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Cureus Jan 2024An average of 60-80% of all menopausal women experience bothersome vasomotor symptoms (VMSs), such as flushing and sweating, within the first seven years of onset.... (Review)
Review
An average of 60-80% of all menopausal women experience bothersome vasomotor symptoms (VMSs), such as flushing and sweating, within the first seven years of onset. However, despite increasing prevalence, these hot flashes remain hard to treat and have a negative effect on the quality of life. Though hormone replacement therapy is commonly utilized as a standard treatment for VMSs, this therapy is not recommended for all women. Specifically, the oral form of hormone replacement therapy is associated with several contraindications, including a history of thromboembolic disease, migraine headache with aura, liver failure, heart disease, and hormone-dependent cancers. For women with these medical conditions, current literature indicates that nonhormonal therapies such as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are suitable alternatives to reduce the frequency and intensity of VMSs. Currently, the only SSRI that is FDA-approved for the treatment of VMSs is paroxetine, but studies show that fluoxetine, citalopram, escitalopram, and sertraline are also proven to provide similar benefits. Similarly, the SNRI venlafaxine has also been well tolerated and has been shown to reduce the frequency and severity of hot flashes. The present investigation reviews the physiology of VMSs and examines the evidence for the use of nonhormonal pharmacologic therapies as treatment for women experiencing hot flashes. These interventions should be considered whenever hormone replacement therapy is contraindicated, with therapy individualized based on the severity of symptoms.
PubMed: 38371081
DOI: 10.7759/cureus.52467 -
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 -
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 -
The Science of the Total Environment Mar 2024The functional conservation of important selective serotonin reuptake inhibitor (SSRI) targets in non-target organisms raises concerns about their potential adverse...
The functional conservation of important selective serotonin reuptake inhibitor (SSRI) targets in non-target organisms raises concerns about their potential adverse effects on the ecosystems. Although the environmental levels of SSRIs like paroxetine (PAR) have risen, the knowledge regarding the effects of long-term exposure to PAR is limited. This study investigated the impact of sub-chronic exposure (21 days) to two sub-lethal concentrations of PAR (40 and 400 μg/L) on the behaviour of adult zebrafish in different scenarios: basal activity (under dark and light conditions), stress response (evoked by sudden light transitions) and stress response recovery. A new framework was employed for the integrative study of fish's swimming performance based on their innate ability to respond to light shifts. Several swimming-associated parameters (e.g., total swimming distance, time of inactivity, swimming angles) and thigmotaxis were monitored for an integrated analysis in each scenario. Data revealed reduced swimming activity, impaired behavioural response to stress and alterations in stress recovery of PAR-exposed fish. An anxiolytic effect was particularly noticeable in fish basal swimming activity in the dark at 400 μg/L and in the behavioural response to stress (from dark to light) and stress recovery (from light to dark) for organisms exposed to 40 μg/L. The detected PAR-induced behavioural modifications suggest a disruption of brain glucocorticoid signalling that may have implications at the individual level (e.g., changing behavioural responses to predators), with potential repercussions on the population and community levels. Therefore, the applied protocol proved sensitive in detecting behavioural changes induced by PAR.
Topics: Animals; Paroxetine; Zebrafish; Ecosystem; Behavior, Animal; Selective Serotonin Reuptake Inhibitors; Swimming; Water Pollutants, Chemical
PubMed: 38280602
DOI: 10.1016/j.scitotenv.2024.170405 -
Oman Medical Journal Nov 2023This study sought to determine the confidence level of mental health practitioners in Oman regarding the use of antidepressants during pregnancy and breastfeeding,...
OBJECTIVES
This study sought to determine the confidence level of mental health practitioners in Oman regarding the use of antidepressants during pregnancy and breastfeeding, assess their knowledge and need for further training in this area, and examine their current prescribing patterns and preferences.
METHODS
A questionnaire-based survey was conducted from May to June 2017 among all practitioners in the psychiatry specialty, including medical officers authorized to prescribe medications, at the Behavioral Medicine Department of Sultan Qaboos University Hospital and Al Masarra Hospital.
RESULTS
Forty-two practitioners (response rate = 89.4%) responded to the questionnaire. Of them, 10 (23.8%) had no experience, while 30 (71.4%) had experience in prescribing antidepressants during both pregnancy and breastfeeding periods. Twenty-seven (64.3%) respondents felt that they were confident in prescribing antidepressants for women during their perinatal period, while 30.0% were neutral. Moreover, 35 (83.3%) participants expressed the need for more training in this area. Furthermore, 34 (81.0%) believed that more training in perinatal psychiatry should be included in the psychiatry curriculum. There was no consistent prescribing pattern (either prescribing or avoiding) among our participating practitioners during the first trimester of pregnancy and breastfeeding periods. The drug of choice in the first trimester of pregnancy was fluoxetine preferred by approximately 85.0% of the practitioners, but avoided by 10.0% of practitioners in the same period. This was followed by amitriptyline (50.0% vs. 23.0%), sertraline (50.0% vs. 9.0%), imipramine (28.0% vs. 84.0%). During breastfeeding, the drug of choice for approximately 74.0% of the practitioners was paroxetine, but avoided by 15.0% of practitioners. This was followed by sertraline (50.0% vs. 8.0%). The most common reasons for prescription during pregnancy were safety, evidence-based practice, and low teratogenicity. For breastfeeding, the main reasons for prescription were low levels of the drug in breast milk, safety, and evidence-based practice. On the other hand, high teratogenicity, neonatal side effects, limited data, and lack of evidence were among the most common reasons behind avoiding prescribing during pregnancy, while high levels of breast milk, neonatal side effects, limited evidence, and safety concerns were the most common reasons during the breastfeeding period.
CONCLUSIONS
There was inconsistency among mental health practitioners in making prescription decisions and in their prescribing patterns.
PubMed: 38264515
DOI: 10.5001/omj.2023.123 -
Frontiers in Pharmacology 2023Depression is strongly associated with Alzheimer's disease (AD). Antidepressants are commonly used in patients before and after their diagnosis of AD. To date, the...
Depression is strongly associated with Alzheimer's disease (AD). Antidepressants are commonly used in patients before and after their diagnosis of AD. To date, the relationship between antidepressants and AD remains unclear. In our study, we administered sertraline or paroxetine to wild type (WT) and APPswe/PSEN1dE9 (APP/PSEN1) transgenic mouse models for up to 12 months. We quantified the drug concentrations using LC-MS/MS analysis and measured serum serotonin level using an ELISA assay. Additionally, we evaluated the amyloid burdens through thioflavin-S and Congo red stainings, and recognition memory using the novel object recognition test. Our findings revealed that mice treated with paroxetine exhibited a significantly higher level of weight gain compared to the control group and increased mortality in APP/PSEN1 mice. After 12 months of antidepressant treatment, the sertraline level was measured at 289.8 ng/g for cerebellum, while the paroxetine level was 792.9 ng/g for cerebellum. Sertraline significantly increased thioflavin-S and Congo red depositions, along with gliosis, in both isocortex and hippocampus of APP/PSEN1 mice compared to the control group. Both antidepressants also led to a decreased recognition index in APP/PSEN1 mice. These findings suggest a potential role of sertraline in AD pathogenesis, emphasizing the need to reassess the use of these antidepressants in patients with AD.
PubMed: 38259283
DOI: 10.3389/fphar.2023.1260838