Antidepressant Group Research Articles

Perfil del Paciente Ambulatorio en Tratamiento con Ansiolíticos y/o Antidepresivos

Tanto los fármacos ansiolíticos, benzodiacepinas hipnóticas como antidepresivos han experimentado un notable aumento en su consumo durante los últimos años. Debido a su actividad a nivel central son ampliamente utilizados en el tratamiento de patologías como insomnio, ansiedad o depresión. El objetivo de este trabajo es conocer el perfil del paciente ambulatorio en tratamiento con alguno de estos principios activos. Para ello se ha llevado a cabo un estudio epidemiológico descriptivo transversal, para el que fue necesaria la resolución de un cuestionario por parte de aquellos pacientes que cumplieran los criterios de inclusión del estudio. Para su elaboración se consultaron las fichas técnicas de todos los principios activos comercializados en España pertenecientes al grupo de ansiolíticos, benzodiacepinas hipnóticas o antidepresivos. Se recogieron un total de 104 cuestionarios cuyos datos fueron almacenados y analizados en una base de datos. Se observó como el consumo de ansiolíticos y antidepresivos es más frecuente en mujeres y aumenta con la edad, siendo mayor el consumo de ansiolíticos en personas jubiladas y el de antidepresivos en trabajadoras en activo, y, en general, los tratamientos son de larga duración. Lorazepam es el fármaco ansiolítico más prescrito, mientras que Escitalopram lo es para el grupo de antidepresivos.

Antidepressants upregulate c-Fos expression in the lateral entorhinal cortex and hippocampal dorsal subiculum: Study in rats

Neural circuits involved in the development of depression are currently poorly understood. To provide insight into this issue, we evaluated the influence of seven clinically effective antidepressants on neuronal activity in thirty rat brain areas. Drugs belonging to all major groups of antidepressants (imipramine, reboxetine, fluoxetine, bupropion, mirtazapine, agomelatine, and phenelzine) were examined; since antidepressants typically require weeks of continued administration before they achieve a therapeutic effect, we administered these drugs for 21 days. The experiments were conducted with male Wistar rats. To identify the neuroanatomical targets for antidepressants, the alterations of c-Fos expression in different brain areas were measured using ELISA assay. The drugs were examined at doses sufficient to produce behavioral effect in the rat forced swim test (FST). All the drugs at the behaviorally relevant doses activated two brain areas, the lateral entorhinal cortex and dorsal subiculum of the hippocampus; none of the drugs affected the c-Fos expression in the medial orbital, prelimbic and infralimbic cortex, caudate putamen, nucleus accumbens core, bed nucleus of stria terminalis, hipothalamic paraventricular nucleus, medial amygdaloid nucleus, lateral habenula, substantia nigra pars compacta and pars reticulata, ventral tegmental area, hippocampal ventral subiculum, dorsal and ventral periaqueductal gray matters, and medial entorhinal cortex. These findings suggest that the stimulation of the lateral entorhinal cortex and hippocampal dorsal subiculum play a role in therapeutic effects of antidepressants.

The Use of Antidepressant Medications During Pregnancy and the Risk of Neonatal Seizures: A Systematic Review.

This review examined the current literature about the potential relationship between the use of antidepressants during pregnancy and neonatal seizures. PubMed was searched for English language reports published between January 1, 1996, and October 31, 2018, by using combinations of the following key words: pregnancy, neonatal outcome, neonatal convulsion, neonatal seizure, SSRI, selective serotonin norepinephrine reuptake inhibitor (SNRI), tricyclic antidepressant (TCA), antidepressants, sertraline, fluoxetine, paroxetine, citalopram, escitalopram, fluvoxamine, venlafaxine, mirtazapine, duloxetine, bupropion, amitriptyline, imipramine, and clomipramine. A total of 9 relevant studies that met the review criteria were examined. The prevalence rates of neonatal seizures in the antidepressant groups and control groups were 0.30% to 0.91% and 0.10% to 0.30%, respectively. The use of selective serotonin reuptake inhibitors was associated with up to 5-fold increase in the risk of neonatal seizures. Compared with the controls, higher risks were reported in newborns of pregnant women using any antidepressant or tricyclic antidepressants albeit in a limited number of studies. Exposure to antidepressants in the third trimester of pregnancy appeared to be associated more with neonatal seizures compared with earlier exposure. Although an increased risk of neonatal seizures in newborns antenatally exposed to antidepressants especially selective serotonin reuptake inhibitors may be suggested, the available studies have severe methodological limitations to enable any firm conclusion.

Journal Digest: Video Games; 3D Mapping; Suicide; Cannabis; Sexting; Sleep Apnea

Journal Digest: Video Games; 3D Mapping; Suicide; Cannabis; Sexting; Sleep Apnea

Managing Depression with Bupleurum chinense Herbal Formula: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Objectives: Bupleurum chinense (BC; Radix Bupleuri) formulae are widely used in herbal medicine clinical practice for major depressive disorder (MDD). This study provides an up-to-date and comprehensive systematic review and meta-analysis of BC formula for MDD. Design: Randomized controlled trials were retrieved from English and Chinese databases, from their inceptions to March 2019. Included studies compared BC formula alone or as integrative medicine to selective serotonin reuptake inhibitor (SSRI) antidepressants. Studies included adults 18-65 years of age. People with other types of depression or physical comorbidities, such as poststroke depression, bipolar, and other mental or physical disorders, were excluded. Meta-analysis was performed using STATA software. Grading of Recommendations Assessment, Development, and Evaluation was also conducted to assess the quality of evidence. Results: Thirty studies compared BC formula to antidepressants and 25 studies compared BC formula plus antidepressants to antidepressants alone. BC formula was more effective than antidepressants at improving depression severity measured on the Hamilton Rating Scale for Depression (HRSD) (standardized mean difference [SMD] -0.35, 95% confidence interval [CI] -0.52 to -0.18, I2 = 81.2%). Integrative use of BC formula plus SSRIs was also superior to SSRIs alone at improving HRSD scores (SMD -1.03, 95% CI -1.43 to -0.62, I2 = 94.2%). However, heterogeneity of the included studies was high and quality was low. The total number and severity of adverse events in the BC formula groups were less than that in the antidepressant groups. Conclusions: BC formula alone or given as integrative medicine with antidepressants reduced depression severity. However, the evidence is low quality and at risk of bias. Well-designed studies are needed to validate the results we identified in this review.

The Effect of Cyp2d6 Gene Polymorphism on the Efficacy and Safety of Mirtazapine in Patients with Depressive Disorders Comorbid with Alcohol

Background: Alcohol dependence is often combined with affective disorders, in particular, depressive disorder, which adversely affects the prognosis of the course of both diseases. For the treatment of a depressive disorder, drugs from the group of tetracyclic antidepressants, of which mirtazapine is a representative, are used. Therapy with mirtazapine is associated with the risk of undesirable drug reactions and pharmacoresistance.
 Aim: To study the effect of CYPD6 isoenzyme activity on the efficacy and safety of mirtazapine therapy in patients with depressive disorders comorbid with alcoholism.
 Methods: The study was conducted on 109 Russian patients with a depressive disorder, comorbid with alcohol dependence. For the correction of depressive disorders within the framework of cyclothymia, mirtazapine was prescribed to patients at a dosage of 1545 mg/day. CYP2D6*4 genotyping (1846G A, rs3892097) was carried out using Real-time polymerase chain reaction with allele-specific hybridization. Efficacy and safety were assessed using validated psychometric scales and an assessment of the severity of adverse drug reactions.
 Results: By the 9th day of the study, the severity of depressive symptoms on the HAMD scale was significantly different in patients with different genotypes: (GG) 7.0 [6.0; 8.0], (GA) 4.0 [3.8; 5.0] (p0.001), safety indicator, estimated on a UKU scale: (GG) 3.0 [3.0; 3.0], (GA) 4.0 [4.0; 5.0] (p0.001). The presence of differences persisted on the 16th day: (GG) 5.0 [3.0; 6.0], (GA) 1.5 [0.8; 3.2] (p0.001), safety indicator, estimated on a UKU scale: (GG) 6.0 [6.0; 7.0], (GA) 8.5 [8.0; 10.0] (p0.001).
 Conclusion: In this study, the effect of CYP2D6 gene polymorphism on the efficacy and safety of therapy with mirtazapine was demonstrated. Carrying a minor allele A is associated with an increased risk of adverse drug reactions, but improving performance profile performance.

Effects of depression on healing and inflammatory responses of acute wounds in rats.

This study aimed to elucidate the effect of depression on the healing of acute wounds in rats. We hypothesized that depression would have negative effects on inflammation and wound healing and that antidepressant therapy would reverse these effects. This study included 100 rats randomly allocated into five groups: control group (CG), depression group (DG), pre-depression group (PDG), antidepressant group (AG), and pre-antidepressant group (PAG). Acute wounds were created on the rats' backs. The groups were subjected to no interventions (CG), aversive stimuli before (PDG) and after (DG) wound creation, and antidepressant treatment before (PAG) and after (AG) wound creation. On the day of wound creation and on days 3, 6, 9, and 12 after wound creation, observations of the wound area and degree of depression (evaluated using the sucrose preference test, open-field test, and weight change) were recorded. On days 6 and 12 after wound creation, venous serum and wound tissues were collected. Tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, IL-6, and IL-10 levels were measured using the enzyme-linked immunosorbent assay. Results showed an initial increase followed by a decrease in the degree of depression in all groups except DG (continuous decline). The wound-healing rate was significantly lower in PDG and DG than in CG; it was higher in AG and PAG than in CG. DG and PDG had higher concentrations of inflammatory cytokines than CG, and AG and PAG had lower concentrations than CG. This indicates that the onset of depression delays the healing of acute wounds and aggravates the inflammatory response in rats. Antidepressant treatment counteracts both of these negative effects.

Esketamine, Antidepressant Combo Safe, More Effective Than Placebo

Esketamine, Antidepressant Combo Safe, More Effective Than Placebo

Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression

Controlled studies have shown short-term efficacy of esketamine for treatment-resistant depression (TRD), but long-term effects remain to be established. To assess the efficacy of esketamine nasal spray plus an oral antidepressant compared with an oral antidepressant plus placebo nasal spray in delaying relapse of depressive symptoms in patients with TRD in stable remission after an induction and optimization course of esketamine nasal spray plus an oral antidepressant. In this phase 3, multicenter, double-blind, randomized withdrawal study conducted from October 6, 2015, to February 15, 2018, at outpatient referral centers, 705 adults with prospectively confirmed TRD were enrolled; 455 entered the optimization phase and were treated with esketamine nasal spray (56 or 84 mg) plus an oral antidepressant. After 16 weeks of esketamine treatment, 297 who achieved stable remission or stable response entered the randomized withdrawal phase. Patients who achieved stable remission and those who achieved stable response (without remission) were randomized 1:1 to continue esketamine nasal spray or discontinue esketamine treatment and switch to placebo nasal spray, with oral antidepressant treatment continued in each group. Time to relapse was examined in patients who achieved stable remission, as assessed using a weighted combination log-rank test. Among the 297 adults (mean age [SD], 46.3 [11.13] years; 197 [66.3%] female) who entered the randomized maintenance phase, 176 achieved stable remission; 24 (26.7%) in the esketamine and antidepressant group and 39 (45.3%) in the antidepressant and placebo group experienced relapse (log-rank P = .003, number needed to treat [NNT], 6). Among the 121 who achieved stable response, 16 (25.8%) in the esketamine and antidepressant group and 34 (57.6%) in the antidepressant and placebo group experienced relapse (log-rank P < .001, NNT, 4). Esketamine and antidepressant treatment decreased the risk of relapse by 51% (hazard ratio [HR], 0.49; 95% CI, 0.29-0.84) among patients who achieved stable remission and 70% (HR, 0.30; 95% CI, 0.16-0.55) among those who achieved stable response compared with antidepressant and placebo treatment. The most common adverse events reported for esketamine-treated patients after randomization were transient dysgeusia, vertigo, dissociation, somnolence, and dizziness (incidence, 20.4%-27.0%), each reported in fewer patients (<7%) treated with an antidepressant and placebo. For patients with TRD who experienced remission or response after esketamine treatment, continuation of esketamine nasal spray in addition to oral antidepressant treatment resulted in clinically meaningful superiority in delaying relapse compared with antidepressant plus placebo. ClinicalTrials.gov identifier: NCT02493868.

The effect of depressive-like behavior and antidepressant therapy on social behavior and hierarchy in rats

BackgroundDepression is common and results in a significant morbidity and economic burden. Depression is associated with pervasive impairments in social functioning, and antidepressant treatments are highly variable in improving these impairments. The objectives of this study were to test the effects of depression on social organization and behavior in a rodent model of depression, and to study the effectiveness of antidepressant medication in improving both symptoms of depression and the social function of depressed animals. MethodsOne hundred-twenty male Sprague-Dawley rats were randomly and equally divided between the control group and depression group. After induction of depression by 5 weeks of chronic unpredictable stress, rats received either antidepressant treatment or placebo. In parallel with the initiation of drug therapy, 20 social groups of six rats were subjected to the complex diving-for-food situation to evaluate their social functioning. Four behavioral tests evaluated symptoms of depression and anxiety at 3 different time points. ResultsWe found that 1) depressed rats were significantly more active and aggressive in all parameters of social organization test compared with the control and antidepressant treatment groups, 2) depressed rats that received antidepressant treatment exhibited social behaviors like the control group, and 3) depression in the experimental groups was not accompanied by symptoms of anxiety. ConclusionsThese results suggest that depression can significantly alter the social behavior and hierarchy in the social group in rats. Investigations of complex social group dynamics offer novel opportunities for translational studies of mood and psychiatric disorders.

Adjuvant therapy with antidepressants for the management of inflammatory bowel disease.

Adjuvant therapy with antidepressants for the management of inflammatory bowel disease.

Interventions for preventing type 2 diabetes in adults with mental disorders in low and middle income countries

Interventions for preventing type 2 diabetes in adults with mental disorders in low and middle income countries

EFFICACY AND SAFETY OF ESKETAMINE NASAL SPRAY PLUS AN ORAL ANTIDEPRESSANT IN ELDERLY PATIENTS WITH TREATMENT-RESISTANT DEPRESSION

Introduction Estimates of 18-40% of elderly patients with depression suffer from treatment-resistant depression (TRD), defined as non-response to at least two antidepressants. Elderly patients experience greater disability and functional decline, decreased quality of life, and greater mortality from suicide than younger patients. Esketamine nasal spray is being investigated for treatment of TRD. We evaluated the efficacy, safety, and tolerability of flexibly dosed esketamine nasal spray (ESK) (28 mg, 56 mg or 84 mg) plus a newly initiated oral antidepressant (AD), compared with AD plus placebo nasal spray (PBO), for the treatment of TRD in elderly patients. Post hoc analyses, performed to better assess the data from this first large clinical trial of TRD in the elderly, are presented in the companion abstract. Methods Patients ≥ 65 years of age (N=138) in this phase 3, double-blind, multicenter, active-controlled study (NCT02422186) were randomized (1:1) to either ESK + AD (n=72) or AD + PBO (n=66). The primary endpoint was the change in the Montgomery–Asberg Depression Rating Scale (MADRS) total score from day 1 (baseline) to the end of a 4-week double-blind treatment phase. Statistical analysis employed mixed-effects model for repeated measures (MMRM), with a weighted combination test to account for an interim analysis for sample size re-estimation, using a one-sided 0.025 significance level. Pre-specified subgroup analyses were performed for ages 65-74 years (n=116) and ≥75 years (n=21). Remote raters, blinded to the treatment arm, conducted the MADRS assessments by telephone. Results The mean (SD) patient age was 70.0 (4.52) years and mean (SD) baseline MADRS total score was 35.2 (6.16). The mean (SD) change in MADRS total scores from baseline to day 28 was -10.0 (12.74) for ESK + AD and -6.3 (8.86) for AD + PBO. Based on MMRM analysis, the median-unbiased estimate of the difference between ESK + AD and AD + PBO was -3.6 (95% CI: -7.20, 0.07; one-sided p=0.029). A treatment difference favoring ESK+AD was seen for the 65-74 years subgroup. The difference in LS mean (SE) change at day 28 was -4.9 (2.04) for 65-74 years (one-sided p=0.009) and -0.4 (5.02) for ≥75 years (one-sided p=0.465). The most common treatment-emergent adverse events (TEAEs) in the ESK + AD group were dizziness (20.8%), nausea (18.1%), headache, fatigue, increased blood pressure, dissociation (12.5% each) and vertigo (11.1%). The most common TEAEs in the AD + PBO group were anxiety, dizziness and fatigue (7.7% each). Conclusions While treatment with ESK + AD did not demonstrate a statistically significant difference vs treatment with AD + PBO using the weighted combination test on the primary outcome, a statistically significant treatment effect was observed for patients aged 65-74 years, but not for the limited number of patients aged ≥75 years. Safety results were consistent with previous studies in younger adult populations; no new safety concerns were identified. This study was funded by Janssen Research & Development, LLC. This research was funded by Janssen Research & Development, LLC

Paroxetine Induces Apoptosis of Human Breast Cancer MCF-7 Cells through Ca2+-and p38 MAP Kinase-Dependent ROS Generation.

Depression is more common in women with breast cancer than the general population. Selective serotonin reuptake inhibitors (SSRIs), a group of antidepressants, are widely used for the treatment of patients with depression and a range of anxiety-related disorders. The association between the use of antidepressant medication and breast cancer is controversial. In this study, we investigated whether and how SSRIs induce the death of human breast cancer MCF-7 cells. Of the antidepressants tested in this study (amitriptyline, bupropion, fluoxetine, paroxetine, and tianeptine), paroxetine most reduced the viability of MCF-7 cells in a time-and dose-dependent manner. The exposure of MCF-7 cells to paroxetine resulted in mitochondrion-mediated apoptosis, which is assessed by increase in the number of cells with sub-G1 DNA content, caspase-8/9 activation, poly (ADP-ribose) polymerase cleavage, and Bax/Bcl-2 ratio and a reduction in the mitochondrial membrane potential. Paroxetine increased a generation of reactive oxygen species (ROS), intracellular Ca2+ levels, and p38 MAPK activation. The paroxetine-induced apoptotic events were reduced by ROS scavengers and p38 MAPK inhibitor, and the paroxetine’s effect was dependent on extracellular Ca2+ level. Paroxetine also showed a synergistic effect on cell death induced by chemotherapeutic drugs in MCF-7 and MDA-MB-231 cells. Our results showed that paroxetine induced apoptosis of human breast cancer MCF-7 cells through extracellular Ca2+-and p38 MAPK-dependent ROS generation. These results suggest that paroxetine may serve as an anticancer adjuvant to current cancer therapies for breast cancer patients with or without depression.

Efficacy and safety of esketamine nasal spray plus an oral antidepressant in elderly patients with treatment-resistant depression

Introduction Estimates of 18-40% of elderly patients with depression suffer from treatment-resistant depression (TRD), defined as non-response to at least two antidepressants. Elderly patients experience greater disability and functional decline, decreased quality of life, and greater mortality from suicide than younger patients. Esketamine nasal spray is being investigated for treatment of TRD. We evaluated the efficacy, safety, and tolerability of flexibly dosed esketamine nasal spray (ESK) (28 mg, 56 mg or 84 mg) plus a newly initiated oral antidepressant (AD), compared with AD plus placebo nasal spray (PBO), for the treatment of TRD in elderly patients. Post hoc analyses, performed to better assess the data from this first large clinical trial of TRD in the elderly, are presented in the companion abstract. Methods Patients ≥ 65 years of age (N=138) in this phase 3, double-blind, multicenter, active-controlled study (NCT02422186) were randomized (1:1) to either ESK + AD (n=72) or AD + PBO (n=66). The primary endpoint was the change in the Montgomery–Asberg Depression Rating Scale (MADRS) total score from day 1 (baseline) to the end of a 4-week double-blind treatment phase. Statistical analysis employed mixed-effects model for repeated measures (MMRM), with a weighted combination test to account for an interim analysis for sample size re-estimation, using a one-sided 0.025 significance level. Pre-specified subgroup analyses were performed for ages 65-74 years (n=116) and ≥75 years (n=21). Remote raters, blinded to the treatment arm, conducted the MADRS assessments by telephone. Results The mean (SD) patient age was 70.0 (4.52) years and mean (SD) baseline MADRS total score was 35.2 (6.16). The mean (SD) change in MADRS total scores from baseline to day 28 was -10.0 (12.74) for ESK + AD and -6.3 (8.86) for AD + PBO. Based on MMRM analysis, the median-unbiased estimate of the difference between ESK + AD and AD + PBO was -3.6 (95% CI: -7.20, 0.07; one-sided p=0.029). A treatment difference favoring ESK+AD was seen for the 65-74 years subgroup. The difference in LS mean (SE) change at day 28 was -4.9 (2.04) for 65-74 years (one-sided p=0.009) and -0.4 (5.02) for ≥75 years (one-sided p=0.465). The most common treatment-emergent adverse events (TEAEs) in the ESK + AD group were dizziness (20.8%), nausea (18.1%), headache, fatigue, increased blood pressure, dissociation (12.5% each) and vertigo (11.1%). The most common TEAEs in the AD + PBO group were anxiety, dizziness and fatigue (7.7% each). Conclusions While treatment with ESK + AD did not demonstrate a statistically significant difference vs treatment with AD + PBO using the weighted combination test on the primary outcome, a statistically significant treatment effect was observed for patients aged 65-74 years, but not for the limited number of patients aged ≥75 years. Safety results were consistent with previous studies in younger adult populations; no new safety concerns were identified. This study was funded by Janssen Research & Development, LLC. This research was funded by Janssen Research & Development, LLC

Evaluation of Forensic Cases in the Pediatric Intensive Care Unit.

Objectives:Traffic accidents, falls, assaults, occupational accidents, intoxications, burns, electric shock, lightning strike, all cases of asphyxia, penetrating and firearm injuries, suspected or definite cases of sexual abuse, and suicide attempts should be evaluated in the forensic category. In this study, we aimed to present our intensive care experiences in forensic cases.Methods:We retrospectively evaluated forensic cases admitted to our Pediatric Intensive Care Unit between 1 February 2017 and 1 September 2018.Results:This study included 153 children, 65 (42.5%) boys and 88 (57.5%) girls. The forensic causes of hospitalizations in the intensive care unit included drug intoxication with a rate of 54.9%, followed by suicide attempts with 24.2%, falling from a high place with 5.2%, child abuse with 5.2%, pedestrian (out-of-vehicle) traffic accidents with 2.6%, drowning in water with 2.6%, road (in-vehicle) traffic accidents with 2%, electric shocks with 2%, and CO (carbon monoxide) poisoning with 1.3%. The drug intoxication was caused by drugs prescribed to the mother and the child with a rate of 40.6% and 27.1%, respectively. Analgesic anti-inflammatory drugs (33.1%) and antidepressant drugs (22.3%) were identified as major causes of intoxication. In addition, paracetamol was the most common cause of intoxication, with a rate of 21.9% among all intoxication cases and 72.5% in the analgesic group. Amitriptyline was the most common agent in the antidepressant group (59.2%). The admission rate to the intensive care unit between 08:00 and 14:00 was 35.1% for suicide attempts and 16.4% for non-suicide attempts, with a statistically significant difference (p=0.025; p<0.05, respectively).Conclusion:Drug intoxications had the highest rate of forensic cases followed in our pediatric intensive care unit. The majority of these intoxications (69.4%) arose from accidental drug ingestion. Therefore, we believe that there may be a significant decrease in the number of hospitalizations of forensic cases associated with drug intoxications in pediatric intensive care units by preventing children’s access to drugs.

Decreased functional connectivity of the insula within the salience network as an indicator for prospective insufficient response to antidepressants.

Insufficient response to treatment is the main cause of prolonged suffering from major depressive disorder (MDD). Early identification of insufficient response could result in faster and more targeted treatment strategies to reduce suffering. We therefore explored whether baseline alterations within and between resting state functional connectivity networks could serve as markers of insufficient response to antidepressant treatment in two years of follow-up. We selected MDD patients (N = 17) from the NEtherlands Study of Depression and Anxiety (NESDA), who received ≥ two antidepressants, indicative for insufficient response, during the two year follow-up, a group of MDD patients who received only one antidepressant (N = 32) and a healthy control group (N = 19) matched on clinical characteristics and demographics. An independent component analysis (ICA) of baseline resting-state scans was conducted after which functional connectivity within the components was compared between groups. We observed lower connectivity of the right insula within the salience network in the group with ≥ two antidepressants compared to the group with one antidepressant. No difference in connectivity was found between the patient groups and healthy control group. Given the suggested role of the right insula in switching between task-positive mode (activation during attention-demanding tasks) and task-negative mode (activation during the absence of any task), we explored whether right insula activation differed during switching between these two modes. We observed that in the ≥2 antidepressant group, the right insula was less active compared to the group with one antidepressant, when switching from task-positive to task-negative mode than the other way around. These findings imply that lower right insula connectivity within the salience network may serve as an indicator for prospective insufficient response to antidepressants. This result, supplemented by the diminished insula activation when switching between task and rest related networks, could indicate an underlying mechanism that, if not sufficiently targeted by current antidepressants, could lead to insufficient response. When replicated, these findings may contribute to the identification of biomarkers for early detection of insufficient response.

Terapija peripartalnih psihičkih poremećaja

During the peripartum period, women are at a greater risk of developing a mental disorder or experiencing an exacerbation of the pre-existing mental disorders. Therapeutic interventions are based primarily on psychotherapy, but if the symptoms are severe and pose a risk to the mother and the child, then the use of drugs, hospitalization or electroconvulsive therapy is considered. Cognitive-behavioral psychotherapy is the first line of treatment in postpartum blues and postpartum depression, panic disorder, generalized anxiety disorder, and mild to moderate obsessive-compulsive disorder. More recent conceptions regarding the use of drugs during the postpartum period indicate that medications should be prescribed if the risk of using them is lower than the risk of complications caused by the symptoms of mental disorders. Nortriptyline or desipramine are recommended from the group of tricyclic antidepressants, but newer generation antidepressants are shown to be safer during pregnancy. Fluvoxamine, paroxetine and sertraline can be used in postpartum period during breastfeeding, while fluoxetine and citalopram should be avoided. The use of first-generation antipsychotics haloperidol and trifluoperazine is recommended in the antepartum period, during which some of second-generation antipsychotics such as quetiapine, olanzapine, risperidone and aripiprazole can also be used. Clozapine should be avoided during breast-feeding. The use of mood stabilizers during pregnancy requires a thorough knowledge of the recommendations, and it is not advised to use them during the postpartum if the patient is breastfeeding. From the group of benzodiazepines, it is recommended to uselorazepam. Every form of therapeutic approach has proven to be more effective in the presence of emotional support from partners and other family members.

A Study on Adverse Effects of Antidepressants in a tertiary care teaching hospital

Objective: To identify the adverse effects of antidepressants at the initiation of therapy. To make causality assessment of the adverse effect identified using WHO ADR probability scale. Materials and Methods: Patients prescribed with at least one antidepressant were randomly selected and monitored for adverse drug reactions (ADRs), irrespective of their age and gender. Results: Of the 100 patients who received antidepressants, 33 patients experienced 10 ADRs. Selective serotonin receptor inhibitors (SSRIs) were the most common therapeutic class of drugs associated with ADRs. Gastrointestinal system was most commonly affected system organ class. Gastritis and dry mouth were the most frequently reported ADRs. Majority of the ADRs were ‘mild’ in their severity. Conclusion: In this study, incidence of adverse reaction to antidepressants was 32% and the most common group of Antidepressants implicated are SSRIs.

The role of psychosomatic factors in the formation of diseases of the digestive system

Psychosomatic disorders are frequent in gastroenterological practice. Visceral pain and motor-evacuation disorders of the gastrointestinal tract is a common symptom of functional gastrointestinal disorders which have a multifactorial etiology. Many patients with these diseases have comorbid behavioral disorders, such as anxiety or depression, and functional gastrointestinal disorders are described as disorders of the “gastrointestinal tract-brain” axis. Chronic stress can change the central pattern of pain, as well as motor activity and permeability of the gastrointestinal tract. The multidirectional treatment for these diseases should include psychotropic drugs and groups of somatic antipsychotics and antidepressants.