Presence Of Antidepressants Research Articles

Rapid microwave-assisted extraction method for the analysis of common antidepressants and metabolites in marine organisms

Presence of antidepressants in aquatic environments could cause adverse effects even at low concentrations. Most published works have detected them in wastewater, and only a few have paid attention to the aquatic organisms that receive these polluted waters. This work presents the development, optimisation and application of an analytical method for the extraction and determination of four widely used antidepressants (venlafaxine, citalopram, sertraline, fluoxetine) and two metabolites (o-desmethylvenlafaxine, norsetraline) from fish tissue by microwave-assisted extraction and ultra high-performance liquid chromatography coupled to tandem mass spectrometry. To demonstrate the applicability of the method, it was validated in different marine organism species (fish, echinoderm, mollusc and algae). Under optimal conditions, recovery ranged between 70 and 120 % and deviation was lower than 20 % in most cases, depending on the species and the tested concentration. As no strong matrix effect was found, applying a clean-up step was unnecessary, although quantification was performed in real samples by matrix-matched calibration. Method quantification limits ranged between 2.32 and 196 ng g−1. Overall, this methodology proved to be a versatile method applicable to different species with good results. The developed analytical method was successfully applied to the extraction and determination of the target compounds from fish taken from offshore aquaculture cages in seawater (Canary Islands). Three main antidepressants were detected, but only two could be quantified: citalopram: 5.83 ng g−1 and sertraline: 6.58 ng g−1.

Wastewater surveillance of 105 pharmaceutical drugs and metabolites by means of ultra-high-performance liquid-chromatography-tandem high resolution mass spectrometry

Water pollution from pharmaceutical drugs is becoming an environmental issue of increasing concern, making water quality monitoring a crucial priority to safeguard public health. In particular, the presence of antidepressants, benzodiazepines, antiepileptics, and antipsychotics require specific attention as they are known to be harmful to aquatic biota. In this study, a multi-class comprehensive method for the detection of 105 pharmaceutical residues in small (30 mL) water samples was developed according to fit-for-purpose criteria and then applied to provide wide screening of samples obtained from four Wastewater Treatment Plants (WWTPs) in northern Italy. The filtered samples (0.22 µm filters) were extracted by SPE, and then eluted. 5 µL of the concentrated samples were analyzed by a UHPLC-QTOF-HRMS method validated for screening purposes. Adequate sensitivity was recorded for all target analytes, with limits of detection below 5 ng/L for 76 out of 105 analytes. A total of 23 out of the 105 targeted pharmaceutical drugs was detected in all samples. Several further compounds were detected over wide concentration intervals, ranging from ng/L to µg/L. In addition, the retrospective analysis of full-scan QTOF-HRMS data was exploited to carry out an untargeted screening of some drugs’ metabolites. As a proof of concept, it was investigated the presence of the carbamazepine metabolites, which is among the most frequently detected contaminants of emerging concern in wastewater. Thanks to this approach, 10,11-dihydro-10-hydroxycarbamazepine, 10,11-dihydro-10,11-dihydroxycarbamazepine and carbamazepine-10,11-epoxide were identified, the latter requiring particular attention, since it exhibits antiepileptic properties similar to carbamazepine and potential neurotoxic effects in living organism.

Transcriptional Modulation of the Hippo Signaling Pathway by Drugs Used to Treat Bipolar Disorder and Schizophrenia.

Recent reports suggest a link between positive regulation of the Hippo pathway with bipolar disorder (BD), and the Hippo pathway is known to interact with multiple other signaling pathways previously associated with BD and other psychiatric disorders. In this study, neuronal-like NT2 cells were treated with amisulpride (10 µM), aripiprazole (0.1 µM), clozapine (10 µM), lamotrigine (50 µM), lithium (2.5 mM), quetiapine (50 µM), risperidone (0.1 µM), valproate (0.5 mM), or vehicle control for 24 h. Genome-wide mRNA expression was quantified and analyzed using gene set enrichment analysis (GSEA), with genes belonging to Hippo, Wnt, Notch, TGF- β, and Hedgehog retrieved from the KEGG database. Five of the eight drugs downregulated the genes of the Hippo pathway and modulated several genes involved in the interacting pathways. We speculate that the regulation of these genes, especially by aripiprazole, clozapine, and quetiapine, results in a reduction of MAPK and NFκB pro-inflammatory signaling through modulation of Hippo, Wnt, and TGF-β pathways. We also employed connectivity map analysis to identify compounds that act on these pathways in a similar manner to the known psychiatric drugs. Thirty-six compounds were identified. The presence of antidepressants and antipsychotics validates our approach and reveals possible new targets for drug repurposing.

Association of US Nurse and Physician Occupation With Risk of Suicide

Nurses are the largest component of the US health care workforce. Recent research suggests that nurses may be at high risk for suicide; however, few studies on this topic exist. To estimate the national incidence of suicide among nurses and examine characteristics of nurse suicides compared with physicians and the general population. This retrospective cohort study used US data from 159 372 suicides reported in the National Violent Death Reporting System from 2007 to 2018. With the use of workforce denominators, sex-specific suicide incidence estimates were generated among nurses, physicians, and the general population (age, ≥30 years). Associations between clinician type and method of suicide and results of toxicology examination at death were calculated, adjusted for sociodemographic characteristics. Statistical analysis was performed from October 16, 2020, to January 10, 2021. Occupation as a nurse or physician. Suicide incidence and characteristics associated with suicides. A total of 2374 suicides among nurses (1912 women [80.5%]; mean [SD] age, 52.8 [11.8] years), 857 suicides among physicians (723 men [84.4%]; mean [SD] age, 59.8 [15.3] years), and 156 141 suicides in the general population (121 483 men [77.8%]; mean [SD] age, 53.1 [14.7] years) were identified. Overall, suicide was more common among nurses compared with the general population (sex-adjusted incidence in 2017-2018, 23.8 per 100 000 vs 20.1 per 100 000; relative risk, 1.18 [95% CI, 1.03-1.36]). Among women in 2017-2018, the suicide incidence among nurses was 17.1 per 100 000 (506 among 2 966 048) vs 8.6 per 100 000 (8879 among 103 731 387) in the general female population (relative risk, 1.99 [95% CI, 1.82-2.18]). In absolute terms, being a female nurse was associated with an additional 8.5 suicides per 100 000 (95% CI, 7.0-10.0 per 100 000) compared with the general population of women. By sex, physician suicide rates were not statistically different from the general population other than among female physicians in 2011-2012 (11.7 per 100 000 [95% CI, 6.6-16.8 per 100 000] female physicians vs 7.5 per 100 000 [95% CI, 7.2-7.7 per 100 000] general population; P = .04). In terms of the characteristics of suicides, clinicians were more likely to use poisoning than the general population; for example, 24.9% (95% CI, 23.5%-26.4%) of nurses used poisoning compared with 16.8% (95% CI, 16.6%-17.0%) of the general suicide population. The presence of antidepressants, benzodiazepines, barbiturates, and opiates was more common among clinician suicides than suicides in the general population. This study suggests that, in the US, the risk of suicide compared with the general population was significantly greater for nurses but not for physicians. Further research is needed to assess whether interventions would be associated with benefit in reducing suicide risk among nurses.

Effects of environmental antidepressants on colour change and locomotor behaviour in juvenile shore crabs, Carcinus maenas.

Juvenile crabs of Carcinus maenas thrive in coastal waters reputed to be the receptacle of continental pollution. Amongst the many pollutants encountered, antidepressants, such as fluoxetine (FLX) and venlafaxine (VEN), often detected at the ng•L-1 range, are particularly worrying because of their action on the levels of monoamines, such as serotonin, noradrenaline and dopamine. In crustaceans, those monoamines are involved in colour change through their action on neuropeptide hormones. In addition, they are known to have a role in different behaviours, such as locomotion. Both colour change and locomotion are strategies used by juvenile crabs to hide and escape from predators. To investigate if the presence of antidepressants may alter behaviours of ecological importance, juvenile crabs were exposed to environmentally realistic concentrations of either 5 ng•L-1 of FLX alone or in combination with VEN at 5 ng•L-1. The ability to change colour depending on the environment and the locomotor activity of juvenile crabs were monitored weekly over 25 days. Animals exposed to antidepressants displayed a different pattern of colour change than the controls, especially those exposed to the combination of FLX and VEN at 5 ng•L-1 each, and were less efficient to adapt to their environment, i.e., they were not as pale and not as dark as controls or crabs exposed to FLX at 5 ng•L-1. Moreover, juvenile crabs exposed to the combination of antidepressants exhibited an enhanced locomotor activity throughout the exposure period with a higher velocity and distance moved as well as more time spend moving. The alteration of cryptic behaviours, such as colour change and locomotion by antidepressants persistently present in marine environment at low concentrations may have an impact on the survival of juvenile of C. maenas on the long term.

PMH30 PREVALENCE AND FACTORS ASSOCIATED WITH NARCOTIC CONTROLLED SUBSTANCE USE AMONG PEOPLE WITH DEPRESSION AND ANXIETY: NHANES 2015-2016

Given the prevalence of anxiety (18.1%) and depression (6.7%) in US adults, and continual fight against opioid addiction, the purpose of the study was to examine the prevalence and other factors associated with narcotic controlled substance use among people with these disorders. The most recent 2015-2016 cycle of the National Health and Nutrition Examination Survey (NHANES) was used as the data source. NHANES captures cross-sectional survey data that is representative of the US civilian population. This study included adults at least 18 years of age, categorized for depression symptom severity using the Patient Health Questionnaire (PHQ-9). The use of prescribed opioids was assessed for each individual. Anxiety information was also identified via new survey questions implemented in this most recent cycle. Descriptive analysis and logistic regression of demographic, medical, and social characteristics were conducted using SAS 9.4. An odds ratio (OR) with 95% confidence interval was used a measure of association. A total of n=991 NHANES participants were included in this analysis. The prevalence of narcotic opioid for the NHANES population with depression was 10.49%. The odds of prescription narcotic opioid use were markedly higher among white participants and for older adults 40-59 (OR= 4.3 CI, 2.46 - 7.56) and ≥60 years (OR= 4.26 CI, 2.28 - 7.97). The odds higher in lower-income families (OR= 4.13 CI, 1.235 - 13.813), and in Medicare beneficiaries (OR= 5.414 CI, 2.867 - 10.224). The use of opioid prescriptions increased with increasing severity of depression symptoms; with moderately severe (OR= 4.074 CI, 2.273 - 7.301) and severe (OR= 3.754 CI, 1.801 - 7.825). The presence of anti-depressants was also associated with higher opioid use. As the healthcare field and patients adapt to the emerging opioid prescribing practices designed to curb the spread of opioid misuse, depression patients should not go unnoticed. Careful management of their needs is necessary.

Antidepressants in a changing ocean: Venlafaxine uptake and elimination in juvenile fish (Argyrosomus regius) exposed to warming and acidification conditions

The presence of antidepressants, such as venlafaxine (VFX), in marine ecosystems is increasing, thus, potentially posing ecological and human health risks. The inherent mechanisms of VFX uptake and elimination still require further understanding, particularly accounting for the impact of climate change-related stressors, such as warming and acidification. Hence, the present work aimed to investigate, for the first time, the effects of increased seawater temperature (ΔT°C = +5 °C) and pCO2 levels (ΔpCO2 ∼1000 μatm, equivalent to ΔpH = −0.4 units) on the uptake and elimination of VFX in biological tissues (muscle, liver, brain) and plasma of juvenile meagre (Argyrosomus regius) exposed to VFX through two different exposure pathways (via water, i.e. [VFX ] ∼20 μg L−1, and via feed, i.e. [VFX] ∼160 μg kg−1 dry weight, dw). Overall, results showed that VFX can be uptaken by fish through both water and diet. Fish liver exhibited the highest VFX concentration (126.7 ± 86.5 μg kg−1 and 6786.4 ± 1176.7 μg kg−1 via feed and water exposures, respectively), as well as the highest tissue:plasma concentration ratio, followed in this order by brain and muscle, regardless of exposure route. Both warming and acidification decreased VFX uptake in liver, although VFX uptake in brain was favoured under warming conditions. Conversely, VFX elimination in liver was impaired by both stressors, particularly when acting simultaneously. The distinct patterns of VFX uptake and elimination observed in the different scenarios calls for a better understanding of the effects of exposure route and abiotic conditions on emerging contaminants’ toxicokinetics.

Impulse control disorders in Parkinson's: Sleep disorders and nondopaminergic associations.

ObjectivesImpulse control disorders (ICDs) are common among patients with Parkinson's disease (PD). Risk factors identified for developing ICDs include young age, family history, and impulsive personality traits. However, the association of these potentially disabling disorders with nondopaminergic drugs and sleep disorders has been understudied. Our objective was to examine the association between ICDs and nondopaminergic medications and sleep disorders.MethodsWe conducted an observational study of 53 patients with PD from the National Institute of Neurology and Neurosurgery. ICDs were diagnosed using the Questionnaire for Impulsive–Compulsive Disorders in Parkinson's Disease Rating Scale (QUIP‐RS). Patients underwent polysomnography screening to diagnose the presence of sleep disorders. We documented the presence of dopaminergic and nondopaminergic medications, including monoamine oxidase type B inhibitors (MAOBIs), antidepressants, sleep inductors, and antipsychotics.Results ICDs were reported in 18.9% of the patients (n = 10), and sleep disorders were diagnosed in 81.1% of patients (n = 43). 32.1% of the patients were on antidepressants, 17% on MAOBIs, 15.1% on sleep inductors, and 1.9% on antipsychotics. We observed that QUIP‐RS A–D subscore depended on the presence of antidepressants (p = .03) and sleep inductors (p = .02). Sleep disorders were not associated with the total QUIP‐RS score (p = .93) or QUIP‐RS A–D subscore (p = .81).ConclusionAntidepressants and sleep inductors were significant predictors for individual QUIP‐RS items and subscores. Our results suggest that nondopaminergic drugs commonly used for PD may be associated with impulse control disorders. We did not identify a relationship between ICDs and polysomnography‐confirmed sleep disorders in patients with PD. Larger and longitudinal studies are needed to confirm our results.

Occurrence of antidepressant residues in the sewage-impacted Vistula and Utrata rivers and in tap water in Warsaw (Poland)

Antidepressants, even at low concentrations, can reveal some adverse effects on aquatic life due to disturbing homeostasis throughout the central and peripheral nervous system both in vertebrates and invertebrates. To date there have not been any reports regarding the presence of these pharmaceuticals in surface and tap waters in Eastern Europe. Therefore the aim of this study was to determine the presence of 21 antidepressant pharmaceuticals at specific points of the main Polish river – the Vistula, a smaller river of the Warsaw region – the Utrata, as well as in tap water samples of Warsaw. Samples were collected twice at one month intervals and analysed using solid-phase extraction (SPE) technique coupled with the liquid chromatography–electrospray ionisation–tandem mass spectrometer (LC–MS/MS) method operated under the multiple reaction monitoring mode (MRM).This is the first study where active compounds such as moclobemid or trazodone in the environment have been investigated.Environmental risk assessment of antidepressants in Poland was estimated on the basis of annuals sale data extracted from the NFZ (Narodowy Fundusz Zdrowia—National Health Service) base of reimbursed pharmaceuticals1. Predicted environmental concentration (PEC) of target pharmaceuticals were compared with their measured concentration (MEC).Moreover, the application of the EMEA/CHMP guideline for environmental risk assessment of the antidepressants was discussed. The highest concentration of antidepressants was observed in the small river Utrata. In tap water only trace amounts of antidepressants including citalopram (up to 1.5ng/l), mianserin (up to 0.9ng/l), sertraline (<3.1ng/l), moclobemid (up to 0.3ng/l) and venlafaxine (up to 1.9ng/l) were detected. However this highlights their inadequate elimination in the drinking waste treatment facility. The presence of antidepressants in drinking water and the aquatic environment could have long-term effects even at low exposure level, especially since synergy amongst pharmaceutical pollutants may occur.

Effect of antidepressant drugs on cytochrome P450 2C11 (CYP2C11) in rat liver

BackgroundRat CYP2C11 (besides CYP2C6) can be regarded as a functional counterpart of human CYP2C9. The aim of the present study was to investigate the influence of classic and novel antidepressant drugs on the activity of CYP2C11, measured as a rate of testosterone 2α- and 16α-hydroxylation. MethodsThe reaction was studied in control liver microsomes in the presence of antidepressants, as well as in microsomes from rats treated intraperitoneally (ip) with pharmacological doses of the tested drugs (imipramine, amitriptyline, clomipramine, nefazodone – 10mg/kg ip; desipramine, fluoxetine, sertraline - 5mg/kg ip; mirtazapine - 3mg/kg ip) for one day or two weeks (twice a day), in the absence of antidepressants in vitro. ResultsThe investigated antidepressant drugs added to control liver microsomes produced certain inhibitory effects on CYP2C11 activity, which were moderate (sertraline, nefazodone and clomipramine: Ki=39, 56 and 66μM, respectively), modest (fluoxetine and amitriptyline: Ki=98 and 108μM, respectively) or weak (imipramine and desipramine: Ki=191 and 212μM, respectively). Mirtazapine had no inhibitory effect on CYP2C11 activity. One-day exposure of rats to the antidepressant drugs did not significantly change the activity of CYP2C11 in liver microsomes; however, imipramine, desipramine and fluoxetine showed a tendency to diminish the activity of CYP2C11. Of the antidepressants studied, only desipramine and fluoxetine administered chronically elevated CYP2C11 activity; those effects were positively correlated with the observed increases in the enzyme protein level. ConclusionThree different mechanisms of the antidepressants-CYP2C11 interaction are postulated: 1) a direct inhibition of CYP2C11 shown in vitro by nefazodone, SSRIs and TADs; 2) in vivo inhibition of CYP2C11 produced by one-day treatment with imipramine, desipramine and fluoxetine, which suggests inactivation of the enzyme by reactive metabolites; 3) in vivo induction of CYP2C11 produced by chronic treatment with desipramine and fluoxetine, which suggests their influence on enzyme regulation.

Aripiprazole Partial Agonism at 5-HT2C

5-HT2C receptor antagonists are thought to contribute toward increased appetite and obesity. Aripiprazole acts as a partial agonist at the 5-HT2C receptor; hence, it is thought to cause little or no significant weight gain when used alone. We theorize that, in the presence of antidepressants with high serotonergic activity, aripiprazole acts as an antagonist at the 5-HT2C receptor, thus increasing the potential for weight gain. Conversely, in environments with low serotonergic activity, aripiprazole acts as an agonist at the 5-HT2C receptor, therefore having less potential for weight gain. A retrospective electronic medical record chart review of the Veterans Integrated Service Network 22 Veterans Affairs database was performed comparing patients' weight and body mass index (BMI) while taking aripiprazole alone (n = 1,177), versus aripiprazole plus a high-serotonergic antidepressant (citalopram, fluoxetine, paroxetine, sertraline, or venlafaxine) (n = 145), versus aripiprazole plus a low-serotonergic antidepressant (bupropion) (n = 77) for a minimum continuous duration of 6 months of aripiprazole monotherapy or combination treatment. The study was conducted from January 2010 through June 2011. In our patient population, only the aripiprazole plus high-serotonergic antidepressants group had a statistically significant increase in weight (P = .0027) and BMI (P = .0016). Our data suggest that, in the presence of antidepressants with high serotonergic activity, aripiprazole may act as an antagonist at the 5-HT2C receptor, resulting in weight gain. Conversely, when aripiprazole is used in the presence of antidepressants with low serotonergic activity, it may act as an agonist and result in little or no weight gain. This varying effect at the 5-HT2C receptor may explain why aripiprazole has not been associated with significant weight gain in previous studies focusing on schizophrenia and bipolar disorder.

S.04.05 Finding gene expression regulators implicated in major depression using formaldehyde assisted isolation of regulatory elements (FAIRE)

The exact cellular mechanisms that underline major depressive disorder (MDD) remain unclear, although evidence suggests that dysregulation of neuronal gene expression plays an important role. In this study we aimed to identify novel transcriptional regulators which become active under the presence of antidepressants and hormones linked to MDD using the FAIRE technique (Formaldehyde assisted isolation of regulatory regions) [2]. The presence of Evolutionary conservation regions (ECRs) across vertebrate genomes has been suggested as indicator of transcriptional regulators [1]. We selected 42K ECRs (based on UCSC genome browser Hg18) to design a custom made Nimblegen CGH microarray (135K per sub-array, n = 3 probes per ECR). DNA isolated with FAIRE was hybridised against ECR microarray. We observed 36 ECRs that became transcriptionally active in cells treated estradiol, lithium and valproate (95% confidence, set at p< 1.1×10−6, based on Bonferroni correction and FDR test) [3]. Our preliminary results indicate that some ECRs can act as regulatory domains after stimuli with 3 of 8 antidepressants and hormones related to MDD in SHSY5Y cells. Although in these cells only a 36 ECRs appear transcriptionally active, the corrected p-values threshold is very conservative. Moreover, this approach might be useful for revealing common genomic elements acting as transcriptional regulators responsive to several stimuli known to be associated to onset of MDD.

Antidepressants at Autopsy in Hispanic Suicidal Youth in Miami-Dade County, Florida*

Controversy has surrounded the use of antidepressants and suicidal behaviors in youth. This study reviewed the Medical Examiner's Office records of 253 persons aged 24 years or younger classified as suicides in Miami-Dade County, Florida, from 1990 to 2007. Information was collected regarding demographic information, suicidal characteristics, psychiatric and psychosocial factors, and toxicology results. Eighty-five percent of the sample was men, and 53.4% of the subjects were Hispanic. Consistent with previous literature, the existence of antidepressants at autopsy was rare; present in only 6% (n=15) of the victims. The occurrence of antidepressants was not significantly different between Hispanics (n=7) and non-Hispanics (n=8). The incidence of antidepressants was weakly correlated with a tendency to be men and no history of psychiatric illness. The presence of antidepressants in Hispanic youth suicide victims was similar to non-Hispanics.

Prevalence of antidepressants and biosimilars in elite sport

The use of prescribed antidepressants by athletes has not been restricted in human sports since 2003, after the antidepressants bupropion and amineptine were removed from the list of prohibited substances. Recent awareness of antidepressants has been stimulated by reports from the media concerning possible misuse of antidepressants among healthy athletes. The prevalence of antidepressants has been monitored over the past ten years with screening procedures routinely used by WADA-accredited laboratories. The growth in antidepressant use among athletes peaked in 2007 and 2008 after a modest increase over the first eight years of this survey. Pharmacy prescriptions for antidepressants in Germany did not show a correlated growth during this period. The increasing variety of antidepressant medications has led to a continued increase in the diversity of antidepressant substances used by athletes and the 'normal' population. The number of different sports affected by the presence of antidepressants has increased in the past decade, especially in endurance sports. The predominance of female antidepressant users in the normal population was reflected in the athletes' group. We concluded from our results that the development of antidepressant prevalence in elite sports did not correlate with that among the general public in Germany.

Depression: more than just serotonin

Serotonin and dopamine neurotransmitter systems in the brain are generally thought to function separately. In the presence of antidepressants that inhibit the reuptake of serotonin, however, their signals may become crossed. New research reveals that, in the presence of selective serotonin reuptake

Antidepressants, depression and suicide: an analysis of the San Diego study

Depression has been consistently reported in 40–50% of suicides. Previous toxicologic studies of suicides have not included diagnostic information, however. This report includes 247 (87%) of 283 suicides in whom it was possible to perform toxicological analyses for tricyclic antidepressants. We wanted to see if any relationships existed among the presence of antidepressants at autopsy, diagnosis of Depression, recent contact with physicians and prescription of antidepressant medication. Toxicology was positive in 19 (8%) subjects. Only 12% of the subjects with a DSM-III diagnosis of Major of Atypical Depression were positive. Lethal blood levels of antidepressants were found in only 4% of all subjects and most of those involved multiple drugs. Also, most of those subjects had co-morbid Depression and Substance Abuse. More than half of the Depressed subjects had been a physician within 90 days from suicide but less than half of these were prescribed antidepressants and only one-third of the latter were positive for antidepressants in toxicology. These data suggest that more suicides might be averted by decisively treating Depressed patients with ADs, including strict monitoring of dosage and compliance, than by not treating them to avoid AD overdoses. Diagnostic caution should be observed to identify co-morbid Substance Abuse when treating patients with Depression and suicidal ideation.