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Background: Shen-Qi-Jie-Yu-Fang (SJF) is composed of eight Chinese medicinal herbs. It is widely used in traditional Chinese medicine for treating postpartum depression (PPD). Previous studies have shown that SJF treats PPD through the neuroendocrine mechanism. Aim: To further investigate the effect of SJF on the immune system, including the inflammatory response system and CD4+CD25+ regulatory T (Treg) cells. Materials and methods: Sprague Dawley rats were used to create an animal model of PPD by inducing hormone-simulated pregnancy followed by hormone withdrawal. After hormone withdrawal, the PPD rats were treated with SJF or fluoxetine for 1, 2, and 4 weeks. Levels of Treg cells in peripheral blood were measured by flow cytometry analysis. Serum interleukin (IL)-1β and IL-6 were evaluated by enzyme-linked immunosorbent assay, and gene and protein expressions of IL-1RI, IL-6Rα, and gp130 in the hippocampus were observed by reverse-transcription polymerase chain reaction and Western blot. Results: Serum IL-1β in PPD rats increased at 2 weeks and declined from then on, while serum IL-6 increased at 1, 2, and 4 weeks. Both IL-1β and IL-6 were downregulated by SJF and fluoxetine. Changes in gene and protein expressions of IL-1RI and gp130 in PPD rats were consistent with changes in serum IL-1β, and were able to be regulated by SJF and fluoxetine. The levels of Treg cells were negatively correlated with serum IL-1β and IL-6, and were decreased in PPD rats. The levels of Treg cells were increased by SJF and fluoxetine. Conclusion: Dysfunction of proinflammatory cytokines and Tregs in different stages of PPD was attenuated by SJF and fluoxetine through the modulation of serum concentrations of IL-1β and IL-6, expressions of IL-1RI, and gp130 in the hippocampus, and CD4+CD25+ Treg cells in peripheral blood. [ABSTRACT FROM AUTHOR]

Background: Physical exercise as adjunctive treatment for hospitalized patients with major depressive disorder (MDD) has been of increasing interest in the past few years. While preliminary findings are promising, these prior studies have been plagued by inclusion of participants at different stages of medication use at study entry. The present study evaluates the effects of a short (10-days) add-on endurance-training intervention in hospitalized MDD patients on antidepressant medication for less than two weeks.Method: Thirty-five participants were randomly assigned to one of three study groups: aerobic exercise (n=14), placebo (stretching) exercise (n=11), or no intervention (control; n=10). The study outcome was the change in the Beck Depression Inventory (BDI-II) total score from baseline to the end of the study period.Results: The intent-to-treat analysis showed significant improvements in BDI-II scores for both the aerobic and the stretching groups. However, comparing pre- to post-study depression changes in these two groups, we found a large effect size in favor of aerobic exercise (Cohen's d=-1.06). No significant change in depressive symptoms was found in the control group.Limitations: The nature of the intervention (i.e., exercise) meant blinding participants to treatments was not possible. Precise information on medication dosage was not available, and the short duration of interventions and lack of follow-up assessment were all limitations.Conclusions: Endurance-training can be a helpful adjunct treatment for hospitalized patients with severe affective disorders in the initial stages of pharmacotherapy. [ABSTRACT FROM AUTHOR]

Insulin-like growth factor-1 (IGF-1) promotes the growth, differentiation, and survival of both neurons and glial cells, and it is believed to exert antidepressant-like activity. Thus, disturbances in the IGF-1 system could be responsible for the course of depression. To date, there have been no papers showing the impact of chronic antidepressant treatment on the IGF-1 network in the olfactory bulb (OB) in an animal model of depression. Prenatal stress was used as model of depression. Twenty-four 3-month-old male offspring of control and stressed mothers were subjected to behavioral testing (forced swim test). The mRNA expression of IGF-1 and IGF-1 receptor (IGF-1R) and the protein level of IGF-1 and its phosphorylation, as well as the concentrations of IGF-binding proteins (IGFBP-2, -4, -3, and -6), were measured in OBs before and after chronic imipramine, fluoxetine, or tianeptine administration. Adult rats exposed prenatally to stressful stimuli displayed not only depression-like behavior but also decreased IGF-1 expression, dysregulation in the IGFBP network, and diminished mRNA expression, as well as IGF-1R phosphorylation, in the OB. The administration of antidepressants normalized most of the changes in the IGF-1 system of the OB evoked by prenatal stress. These results suggested a beneficial effect of chronic antidepressant drug treatment in the alleviation of IGF-1 family malfunction in OBs in an animal model of depression. [ABSTRACT FROM AUTHOR]

Background: Antipsychotics are often used to treat neuropsychiatric symptoms in dementia, but the evidence for effect is limited. Antipsychotics have been associated with increased risk of adverse events and mortality in patients with dementia, leading to safety regulations worldwide.Objective: To investigate time trends in use of antipsychotics and other psychotropic drugs in dementia care.Methods: The study included longitudinal data on all Danish residents ≥65 years. The study population was defined on January 1 of each year from 2000-2012. Data included prescriptions, discharge diagnoses, and somatic and psychiatric comorbidities. Multivariate time trend analyses of psychotropic drug use in patients with dementia within 4-year age bands were performed.Results: Overall, among patients with dementia the prevalence of antipsychotic drug use decreased from 31.3% in 2000 to 20.4% in 2012. The decreasing use of antipsychotics was accompanied by decreasing use of anxiolytics and hypnotics/sedatives, but an increase in the use of antidepressants from 43.3% in 2000 to 53.8% in 2012. These changes were significant across almost all age groups. Treatment intensity among patients using antipsychotics increased as the annual median number of defined daily doses (DDD) increased from 33.3 to 42.0 DDD.Conclusions: The changing patterns of psychotropic drug use may be caused by warnings against use of antipsychotics. Further research is needed to explore the implications for patient safety. [ABSTRACT FROM AUTHOR]

Norepinephrine reuptake inhibitors (NRIs) are a class of antidepressant drugs that act as reuptake inhibitors for the neurotransmitters norepinephrine and epinephrine. The present review provides an account of analytical methods published in recent years for the determination of NRI drugs. NRIs are atomoxetine, reboxetine, viloxazine and maprotiline. NRIs with less activity at other sites are mazindol, bupropion, tapentadol, and teniloxazine. This review focuses on the analytical methods including chromatographic, spectrophotometric, electroanalytical, and electrophoresis techniques for NRI analysis from pharmaceutical formulations and biological samples. Among all of the published methods, liquid chromatography with UV-vis or MS-MS detection is the most popular technique. The most the common sample preparation techniques in the analytical methods for NRIs include liquid-liquid extraction and solid-phase extraction. Besides the analytical methods for single components, some of the simultaneous determinations are also included in this review. [ABSTRACT FROM AUTHOR]

Introduction The major depressive disorder (MDD) arises from the interaction of environmental, genetic and epigenetic factors, producing a deficit in monoaminergic transmission within the brain. However, our understanding of its pathophysiology is quite limited. Objective To reach an integrative view of the MDD pathophysiology, as well as the mechanisms of action of antidepressant drugs. Method We used the PubMed database to search for the documents by using the appropriate key words. Most of them are experimental research and molecular genetics and brain imaging studies in humans. Results The pathophysiology of MDD is characterized by: i) shrinkage of the cingulate anterior cortex; ii) hyper-metabolism of the Cg25 area; iii) lower expression of the 5-HT1A receptor; iv) enhanced expression of monoamine oxidase A. Besides, certain gene polymorphisms are strongly linked to the pathophysiology, and there is evidence that 5-HT1A receptor expression is reduced by psychological stress. Antidepressants reverse the hyper-metabolic state of Cg25, stimulate neurogenesis and the cAMP pathway. We found that imipramine increases and reduces the expression of Gαs and Gαz, respectively (data no published). Discussion and conclusion The disruption in monoaminergic transmission could be mediated by: i) the G1463A hTPH2 polymorphism that reduces the serotonin synthesis; ii) the C(-1019)G 5-HT1A polymorphism that increases the receptor expression in the dorsal rafe, and reduces serotonin release; iii) an increase in monoamine degradation. The reduced 5-HT1A expression is discussed considering its inhibitory properties in the prefrontal cortex. The effects of imipramine on Gαs and Gαz are in agreement with the antidepressant-induced stimulation of the cAMP pathway. [ABSTRACT FROM AUTHOR]

A considerable amount of literature has been published on antidepressants and cardiac ion channel dysfunction. The antidepressant paroxetine has been associated with Brugada syndrome and long QT syndrome, albeit on the basis of conflicting findings. The cardiac voltage-gated sodium channel (Na V 1.5) is related to both of these syndromes, suggesting that paroxetine may have an effect on this channel. In the present study, we therefore carried out patch clamp experiments to examine the effect of paroxetine on human Na V 1.5 channels stably expressed in human embryonic kidney 293 (HEK-293) cells as well as on action potentials of isolated rabbit left ventricular cardiomyocytes. Additionally, computer simulations were conducted to test the functional effects of the experimentally observed paroxetine-induced changes in the Na V 1.5 current. We found that paroxetine led to a decrease in peak Na V 1.5 current in a concentration-dependent manner with an IC 50 of 6.8 ± 1.1 µM. In addition, paroxetine caused a significant hyperpolarizing shift in the steady-state inactivation of the Na V 1.5 current as well as a significant increase in its rate of inactivation. Paroxetine (3 µM) affected the action potential of the left ventricular cardiomyocytes, significantly decreasing its maximum upstroke velocity and amplitude, both of which are mainly regulated by the Na V 1.5 current. Our computer simulations demonstrated that paroxetine substantially reduces the fast sodium current of human left ventricular cardiomyocytes, thereby slowing conduction and reducing excitability in strands of cells, in particular if conduction and excitability are already inhibited by a loss-of-function mutation in the Na V 1.5 encoding SCN5A gene. In conclusion, paroxetine acts as an inhibitor of Na V 1.5 channels, which may enhance the effects of loss-of-function mutations in SCN5A .

These are the preliminary results of a 12-week non-randomized, open-label, non-inferiority study comparing the effectiveness of trazodone in an extended-release formulation (XR) versus SSRIs in the treatment of major depressive disorder (MDD). Participants ( n = 76) were recruited, and 42 were assigned to the trazodone XR group and 34 to the SSRIs group. The choice of drug was based on clinical presentation and relied upon the attending physician. Assessments were made at five observation time points, at the following weeks: 0, and after 2, 4, 8, and 12 weeks. The evaluations included: symptoms of depression (MADRS, QIDS-clinician, and self-rated versions-primary study endpoints), anhedonia (SHAPS), anxiety (HAM-A), insomnia (AIS), psychosocial functioning (SDS), and therapeutic efficacy (CGI). At baseline, the trazodone group had significantly more severe depressive, anxiety, and insomnia symptoms and worse psychosocial functioning compared to the SSRIs group. After 12 weeks, trazodone XR was more effective than SSRIs in reducing the severity of insomnia and depression. There were no differences between the groups in the frequencies of therapeutic response and remission, which indicated the non-inferiority of the trazodone XR treatment. In conclusion, our results showed that in a "real world" setting, trazodone XR is effective in the treatment of patients with MDD.

Antidepressants are an important class of drugs to treat various types of depression. The determination of antidepressants is crucial in biological samples to control adverse effects in humans and study pharmacokinetics and bioavailability. Direct measurement of antidepressants in biological and water samples is a considerable challenge for analysts due to their low concentration, the high matrix effects of real samples, and the presence of metabolites of these drugs in biological samples. The challenge leads to using sample preparation processes as a critical step in determining antidepressants. Extraction and microextraction procedures have been widely utilized as sample preparation procedures for these drugs. The purposes of extraction or microextraction methods for antidepressant medications are to preconcentrate the analyte, reduce the matrix effects, increase the selectivity of the procedures, and convert the sample to a suitable format for introducing it into detection systems. In the review, the various extraction and microextraction methods of these drugs in biological, real water, and wastewater samples were investigated. The theory of each technique was briefly addressed to understand the features and factors affecting each method. The extraction and microextraction methods were classified based on their application for antidepressants, and the advantages and disadvantages of each technique were reviewed. The new developments to overcome the limitations of each procedure were discussed. The investigation indicated the number of applications of liquid-phase microextraction for extracting antidepressants has been almost equal to that of solid-phase microextraction.

Pregnancy is a sensitive period when women experience major hormonal and psychological changes. A high prevalence of the symptoms of depression and manifested major depression rates have been reported during this period, leading to negative outcomes both for mothers and the offspring. Despite its prevalence, the aetiology of depression is not yet fully understood. Nonetheless, alterations in cortisol levels have been proposed as a reliable biomarker to identify pregnant women at risk of perinatal depression. Hair cortisol has recently been extensively used in bio-psychological studies as a suitable non-invasive biomarker for several neuropsychiatric disorders. Various studies have published evidence regarding the relationship between cortisol fluctuations during the perinatal period, measured both in hair and in other substrates, and the onset of perinatal symptoms of depression. This current review provides an overview of cortisol level changes measured in women's hair during pregnancy or the postpartum period and its association with perinatal symptoms of depression. Further studies, including repetitive measurement of both hair cortisol and depression throughout the prenatal period, must be performed to clarify the relationship between cortisol levels and perinatal symptoms of depression., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

CONTEXT: Most double-blind studies of efficacy and tolerability of sertraline as compared to tricyclics in the treatment of late-life major depression have used amitriptyline as a standard, leading to the inevitable conclusion that the former drug is better tolerated than the latter, with both being equally efficacious. OBJECTIVE: To compare the antidepressant efficacy and tolerability of sertraline (50 mg/day) and imipramine (150 mg/day) in the first 6 weeks of the treatment of major depression in the elderly. DESIGN: A randomized double-blind parallel study with 6 weeks of follow-up. SETTING: The psychogeriatric clinic at the Institute of Psychiatry, Hospital das Clínicas, Faculty of Medicine of the University of São Paulo. PARTICIPANTS: 55 severe and moderately depressed non-demented outpatients aged 60 years or more. INTERVENTION: Patients were assigned to sertraline 50 mg/day or imipramine 150 mg/day. MAIN MEASUREMENTS: CAMDEX interview. Psychiatric diagnosis followed the guidelines for "Major Depressive Episode" according to DSM-IV criteria. Severity of symptoms was evaluated using the "CGI" and "MADRS" scales. Cognitive state was assessed using the Mini-Mental State Examination. Side effects were assessed using the "Safetee-Up" schedule. RESULTS: Both groups had a significant decrease in depressive symptoms according to the MADRS scores after 6 weeks of treatment (P = 0.01). No significant differences between groups were detected regarding treatment outcome (t = 0.4; P = 0.7). Although the dropout rate was greater in the imipramine group, the overall tolerability among patients who completed the 6-week trial was similar in both test groups. CONCLUSIONS: Both sertraline and imipramine exhibited good efficacy and an acceptable side-effect profile for elderly depressed patients after 6 weeks of antidepressant treatment.

Patients suffering from major depression often experience memory deficits even after the remission of mood symptoms, and many antidepressant drugs do not affect, or impair, memory in animals and humans. However, some antidepressant drugs, after a single dose, enhance cognition in humans (Harmer et al., 2009). To compare different classes of antidepressant drugs for their potential as memory enhancers, we used a version of the novel object recognition task in which rats spontaneously forget objects 24 hr after their presentation. Antidepressant drugs were injected systemically 30 min before or directly after the training phase (Session 1 [SI]). Post-Si injections were used to test for specific memory-consolidation effects. The noradrenaline reuptake inhibitors reboxetine and atomoxetine, as well as the serotonin noradrenaline reuptake inhibitor duloxetine, injected prior to SI significantly enhanced recognition memory. In contrast, the serotonin reuptake inhibitors citalopram and paroxetine and the cyclic antidepressant drugs desipramine and mianserin did not enhance recognition memory. Post-Si injection of either reboxetine or citalopram significantly enhanced recognition memory, indicating an effect on memory consolidation. The fact that citalopram had an effect only when injected after SI suggests that it may counteract its own consolidation-enhancing effect by interfering with memory acquisition. However, pretreatment with citalopram did not attenuate reboxetine's memory-enhancing effect. The Dl/5-receptor antagonist SCH23390 blunted reboxetine's memory-enhancing effect, indicating a role of dopaminergic transmission in reboxetine-induced recognition memory enhancement. Our results suggest that antidepressant drugs specifically inhibiting noradrenaline reuptake enhance cognition and may be beneficial in the treatment of cognitive symptoms of depression. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the prescribing patterns of antidepressants (ADs) by primary care providers to youth, adults, and seniors, from 2006 to 2012, using data from electronic medical records (EMRs). Method: This was a retrospective cross-sectional database study that used primary care data from the Canadian Primary Care Sentinel Surveillance Network (CPCSSN). Data on more than 600 000 Canadian primary care patients were used to determine the prevalence and incidence of AD prescribing to patients 15 years and older who had an encounter in the years of study (from 2006 to 2012). Each study year was evaluated independently. Results: The study population consisted of 86 927 patients in 2006 (mean age 48.1 years [SD 18.7], 38% male) and grew to 273 529 (mean age 49.6 years [SD 19.3], 40% male) in 2012. The prevalence of AD prescribing increased from 9.20% in 2006 to 12.80% in 2012 (P < 0.001). While the incidence rate of AD prescribing dropped from 3.54% in 2006 to 2.72% in 2008 (P < 0.001) the rate started to significantly rise again, reaching an incidence of 3.07% by 2012 (P < 0.001). Conclusions: The prevalence of AD prescribing by primary care providers in Canada continued to rise from 2006 to 2012. Conversely, incidence has remained stable or declined during the 6-year study period. While many complex factors likely contribute to the observed prevalence and incidence rates, our findings suggest that the guidelines indicating the efficacy of long-term AD therapy for patients with highly recurrent or severe depression are being followed. [ABSTRACT FROM AUTHOR]

Background: Clinical practice guidelines consider the use of antidepressants as one of the standard treatments for anxiety disorders, due to the significant improvements obtained in quality of life and functional disability. In addition, in patients who have not achieved a favorable response after 3 months of psychotherapy, antidepressants are recommended as part of a combined treatment approach. This combination with psychotropic drugs and psychotherapy appears to be indicated from baseline in patients with moderate, severe or recurrent depression. In the last decade, antidepressant prescription rates in general practice have increased between 4 and 10 times. Depression presents high rates of relapse and recurrence. Treatment is often interrupted prematurely, leading to increases in both relapse rates and health care costs. Few studies have analysed the chronic use of antidepressant drugs and long-term adherence. Objective: To evaluate compliance with antidepressant treatment between 2003 and 2011 and to explore the associated factors. Methods: Retrospective cohort study of antidepressant dispensing. Setting: Health Region of Lleida between 2003 and 2011. Participants: Patients with chronic prescription of antidepressants (ATC code NO6A) during 2003 were followed up until December 2011. The sample comprised 3684 subjects. Main measures: The compliance rate was calculated on the basis of the number of units withdrawn from the pharmacy and the theoretical number of units required according to the scheduled duration of treatment: compliance was defined in cases with scores greater than or equal to 80 %. Results: 12.5 % of patients received chronic antidepressant treatment for at least 4 years. Mean age was 54 years, and 73.2 % of patients were female. Almost a third (32.4 %) presented anxiety disorders and 26.5 % mood disorders. The overall compliance rate was 22 % (28 % in patients with depression, and 21 % in patients with anxiety). According to gender, compliance rates were 21.4 % for males and 22.4 % for females. Compliance was more likely in patients with polypharmacy. Conclusions: One in 4 patients complied with treatment. Factors associated with better compliance were polypharmacy and diagnosis of depressive or mixed anxiety-depressive disorder. [ABSTRACT FROM AUTHOR]

The use of antidepressants in treatment of depression in course of bipolar disorders (BD) is controversial. In case of no improvement during monotherapy with mood stabilizer, the use of antidepressants is often necessary. The safety of this group (in context of phase change, mixed states and rapid cycling) is essential and is the subject of many research. In the paper, the authors review the literature concerning efficacy and safety of use of antidepressants in the treatment of affective disorders and long-term impact on the course of the disease. Selection of articles have been made by searching the Medline and Pubmed databases using keywords: antidepressant drugs, bipolar depression, bipolar disorder, efficacy, safety, mania, hypomania. The risk of mania is greater in bipolar disorder type I, than in type II or during treatment with Tricyclic antidepressants (TCAs) and treatment with venlafaxine. The use of SSRIs and bupropion is associated with a relatively small increase of phase change risk. There are different opinions concerning recommended duration of antidepressant treatment. Generally antidepressant use should end after 2-3 months of remission, the risk of recurrence of depression after discontinuation of antidepressants is, however, higher than in case of continuation. In BD type II or BD spectrum, antidepressant monotherapy is allowed in severe depression. In bipolar disorder type I and in case of phase change after antidepressants use in the past, use of antidepressants should be very cautious. Antidepressants are contraindicated in rapid cycling and in mixed episodes. Further work is needed to evaluate the efficacy and safety of antidepressants use. [ABSTRACT FROM AUTHOR]

Background Contact hypersensitivity (CHS) reaction induced by a topical application of hapten is a cell-mediated antigen-specific type of skin inflammation mediated by interaction of several subtypes of T cell subpopulations. Recently, it has been shown that antidepressant drugs inhibit CHS reaction, although the mechanism of this effect remains unknown. The aim of the present study was to investigate the effect of 2-week desipramine or fluoxetine administration on the CHS reaction induced by picryl chloride (PCL) application in B10.PL mice and in knock-out mice established on B10.PL background: TCRδ −/− mice lacking TCRγδ T lymphocytes; β 2 m −/− mice lacking CD8 + T lymphocytes and CD1d −/− mice lacking CD1d dependent natural killer T (NKT) lymphocytes. Methods B10.PL, TCRδ −/− , β 2 m −/− and CD1d −/− mice were divided into six groups: 1) vehicle-treated negative control group; 2) desipramine-treated negative control group; 3) fluoxetine-treated negative control group; 4) vehicle and PCL-treated group (positive control group); 5) desipramine and PCL-treated group; and 6) fluoxetine and PCL-treated group. CHS to PCL was tested by evaluation of ear swelling. Metabolic activity of spleen and lymph node cells were estimated by MTT test. Results The antidepressants significantly suppressed the CHS reaction in B10.PL mice: desipramine by 55% and fluoxetine by 42% compared to the positive control. This effect was even stronger in TCRδ −/− mice, in which fluoxetine reduced the ear swelling by 73% in comparison with the vehicle-treated positive control group. On the other hand, desipramine and fluoxetine did not inhibit CHS reaction in β 2 m −/− and CD1d −/− mice. Moreover, PCL increased metabolic and/or proliferative activity of splenocytes in all four strains of mice whereas the antidepressants decreased this activity of splenocytes in B10.PL, TCRδ −/− and CD1d −/− mice. Conclusion The results of the present study show that lack of CD8 + T cells or NKT cells abolishes the immunosuppressive effect of antidepressant drugs on PCL-induced CHS reaction in mice. These results suggest that antidepressant drug-induced inhibition of CHS reaction is connected with their inhibitory effect on ability of CD8 + T cells and NKT cells to induce and/or escalate CHS reaction. TCRγδ cells seem not to be involved in antidepressant-induced suppression of CHS. [ABSTRACT FROM AUTHOR]

With the aim of obtaining information about drug-drug interaction (DDI) between acetaminophen and some of antidepressant drugs (fluoxetine, sertraline and nortriptyline), in the present work we studied the electrochemical oxidation of acetaminophen (paracetamol) in the presence of these drugs by means of cyclic voltammetry and Controlled-potential coulometry. The reaction between N-acetyl-p-benzoquinone-imine (NAPQI) produced from electrooxidation of acetaminophen and antidepressant drugs (see scheme 1) cause to reduce the concentration of NAPQI and decreases the effective concentration of antidepressants. The cyclic voltammetric data were analyzed by digital simulation to measure the homogeneous parameters for the suggesting electrode mechanism. The calculated observed homogeneous rate constants (kobs) for the reaction of electrochemically generated N-acetyl-para benzoquinn-imine with antidepressant drugs was found to vary in the order kobsnortriptyline > kobssertraline > kobsfluoxetine at biological pH. [ABSTRACT FROM AUTHOR]

Objective: Aim of this study was to retrospectively evaluate poisoning cases in an intensive care unit (ICU) in order to determine the profile of poisoning cases, update epidemiological data in Adiyaman, and contribute to data about poisoning in our country. Methods: Between 01-01-2012 and 31-12-2013 174 patients (116 males, 58 females) with a mean age of 23.7 years were treated. Demographic characteristics, reasons and ways of poisoning, types of toxic substances, length of their ICU stay and prognosis were evaluated. Results: 2733 patients admitted to the intensive care unit were 174 poisoning cases. Poisoning ways were suicide by drug overdose (n=162, 93.1%), and accidental poisoning (n=12,6.9%).119 patients (66.5%) had single drug intake, thirty-three patients (18.4%) with multiple drug intake, and 16 (8.9%) were poisoned by organic phosphates. The most common drug used for suicide was antidepressants (n=87.5%). 32 patients (18.4%) took analgesics and anti-inflammatory drugs. A total of 152 patients taking the drug, 22 patients were poisoned by other means. The median length of patient stay was 2 days (range 1-20 days). Ninety-nine patients (56.9%) recovered and were discharged. 72 patients (41.4%) were admitted to inpatient after intensive care unit. Patients were followed up by asking poisoning suicidal psychiatric consultation.1 patient was followed up for 20 days in intensive care due to alcohol poisoning but was died.2 patients (1.1%) were referred to a center forward. Conclusion: Majority of the patients were females, who took drugs with suicidal intention. Frequent use of antidepressants, which are not subject to control by authorities, to commit suicide was remarkable. [ABSTRACT FROM AUTHOR]

Aims Worrying data indicate that excessive caffeine intake applies to patients suffering from mental disorders, including depression. It is thus possible to demonstrate the usefulness of caffeine and its derivatives in the treatment of depression. The main goal of the present study was to evaluate the influence of caffeine (5 mg/kg) on the activity of moclobemide (1.5 mg/kg), venlafaxine (1 mg/kg), bupropion (10 mg/kg), and milnacipran (1.25 mg/kg). Moreover, we assessed the influence of caffeine on their serum and brain levels using high-performance liquid chromatography. Main methods The experiment was carried out on naïve adult male Albino Swiss mice. Caffeine and tested drugs were administered intraperitoneally. The influence of caffeine on the activity of selected antidepressant drugs was evaluated in forced swim test (FST). Locomotor activity was estimated to verify and exclude false positive/negative results. To assess the influence of caffeine on the levels of studied antidepressant drugs, their concentrations were determined in murine serum and brains using high-performance liquid chromatography. Key findings Caffeine potentiated activity of all antidepressants examined in FST and the observed effects were not due to the increase in locomotor activity in the animals. Only in the case of co-administration of caffeine and milnacipran an increased milnacipran concentration in serum was observed without affecting its concentration in the brain. Significance Caffeine potentiates the activity of antidepressant drugs from different chemical groups. The interactions of caffeine with venlafaxine, bupropion and moclobemide occur in pharmacodynamic phase, whereas the interaction of caffeine–milnacipran occurs, at least partially, in pharmacokinetic phase. [ABSTRACT FROM AUTHOR]

Background: Antidepressant drugs such as fluoxetine are of the most commonly used drugs among the public. These drugs may impact the regulation of bone cell functioning, and thus affect orthodontic tooth movement. The aim of this study was to determine the effect of fluoxetine on tooth movements during orthodontic treatment in rats. Materials and Methods: In this study, 30 male rats were randomly assigned into two groups and injected with fluoxetine 10 mg/kg (experimental group) and normal saline (control group) for a period of 1-month intraperitoneally 5 times/week. Then, the rats were anesthetized and a nickeltitanium closed-coil spring was placed between the left maxillary first molar and left maxillary central incisors of all samples, and then fluoxetine (experimental group) and normal saline (control group) were injected for another 3 weeks by the same method. After measuring tooth movements, rats were sacrificed, and histomorphometric analyses were conducted and the obtained data were statistically analyzed using independent t-test and the significance was set at 0.05. Results: Following the fluoxetine injection, the mean amount of tooth movements in the experimental group was reduced compared to the control group, which was not statistically significant (P = 0.14). There was no significant difference between the two groups regarding bone apposition rate (P = 0.83), external root resorption rate (P = 0.1), and mean number of root resorption lacunae (P = 0.16). Conclusion: Within the limitations of this study, systemic use of fluoxetine may cause insignificant reduction of tooth movement rate in rats; however, this subject needs more evaluations. [ABSTRACT FROM AUTHOR]

The prefrontal cortex (PFC) plays a crucial role in cognitive and affective functions. It contains a rich serotonergic (serotonin, 5-HT) innervation and a high density of 5-HT receptors. Endogenous 5-HT exerts robust actions on the activity of pyramidal neurons in medial PFC (mPFC) via excitatory 5-HT 2A and inhibitory 5-HT 1A receptors, suggesting the involvement of 5-HT neurotransmission in cortical functions. However, the underlying mechanisms must be elucidated. Here we examine the role of 5-HT 2A receptors in the processing of emotional and cognitive signals evoked by increasing the 5-HT tone after acute blockade of the 5-HT transporter. Fluoxetine (5–20 mg/kg i.p.) dose-dependently reduced the immobility time in the tail-suspension test in wild-type (WT) and 5-HT 2A knockout (KO2A) mice, with non-significant differences between genotypes. Fluoxetine (10 mg/kg i.p.) significantly impaired mice performance in the novel object recognition test 24 h post-administration in WT, but not in KO2A mice. The comparable effect of fluoxetine on extracellular 5-HT in the mPFC of both genotypes suggests that presynaptic differences are not accountable. In contrast, single unit recordings of mPFC putative pyramidal neurons showed that fluoxetine (1.8–7.2 mg/kg i.v.) significantly increased neuronal discharge in KO2A but not in WT mice. This effect is possibly mediated by an altered excitatory/inhibitory balance in the PFC in KO2A mice. Overall, the present results suggest that 5-HT 2A receptors play a detrimental role in long-term memory deficits mediated by an excess 5-HT in PFC. [ABSTRACT FROM AUTHOR]

Alzheimer's disease is the leading cause of dementia in the elderly. Depression is a common psychiatric disorder affecting individuals across life span and often arises in the context of pre-dementia, dementia, and Alzheimer's disease. The present study aimed to investigate the effects of the antidepressant drugs clomipramine (14.2 and 56.9 μmol/kg), fluoxetine (14.5 and 57.8 μmol/kg), and sertraline (14.6 and 58.4 μmol/kg) compared with acetylcholinesterase inhibitor donepezil (12 μmol/kg) on oxidative stress, memory impairment, and depressant-like behavior in a model of Alzheimer's disease induced by prolonged intraperitoneal administration of aluminum chloride (AlCl) (10 mg/kg/day for 60 days) in rats. Results indicated that the latency to find the hidden platform in Morris water maze (MWM) test increased by 100 %, while the immobility duration in forced swimming test (FST) increased by 51 % in AlCl-treated rats. The administration of AlCl resulted in increased brain malondialdehyde (MDA) by 58.6 % and nitric oxide (nitrite) concentrations by 71.7 %, while reduced glutathione (GSH) decreased by 35.6 % compared with the vehicle-treated group. Catalase and paraoxonase 1 (PON1) activities in the brain decreased by 41.8 and 18.3 %, respectively. Serum acetylcholinesterase (AChE) increased by 47.8 % and brain butyrylcholinesterase (BuChE) decreased by 23.1 % after AlCl treatment. In AlCl-treated rats, memory performance in the MWM test improved following donepezil and the highest dose of clomipramine, fluoxetine, and sertraline. The immobility duration in the FST was decreased by sertraline. Significant decrease in brain MDA occurred after treatment with clomipramine, fluoxetine, and a lower dose of sertraline. Reduced glutathione level increased by donepezil, clomipramine, and 57.8 μmol/kg fluoxetine. The level of nitric oxide decreased by donepezil (42.6 %), clomipramine (45.0 and 62.9 %), fluoxetine (21.9 and 40.9 %), and 14.6 μmol/kg sertraline (28.7 %). Catalase activity was restored by donepezil, fluoxetine, and sertraline and markedly increased by 56.9 μmol/kg clomipramine. Paraoxonase 1 activity was increased by 14.2 μmol/kg clomipramine. BuChE activity was unaltered, but AChE activity was decreased by donepezil, clomipramine, and fluoxetine compared with the AlCl control group. AlCl resulted in neurodegeneration (gliosis), extensive dark neurons with corkscrew dendrites, and degeneration of some Purkinje cell. Following donepezil treatment, no dark neurons were observed, while increased granular cell layer was observed after the administration of a high dose of clomipramine, fluoxetine, or sertraline. The results suggested that in rats treated with AlCl, (i) donepezil, sertraline, clomipramine, and fluoxetine improve memory performance; (ii) sertraline was particularly effective in improving depressive-like behavior in this model and might be of value in the treatment of depressive symptoms associated with Alzheimer's disease; (iii) donepezil, clomipramine, and fluoxetine alleviated oxidative stress; and (iv) neurodegeneration in this model could be modulated by antidepressant drugs and donepezil. [ABSTRACT FROM AUTHOR]

Major depression is a severe psychiatric syndrome with very high prevalence and socio-economic impact. Its pathophysiology is poorly known, yet several neurotransmitter systems and brain areas have been implicated. Selective serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitors (SSRI) and serotonin and norepinephrine reuptake inhibitors (SNRI) are most used antidepressant treatments. However, these drugs show slow onset of action and limited efficacy, making necessary the use of drug augmentation strategies or more aggressive interventions. Two important observations have emerged in recent years indicating that more rapid and effective antidepressant treatments are possible. Hence, the deep brain stimulation (DBS) of ventral anterior (subgenual) cingulate cortex (Cg25) evokes rapid mood improvements in subgroups of treatment-resistant depressive patients, likely mediated by a functional remodelling of cortico-limbic circuits. On the other hand, the non-competitive NDMA receptor antagonist ketamine can also evoke rapid (e.g., 2 h) and persistent (up to 1 wk) improvements in some treatment-resistant patients. Moreover, recent preclinical observations indicate the antidepressant capacity of mGluR agents. Overall, this supports the usefulness of glutamatergic transmission as a new area in antidepressant drug development. On the monoamine side, new preclinical and clinical research should clarify the different roles played by 5-HT receptors in depression as well as the brain areas and circuits responsible for therapeutic improvement. This will lead to the synthesis of new agents blocking the serotonin (and possibly norepinephrine) transporter which will also activate or block 5-HT receptors playing respectively positive (e.g., postsynaptic 5-HT 1A , 5-HT 4 ) or negative (e.g., presynaptic 5-HT 1A ,/ 1B , 5-HT 2A , 5-HT 2C ,5-HT 3 , etc.) roles in antidepressant effects. [ABSTRACT FROM AUTHOR]

In the present work, an efficient and environmental friendly method of ionic-liquid-based emulsified microextraction procedure accelerated by ultrasound radiation has been developed. Subsequently, its performance was compared with dispersive liquid-liquid microextraction and ultrasound-assisted surfactant-based emulsification microextraction methods. The optimization of experimental conditions was carried out by combination of central composite design and response surface methodology. The optimum conditions of variables were set as follows: 50 μL of 1-hexyl-3-methylimidazolium hexafluorophosphate (extracting solvent), 10 min ultrasound time, and 10 min vortex time for agitating 6 mL sample solution in pH 3 in the presence of 4 mg sodium dodecyl sulfate without addition of salt and 200 μL of methanol as diluent solvent. Under these conditions, the responses are linear for doxepin and perphenazine in the range of 0.3-1000 and 5-1000 μg/L, respectively. The limits of detection were 0.1 μg/L for doxepin and 1 μg/L for perphenazine. Relative standard deviations were lower than 3.5 for the determination of both species. Finally, the method was used for the preconcentration and determination of doxepin and perphenazine in urine sample with relative recoveries in the range of 89-98%. [ABSTRACT FROM AUTHOR]

Objective: There is a strong association between depression and anxiety. Duloxetine, an antidepressant agent, is also used in the treatment of anxiety. Hydroxyzine is preferred over benzodiazepines in the treatment of anxiety. Present study was designed to study the impact of a combination of duloxetine with hydroxyzine in treatment of anxiety. Materials and Methods: Mice received intraperitoneal injection of normal saline (10 ml/kg), duloxetine alone (10 mg/kg), hydroxyzine alone (10 mg/kg), and hydroxyzine plus duloxetine (5 mg/kg, each). Results: The in vivo results (elevated plus maze and light/dark transition tests) showed significant anxiolytic activity with the hydroxyzine treatment than the control group. The brain monoamines were significantly increased in hippocampi, cerebral cortices, and whole brain in drug-treated groups than in the control group. The group receiving the combination showed similar results in the in vivo models and in vitro tests (brain monoamine estimations) than respective monotherapies, with the exception of a greater increase of norepinephrine levels in cerebral cortices in duloxetine-treated group. Conclusion: Combination of duloxetine with hydroxyzine is not beneficial in anxiolytic treatment than the respective monotherapies. There is a need to study the pharmacokinetic drug-drug interactions to understand the present study outcomes. [ABSTRACT FROM AUTHOR]

Background. Major depression, is one of the most prevalent mental disorders in Europe and the USA. The dramatic rise in pharmacological antidepressants is mainly due to increase in use of selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors and other new generation antidepressants. In clinical practice, optimum individual doses are often guided by trial-and-error. This article reviews the available literature on therapeutic monitoring of antidepressant drugs. Methods. A search using MEDLINE (english-language reports, 1983 - August 2012) with the key words for antidepressant drugs and therapeutic drug monitoring. Results. There is a need for monitoring antidepressants due to wide interindividual pharmacokinetic variability. At the same drug dose, a more than 20-fold variation in steady state concentration of drug in the body may result: people differ in their ability to absorb, distribute, metabolise and excrete drugs for reasons of concurrent disease, age, gender, smoking and eating habits, concomitant medication and genetics. Conclusions. Monitoring of antidepressant drugs enables us to individualise drug doses based on rational therapy, minimalise side effects, reduce morbidity and mortality and cut the cost of health care. Phenotyping and genotyping could increase therapeutic drug monitoring furthere. [ABSTRACT FROM AUTHOR]

Numerous studies in the field of psychopharmacological treatment have investigated the possible contribution of genetic variability between individuals to differences in drug efficacy and safety, motivated by the wide individual variation in treatment response. Genomewide analyses have been conducted in several large-scale studies on antidepressant drug response. However, no consistent findings have emerged from these studies. In a recent meta-analysis of genomewide data from the three studies capturing common variation for association with symptomatic improvement and remission revealed the absence of any strong genetic association and failed to replicate results of individual studies in the pooled data. However, there are good reasons to consider the possible importance of pharmacogenetic variants separately. These variants explain a large portion of the manifold variability in individual drug metabolism. More than 20 psychotropic drugs have now been relabelled by the FDA adding information on polymorphic drug metabolism and therapeutic recommendations. Furthermore, dose recommendations for polymorphisms in drug metabolizing enzymes, first and foremost CYP2D6 and CYP2C19, have been issued with the advice to reduce the dosage in poor metabolizers to 50% or less (in eight cases), or to choose an alternative treatment. Beside the well-described role in hepatic drug metabolism, these enzymes are also expressed in the brain and play a role in biotransformation of endogenous substrates. These polymorphisms may therefore modulate brain metabolism and affect the function of the neural substrates of cognition and emotion. [ABSTRACT FROM AUTHOR]

The present paper describes a simple, rapid, reproducible, and highly sensitive spectrophotometric method for the determination of the tricyclic antidepressant drugs: amitriptyline hydrochloride (AMT), imipramine hydrochloride (IMH), clomipramine hydrochloride (CPH) and desipramine hydrochloride (DPH) in pure and in pharmaceutical preparations. The method is based on the bromination of the above drugs with known excess of bromine. The unreacted bromine is determined based on its ability to bleach the dye methyl red quantitatively at 520 nm. Regression analysis of Beer-Lambert plots showed a good correlation in the concentration range 0.0-2.5, 0-1.4, 0-1.4, and 0-1.0 μg/ml for AMT, IMH, CPH, and DPH, respectively. The molar absorptivity values were found to be 0.65 × 10, 1.41 × 10, 1.93 × 10, and 2.96 × 10l/mol/cm, with the corresponding Sandell's sensitivity values were 0.0048, 0.0022, 0.0018, and 0.0010 μg/cm2 for AMT, IMH, CPH, and DPH, respectively. The limits of detection (LOD) and quantification (LOQ) are also reported for the developed method. Intra- and inter-day accuracy and precision was established according to the current ICH guidelines. Application of the procedure to the analysis of various pharmaceutical preparations gave reproducible and accurate results. Further, the validity of the proposed method was confirmed by applying the standard addition technique, and the results obtained are in good agreement with those obtained by the official method. [ABSTRACT FROM AUTHOR]

Depressive disorders are the most common psychiatric pathology. Because the classic monoaminergic theory of depression has certain drawbacks the role of adult neurogenesis and its abnormalities in the development of depression have become widely debated in the literature during the last decade. However, the main bulk of the data that form the basis of this hypothesis were obtained in animal-model experiments, whereas the data about changes in adult neurogenesis during psychiatric pathology in the human brain remain scattered. Therefore, the purpose of this article is to present an overview of the existing data concerning changes in adult neurogenesis in the hippocampal neurogenic zone during different depressive disorders in humans. [ABSTRACT FROM AUTHOR]

• Dispersive micro-solid phase extraction (D-μSPE) for antidepressant drugs (AD) • Fe 3 O 4 @Polydopamine nanoparticles (Fe 3 O 4 @PDA NPs) shows strong affinity towards AD • Sodium dodecyl sulfate (SDS) micellar eluents in D-μSPE are used for the first time • SDS micellar eluents is clearly advantageous over classic hydro-organic eluents • Excellent stability and reusability of Fe 3 O 4 @PDA NPs In this paper, the potential of micellar solutions of the anionic surfactant sodium dodecyl sulfate (SDS) as eluents in dispersive micro-solid phase extraction (D-μSPE) using polydopamine-coated magnetite nanoparticles (Fe 3 O 4 @PDA NPs) for the extraction and preconcentration of seven basic drugs (bupropion, citalopram, fluoxetine, mianserin, nomifensine, trimipramine, and viloxazine) is explored for the first time (to the best to our knowledge) and compared with conventional hydro-organic eluents. The impact of the sample solution p H , Fe 3 O 4 @PDA NPs and PDA coating amounts and extraction time on the extraction efficiency (EE), as well as the composition of the eluent on the overall efficiency (OE) are studied. Under the selected experimental conditions (50 mg of Fe 3 O 4 @PDA NPs, 100 μL of 1 M NH 3 , 5 min of extraction time and 0.15 M SDS at p H 2.6 as eluent), EE and OE values were higher than 90% for all compounds and for the most hydrophobic compounds (trimipramine, fluoxetine and mianserin), respectively. The results shown in this paper demonstrate the suitability of Fe 3 O 4 @PDA NPs as a sorbent for the extraction of antidepressants as well as the advantages of using SDS micellar solutions over classic hydro-organic eluents containing methanol, acetonitrile or tetrahydrofuran. Finally, the stability and reusability of the Fe 3 O 4 @PDA NPs is proven. [ABSTRACT FROM AUTHOR]

The incidence and prevalence of sleep disorders continue to increase in the elderly populace, particularly those suffering from neurodegenerative and neuropsychiatric disorders. This not only affects the quality of life but also accelerates the progression of the disease. There are many reasons behind sleep disturbances in such patients, for instance, medication use, nocturia, obesity, environmental factors, nocturnal motor disturbances and depressive symptoms. This review focuses on the mechanism and effects of sleep dysfunction in neurodegenerative and neuropsychiatric disorders. Wherein we discuss disturbed circadian rhythm, signaling cascade and regulation of genes during sleep deprivation. Moreover, we explain the perturbation in brainwaves during disturbed sleep and the ocular perspective of neurodegenerative and neuropsychiatric manifestations in sleep disorders. Further, as the pharmacological approach is often futile and carries side effects, therefore, the non-pharmacological approach opens newer possibilities to treat these disorders and widens the landscape of treatment options for patients. [Display omitted] [ABSTRACT FROM AUTHOR]

A novel and efficient synthetic approach to enantiopure 3-substituted pyrrolidine skeleton from readily available ( S )-PMB glycidyl ether as a starting material and its application to the asymmetric synthesis of pyrrolidine core 1 of serotonin norepinephrine reuptake inhibitors (SNRIs) 2 and 3 are described. The synthesis utilizes the organocatalyzed asymmetric Michael addition reaction as key step. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this article is to offer a personal perspective on managing melancholia by interpreting both the limited salient evidence base and offering clinical observations.Conclusions: It is suggested that medication needs to be prioritised, that not all antidepressants are equally potent for those with melancholia and that as response to a single antidepressant alone (especially a narrow-spectrum one) is low, management commonly requires broader-spectrum antidepressant drugs and augmentation strategies. [ABSTRACT FROM AUTHOR]

Depression in the elderly is a significant health issue that has the potential to seriously affect physical and emotional well-being. Therefore, the treatment of geriatric depression is necessary. Antidepressant treatment in older depressed patients is efficacious, but differences in the effectiveness of different classes of antidepressants have not been demonstrated. However, differences in tolerability profile are most recognizable in the elderly. With ageing, a series of changes occur in the elderly that modify both the pharmacokinetics and pharmacodynamics of antidepressants and may influence the efficacy, tolerability and safety of treatment in the elderly. Comorbidities require the use of other drugs, which increases the possibility of drug-drug interactions. Given these aspects, individualized therapy for each elderly patient is needed to achieve acceptable risk-benefit ratio. Effective treatment of depression in the elderly, which may require combined pharmacological with psychosocial treatment, can decrease both morbidity and mortality; it also may lead to reduced demands on family members and on health-care and social services. [ABSTRACT FROM AUTHOR]