Side Effects Of Antidepressants Research Articles

Bioinformatics and computational chemistry approaches to explore the mechanism of the anti-depressive effect of ligustilide

Depression affects people with multiple adverse outcomes, and the side effects of antidepressants are troubling for depression sufferers. Aromatic drugs have been widely used to relieve symptoms of depression with fewer side effects. Ligustilide (LIG) is the main component of volatile oil in angelica sinensis, exhibiting an excellent anti-depressive effect. However, the mechanisms of the anti-depressive effect of LIG remain unclear. Therefore, this study aimed to explore the mechanisms of LIG exerting an anti-depressive effect. We obtained 12,969 depression-related genes and 204 LIG targets by a network pharmacology approach, which were intersected to get 150 LIG anti-depressive targets. Then, we identified core targets by MCODE, including MAPK3, EGF, MAPK14, CCND1, IL6, CASP3, IL2, MYC, TLR4, AKT1, ESR1, TP53, HIF1A, SRC, STAT3, AR, IL1B, and CREBBP. Functional enrichment analysis of core targets showed a significant association with PI3K/AKT and MAPK signaling pathways. Molecular docking showed strong affinities of LIG with AKT1, MAPK14, and ESR1. Finally, we validated the interactions between these proteins and LIG by molecular dynamics (MD) simulations. In conclusion, this study successfully predicted that LIG exerted an anti-depressive effect through multiple targets, including AKT1, MAPK14, and ESR1, and the pathways of PI3K/AKT and MAPK. The study provides a new strategy to explore the molecular mechanisms of LIG in treating depression.

Journal Digest: CBT With Cardiac Rehab, PMDD Neurochemistry, and More

Journal Digest: CBT With Cardiac Rehab, PMDD Neurochemistry, and More

“Keeping an eye on amylase”. Side effects of antidepressants

IntroductionBoth in consultations with the general practitioner and with the psychiatrist, antidepressants are one of the most used drugs (1). These have multiple indications, and there are different groups according to their mechanism of action. In relation to this case, we are going to talk about Venlafaxine, a dual-type antidepressant, that is, it inhibits the reuptake of serotonin and norepinephrine. One of the most common side effects is digestive discomfort, which usually resolves after a few weeks (2). However, we should not ignore these symptoms, since they can hide something more serious.ObjectivesPresentation of a clinical case on a patient who presented an increase in pancreatic amylase after starting treatment with Venlafaxine.MethodsBibliographic review including the latest articles in Pubmed on side effects of antidepressant treatment, and more specifically at the gastrointestinal level (in this case we will talk about pancreatitis).ResultsWe present the case of a 49-year-old woman, who was hospitalized 2 years ago, due to a first depressive episode. During this admission, psychopharmacological treatment was started for the first time, on that occasion with a selective serotonin reuptake inhibitor (SSRI), treatment of first choice (3). The patient had no side effects at that time, but the response was very modest, so it was decided to replace that antidepressant with Venlafaxine (with dual action), up to 150mg. The depressive symptoms improved markedly, however the patient began to feel digestive discomfort (which at first did not seem to be of great importance). A general analysis was performed, in which an increase in lipase (978 U/L) and amylase (528 U/L) was detected. An echoendoscopy, an abdominal scan, and a magnetic resonance cholangiography were performed; Pancreatitis secondary to drugs was suspected (a severe condition). Luckily, no significant lesions were found in the tests, and the levels of amylase and lipase decreased when Venlafaxine treatment was withdrawn (without reaching the normal range). The patient was discharged and continued to attend consultations. In the last control, amylase had dropped to 225 U/L. His abdominal pain disappeared. Treatment with Vortioxetine (a multimodal antidepressant) was started, however the amylase levels continue to be monitored, and the patient continues to see the gastroenterologist.ConclusionsGastrointestinal side effects are very common when taking antidepressant treatment, and in most cases they do not usually represent a serious problem.However, it is described in the scientific literature that in some cases, acute pancreatitis secondary to some drugs, including Venlafaxine, can occur (4). In order to detect it, it is necessary to perform a blood test and sometimes also other complementary tests.For its treatment, the fundamental thing is to withdraw the causing drug, trying to find other alternatives, and carry out a control to monitor possible complicationsDisclosure of InterestNone Declared

Is the total score of the Hamilton Depression Rating Scale affected by side effects of SSRIs and SNRIs?

Abstract This talk will focus on the pitfalls of using multidimensional rating scales to measure the severity of depression – with particular emphasis on the Hamilton Depression Rating Scale (HDRS-17). First, the history behind the development of the HDRS-17 will be briefly covered. Second, it will be argued that the HDRS-17 measures symptoms that overlap with common antidepressant side effects (gastrointestinal dysfunction, sexual dysfunction, somatic anxiety and sleep disturbances), making it possible that side effects of antidepressant treatment are erroneously rated as symptoms of depression. The rest of the talk will focus on the results of a recent study (1) in which we used individual-level data from antidepressant treatment trials to assess whether side effect ratings co-vary with HDRS-17 ratings. Specifically, data from all HDRS-17-rated, industry-sponsored pre- and post-marketing trials (n = 4647) comparing the serotonin and noradrenaline reuptake inhibitor, duloxetine, to placebo and/or to a selective serotonin reuptake inhibitor were pooled. Severity was assessed for side effects related to sleep, somatic anxiety, gastrointestinal function, and sexual dysfunction. Analysis of covariance was used to assess the relation between these side effects and ratings of relevant HDRS-17-derived outcome parameters. Side effects related to sleep, somatic anxiety and sexual dysfunction significantly and exclusively associated with higher scores on HDRS-17 items measuring the corresponding domains. Side effects related to gastrointestinal function associated with higher HDRS-17 item scores on all assessed domains. Treatment outcome was significantly related to side effect severity when assessed using HDRS-17-sum (beta 0.32 (0.074), p < 0.001), but not when the HDRS-6-sum-score (beta 0.035 (0.043), p = 0.415) or the depressed mood item (beta 0.007 (0.012), p = .527) were used as effect parameters. That some HDRS-17 items co-vary with common antidepressant side effects likely leads to an underestimation of antidepressant efficacy. Finally, based on data from a recent study (2), it will be argued that the Montgomery-Åsberg Depression Rating Scale is biased in the same direction as the HDRS-17 (underestimates antidepressant efficacy), albeit to a lesser extent.

Clinical and genetic aspect of resistant depression in adolescents

The work considers and distinguishes the psychopathological symptom complexes of depression in adolescents that are resistant to therapy: anxious, obsessive, behavioral. The level of spontaneous and induced mutagenesis in the blood lymphocytes of adolescents with depression was determined in vitro, which was twice the level of chromosomal aberrations after introducing a mutagen into the culture mixture, which indicates a pronounced individual and group hidden chromosomal instability of patients with depression. The constants of the lack of effectiveness of therapeutic intervention in adolescents with depression were determined (infantilism, personal anxiety, cogni- tive component of depression, noncompliance, addictions, comorbidity of depression with anorexia nervosa, suicidal behavior, recurrent depression, insufficient titration of antidepressant medication, unpleasant side effects of antidepressants).

The acceptability of antidepressant treatment in people living with HIV in Malawi: A patient perspective

ABSTRACT Depression is common among people living with HIV (PLWH). Measurement-based care models that measure depression severity and antidepressant side effects, and use an algorithm to guide antidepressant prescription by non-specialized health workers represent an evidence-based treatment for severe depression in sub-Saharan Africa. We conducted in-depth interviews from June to December 2018 with eleven patients enrolled in Project SOAR-Mental Health, a pilot project integrating depression treatment into HIV care in Malawi. Patients treated with amitriptyline or fluoxetine participated in interviews exploring antidepressant acceptability through patient knowledge, side effect severity, pill burden, adherence, perceived efficacy, and tolerability. Patients described a lack of detailed antidepressant education from their providers. Variable, typically self-limiting side effects were reported from both amitriptyline and fluoxetine. While most side effects were mild, three patients reported functional impairment. Patients reported high adherence, though the additional pill burden was a challenge. Most patients found the antidepressants efficacious, tolerable, beneficial and acceptable. Although patient psychoeducation is notably lacking as a facet of clinical management, antidepressant prescription by primary care providers appears acceptable for comorbid severe depression in PLWH initiating HIV care in sub-Saharan Africa. Health workers should be mindful of dosing to minimise side effects and considerate of the additional pill burden. Trial registration: ClinicalTrials.gov ID [NCT03555669]. Retrospectively registered on 13 June 2018.

Emotional side effects of antidepressants: a systematic review

Emotional side effects of antidepressants: a systematic review

Flies aid understanding of antidepressant side effects.

Flies aid understanding of antidepressant side effects.

Prevalence of undernourishment and associated factors among adults with major depressive disorder at two public hospitals in Northwest Ethiopia: a cross-sectional study

ObjectiveUndernourishment is overlooked in people with major depressive disorder (MDD); however, it could have huge impacts on recovery, functioning and quality of life. This study aimed to assess the prevalence...

Can fluoxetine mitigate mental health decline in musculoskeletal trauma patients: a pilot single-center randomized clinical trial

BackgroundMusculoskeletal trauma is one of the leading causes of disability in the USA and its negative quality of life impact extends beyond that of physical recovery. More than 50% of victims of musculoskeletal trauma suffer lasting mental health issues and post-traumatic stress disorder (PTSD) symptomology following their injury. These symptoms can develop across all spectrums of patients and are independent predictors of poor outcome. Access to mental health care is limited, expensive, and time intensive, and a large majority of the trauma population do not get to utilize this valuable resource. This leaves the burden of management on the orthopedic team, as they are often the only point of contact for the patient within the medical system.MethodsThis is a single-center, repeated measures, randomized controlled pilot study including up to 100 orthopedic trauma patients aged between 18 and 85 years of age. Subjects are approached during their index hospitalization and are randomized to one of two pharmaceutical interventions, fluoxetine (also known as Prozac) or calcium, for 9 months. Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) that is supported for the treatment of PTSD by the American Psychiatric Association. It is low-cost and has minimal side effects and withdrawal symptoms if stopped suddenly. Calcium is a supplement with minimal side effects that is used in our study for its bone-healing potential. Feasibility will be indexed by recruitment feasibility, randomization feasibility, medical adherence, anti-depressant side effects, and fracture union rate. Subjects will complete physical and mental health surveys at baseline, 2 weeks, 6 weeks, 3 months, 6 months, and 1 year.DiscussionThe goals of this exploratory clinical trial are to: develop a safe, feasible, and time-limited protocol effect of immediate (post-injury) treatment with fluoxetine for use by orthopedic providers and other non-mental health care providers treating victims of musculoskeletal trauma (Aim 1), and test the for preliminary effects of the protocol on development of PTSD symptomology and physical recovery in these patients (Aim 2). This study is novel in that it strives to prevent the development of symptomology from the time of injury and empowers surgeons to manage their patients in a more holistic manner.Trial registrationClinicalTrials.gov, NCT04850222. Registered on April 20, 2021.

Risks of Digestive System Side-Effects of Selective Serotonin Reuptake Inhibitors in Patients with Depression: A Network Meta-Analysis.

PurposeSelective serotonin reuptake inhibitors (SSRIs) are the preferred treatments for depression. The most common adverse drug reactions are symptoms involving the digestive system, leading to low compliance in patients with depression. Therefore, it is important to assess the safety of SSRIs with respect to the digestive system. Several meta-analyses have compared the risks of digestive side effects of SSRIs and other antidepressants. We aimed to compare the risks of various SSRIs (fluoxetine, escitalopram, citalopram, paroxetine, and sertraline) for adverse reactions of the digestive system.MethodsSystematic searches returned 30 randomized controlled trials (n = 5004) of five antidepressants and placebos.ResultsFluoxetine had the lowest probability of digestive side effects, ranking fifth at 0.548. Sertraline had the highest probability of digestive side effects, with a probability of 0.611. For gastrointestinal tolerability, escitalopram was better than paroxetine (odds ratio [OR] =0.62, 95% confidence interval [CI] 0.43–0.87) and sertraline (OR=0.56, 95% CI 0.32–0.99).ConclusionFluoxetine exhibited distinct advantages compared to other SSRIs, while sertraline had the greatest likelihood of digestive system side effects. These findings will help doctors understand the relative advantages of various antidepressants.

Cardiovascular side effects of non-SSRI antidepressants are of concern in high-risk patients

Cardiovascular side effects of non-SSRI antidepressants are of concern in high-risk patients

Опыт лечения соматизированной депрессии в общей медицинской практике

Somatic and vegetative-somatic depressive symptom clusters (decreased libido, abnormal body sensations, etc.) are one of the reasons for the prolonged patient's follow-up and delayed start of antidepressant therapy. However, many vegetative-somatic side effects of antidepressants (somnolence, hyperphagia, deterioration of sexual function, etc.) can cause poor patient compliance and premature discontinuation of thymoleptic therapy. Modern antidepressants, such as trazodone (Trittico) successfully stop various somatic manifestations of depression and eliminate the adverse somatic effects of the previous psychotropic medication. The paper presents clinical cases of effective trazodone therapy in a woman with somatic depression and a man with depression and SSRI-induced decrease in libido.

Parkinson and depression: review and outlook.

Depression in Parkinson's Disorder (DPD) has been estimated to appear in up to 40% of people with PD and negatively impacts quality of life, motor and cognitive deficits and functional disability. Knowledge of the pathophysiology of DPD is unclear, DPD may be related to dysfunction in subcortical nuclei and the prefrontal cortex, striatal-thalamic-prefrontal and basotemporal limbic circuits, brainstem monoamine, and indolamine (i.e. dopamine, serotonin, and norepinephrine) systems. DPD is characterized by sadness, loss of interest, increased exhaustibility, feelings of helplessness, reduced drive, dysphoria, irritability, and pessimism about future. The diagnosis is complicated by overlap with PD symptoms, Detection of depression in PD should be made by psychometric depression scales. DPD is underrecognized and undertreated in clinical practice. Treatment mainly includes antidepressive medications and behavioral interventions as psychotherapy. Dopamine agonists showed some antidepressant effects, there are no sufficient numbers of RCTs. Important randomized clinical trials (RCTs) are summarized. SSRIs and SNRIs have a satisfying efficacy in DPD. TCAs are also good for improving depression. Side effects of different antidepressants (e.g. TCAs, SSRIs, SNRIs, bupropion, MAOIs) and potential interactions should be considered. In existing guidelines so far no statements, algorithms and recommendations are given for diagnosis and treatment of DPD. Methodologically adequate designed RCTs and comparative studies (NIS) which offer evidence-based results are urgently needed having the impact of DPD in mind.

Emotional Blunting in Patients With Major Depressive Disorder: A Brief Non-systematic Review of Current Research.

Emotional blunting is frequently reported by patients with major depressive disorder (MDD) and has been identified as one of the most prominent side effects of antidepressants leading to medication discontinuation. However, antidepressant-induced emotional blunting remains largely unexplored—there lacks a clinical definition of this condition, and no agreeing conclusion has been reached regarding its etiology. Current research suggests that the onset of diminished emotional response may be related to antidepressant dose, with higher doses being more likely to induce emotional blunting. Consequently, most clinicians either reduce the dose or switch to another drug when treating this symptom. Overall, more comprehensive clinical assessments or interviews specifically designed to evaluate antidepressant-induced emotional blunting in MDD patients are in need to elucidate the neuropsychological mechanisms behind this increasingly prevalent symptom.

Methylome-wide association study of antidepressant use in Generation Scotland and the Netherlands Twin Register implicates the innate immune system

Antidepressants are an effective treatment for major depressive disorder (MDD), although individual response is unpredictable and highly variable. Whilst the mode of action of antidepressants is incompletely understood, many medications are associated with changes in DNA methylation in genes that are plausibly linked to their mechanisms. Studies of DNA methylation may therefore reveal the biological processes underpinning the efficacy and side effects of antidepressants. We performed a methylome-wide association study (MWAS) of self-reported antidepressant use accounting for lifestyle factors and MDD in Generation Scotland (GS:SFHS, N = 6428, EPIC array) and the Netherlands Twin Register (NTR, N = 2449, 450 K array) and ran a meta-analysis of antidepressant use across these two cohorts. We found ten CpG sites significantly associated with self-reported antidepressant use in GS:SFHS, with the top CpG located within a gene previously associated with mental health disorders, ATP6V1B2 (β = −0.055, pcorrected = 0.005). Other top loci were annotated to genes including CASP10, TMBIM1, MAPKAPK3, and HEBP2, which have previously been implicated in the innate immune response. Next, using penalised regression, we trained a methylation-based score of self-reported antidepressant use in a subset of 3799 GS:SFHS individuals that predicted antidepressant use in a second subset of GS:SFHS (N = 3360, β = 0.377, p = 3.12 × 10−11, R2 = 2.12%). In an MWAS analysis of prescribed selective serotonin reuptake inhibitors, we showed convergent findings with those based on self-report. In NTR, we did not find any CpGs significantly associated with antidepressant use. The meta-analysis identified the two CpGs of the ten above that were common to the two arrays used as being significantly associated with antidepressant use, although the effect was in the opposite direction for one of them. Antidepressants were associated with epigenetic alterations in loci previously associated with mental health disorders and the innate immune system. These changes predicted self-reported antidepressant use in a subset of GS:SFHS and identified processes that may be relevant to our mechanistic understanding of clinically relevant antidepressant drug actions and side effects.

Clinical validation of a combinatorial PharmAcogeNomic approach in major Depressive disorder: an Observational prospective RAndomized, participant and rater-blinded, controlled trial (PANDORA trial)

BackgroundMajor depressive disorder (MDD) is a common, chronic, debilitating mood disorder that causes serious functional impairment and significantly decreased quality of life. Pharmacotherapy represents the first-line treatment option; however, only approximately one third of patients respond to the first treatment because of the ineffectiveness or side effects of antidepressants. Precision medicine in psychiatry might offer clinicians the possibility to tailor treatment according to the best possible evidence of efficacy and tolerability for each subject. In this context, our study aims to carry out a clinical validation of a combinatorial pharmacogenomics (PGx) test in an Italian MDD patient cohort with advocacy license independence.MethodsOur study is a prospective participant- and rater-blinded, randomized, controlled clinical observational trial enrolling 300 MDD patients who are referred to psychiatric services to receive a new antidepressant due to the failure of their current treatment and/or the onset of adverse effects. Eligible participants are randomized to the TGTG group (Treated with Genetic Test Guide) or TAU group (Treated as Usual). For all subjects, DNA is collected with a buccal brush. The primary outcome is the reduction in depressive symptomatology. The secondary outcomes involve a range of scales that assess MDD symptoms and social functioning outcomes. The assessment is performed at four timepoints: baseline and 4, 8, and 12 weeks.DiscussionThis project represents the first randomized controlled clinical trial to investigate whether a non-commercial PGx test improves outcomes in an MDD naturalistic cohort. Moreover, the identification of new genetic variants associated with non-response or side effects will improve the efficacy of the test, leading to further cost-saving.Trial registration numberClinicalTrials.gov NCT04615234. Registered on November 4, 2020.

Curative effect of the combined therapy of warm acupuncture at back-shu points of five zang organs and western medicine on depression of yang deficiency pattern and its attenuating effect

To compare the therapeutic results and the occurrence of adverse reactions of medicine between the combined therapy of warm acupuncture at back-shu points of five zang organs and the western medicine and the simple wes-tern medication, and observe the therapeutic effect and attenuating effect of this combined therapy in treatment on depression of yang deficiency pattern. A total of 80 patients with depression of yang deficiency pattern were randomly divided into an observation group and a control group （39 cases/group）. In the control group, escitalopram oxalate tablets were administered orally every day. In the observation group, on the base of the medication as the control group, warm acupuncture therapy was exerted at back-shu points of five zang organs, for 30 min each time, 5 times a week. The duration of treatment was 6 weeks in two groups. Before and after treatment, the scores of Hamilton depression scale (HAMD) and the antidepressant side effect scale (SERS) were evaluated and electroencephalogram (EEG) was detected; and the curative effect was assessed according to HAMD reduction rate in patients of the two groups. After treatment, the HAMD and SERS scores were lower than those before treatment in both groups. Compared with the control group, the HAMD and SERS scores were lower (P<0.05, P<0.01), and the EEG result was improved (P<0.01) in the observation group. The clinical total effective rate of the observation group was 97.43% (38/39), higher than 92.30% (36/39) of the control group (P<0.05). The combined therapy of warm acupuncture at back-shu points of five zang organs and western medicine effectively relieves depression of yang deficiency pattern in the patients and its overall therapeutic effect is better than simple western medication, besides, the combined therapy alleviates the adverse reactions induced by simple western medication.

Understanding genetic risk factors for common side effects of antidepressant medications

BackgroundMajor depression is one of the most disabling health conditions internationally. In recent years, new generation antidepressant medicines have become very widely prescribed. While these medicines are efficacious, side effects are common and frequently result in discontinuation of treatment. Compared with specific pharmacological properties of the different medications, the relevance of individual vulnerability is understudied.MethodsWe used data from the Australian Genetics of Depression Study to gain insights into the aetiology and genetic risk factors to antidepressant side effects. To this end, we employed structural equation modelling, polygenic risk scoring and regressions.ResultsHere we show that participants reporting a specific side effect for one antidepressant are more likely to report the same side effect for other antidepressants, suggesting the presence of shared individual or pharmacological factors. Polygenic risk scores (PRS) for depression associated with side effects that overlapped with depressive symptoms, including suicidality and anxiety. Body Mass Index PRS are strongly associated with weight gain from all medications. PRS for headaches are associated with headaches from sertraline. Insomnia PRS show some evidence of predicting insomnia from amitriptyline and escitalopram.ConclusionsOur results suggest a set of common factors underlying the risk for antidepressant side effects. These factors seem to be partly explained by genetic liability related to depression severity and the nature of the side effect. Future studies on the genetic aetiology of side effects will enable insights into their underlying mechanisms and the possibility of risk stratification and prophylaxis strategies.

Effectiveness and tolerability of eight-week treatment with dosulepin hydrochloride in patients with major depressive disorder not responding to four consecutive weeks of treatment with single selective serotonin reuptake inhibitor

Background: Though manageable, major depressive disorder remains an underdiagnosed and undertreated condition. The objective of this study was to assess the effectiveness and safety of 8 weeks of treatment with the tricyclic antidepressant dosulepin hydrochloride in patients with depressive episodes not responsive to 4 consecutive weeks of treatment with a single selective serotonin reuptake inhibitor (SSRI).Methods: Patients diagnosed with depressive episode without psychotic symptoms (by ICD-10 diagnostic criteria for research), mini-mental state examination score of ≥24, and not responsive to four weeks of treatment with SSRIs (&lt;50% reduction in depressive symptoms) were enrolled. The main outcome measures were mean change in the Hamilton depression, Hamilton anxiety, and insomnia severity index scores at Week 8 compared to baseline. Adverse events were recorded for safety assessment.Results: A total of 94 patients were enrolled, of which, 90 (95.7%) patients completed the study. Compared to baseline, 8 weeks of treatment significantly changed the HAM-D score by -12.7 (p&lt;0.0001), HAM-A score by -8.3 (p&lt;0.0001), and ISI score by -10.5 (p&lt;0.0001). One patient reported anemia and was withdrawn from the study. Dry mouth and insomnia followed by headache, blurred vision, and drowsiness were the most commonly reported side effects as measured with the antidepressant side-effects checklist. Most side effects were of mild intensity and were related to study medication.Conclusions: Eight weeks of treatment with dosulepin hydrochloride resulted in significant and clinically relevant improvements in depression, anxiety, and insomnia symptoms in Indian patients with MDD.