vocalization, destructive behavior, and urination when left...
An 8-month-old spayed female golden retriever × standard poodle dog was presented for assessment because of vocalization, destructive behavior, and urination when left home alone and confined in a crate. Previous treatments included multiple medications, graduated departures, decoupling of departure cues, and punishmentbased techniques. Adverse reactions to paroxetine and lorazepam were noted before successful treatment with clomipramine, "safe haven" training, and behavior modification. Key clinical message: Separation anxiety is a common behavioral disorder in dogs. It is often treatable but may require changes in the approach to both medication and behavior modification based on patient and client factors.
Topics: Humans; Dogs; Female; Animals; Behavior Therapy; Dog Diseases; Anxiety
PubMed: 38304480
DOI: No ID Found -
Human Genomics Feb 2024Individual assessment of CYP enzyme activities can be challenging. Recently, the potato alkaloid solanidine was suggested as a biomarker for CYP2D6 activity. Here, we...
BACKGROUND
Individual assessment of CYP enzyme activities can be challenging. Recently, the potato alkaloid solanidine was suggested as a biomarker for CYP2D6 activity. Here, we aimed to characterize the sensitivity and specificity of solanidine as a CYP2D6 biomarker among Finnish volunteers with known CYP2D6 genotypes.
RESULTS
Using non-targeted metabolomics analysis, we identified 9152 metabolite features in the fasting plasma samples of 356 healthy volunteers. Machine learning models suggested strong association between CYP2D6 genotype-based phenotype classes with a metabolite feature identified as solanidine. Plasma solanidine concentration was 1887% higher in genetically poor CYP2D6 metabolizers (gPM) (n = 9; 95% confidence interval 755%, 4515%; P = 1.88 × 10), 74% higher in intermediate CYP2D6 metabolizers (gIM) (n = 89; 27%, 138%; P = 6.40 × 10), and 35% lower in ultrarapid CYP2D6 metabolizers (gUM) (n = 20; 64%, - 17%; P = 0.151) than in genetically normal CYP2D6 metabolizers (gNM; n = 196). The solanidine metabolites m/z 444 and 430 to solanidine concentration ratios showed even stronger associations with CYP2D6 phenotypes. Furthermore, the areas under the receiver operating characteristic and precision-recall curves for these metabolic ratios showed equal or better performances for identifying the gPM, gIM, and gUM phenotype groups than the other metabolites, their ratios to solanidine, or solanidine alone. In vitro studies with human recombinant CYP enzymes showed that solanidine was metabolized mainly by CYP2D6, with a minor contribution from CYP3A4/5. In human liver microsomes, the CYP2D6 inhibitor paroxetine nearly completely (95%) inhibited the metabolism of solanidine. In a genome-wide association study, several variants near the CYP2D6 gene associated with plasma solanidine metabolite ratios.
CONCLUSIONS
These results are in line with earlier studies and further indicate that solanidine and its metabolites are sensitive and specific biomarkers for measuring CYP2D6 activity. Since potato consumption is common worldwide, this biomarker could be useful for evaluating CYP2D6-mediated drug-drug interactions and to improve prediction of CYP2D6 activity in addition to genotyping.
Topics: Humans; Cytochrome P-450 CYP2D6; Genome-Wide Association Study; Paroxetine; Biomarkers; Genotype; Diosgenin
PubMed: 38303026
DOI: 10.1186/s40246-024-00579-8 -
Therapeutic Drug Monitoring Apr 2024Compared with antipsychotics, the relationship between antidepressant blood (plasma or serum) concentrations and target engagement is less well-established.
BACKGROUND
Compared with antipsychotics, the relationship between antidepressant blood (plasma or serum) concentrations and target engagement is less well-established.
METHODS
We have discussed the literature on the relationship between plasma concentrations of antidepressant drugs and their target occupancy. Antidepressants reviewed in this work are citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, venlafaxine, duloxetine, milnacipran, tricyclic antidepressants (amitriptyline, nortriptyline, and clomipramine), bupropion, tranylcypromine, moclobemide, and vortioxetine. Four electronic databases were systematically searched.
RESULTS
We included 32 articles published 1996-2022. A strong relationship between serotonin transporter (SERT) occupancy and drug concentration is well established for selective serotonin reuptake inhibitors. Lower limits of recommended therapeutic reference ranges largely corroborate with the findings from positron emission tomography studies (80% SERT occupancy). Only a few novel studies have investigated alternative targets, that is, norepinephrine transporters (NETs), dopamine transporters (DATs), or monoamine oxidase A (MAO-A). For certain classes of drugs, positron emission tomography study data are inconclusive. Low DAT occupancy after bupropion treatment speculates its discussed mechanism of action. For MAO inhibitors, a correlation between drug concentration and MAO-A occupancy could not be established.
CONCLUSIONS
Neuroimaging studies are critical in TDM-guided therapy for certain antidepressants, whereas for bupropion and MAO inhibitors, the available evidence offers no further insight. Evidence for selective serotonin reuptake inhibitors is strong and justifies a titration toward suggested ranges. For SNRIs, duloxetine, and venlafaxine, NETs are sufficiently occupied, well above the SERT efficacy threshold. For these drugs, a titration toward higher concentrations (within the recommended range) should be considered in case of no response at lower concentrations.
Topics: Humans; Selective Serotonin Reuptake Inhibitors; Venlafaxine Hydrochloride; Bupropion; Duloxetine Hydrochloride; Monoamine Oxidase Inhibitors; Antidepressive Agents; Positron-Emission Tomography; Monoamine Oxidase
PubMed: 38287888
DOI: 10.1097/FTD.0000000000001142