Antidepressant Concentrations Research Articles

Serum concentrations of antidepressants, antipsychotics, and antiepileptics over the bariatric surgery procedure

PurposeAs a substantial proportion of bariatric surgery patients use psychotropic/antiepileptic drugs, we investigated the impact of this procedure on serum concentrations.MethodsIn a naturalistic, longitudinal, prospective case series, we compared dose-adjusted trough concentrations of antidepressants, antipsychotics, or antiepileptics in consecutive patients before and after bariatric surgery. Adherence to treatment over 2 weeks preceding each sampling was considered.ResultsIn all, 85 participants were included (86% female, median age 45 years, median body mass index 42 kg/m2). They were being treated with 18 different psychotropic/antiepileptic drugs (7 substances: 6–17 individuals, 11 substances: 1–4 individuals) and contributed 237 samples over a median of 379 days after surgery. For four out of seven substances with pre-/post-surgery samples available from six or more individuals, the dose-adjusted concentration was reduced (sertraline: 51%, mirtazapine: 41%, duloxetine: 35%, citalopram: 19%). For sertraline and mirtazapine, the low-calorie-diet before surgery entirely explained this reduction. A consistent finding, irrespective of drug, was the association between the mean ratio of the post-/pre-diet dose-adjusted concentration and the lipophilicity of the drug (logD; correlation coefficient: −0.69, P = 0.0005), the low-calorie diet often affecting serum concentration more than the surgery itself.ConclusionsSerum concentrations of psychotropic/antiepileptic drugs vary after bariatric surgery and can be hard to predict in individual patients, suggesting that therapeutic drug monitoring is of value. Conversely, effects of the pre-surgery, low-calorie diet appear generalizable, with decreased concentrations of highly lipophilic drugs and increased concentrations of highly hydrophilic drugs. Interaction effects (surgery/dose/concentration) were not evident but cannot be excluded.

Fast-Trk(B)ing the mechanism of antidepressants

The mechanism by which antidepressants elicit clinical improvements has proven elusive. In a recent publication in Cell, Casarotto etal. (2021) reveal a surprising direct interaction between antidepressants and TrkB. This link provides an important mechanistic insight into synaptic remodeling that may assist in the design of improved antidepressant therapeutics.

Therapeutic Drug Monitoring of Antidepressants for the Treatment of Chronic Musculoskeletal Pain With and Without Depression.

Antidepressants are recommended for the treatment of chronic musculoskeletal pain; however, target serum concentrations based on therapeutic drug monitoring (TDM) have not been established. Therefore, the authors analyzed routine care TDM data of antidepressants in patients with chronic pain with and without depression in terms of treatment outcomes in an interdisciplinary multimodal pain treatment (IMPT) program. Patients with chronic musculoskeletal pain and TDM for amitriptyline (n = 45) or duloxetine (n = 30) were retrospectively included. The German pain questionnaire for pain intensity and the Depression Anxiety Stress scale were applied at T0 and at the end of the IMPT program (T1). A relief of pain intensity score ≥2 was considered as a positive outcome. Comorbid depression was diagnosed based on ICD-10 criteria. Serum concentrations of antidepressants were measured for routine clinical care TDM. After IMPT, stress improved in all subgroups, and depressive symptoms improved only in the duloxetine group. Overall, 40% and 27% of patients in the amitriptyline and duloxetine subgroup, respectively, were responders in terms of maximum pain score relief. Responders with comorbid depression were treated with a dose that led to a 1.7-fold higher serum concentration of the active moiety of amitriptyline (amitriptyline + nortriptyline) compared with nonresponders. Similarly, a 2.3-fold higher serum concentration was observed in depressed responders than in nondepressed responders (at minimum 131.5 ng/mL). Dosing of antidepressants for chronic pain relief should specifically take comorbid depression into account. TDM may provide better outcomes of pain relief in an IMPT setting in patients with comorbid depression.

The adsorption of amitriptyline and nortriptyline on activated carbon, diosmectite and titanium dioxide

The adsorption of the tricyclic antidepressants amitriptyline and nortryptyline was studied. Activated carbon, diosmectite and nano-sized titanium dioxide were selected as adsorbent materials. After monitoring the effect of contact time on the amount adsorbed, it was determined that the adsorption kinetics follow a pseudo-second kinetic equation. The system reached equilibrium more rapidly in the case of nortryptyline adsorption compared to amitryptyline. After evaluation of the adsorption isotherms, it was stated that the adsorption in the case of amitriptyline better corresponds to the Freundlich model, on the contrary, the adsorption of nortryptyline can be described by the Langmuir model. The adsorption of amitriptyline on all three adsorbents was approximately twice as high as that of nortryptyline. Activated carbon has the highest adsorption capacity for both drugs. The specific adsorption capacities are as follows. For amitriptyline: activated carbon 3.75 mmol g−1, diosmectite 3.30 mmol g−1, titanium dioxide 2.97 mmol g−1; for nortriptyline: activated carbon 1.87 mmol g−1, diosmectite 1.82 mmol g−1, titanium dioxide 0.79 mmol g−1. In addition, the zeta potential of the individual adsorbent materials was also monitored depending on the pH and the amount of antidepressants absorbed. pH and ionic strength significantly affect the critical micellar concentration of antidepressants. This is subsequently reflected in the different adsorption behavior of amitriptyline and nortryptyline.

Impact of Body Mass Index on Serum Concentrations of Antidepressants and Antipsychotics.

Rates of overweight and obesity are higher in patients suffering from psychiatric disorders than in the general population. Body composition and enzyme functions are affected by overweight, and consequently, the pharmacokinetics of drugs may vary in overweight patients. Thus, overweight and obesity are important factors in psychiatric disorders and their treatment. This analysis aimed to investigate the impact of body mass index (BMI) on serum concentrations of the antidepressant drugs amitriptyline, doxepin, escitalopram, mirtazapine, and venlafaxine, and the antipsychotic drugs clozapine, quetiapine, and risperidone, taking into account the following confounding parameters: age, sex, and smoking habit. Inpatients and outpatients (N = 1657) who took at least one of the target drugs were included in this retrospective analysis. Serum concentrations of the target drugs and their metabolites were determined at the Department of Psychiatry, Psychosomatics, and Psychotherapy of the University Hospital of Würzburg during routine therapeutic drug monitoring (January 2009-December 2010), which was performed in the morning (trough level) at steady state. Dose-corrected serum concentrations (CD) of the active moiety of doxepin and venlafaxine and of O-desmethylvenlafaxine were negatively associated with BMI (partial Pearson correlation, R = -0.267, P = 0.002; R = -0.206, P ≤ 0.001; R = -0.258, P ≤ 0.001), and the CDs were different in normal weight, overweight, and obese patients (analysis of covariance, P = 0.004, P < 0.001, P ≤ 0.001). No association was found between BMI and serum concentrations of amitriptyline, escitalopram, mirtazapine, clozapine, quetiapine, and risperidone. In obese patients, higher doses of doxepin and venlafaxine are necessary to achieve similar serum concentrations as in normal weight patients and to avoid treatment-resistant depression.

Effects of antidepressants in the reproduction of aquatic organisms: a meta-analysis

Pharmaceuticals are widespread contaminants across the aquatic systems and despite the role that these compounds play in society today, little is known about their effects in aquatic organisms once they are released into the environment. This study aims to provide quantitative insight on the effects of antidepressants on the reproduction of fish and crustaceans with a multilevel meta-analysis. A systematic literature search identified 19 studies investigating effects of antidepressant exposure in fish or crustaceans’ reproduction, according to specific selection criteria. Heterogeneity analysis was performed and the moderating effect of the range of exposure concentrations, exposure time, organism group and toxicant was tested. Additionally, publication bias was also addressed. The results showed that, overall, there is no significant association between antidepressant exposure and the reproduction of fish and crustaceans, however, moderator analysis revealed that the range of concentrations is a significant moderator for fish and crustacean fecundity, showing contrary results between the two groups. Antidepressant concentration had a small, yet positive effect on fish fecundity, meaning that increased concentrations resulted in increased fish fecundity, whilst a negative effect on crustaceans’ fecundity was apparent with increasing concentrations. This difference could be related to data artifacts, or, more likely, evidencing a hormetic dose-response curve, with different ranges of exposure concentrations considered in studies on fish and crustaceans. Antidepressants have shown effects on reproductive outcomes in aquatic organisms, based on individual studies and narrative reviews. However, our results show that other factors can have an important role. Additionally, data available for a quantitative assessment is scarce, focusing mainly on a few freshwater species, low concentration ranges and one SSRI compound, fluoxetine. Thus, more research on the subject is needed since meta-analysis are only as statistically powerful as the number of, good quality, studies they include.

Use of Antidepressants in Older People during a 10-Year Period: An Observational Study on Prescribed Doses and Serum Levels.

BackgroundAccording to previous studies, older patients frequently have serum concentrations of antidepressant medication above the recommended reference range.ObjectiveThe aim of this study was to investigate whether prescribed doses of antidepressants and the proportion of individuals with serum concentrations above the recommended reference range in older individuals (≥ 65 years) have changed over a 10-year period in Norway.MethodsSerum concentration measurements and prescribed daily doses of antidepressants in 2007 and 2017 were extracted from a therapeutic drug monitoring (TDM) database at the Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway. The database contains routine follow-up serum concentration measurements of psychotropic drugs for patients from all parts of the country. For citalopram, escitalopram, sertraline, mirtazapine and venlafaxine, the differences between 2007 and 2017 in mean prescribed doses and the proportion of patients with at least one serum concentration above the reference range, according to the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) guidelines, were compared. For the proportion of patients with serum concentrations above the recommended reference range, differences between individuals aged 65–79 and ≥ 80 years were also examined.ResultsThe analyses of prescribed doses included 806 patients from 2007 and 1932 patients from 2017, with 972 and 2441 TDM samples, respectively. Between 2007 and 2017, modest reductions in prescribed daily doses were observed for citalopram (20 vs. 17 mg/day) and escitalopram (11 vs. 10 mg/day), but the proportion of patients with serum concentrations above the recommended reference range was unchanged for both drugs, i.e. 11.5% vs. 12.4% for citalopram and 3.6% vs. 2.9% for escitalopram. For mirtazapine and venlafaxine, prescribed doses were reduced from 28 to 25 mg/day and 150 to 125 mg/day, respectively. A significant reduction in the proportion of individuals with serum concentrations above the recommended reference range was observed for mirtazapine (27.1% vs. 11.5%) and for individuals aged ≥ 80 years using venlafaxine (60.0% vs. 30.0%). For sertraline, no differences in prescribed doses or serum concentrations above the recommended reference range were observed.ConclusionsOver a 10-year period, prescribed doses of antidepressants have been slightly reduced in older Norwegian patients, but a considerable proportion is still exposed to high serum concentrations of antidepressants.Electronic supplementary materialThe online version of this article (10.1007/s40266-020-00784-9) contains supplementary material, which is available to authorized users.

Concentrations of Antidepressants, Antipsychotics, and Benzodiazepines in Hair Samples from Postmortem Cases

Certain postmortem case constellations require intensive investigation of the pattern of drug use over a long period before death. Hair analysis of illicit drugs has been investigated intensively over past decades, but there is a lack of comprehensive data on hair concentrations for antidepressants, antipsychotics, and benzodiazepines. This study aimed to obtain data for these substances. A LC-MS/MS method was developed and validated for detection of 52 antidepressants, antipsychotics, benzodiazepines, and metabolites in hair. Hair samples from 442 postmortem cases at the Institute of Legal Medicine of the Charité-University Medicine Berlin were analyzed. Postmortem hair concentrations of 49 analytes were obtained in 420 of the cases. Hair sample segmentation was possible in 258 cases, and the segments were compared to see if the concentrations decreased or increased. Descriptive statistical data are presented for the segmented and non-segmented cases combined (n = 420) and only the segmented cases (n = 258). An overview of published data for the target substances in hair is given. Metabolite/parent drug ratios were investigated for 10 metabolite/parent drug pairs. Cases were identified that had positive findings in hair, blood, urine, and organ tissue. The comprehensive data on postmortem hair concentrations for antidepressants, antipsychotics, and benzodiazepines may help other investigators in their casework. Postmortem hair analysis results provide valuable information on the drug intake history before death. Pattern changes can indicate if drug intake stopped or increased before death. Results should be interpreted carefully and preferably include segmental analysis and metabolite/parent drug ratios to exclude possible contamination.

Characterization of neurotransmitter profiles in Daphnia magna juveniles exposed to environmental concentrations of antidepressants and anxiolytic and antihypertensive drugs using liquid chromatography-tandem mass spectrometry.

It has been reported that antidepressant, anxiolytic and antihypertensive drugs alter the behavior and reproduction of the microcrustacean Daphnia magna at very low concentrations. However, there is little evidence for how these drugs act on their neurotransmitter targets. A method based on hydrophilic interaction liquid chromatography coupled with tandem mass spectrometry has been developed and applied for the first time using D. magna extracts and validated by studying the changes in the levels of a suite of neurotransmitters caused by five different neuroactive pharmaceuticals (fluoxetine, venlafaxine, carbamazepine, propranolol, and diazepam) dosed at 100 ng/L. Sample extraction and chromatographic and detection conditions were optimized for accurate detection of the selected neurotransmitters in whole D. magna organisms. The method allowed the simultaneous quantification of eight neurotransmitters belonging to six neuroendocrine systems: the dopaminergic, adrenergic, GABAergic, serotoninergic, histaminergic, and cholinergic systems. Neurotransmitters were eluted with a ZIC-HILIC column and quantified by tandem mass spectrometry in positive electrospray ionization mode performed in multiple reaction monitoring mode. All method validation assays (i.e., quality controls for linearity, sensitivity, accuracy, precision, stability, recovery, matrix effect, and carryover) were compliant with the standard requirements for similar analysis. Exposure to fluoxetine enhanced serotonin concentrations, whereas exposure to diazepam decreased the levels of dopamine, and exposure to propranolol increased the levels of norepinephrine. Exposure to both propranolol and diazepam decreased the levels of histamine. The results show the usefulness of this approach for environmental neurotoxicity studies. Graphical abstract.

Analysis of four antidepressants in plasma and urine by gas chromatography-mass spectrometry combined with sensitive and selective derivatization

A sensitive and selective method was developed for simultaneous determination of four antidepressants (ATDs) in plasma and urine samples by gas chromatography- mass spectrometry (GC–MS) based on an N-nitrosation reaction. In this study, fluoxetine (Flu), nortriptyline (Nor), maprotiline (Map), and paroxetine (Paro) were first derivatized with sodium nitrite to appropriate N-nitrosamines under acidic condition, then the derivatives were easier to detect by GC–MS. The derivatization conditions including the amount of hydrochloric acid, the amount of sodium nitrite, reaction temperature, reaction time and the extraction reagents were optimized. Under the optimal conditions, the limit of detections (LODs) and limit of quantitations (LOQs) were in the range of 0.04–1.38 μg L−1 and 0.14–4.62 μg L−1, respectively. Low, medium, and high concentrations of antidepressants were added in plasma and urine samples, spiked recovery ranged from 85.88%–110.34% for plasma and 80.64%–113.07% for urine, respectively. The derivatization reaction was very quickly, only 5 min was needed for the reaction process, in addition, the proposed method exhibited superior sensitivity and selectivity, it showed sufficient advantages for determination of Flu, Nor, Map, and Paro in plasma and urine of patients.

Abcb1ab p-glycoprotein is involved in the uptake of the novel antidepressant vortioxetine into the brain of mice

A clinically important and well-studied transporter of the blood-brain barrier (BBB) is P-glycoprotein (P-gp), the gene product of ABCB1. Animal studies have shown that brain concentrations of many antidepressants depend on P-gp. However, biochemical properties, which might allow the prediction of pharmacodynamical involvement of P-gp have not yet been identified, hence thorough experimental testing of each novel drug is needed to determine its P-gp substrate status. In the current study, we tested the P-gp substrate status for the antidepressant vortioxetine using double abcb1ab knock-out (KO) mice. Cerebral concentrations of vortioxetine were 2.3 times higher in P-gp deficient mice compared to wildtype (WT) controls. No significant difference was found regarding the concentration of the drug in the plasma and other organs (liver, kidney, spleen) between KO and WT mice. The results of our study provide conclusive in-vivo evidence that in mice vortioxetine's brain bioavailability is P-gp dependent, expanding previous findings on this topic.

Antidepressants in breast milk; comparative analysis of excretion ratios.

Despite increasing prescription rates of antidepressants in pregnant and breastfeeding women over the past decades, evidence of drug exposure for neonates through lactation is very sparse. Concentrations of three antidepressants citalopram, sertraline, and venlafaxine were measured in maternal blood and breast milk in 17 women receiving antidepressant therapy during breastfeeding period. We also computed concentration-by-dose-ratios (C/D) and milk to serum (plasma) penetration ratios (M/P). Non-parametric tests were applied. Serum concentration of citalopram and daily dosage correlated positively while daily dosage and mother milk concentration did not (rho = 0.939, p = 0.005, and rho = 0.772, p > 0.05 respectively). A significant correlation was also found between serum and milk concentrations (rho = 0.812, p = 0.05). Venlafaxine daily dosage correlated positively with the active moiety milk concentration (rho = 0.949, p = 0.014). No significant correlations were reported for sertraline. The amount of antidepressant concentrations to which neonates may be exposed, assessed as absolute infant dose (AID), was particularly low with the highest median AID being 0.16mg/kg/day for venlafaxine. No significant difference was detected for the M/P ratios between different drugs (p > 0.05), whereas the comparison of C/D ratios revealed lower values in the sertraline group, with the highest values reported for citalopram group (p = 0.007 for serum concentrations and p = 0.008 for mother milk). Findings suggest that breastfeeding under antidepressant treatment constantly exposes children with measurable drug concentrations. As daily dosage and serum concentration of the antidepressants did not predict drug concentrations in mother milk, measuring of drug concentrations in milk helps to quantify drug exposure during breastfeeding. More data-even data of drug concentrations in breastfed children-are needed to better assess the effects of drug exposure on children's development.

Comparative Study of Postmortem Concentrations of Antidepressants in Several Different Matrices

Peripheral blood (PB) is considered to be the golden standard for measuring postmortem drug concentrations. In several cases, PB is however not available, but information regarding drug findings might still be crucial in order to determine the cause of death. Antidepressants are frequently detected in postmortem samples from forensic toxicology cases, but the literature investigating concentrations in other matrices than peripheral and heart blood is limited.We here describe a study for comparison of concentrations for a large number of different drugs in six different matrices. A total of 173 postmortem cases were included in the study material. The results from 44 cases with findings of antidepressants (amitriptyline/nortriptyline, citalopram, mianserin, mirtazapine, paroxetine, sertraline, trimipramine and venlafaxine) are presented in this article. Concentrations in peripheral and cardiac blood (CB), pericardial fluid (PF), two muscle samples and vitreous humour (VH) are compared. Ratios between concentrations in different matrices have also been compiled from available literature.All the investigated antidepressants were detected in all different matrices, and comparable concentration levels were found in the different matrices with a few exceptions. Concentrations in VH were generally lower than in the other matrices, and in a few cases with low concentrations in blood the antidepressants were not detected in VH. For most of the cases, ratios of 0.5-2 were found between concentration in PB and that in the other matrices. Some deviant concentrations where however found.This study shows that CB, PF, muscle and VH can provide important indications of the corresponding concentrations in PB when PB is not available.

Therapeutic Drug Monitoring of Antidepressants.

For a number of antidepressants in current clinical use, concentrations in serum or plasma are a more reliable index of target drug concentrations than is dosage. For such drugs, therapeutic drug monitoring (TDM) may be a useful clinical guide for the purpose of maximizing the likelihood of favorable therapeutic outcome while minimizing the probability of clinical ineffectiveness or adverse side effects. TDM is of greatest benefit when a therapeutic range of serum concentrations has been well established. Even if such a range is not definitively determined, TDM can be of help in situations in which patients are refractory to therapy despite adequate or high dosages, when adverse events supervene even with low doses, or when noncompliance with the intended dosage plan is suspected. Serum antidepressant concentrations from TDM should be interpreted in the full context of the patient's demographic characteristics and clinical status, along with an understanding of the pharmacokinetics of the medication being taken, the timing of the sample in relation to the dosage regimen, and the specific laboratory assay procedure. TDM measurements may be costly, and the potential benefits of the information need to be weighed against the cost to the patient or to the health care system.

Researcher Discusses Goals and Challenges of Perinatal Mental Illness

Back to table of contents Previous article Next article Clinical and Research NewsFull AccessResearcher Discusses Goals and Challenges of Perinatal Mental IllnessNick ZagorskiNick ZagorskiSearch for more papers by this authorPublished Online:20 Jul 2017https://doi.org/10.1176/appi.pn.2017.7b9AbstractKatherine Wisner, M.D., a pioneer in the area of perinatal mental health, says the paucity of clinical studies on pregnant women makes it difficult to weigh the risks of mental illness against the risks of medication treatment.Katherine Wisner, M.D., the recipient of APA’s 2017 Award for Research in Psychiatry, considers pregnant women to be the last therapeutic orphans of modern medicine.Philip Wang, M.D., Ph.D., director of APA’s Division of Research, presents Katherine Wisner, M.D., with APA’s 2017 Award for Research.David HathcoxToday, most everyone acknowledges that pregnant women get sick, and sick women get pregnant, Wisner told an audience during the award lecture at APA’s 2017 Annual Meeting. However, it was once believed that pregnancy protected women from illness, especially mental illness, said Wisner, the Norman and Helen Asher Professor of Psychiatry and Behavioral Sciences and Obstetrics and Gynecology at Northwestern University Feinberg School of Medicine.Wisner recalled a conversation durig her residency in an obstetrics ward with a supervisor about a patient who showed telltale signs of depression. “My supervisor dismissed the idea, for she told me, ‘She cannot be depressed, because she is pregnant, and pregnant women are fulfilled.’”But among the many health risks facing women during pregnancy, mental illnesses such as depression and bipolar disorder are some of the most common and debilitating to both mother and child. “We hear a lot about the many risks of maternal mental illness on childbirth, but mental illness also affects the maternal ability to nurture the infant over time,” Wisner said. “And that leads to long-term developmental impairments in the child.”Wisner has dedicated her career to understanding the complex effects of psychiatric illness during the perinatal period and has provided tremendous insight into the prevalence of these problems as well as the effects of psychotropic treatments during pregnancy.The benefits and risks of medication during pregnancy, particularly antidepressants, has garnered much attention in the news over the past few years, Wisner noted during the lecture. But conflicting and ambiguous data from recent studies have led to confusion and doubt among clinicians and their pregnant patients. Wisner noted that the actual data on how medications such as antidepressants affect pregnancy are sparse, since pregnant women are often excluded from clinical trials. Most findings come from retrospective, population analyses of mothers following birth—the kind of studies where sampling biases or other external factors can readily influence results.“Both major depressive disorder and antidepressants can impact maternal, fetal, and infant outcomes,” she said. However, other confounders, including medical comorbidity, poor nutrition, and substance use, can also influence outcomes. Obesity is one such confounding factor, Wisner explained, as she discussed concerns linking antidepressants to an increased risk of birth defects. Wisner noted that it is not widely appreciated that obesity is associated with birth defects like spina bifida or congenital heart defects, and depressed women tend to have a higher risk of being overweight or obese.“Even if the depression or medication underlies some of the risk, these birth defects are pretty rare, and the absolute risk is low,” a point often downplayed in studies exploring these risks and the media coverage of such studies, she said. That is not to suggest that potential risks should be discounted; physicians should be aware of all potential benefits and risks when prescribing to a pregnant woman, Wisner said. And uncovering those risks will require addressing some fundamental questions.“We still don’t know how to optimally treat pregnant women,” she said. “What are the ideal doses? Research has shown that plasma concentrations of antidepressants seem to drop over the course of pregnancy, so adjustments are needed.”Wisner hopes to answer these and other questions with her latest project, a National Institute of Child Health and Human Development–funded study called OPTI-MOM. This study is enrolling 200 pregnant women with depression who are taking antidepressants and sequencing their genetic data on drug metabolizing enzymes. Wisner’s team will periodically take blood samples from the women during the course of pregnancy and analyze the concentrations of antidepressants in these women of differing metabolic profiles.The findings may lead to the development of tailored treatment algorithms for antidepressants during pregnancy, which will be one more important step to finding these therapeutic orphans a home. ■ ISSUES NewArchived

Antidepressants in urban wastewater treatment plant: occurrence, removal and risk assessment

&lt;p&gt;In this study, an analytical methods for determination of antidepressants including (diazepam (DZP), lorazepam (LZP), carbamazepine (CBZ), fluoxetine (FLU)) was developed. The concentration of antidepressants was monitored in Konya Urban Wastewater Treatment Plant influent and effluent samples for one years. &amp;nbsp;Environmental risk assessment was performed with detected concentration with treatment plant effluent wastewater by hazard quotient (HQ) methods. Oasis HLB cartridges with SPE system was used for extraction of wastewater samples. The effect of sample volume and pH, different analyte concentration, pretreatment and matrix on efficiency of cartridges were optimized. Quantitative analyses of the target compounds were performed by LC/MS-MS system. Recoveries of antidepressant compounds from fortified wastewater were over 87% for three different fortification levels. The limits of detection were determined between 0.006 and 0.118 ng l&lt;sup&gt;-1&lt;/sup&gt;. CBZ, FLU and LZP concentration in influent varied from 6.3 to 135.6 ng l&lt;sup&gt;-1&lt;/sup&gt;, &amp;lt;dl to 2.6 ng l&lt;sup&gt;-1&lt;/sup&gt;, &amp;lt;dl to 4.8 ng l&lt;sup&gt;-1&lt;/sup&gt;, respectively, while DZP was not detected. CBZ, DZP, FLU and LZP concentrations in the effluent was determined as &amp;lt;dl-245.1 ng l&lt;sup&gt;-1&lt;/sup&gt;, &amp;lt;dl-0.21 ng l&lt;sup&gt;-1&lt;/sup&gt;, &amp;lt;dl-2.7 ng l&lt;sup&gt;-1&lt;/sup&gt;, &amp;lt;dl-2.2 ng l&lt;sup&gt;-1&lt;/sup&gt;, respectively. Antidepressants were generally removed in January, February, and August. The high removal was determined for CBZ compounds as %100 at January. The low removal was determined for FLU compounds as %2.4 at January.&lt;/p&gt; &lt;p&gt;While the HQ values for DZP, LZP, CBZ were determined below 0.1 which means insignificant risk to aquatic organisms, HQ values for FLU determined above 0.1 which means low risk to aquatic organism&lt;/p&gt;

ABCB1 genotyping in the treatment of depression.

P-glycoprotein (P-gp), the gene product of ABCB1, is a drug transporter at the blood-brain barrier and could be a limiting factor for entrance of antidepressants into the brain, the target site of antidepressant action. Animal studies showed that brain concentrations of many antidepressants depend on P-gp. In humans, ABCB1 genotyping in the treatment of depression rests on the assumption that genetic variations in ABCB1 explain individual differences in antidepressant response via their effects on P-gp expression at the blood-brain barrier. High P-gp expression is hypothesized to lead to lower and often insufficient brain concentrations of P-gp substrate antidepressants. In this review, we summarize 32 studies investigating the question of whether ABCB1 polymorphisms predict clinical efficacy and/or tolerability of antidepressants in humans and evaluate the clinical application status of ABCB1 genotyping in depression treatment.

Antidepressants Accumulate in Lipid Rafts Independent of Monoamine Transporters to Modulate Redistribution of the G Protein, Gαs

Depression is a significant public health problem for which currently available medications, if effective, require weeks to months of treatment before patients respond. Previous studies have shown that the G protein responsible for increasing cAMP (Gαs) is increasingly localized to lipid rafts in depressed subjects and that chronic antidepressant treatment translocates Gαs from lipid rafts. Translocation of Gαs, which shows delayed onset after chronic antidepressant treatment of rats or of C6 glioma cells, tracks with the delayed onset of therapeutic action of antidepressants. Because antidepressants appear to specifically modify Gαs localized to lipid rafts, we sought to determine whether structurally diverse antidepressants accumulate in lipid rafts. Sustained treatment of C6 glioma cells, which lack 5-hydroxytryptamine transporters, showed marked concentration of several antidepressants in raft fractions, as revealed by increased absorbance and by mass fingerprint. Closely related molecules without antidepressant activity did not concentrate in raft fractions. Thus, at least two classes of antidepressants accumulate in lipid rafts and effect translocation of Gαs to the non-raft membrane fraction, where it activates the cAMP-signaling cascade. Analysis of the structural determinants of raft localization may both help to explain the hysteresis of antidepressant action and lead to design and development of novel substrates for depression therapeutics.

Serum and oral fluid concentrations of antidepressants and antipsychotics in psychiatric patients

Therapeutic drug monitoring has become increasingly important in psychiatric therapy but is yet not implemented as a daily routine in clinical settings. In the course of establishing new, non-invasive procedures, other materials than blood such as oral fluid have to be evaluated.

A clinical validation study for application of DBS in therapeutic drug monitoring of antidepressants.

A bridging study of plasma and DBS concentrations for therapeutic drug monitoring of antidepressants was performed. RESULTS & METHODOLOGY: Potassium-based hematocrit analysis was included. In addition, we defined acceptance criteria based on the differences between individual data points of plasma and DBS concentrations. These criteria were applied to test acceptability of error found in predicted nortriptyline plasma concentrations. Potassium-based hematocrit predicted a negative bias for DBS concentrations of amitriptyline, but not for the other compounds. To predict plasma concentrations of antidepressants based on DBS concentrations, a factor of 0.8, 0.65, 0.84 and 0.78 was found for nortriptyline, desmethylclomipramine, venlafaxine and desmethylvenlafaxine, respectively. Application of the factor and newly formulated acceptance criteria demonstrated prediction of nortriptyline plasma concentrations based on DBS concentrations.