Serotonergic Antidepressants Research Articles

ANTIANXIETY EFFECT OF ETHANOLIC EXTRACT OF FRUITS OF LIMONIA ACIDISSIMA IN SWISS ALBINO MICE

Anxiety disorder is one of the most common mental ailments exhibited by human. It is characterized by motor tension, sympathetic hyperactivity and apprehension and vigilance syndromes. A part from very few chemical remedies available like benzodiazepine and serotonin modulators, not much treatment options are at hand that safely and effectively alleviate anxiety. The ethanol extract of the fruits of plant Limonia acidissima was evaluated for its anti-anxiety activity in swiss albino mice at dose 200mg/kg and 400mg/kg body weight. Anti-anxiety was assessed by using elevated plus maze (EPM) and light and dark model methods. The ethanolic extract exhibit anxiolytic effect in experimental mice. So it is supports the use of Limonia acidissima as anxiolytic agents. Further investigation should be made to elucidate the active constituent of responsible for the activity.

Antidepressant Drugs Effects on Blood Pressure.

Individuals suffering from depressive disorders display a greater incidence of hypertension compared with the general population, despite reports of the association between depression and hypotension. This phenomenon may depend, at least in part, on the use of antidepressant drugs, which may influence blood pressure through different effects on adrenergic and serotoninergic pathways, as well as on histaminergic, dopaminergic, and cholinergic systems. This review summarizes extant literature on the effect of antidepressant drugs on blood pressure. Selective serotonin reuptake inhibitors are characterized by limited effects on autonomic system activity and a lower impact on blood pressure. Thus, they represent the safest class—particularly among elderly and cardiovascular patients. Serotonin–norepinephrine reuptake inhibitors, particularly venlafaxine, carry a greater risk of hypertension, possibly related to greater effects on the sympathetic nervous system. The norepinephrine reuptake inhibitor reboxetine is considered a safe option because of its neutral effects on blood pressure in long-term studies, even if both hypotensive and hypertensive effects are reported. The dopamine–norepinephrine reuptake inhibitor bupropion can lead to blood pressure increases, usually at high doses, but may also cause orthostatic hypotension, especially in patients with cardiovascular diseases. The norepinephrine–serotonin modulators, mirtazapine and mianserin, have minimal effects on blood pressure but may rarely lead to orthostatic hypotension and falls. These adverse effects are also observed with the serotonin-reuptake modulators, nefazodone and trazodone, but seldomly with vortioxetine and vilazodone. Agomelatine, the only melatonergic antidepressant drug, may also have limited effects on blood pressure. Tricyclic antidepressants have been associated with increases in blood pressure, as well as orthostatic hypotension, particularly imipramine. Oral monoamine–oxidase inhibitors, less frequently skin patch formulations, have been associated with orthostatic hypotension or, conversely, with hypertensive crisis due to ingestion of tyramine-containing food (i.e., cheese reaction). Lastly, a hypertensive crisis may complicate antidepressant treatment as a part of the serotonin syndrome, also including neuromuscular, cognitive, and autonomic dysfunctions. Clinicians treating depressive patients should carefully consider their blood pressure status and cardiovascular comorbidities because of the effects of antidepressant drugs on blood pressure profiles and potential interactions with antihypertensive treatments.

Serotonergic antidepressants and hospitalization for bleeding in patients supported with a continuous flow left ventricular assist device

Continuous flow left ventricular assist devices (CF -LVAD) improve survival in patients with advanced heart failure, but confer risk of bleeding complications. Serotonergic antidepressants (SA) are commonly used in heart failure patients receiving LVADs, but their inhibitory effect on platelet function may contribute to bleeding risk. We performed a retrospective analysis of LVAD patients at our institution from 2016 -2019 comparing patients treated with SA after LVAD to those without SA. Demographic and clinical variables related to bleeding were collected on discharge from index hospitalization for CF-LVAD implantation and on admission for any bleeding event. The primary endpoint was incidence of bleeding requiring hospitalization after discharge. Secondary endpoints included overall number of admissions for bleeding, time to first hospitalization for a bleeding event, and incidence rate of hospitalizations for bleeding per patient year. 100 patients met inclusion criteria for the study. A total of 5 patients without a history of SA use and 31 patients who were prescribed SA after CF -LVAD implant were readmitted for a bleeding event after initial implant hospitalization (15% vs 46%, p=0.004). Bleeding rate per person year (0.3 vs 0.61, p=0.01) were significantly less in patients without SA use. Age-adjusted multivariable analysis found SA use to be associated with a hospitalization for bleeding (HR 2.3, 95% CI 0.99 -5.4). The higher incidence of hospitalization for bleeding was driven by non-gastrointestinal anatomical sites (6% vs 28%, p=0.02) with a HR 7.7 (95% CI 0.96 -62). SA treatment after CF-LVAD implantation was associated with an increased risk for bleeding complications requiring hospitalization, particularly non-gastrointestinal bleeding.

Sex-related effects in major depressive disorder: Results of the European Group for the Study of Resistant Depression.

BackgroundSex‐related effects on the evolution and phenotype of major depressive disorder (MDD) were reported previously.MethodsThis European multicenter cross‐sectional study compared sociodemographic, clinical, and treatment patterns between males and females in a real‐world sample of 1410 in‐ and outpatients with current MDD.ResultsMale MDD patients (33.1%) were rather inpatients, suffered from moderate to high suicidality levels, received noradrenergic and specific serotonergic antidepressants (ADs) as first‐line AD treatment, generally higher mean AD daily doses, and showed a trend towards a more frequent administration of add‐on treatments. Female MDD patients (66.9%) were rather outpatients, experienced lower suicidality levels, comorbid thyroid dysfunction, migraine, asthma, and a trend towards earlier disease onset.ConclusionsThe identified divergencies may contribute to the concept of male and female depressive syndromes and serve as predictors of disease severity and course, as they reflect phenomena that were repeatedly related to treatment‐resistant depression (TRD). Especially the greater necessity of inpatient treatment and more complex psychopharmacotherapy in men may reflect increased therapeutic efforts undertaken to treat suicidality and to avoid TRD. Hence, considering sex may guide the diagnostic and treatment processes towards targeting challenging clinical manifestations including comorbidities and suicidality, and prevention of TRD and chronicity.

Kleptomania, a symptom of depression or frontotemporal dementia?

Three patients were presented in order to make differential diagnosis between affective disorder and dementia. All patients have diagnosis of affective disorder and they were in stable remission under antidepressive therapy. When pathological stealing occurred, there was a diagnostic dilemma: is it a new manifestation of affective disorder, rare side effect of serotonergic antidepressants or symptom of dementia. Neuroimaging methods, as well as neuropsychological testing identified that in these patients other symptoms of prefrontal dementia also existed. Frontotemporal dementia (FTD) is frequently misdiagnosed with depression, and so far, inadequately treated with higher doses of antidepressants. Such therapy could worsen clinical feature. These patients were successfully treated with combination of memantine and low doses of serotonergic antidepressants. In the future, multicentric investigation should be conducted to confirm effective therapeutic combination of psychopharmacs in cases of pathological stealing in FTD.

Drug Repurposing: A Network-based Approach to Amyotrophic Lateral Sclerosis.

The continuous adherence to the conventional "one target, one drug" paradigm has failed so far to provide effective therapeutic solutions for heterogeneous and multifactorial diseases as amyotrophic lateral sclerosis (ALS), a rare progressive and chronic, debilitating neurological disease for which no cure is available. The present study is aimed at finding innovative solutions and paradigms for therapy in ALS pathogenesis, by exploiting new insights from Network Medicine and drug repurposing strategies. To identify new drug-ALS disease associations, we exploited SAveRUNNER, a recently developed network-based algorithm for drug repurposing, which quantifies the proximity of disease-associated genes to drug targets in the human interactome. We prioritized 403 SAveRUNNER-predicted drugs according to decreasing values of network similarity with ALS. Among catecholamine, dopamine, serotonin, histamine, and GABA receptor modulators, as well as angiotensin-converting enzymes, cyclooxygenase isozymes, and serotonin transporter inhibitors, we found some interesting no customary ALS drugs, including amoxapine, clomipramine, mianserin, and modafinil. Furthermore, we strengthened the SAveRUNNER predictions by a gene set enrichment analysis that confirmed modafinil as a drug with the highest score among the 121 identified drugs with a score > 0. Our results contribute to gathering further proofs of innovative solutions for therapy in ALS pathogenesis.

Sex differences in pharmacological treatment of major depressive disorder: results from the AMSP pharmacovigilance program from 2001 to 2017

Data on drug prescription for outpatients with major depressive disorder (MDD) suggest women are more likely to be treated with psychotropic drugs, while data on sex differences regarding pharmacological treatment of psychiatric inpatients are currently not available. Drug utilization data from the program “Drug Safety in Psychiatry” (German: Arzneimittelsicherheit in der Psychiatrie, AMSP) of 44,418 psychiatric inpatients with MDD were analyzed for sex differences between 2001 and 2017. Sex differences were analyzed using relative risks (RR) and 95% confidence intervals (95% CI). Time trends were analyzed by comparing the first (2001–2003) with the last time period (2015–2017). In general, men and women were equally likely to use psychotropic drugs. Monotherapy was more common in men. Women were more likely to utilize ≥ 4 psychotropic drugs. Antidepressant drugs (ADDs) were the most prescribed drug class. Men had a higher utilization of noradrenergic and specific serotonergic antidepressants (RR 1.15; 95% CI 1.12–1.19), especially mirtazapine (RR 1.16; 95% CI 1.12–1.19), but also of other ADDs such as bupropion (RR 1.50; 95% CI 1.35–1.68). Males had a slightly higher utilization of second-generation antipsychotic drugs (RR 1.06; 95% CI 1.03–1.09) and were less often treated with low-potency first-generation antipsychotic drugs (RR 0.86; 95% CI 0.83–0.90). Tranquilizing (e.g., benzodiazepines; RR 0.89; 95% CI 0.86–0.92) and hypnotic drugs (e.g., Z-drugs; RR 0.85; 95% CI 0.81–0.89) were less utilized in the treatment of male patients. Not all sex differences were stable over time. More sex differences were detectable in 2015–2017 than in 2001–2003. Findings suggest that certain psychotropic drugs are preferred in the treatment of men vs. women, however, sex differences found in this study are not as large as in ambulatory settings. To make evidence-based sex-specific recommendations in the treatment of MDD, differences in drug response and tolerability need to be further researched.

817 A Case of Parasomnia Overlap Disorder in a Patient on Lithium

Abstract Introduction The literature contains few case reports of parasomnia overlap disorder. There are also few case reports of lithium inducing sleep walking behaviors. Here we seek to present a case of a patient with multiple parasomnias, is taking a number of psychotropic medications for bipolar I disorder, and is on PAP for OSA. Report of case(s) The patient is a 43 year old male with a history of occasional mild sleep walking since childhood that remitted approximately 10 years prior to the onset of treatment, but returned when he traveled out of area for a family gathering approximately one year prior to presentation in the sleep clinic. He reported not only the return of sleepwalking, on a nightly basis, as well as more severe symptoms (including enuresis and violence/aggression). He also reported several episodes of dream enactment, as well as a history of sleep paralysis and vivid hypnogogic hallucinations, both of which had been improved in the last year. He denied any history of cataplexy. He did complain of symptoms of significant RLS symptoms. He was partially compliant with CPAP for obstructive sleep apnea, though the sleep behaviors continued regardless of CPAP usage. His psychiatrist had started him on clonazepam (titrated to 2mg/night) prior to his intake in the sleep clinic, but with minimal benefit. His other medications included propranolol 40mg BID, lithium 900mg/1200mg, oxcarbazepine 600mg bid, lamictal 225mg bid, lurasidone 80mg qday, and benztropine 2mg bid. Attended polysomnography demonstrated five episodes of sleep behaviors, as well as loss of atonia during REM, and severe obstructive sleep apnea (AHI of 61.2). Conclusion The patients various parasomnias could be due to the side effects of his psychotropic medications, represent a genetic or structural defect that is causing the various parasomnias, or be due to or worsened by his undertreated obstructive sleep apneas. His workup and treatment is still ongoing, but he has continued on clonazepam 2mg but taken 2 hours earlier, and has started a new APAP. Because of the severity of his bipolar disorder (including severe suicidal ideation), he is not a candidate to tapering the lithium or to taking serotonergic antidepressants. Support (if any):

The Role of Inflammatory Proteins in Anti-Glucocorticoid Therapy for Treatment-Resistant Depression.

Background: Optimising treatments for patients with treatment-resistant depression (TRD) is key to reducing the burden of this severe illness. The anti-glucocorticoid medication metyrapone has mixed evidence supporting a role as a possible augmentation treatment in TRD. The degree of treatment resistance in depression has been associated prospectively and retrospectively with elevated inflammation, and inflammatory activity may influence responses to antidepressant treatments. Aims: To investigate whether levels of pro-inflammatory cytokines are associated with clinical outcomes to metyrapone or placebo. Methods: A double-blind RCT randomised patients with TRD to 3 weeks of placebo or metyrapone augmentation to ongoing serotonergic antidepressants. No benefit of metyrapone was reported in the primary analysis. The current study assessed levels of pro-inflammatory proteins interleukin-6 (IL-6), tumour necrosis factor (TNFα), c-reactive protein (CRP) and interleukin-10 (IL-10) before randomisation and after treatment as potential moderators and/or mediators of clinical outcomes. Results: The three pro-inflammatory proteins (but not IL-10) were elevated in this sample of patients with TRD compared to a non-affected control group. High pre-treatment IL-6 levels predicted a poorer response in the trial overall but did not moderate response to metyrapone versus placebo. Changes in IL-6 indirectly mediated depression outcome, with metyrapone increasing IL-6 levels and IL-6 increase associated with a poorer outcome on depression. Other inflammatory proteins did not mediate or moderate treatment outcomes. Interpretation: Metyrapone is hypothesised to have a therapeutic effect in depression on the basis of inhibiting the synthesis of cortisol. In this study, metyrapone did not reduce cortisol, possibly due to glucocorticoid system overcompensation). The mediation effect of IL-6 may support this and perhaps help to indicate why the treatment was not effective.

Efficacy of Vortioxetine Monotherapy for Posttraumatic Stress Disorder: A Randomized, Placebo-Controlled Trial.

There are few efficacious pharmacological treatments for posttraumatic stress disorder (PTSD) and many patients fail to benefit from existing treatments. Vortioxetine, a recently developed antidepressant, acts as a serotonin modulator through inhibition of the serotonin transporter and actions at multiple types of serotonin receptors. Its unique pharmacodynamic profile suggests it may have efficacy for the treatment of PTSD. We conducted a 12-week placebo-controlled, randomized clinical trial of vortioxetine (flexibly dosed from 10 to 20 mg/d) versus placebo in adults with PTSD. The primary outcome was change from baseline in the past-month version of the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), analyzed using a mixed-model repeated-measures analysis of variance. Forty-one patients were randomized, and 32 (78%) completed the 12 weeks of treatment. The mean reduction in CAPS-5 scores at week 12 did not significantly differ between the 2 arms; the effect size for the difference in changes between vortioxetine and placebo on CAPS-5 total scores at week 12 was Cohen d = 0.29. However, at week 8, the drug-placebo difference was d = 0.78, which met the multivariate criteria for statistical significance, P = 0.014. In this study of 41 patients, vortioxetine did not demonstrate superiority over placebo for adults with PTSD. Future PTSD trials may benefit from stratifying the randomization based on number of years since the index traumatic event and a history of failure to respond to treatment.

The impact of insulin on the serotonergic system and consequences on diabetes-associated mood disorders.

The idea that insulin could influence emotional behaviours has long been suggested. However, the underlying mechanisms have yet to be solved and there is no direct and clear-cut evidence demonstrating that such action involves brain serotonergic neurones. Indeed, initial arguments in favour of the association between insulin, serotonin and mood arise from clinical or animal studies showing that impaired insulin action in type 1 or type 2 diabetes causes anxiety- and depressive symptoms along with blunted plasma and brain serotonin levels. The present review synthesises the main mechanistic hypotheses that might explain the comorbidity between diabetes and depression. It also provides a state of knowledge of the direct and indirect experimental evidence that insulin modulates brain serotonergic neurones. Finally, it highlights the literature suggesting that antidiabetic drugs present antidepressant-like effects and, conversely, that serotonergic antidepressants impact glucose homeostasis. Overall, this review provides mechanistic insights into how insulin signalling alters serotonergic neurotransmission and related behaviours bringing new targets for therapeutic options.

Homicide attempt due to medication induced mania

Bipolar disorders are a group of mental disorders characterized by fluctuations in mood, with depressive symptoms generally dominating the course of disorder. Research on the efficacy of serotonergic antidepressants in bipolar depression is controversial and as a result, treatment of depressive symptoms in bipolar disorder is difficult. A particularly difficult situation arises when bipolar disorder is unrecognized and the depressive state is treated as major depressive disorder with the use of serotonergic antidepressants, which can result in the phenomenon of antidepressant induced mania (AIM). In this report, we present a case of antidepressant induced mania (AIM) with homicidal ideation after initiation of serotonergic antidepressants. Here, we discuss the importance of monitoring for bipolar disorder after prescribing serotonergic antidepressant therapy as well as medico-legal considerations.

Treatment of Comorbid Psychiatric Disorders with Bipolar Disorder.

Life time psychiatric comorbidities of bipolar disorders are highly prevalent. Anxiety disorders, alcohol-substance use disorders, obsessive-compulsive disorder and attention deficit and hyperactivity disorder are the most common comorbid psychiatric conditions in bipolar disorders. Psychiatric comorbidity of bipolar disorders is strongly associated with poor treatment response, higher recurrence of mood episodes, suicide attempts, rapid-cycling, worse general functioning and quality of life. Therefore, considering the huge impact of comorbidity on the bipolar disorder illness course, treatment is usually challenging. The primary aim of the treatment in psychiatric comorbidity of bipolar disorder should be mood stabilization and prevention of mood episodes. Then, first line treatment options recommended for the specific psychiatric disorders might be preferred for the treatment of bipolar disorder comorbidity. With this rationale, quetiapine can be listed as a first line treatment for anxiety disorders comorbidity in bipolar disorders while serotonergic antidepressants and olanzapine are recommended as second line options. For the treatment of alcohol-substance use disorders comorbidity, first line mood stabilizers such as valproate and lithium and new generation antipsychotic quetiapine seem to be the leading options. Serotonergic antidepressants for obsessive-compulsive disorder and stimulants for the attention-deficit hyperactivity disorders are the key treatment choices. However, both treatment agents might cause to manic switch and mood destabilization. Thus, clinicians should be aware of these complications when prescribing in bipolar disorders comorbidity.

The relationship between oxytocin blood concentrations and antidepressants over pregnancy and the postpartum

Antidepressant treatment of perinatal depression is increasingly common and accepted in clinical guidelines. It has been suggested that serotonergic antidepressants may effect changes in the oxytocinergic system, including oxytocin levels, and that this may be one of the beneficial mechanisms of action for these drugs. Furthermore, oxytocin has been associated with the quality of the parent-child relationship, which may be important in treatment of perinatal depression. This study will explore if there is a relationship between antidepressant use over the perinatal period and oxytocin levels. Data from a pregnancy cohort study are used from 279 women across three groups: women taking antidepressants in pregnancy (n = 48), women with untreated depression (n = 31) and healthy control women (n = 200). Data included antidepressant use, maternal depression and oxytocin plasma concentrations in pregnancy and up to 12 months postpartum. We found that concurrent oxytocin blood concentrations were not associated with perinatal antidepressant use. However, oxytocin blood concentrations increased more steeply in those on antidepressants across the perinatal period compared to control women. A steeper increase for Selective Serotonergic Reuptake Inhibitors was observed, however, this effect was on the boarder of statistical significance. In conclusion, although antidepressant use and oxytocin was not associated at any time point, women taking antidepressants during pregnancy had larger increases in oxytocin over the perinatal period. Future research could examine specific agents and class of antidepressant and the relationship to parenting.

Risk of Intracranial Hemorrhage With Concomitant Use of Antidepressants and Nonsteroidal Anti-inflammatory Drugs: A Nested Case-Control Study.

Whereas previous studies found that concomitant antidepressant and nonsteroidal anti-inflammatory drug (NSAIDs) use may increase the risk of gastrointestinal bleeding, either drug alone increases the risk of intracranial hemorrhage (ICH). To assess the risk for ICH in patients on concomitant treatment with antidepressants and NSAIDs. This was a nested case-control study using national insurance claims data in Taiwan between 2005 and 2013. Drug exposure was measured and compared during 3 time windows: 1 to 30, 31 to 60, and 61 to 90 days before the index date, which is the date of the ICH event. Both traditional and newer-generation antidepressants were considered in this study. Patients exposed to both antidepressants and NSAIDs 1 to 30 days before the index date presented a 50% increased odds of developing ICH (OR: 1.53; 95% CI: 1.31-1.80) compared with patients receiving antidepressants alone. Specifically, the concomitant use of nonselective NSAIDs and antidepressants increased these odds compared with antidepressants alone (OR: 1.56; 95% CI: 1.31-1.84), but using a selective cyclooxygenase-2 inhibitor with antidepressant did not alter ICH risk. Regarding antidepressant class, newer-generation antidepressants generally increase the odds of developing ICH by 60% when used concomitantly with NSAIDs. Our results suggested that the concomitant use of antidepressants and NSAIDs was associated with an increased odds of developing ICH. NSAIDs, especially nonselective NSAIDs, and serotonergic antidepressants played an important role in this risk. Given the prevalent use of these 2 classes of drugs, this potential drug interaction deserves more attention.

Serotonin Transporter Gene Promoter Hypomethylation as a Predictor of Antidepressant Treatment Response in Major Depression: A Replication Study.

BackgroundThe serotonin transporter gene (SLC6A4; 5-HTT; SERT) is considered a prime candidate in pharmacogenetic research in major depressive disorder (MDD). Besides genetic variation, recent advances have spotlighted the involvement of epigenetic mechanisms such as DNA methylation in predicting antidepressant treatment response in “pharmaco-epigenetic” approaches. In MDD, lower SLC6A4 promoter methylation has been suggested to predict impaired response to serotonergic antidepressants. The present study sought to replicate and extend this finding in a large, independent sample of MDD patients.MethodsThe sample comprised n = 236 Caucasian patients with MDD receiving antidepressant medication in a naturalistic treatment setting. Functional DNA methylation of 9 CpG sites located in the SLC6A4 promoter region was analyzed via direct sequencing of sodium bisulfite– treated DNA extracted from blood cells. Patients were assessed over the course of a 6-week in-patient treatment using the Hamilton Depression Scale (HAM-D).ResultsResults confirm relative SLC6A4 hypomethylation to predict impaired antidepressant response both dimensionally and categorically (HAM-D reductions < 50%) and to furthermore be indicative of nonremission (HAM-D > 7). This also held true in a homogenous subgroup of patients continuously treated with selective serotonin reuptake inhibitors or serotonin/noradrenaline reuptake inhibitors (n = 110).ConclusionsImpaired response to serotonergic antidepressants via SLC6A4 hypomethylation may be conveyed by increased gene expression and consequently decreased serotonin availability, which may counteract the effects of serotonergic antidepressants. The present results could in the future inform clinical decision-making towards a more personalized treatment of MDD.

Serotonergic antidepressants for sleep disturbances in perimenopausal and postmenopausal women: a systematic review and meta-analysis.

Although previous meta-analyses mainly focused on the effects of hormonal treatment against menopausal sleep disturbances, the therapeutic role of antidepressants has not been systematically addressed. To study the therapeutic benefit and safety of antidepressants in menopausal sleep disturbances. Randomized controlled trials assessing the therapeutic effects of antidepressants against menopausal sleep problems were identified from the PubMed, Cochrane Library, and Science Direct databases from inception to March 1, 2020. Studies that were clinical trials with placebo controls were included. Subgroup analyses were conducted according to a random effects model. Analysis of seven eligible randomized controlled trials including a total of 1,949 perimenopausal and postmenopausal women showed the effectiveness of serotonergic antidepressants against sleep disturbances despite the small effect size (Hedge g = 0.24, 95% CI = 0.11-0.38). The efficacy remained significantly better than that of placebo for postmenopausal women (Hedge g = 0.25, 95% CI = 0.04-0.45), participants with hot flashes (Hedge g = 0.18, 95% CI = 0.02-0.34), and those without diagnosis of major depressive disorder (Hedge g = 0.23, 95% CI = 0.06-0.40). There was no difference in therapeutic benefit between sedating and nonsedating serotonergic antidepressants. Besides, the dropout rate did not differ between antidepressant and placebo groups. Our results showed that serotonergic antidepressants were effective against sleep disturbances in perimenopausal and postmenopausal women. The efficacy remained significant for women without major depressive disorder. The dropout rates were also comparable between serotonergic antidepressants and placebo groups.

Synthesis of three-dimensional nickel ferrite nanospheres decorated activated graphite nanoplatelets for electrochemical detection of vortioxetine with pharmacokinetic insights in human volunteers.

An innovative electrochemical nanoprobe was developed for determination of vortioxetine (VORT), a serotonergic antidepressant drug, for the first time. The fabrication of thenanoprobe isbased on decoration of aglassy carbon electrode with three-dimensional nickel ferrite nanospheres modified activated graphite nanoplatelets (3D NiFe2O4 NS/AGNP/GCE). The morphological characterization of the nanoprobe was carried out via scanning electron microscope (SEM), transmission electron microscope (TEM), Fourier transform infrared spectroscopy (FT-IR), Raman spectroscopy, energy dispersive X-ray spectroscopy (EDS), N2-adsorption-desorption isotherm, and powder X-ray spectroscopy (PXRD). In addition, the electrochemical behavior of the nanoprobe was described usingcyclic voltammetry (CV), differential pulse voltammetry(DPV), and electrochemical impedance spectroscopy (EIS). A well-defined and irreversible peak at 0.82V was seen at the surface of 3D NiFe2O4 NS/AGNP/GCE. The proposed nanoprobe exhibited outstanding electro-catalytic activity towards VORT oxidation. Under the optimized conditions, the anodic oxidation currents were linearly proportional to VORT concentration at the working range 1.8-90nM with aLOD of 0.55nM. The nanoprobe was used to determine VORT in pharmaceutical tablets and human plasma samples. Satisfactory recoveries and RSD percentages were obtained in the range 103.8-107.7% (RSD% = 2.7-3.1%) and 101.4-105.3% (RSD % = 2.8-3.4%) for tablets and plasma samples, respectively. Moreover, the method was used to monitor VORT during apharmacokinetic study in human volunteers with satisfactory results. The 3D NiFe2O4 NS/AGNP/GCE shows excellent sensitivity, reproducibility, and selectivity towards VORT detection. The proposed electrode could be utilized as simple, rapid, and inexpensive sensing tool for routine analysis and during pharmacokinetic/pharmacodynamic investigations. Graphical abstract.

Depression and dementia: differentiation and comorbidity

The relationship between cognitive impairment (CI) and depression is complicated: h\the latter can be one of the symptoms of Alzheimer’s disease or may precede the onset of CI. Depression also has cognitive symptoms that alter the clinical presentation of the disease. Patients with depressive pseudodementia experience difficulties concentrating, confusion concurrent with impaired memory and thinking, whereas the patient’s answers to certain questions often resemble the vague pseudoamnestic pattern of the impairment. Mnestic disorders occur in at least 40% of patients with depression, and if the latter is diagnosed in the patient who already has dementia, the rate of cognitive decline may be faster. The mechanisms underlying the development of CI can also affect the development of depression. When assessing the risk of dementia in depression, it is necessary to take into account the time from the onset of a major depressive episode until moderate CI appears, to carry out a detailed analysis of neuropsychological testing for Alzheimer’s disease and to use the current lifetime markers for amyloidosis and neurodegeneration. Serotonergic antidepressants and non-pharmacological cognitive behavioral and psychotherapeutic procedures play the most important role in the treatment of depression and dementia.

The impact of β-cyclodextrin on biological and chemical properties of mianserin hydrochloride in aqueous solution

Mianserin hydrochloride (MIA), a drug, which belongs to a group of tetracyclic, noradrenergic and specific serotonergic antidepressants, is one of the commonly used psychotropic drugs. Despite its important uses and having a number of other potential utilizations, MIA has quite significant side effects on a patient health, including some cytotoxicity. The MIA toxicity could be reduced by drug encapsulation inside a non-toxic carrier, like β-cyclodextrin molecules (β-CD). Cyclodextrins are cone shaped supramolecules with hydrophobic interior, where hydrophobic parts of molecule can be included, and with hydrophilic rims consisting of primary and secondary hydroxyl groups, which can interact with water molecules. This study investigated the characteristic and mechanism for interaction of MIA with β-CD, and evaluated the effects of complexation on MIA cytotoxicity. Chemical shift differences for protons in mianserin hydrochloride and β-cyclodextrin molecules, induced by the formation of the inclusion complexes, have been determined by proton nuclear magnetic resonance spectroscopy. The other chemical properties of mianserin hydrochloride in aqueous solution in the presence of β-cyclodextrin has been examined at 298.15 K with the use of mass spectrometry and circular dichroism. The results showed that interaction of MIA with β-CD occurred through incorporation of MIA aromatic rings inside probably more than one β-CD molecules. The effects of β-cyclodextrin, mianserin hydrochloride and complexes thereof on the viability of Chinese hamster cells were investigated in order to estimate the cytotoxicity of the drug. The viability of B14 cells treated with MIA + β-CD is higher than with MIA and the protective effect is the highest for complexes of MIA:β-CD in a 1:4 ratio.