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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 -
Journal of Biomolecular Structure &... Jan 2024Non-muscle invasive bladder cancer (NMIBC) refers to a subtype of bladder carcinoma where cancer is localized in the inner lining of bladder. NMIBC consider as one of...
Non-muscle invasive bladder cancer (NMIBC) refers to a subtype of bladder carcinoma where cancer is localized in the inner lining of bladder. NMIBC consider as one of most costly malignancy and requires significant surgical and therapeutic measure. However, recurrence and progression of tumor is common in treated patients. Here we presented an integrated OMICs approach for the identification and inhibition of NMIBC specific genes. We utilized a case study where three group of patients were compared: 1) Relapsed tumors 2) recurrent tumors and 3) tumor in progression. Common transcriptome signature between patients facing recurrence and progression allowed us to identify three NMIBC specific genes FLT-1, WHSC-1 and CD34. We further utilized novel approach of Co-expressed gene-set enrichment analysis (COGENA) on the differentially expressed genes of this case study. Three drugs (paroxetine, adiphenine and H-89) with role of receptors inhibition were identified and predicted as repurposed drugs for the inhibition NMIBC specific genes. We further tested this hypothesis by performing molecular docking and simulation analysis between cancer specific proteins and drugs. FLT-1 have shown significant stable interaction with both drugs paroxetine and adiphenine whereas WHSC-1 have shown compact interaction with adiphenine and H-89. In the light of these evidence, we suggest that adiphenine could be repositioned as alternate targeted medicine for the treatment of NMIBC. In the future, this study will help for strengthening the strategies development at the molecular level for the control of carcinomas at early as well as detection of active and binding site, receptor-ligand interaction and also make drug repurposing for the early treatment of the carcinomas.Communicated by Ramaswamy H. Sarma.
PubMed: 38247255
DOI: 10.1080/07391102.2024.2302343 -
Cureus Dec 2023Symptoms caused by a selective serotonin reuptake inhibitor (SSRI) overdose are often mild and can be managed with supportive care and close monitoring, even when...
Symptoms caused by a selective serotonin reuptake inhibitor (SSRI) overdose are often mild and can be managed with supportive care and close monitoring, even when complicated by serotonin syndrome. There are limited pharmacokinetic data regarding massive overdoses of paroxetine, and the severity of an SSRI overdose is likely to be underestimated. We describe a fatal case of severe serotonin syndrome and acute respiratory distress syndrome (ARDS) following an overdose of controlled-release paroxetine. A 53-year-old male with depression presented with altered consciousness. He had ingested controlled-release paroxetine along with other medications. On arrival, he had ocular flutter and myoclonus, and blood examinations revealed acute kidney injury and rhabdomyolysis, which suggested serotonin syndrome. Computed tomography (CT) showed pharmacobezoars in the esophagus and stomach. Symptoms of serotonin syndrome and hypotension persisted despite administration of high doses of vasopressors with endotracheal intubation. We performed endoscopic decontamination to remove pharmacobezoars from the stomach. Finally, he developed severe ARDS and died due to respiratory failure on day 23. Sequential serum concentrations of paroxetine were 5.38 µg/mL at admission and 3.21 µg/mL on day 7, both above lethal levels. This case highlights the potential for fatal complications and prolonged toxicity in the case of a massive overdose of controlled-release paroxetine. We should recognize that such an overdose may be life-threatening and should consider aggressive interventions including endoscopic decontamination. A better understanding of the pharmacokinetics of a massive SSRI overdose would be helpful for optimal management.
PubMed: 38229825
DOI: 10.7759/cureus.50691 -
Pathogens and Disease Feb 2024Infections caused by Cryptococcus gattii mainly affect immunocompetent individuals and the treatment presents important limitations. This study aimed to validate the...
Infections caused by Cryptococcus gattii mainly affect immunocompetent individuals and the treatment presents important limitations. This study aimed to validate the efficacy of selective serotonin reuptake inhibitors (SSRI), fluoxetine hydrochloride (FLH), and paroxetine hydrochloride (PAH) in vitro against C. gattii. The antifungal activity of SSRI using the microdilution method revealed a minimal inhibitory concentration (MIC) of 31.25 µg/ml. The combination of FLH or PAH with amphotericin B (AmB) was analyzed using the checkerboard assay and the synergistic effect of SSRI in combination with AmB was able to reduce the SSRI or AmB MIC values 4-8-fold. When examining the effect of SSRI on the induced capsules, we observed that FLH and PAH significantly decreased the size of C. gattii capsules. In addition, the effects of FLH and PAH were evaluated in biofilm biomass and viability. The SSRI were able to reduce biofilm biomass and biofilm viability. In conclusion, our results indicate the use of FLH and PAH exhibited in vitro anticryptococcal activity, representing a possible future alternative for the cryptococcosis treatment.
Topics: Humans; Cryptococcus gattii; Selective Serotonin Reuptake Inhibitors; Cryptococcus neoformans; Antifungal Agents; Amphotericin B; Microbial Sensitivity Tests; Fluoxetine; Paroxetine; Biofilms
PubMed: 38204138
DOI: 10.1093/femspd/ftae001 -
Journal of Affective Disorders Jan 2024Depressive disorder in adolescents is a major health problem with inadequate treatment. Omega-3 (ω3) polyunsaturated fatty acids are a promising adjuvant therapy in... (Randomized Controlled Trial)
Randomized Controlled Trial
Omega-3 supplementation improves depressive symptoms, cognitive function and niacin skin flushing response in adolescent depression: A randomized controlled clinical trial.
BACKGROUND
Depressive disorder in adolescents is a major health problem with inadequate treatment. Omega-3 (ω3) polyunsaturated fatty acids are a promising adjuvant therapy in adult depression. The primary objective of this study was to investigate the efficacy of adjuvant ω3 treatment on depressive symptoms in adolescent depression. Secondarily, we explored the effects of ω3 on cognitive function and memory and niacin skin flushing response (NSFR), as their robust associations with adolescent depression.
METHODS
A total of 71 adolescents with depression (aged 13-24; 59.2 % female) were randomly assigned to receive ω3 plus Paxil (n = 34) or Paxil alone (n = 37) for 12 weeks. Primary outcome was depression severity according to scores on Montgomery-Asberg Depression Rating Scale (MADRS). Secondary outcomes were cognitive function and memory, and NSFR.
RESULTS
Significant improvements in depressive symptoms over time (p = 0.00027 at week 12) were observed in the ω3 + Paxil group compared with Paxil group. Additionally, in the ω3 + Paxil group, significant improvements in memory over time, and greater cognitive function and NSFR were also observed compared with the Paxil group; the NSFR was negatively correlated with MADRS scores at baseline.
LIMITATIONS
The trial was open label; thus, the outcome measures should be viewed as preliminary since inherent bias in outcomes due to the potential of a placebo effect.
CONCLUSIONS
Our results demonstrate that adjuvant ω3 treatment is effective for reducing depressive symptoms as well as improving cognitive function, memory and the NSFR; these results suggest ω3 is a promising adjuvant treatment for adolescent depression.
Topics: Adult; Adolescent; Female; Humans; Male; Niacin; Depression; Paroxetine; Cognition; Dietary Supplements
PubMed: 38190276
DOI: 10.1016/j.jad.2023.10.151 -
Psychiatry Research. Neuroimaging Mar 2024Functional neuroimaging studies have demonstrated abnormal activity and functional connectivity (FC) of the amygdala among individuals with major depressive disorder... (Review)
Review
Functional neuroimaging studies have demonstrated abnormal activity and functional connectivity (FC) of the amygdala among individuals with major depressive disorder (MDD), which may be rectified with selective serotonin reuptake inhibitor (SSRI) treatment. This systematic review aimed to identify changes in the amygdala on functional magnetic resonance imaging (fMRI) scans among individuals with MDD who received SSRIs. A search for fMRI studies examining amygdala correlates of SSRI response via fMRI was conducted through OVID (MEDLINE, PsycINFO, and Embase). The end date was April 4th, 2023. In total, 623 records were screened, and 16 studies were included in this review. While the search pertained to SSRIs broadly, the included studies were escitalopram-, citalopram-, fluoxetine-, sertraline-, and paroxetine-specific. Decreases in event-related amygdala activity were found following 6-to-12-week SSRI treatment, particularly in response to negative stimuli. Eight-week courses of SSRI pharmacotherapy were associated with increased event-related amygdala FC (i.e., with the prefrontal [PFC] and anterior cingulate cortices, insula, thalamus, caudate nucleus, and putamen) and decreased resting-state effective connectivity (i.e., amygdala-PFC). Preliminary evidence suggests that SSRIs may alter amygdala activity and FC in MDD. Additional studies are needed to corroborate findings. Future research should employ long-term follow-ups to determine whether effects persist after treatment termination.
Topics: Humans; Selective Serotonin Reuptake Inhibitors; Depressive Disorder, Major; Magnetic Resonance Imaging; Antidepressive Agents; Amygdala
PubMed: 38183847
DOI: 10.1016/j.pscychresns.2023.111777 -
Neuropsychopharmacologia Hungarica : a... Dec 2023Yawning is a normal, stereotyped physiological event in humans and animal kingdom. When excessive (>3 per 15 minutes), it is termed as pathological yawning (PY). PY...
INTRODUCTION
Yawning is a normal, stereotyped physiological event in humans and animal kingdom. When excessive (>3 per 15 minutes), it is termed as pathological yawning (PY). PY could be due to many causes but more commonly associated with side-effect of drugs, notably involving those used in psychopharmacology. Though there are isolated case reports and case-series, there are no large-scale reports of PY. This work attempted to address this lacuna.
MATERIAL AND METHODS
The current work attempted to identify characteristics of PY as collated from adverse drug effect databases of Australia (Database of Adverse Event Notifications), Canada (Canada Vigilance Adverse Reaction Online Database) and the United States of America (FDA Adverse Event Reporting System - FAERS). These databases collect and provide public access to reports of adverse events related to drugs and therapeutic goods. They act as a prime pharmacovigilance tool as well as a first-line resource for healthcare professionals, researchers, and the public to monitor the safety of these products and make informed decisions. In the first week of June 2023, open access, unrestricted adverse effect of drug databases were explored, using the word "YAWNING" as the only search term for the side effect of any drug without any restrictions. The collected details of PY cases with their gender, age, reason for drug use, other concomitant complaints as well as the nature of adverse event(s) and its treatment requirements were assessed. Descriptive statistics were used.
RESULT
Of the 2655 instances in USA database, 398(15%) had more than 1 suspect drug and in total 578 medications involved. The most commonly involved drugs were apomorphine, sertraline, fluoxetine and paroxetine. In all 341(12.8%) cases reported of YAWN alone or with one another sleep disorder, the most common off ending drug were fluoxetine hydrochloride.
DISCUSSION AND CONCLUSION
The neural mechanism and physiology of yawning are explained. This study stresses that a health care professional, particularly mental health professionals and neurologists, should be aware of the importance of PY to deliver the best for the patients under their care. (Neuropsychopharmacol Hung 2023; 25(4): 194-205)
Topics: Humans; United States; Adverse Drug Reaction Reporting Systems; Yawning; Incidence; United States Food and Drug Administration; Psychotropic Drugs
PubMed: 38170730
DOI: No ID Found -
Journal of Affective Disorders Mar 2024The neurophysiological mechanisms underlying generalized anxiety disorder (GAD) with or without depressive symptoms are obscure. This study aimed to uncover them and...
BACKGROUND
The neurophysiological mechanisms underlying generalized anxiety disorder (GAD) with or without depressive symptoms are obscure. This study aimed to uncover them and assess their predictive value for treatment response.
METHODS
We enrolled 98 GAD patients [58 (age: 33.22 ± 10.23 years old, males/females: 25/33) with and 40 (age: 33.65 ± 10.49 years old, males/females: 14/26) without depressive symptoms] and 54 healthy controls (HCs, age: 32.28 ± 10.56 years old, males/females: 21/33). Patients underwent clinical assessments and resting-state functional MRI (rs-fMRI) at baseline and after 4-week treatment with paroxetine, while HCs underwent rs-fMRI at baseline only. Regional homogeneity (ReHo) was employed to measure intrinsic brain activity. We compared ReHo in patients to HCs and examined changes in ReHo within the patient groups after treatment. Support vector regression (SVR) analyses were conducted separately for each patient group to predict the patients' treatment response.
RESULTS
Both patient groups exhibited higher ReHo in the middle/superior frontal gyrus decreased ReHo in different brain regions compared to HCs. Furthermore, differences in ReHo were detected between the two patient groups. After treatment, the patient groups displayed distinct ReHo change patterns. By utilizing SVR based on baseline abnormal ReHo, we effectively predicted treatment response of patients (p-value for correlation < 0.05).
LIMITATIONS
The dropout rate was relatively high.
CONCLUSIONS
This study identified shared and unique neural substrates in GAD patients with or without depressive symptoms, potentially serving as biomarkers for treatment response prediction. Comorbid depressive symptoms were associated with differences in disease manifestation and treatment response compared to pure GAD cases.
Topics: Humans; Male; Female; Young Adult; Adult; Brain Mapping; Depression; Prognosis; Magnetic Resonance Imaging; Brain
PubMed: 38160885
DOI: 10.1016/j.jad.2023.12.067