Antidepressant Selection Research Articles

Antidepressant Medications and Weight Change: A Narrative Review.

Antidepressant medications are the first-line treatment option for moderate to severe major depressive disorder. However, most antidepressants have numerous documented adverse events, including cardiometabolic effects and weight gain, which are major public health concerns. Antidepressant agents provide varying risk of associated weight gain, including significant within-class differences. Some agents, such as mirtazapine, show significant levels of weight gain, while others, such as bupropion, demonstrate weight-loss effects. Current findings suggest the role of histamine and serotonin off-target appetite-promoting pathways in adverse weight-gain effects. Therefore, controlling for undesired weight effects is an important consideration for the selection of antidepressants.

The affinity and selectivity of α-adrenoceptor antagonists, antidepressants, and antipsychotics for the human α1A, α1B, and α1D-adrenoceptors.

α1‐adrenoceptor antagonists are widely used for hypertension (eg, doxazosin) and benign prostatic hypertrophy (BPH, eg, tamsulosin). Some antidepressants and antipsychotics have been reported to have α1 affinity. This study examined 101 clinical drugs and laboratory compounds to build a comprehensive understanding of α1‐adrenoceptor subtype affinity and selectivity. [3H]prazosin whole‐cell binding was conducted in CHO cells stably expressing either the full‐length human α1A, α1B, or α1D‐adrenoceptor. As expected, doxazosin was a high‐affinity nonselective α1‐antagonist although other compounds (eg, cyclazosin, 3‐MPPI, and ARC239) had higher affinities. Several highly α1A‐selective antagonists were confirmed (SNAP5089 had over 1700‐fold α1A selectivity). Despite all compounds demonstrating α1 affinity, only BMY7378 had α1D selectivity and no α1B‐selective compounds were identified. Phenoxybenzamine (used in pheochromocytoma) and dibenamine had two‐component‐binding inhibition curves at all three receptors. Incubation with sodium thiosulfate abolished the high‐affinity component suggesting this part is receptor mediated. Drugs used for hypertension and BPH had very similar α1A/α1B/α1D‐adrenoceptor pharmacological profiles. Selective serotonin reuptake inhibitors (antidepressants) had poor α1‐adrenoceptor affinity. Several tricyclic antidepressants (eg, amitriptyline) and antipsychotics (eg, chlorpromazine and risperidone) had high α1‐adrenoceptor affinities, similar to, or higher than, α blockers prescribed for hypertension and BPH, whereas others had poor α1 affinity (eg, protriptyline, sulpiride, amisulpiride, and olanzapine). The addition of α blockers for the management of hypertension or BPH in people already taking tricyclic antidepressants and certain antipsychotics may not be beneficial. Awareness of the α‐blocking potential of different antipsychotics may affect the choice of drug for those with delirium where additional hypotension (eg, in sepsis) may be detrimental.

Effects of Transient and Prolonged Uncontrollable Stress on Animals of Dominant and Subordinate Social Status with Different Types of Stress Reactions

The aim of the present work was to study the effects of transient and prolonged uncontrollable stress on the behavior of animals with different types of stress reactions and social status. Transient stress (forced swimming for 5 min) led to suppression of movement activity in subordinate animals with the inactive type of stress reaction, while only one behavioral component of the stress reactions – grooming – appeared in active dominant animals. Exposure to prolonged uncontrollable stress (immobilization in tight cages for 4 h/day for five days) in active dominants, in contrast to inactive subordinates, produced signs of a depression-like state apparent as a significant decrease in body weight, increases in anhedonia and anxiety, decreases in movement and exploratory activity on day 5, and increases in pain thresholds compared with baseline. Subordinates with the inactive type of stress reactions showed stress reactions on day 5 of exposure consisting of decreases in movement and exploratory activity and increases in anxiety. Transient and prolonged uncontrollable stress had different actions on animals with different social status and behavioral strategies. These data may be useful for individual selection of appropriate antidepressants on the basis of psychophysiological characteristics.

Symptom-based selection of antidepressants

Most evidence-based pharmacological guidelines recommend selective serotonin reuptake inhibitors, serotoninnorepinephrine reuptake inhibitors, norepinephrine-dopamine reuptake inhibitors or norepinephrine and specific serotonin antidepressants as the first-line treatment for major depression. Since the clinical factors associated with treating patients with depression are relatively complex, it can be challenging to apply the recommendations of evidence-based medicine verbatim. Furthermore, the diagnostic criteria of major depressive disorders, which are defined in a polythetic and operational manner, inevitably result in their heterogeneity. Studies have inferred that depressive syndrome may be connected with “family resemblance” rather than being shared with a neurobiological essence. Therefore, the symptom-based selection of antidepressants can be supported by a network analysis that provides a novel perspective on the symptom structure of major depression. The symptom-based treatment algorithm suggests treatment options that can be applied to the symptoms that are included in and excluded from the diagnosis criteria of major depressive disorder. The symptom-based selection of antidepressants and other psychotropic agents involves matching the deconstructed symptoms of depression to the specific neuroanatomical regions and neurotransmitters. This ensures timely and optimized treatment options for patients with depression.

Some Forensic Aspects on Antidepressants Drugs

Antidepressants are the most prescribed for depression. The exact mechanism of action of antidepressant is unknown. The prevailing theory is that antidepressants increase the concentration of one or more brain chemicals (neurotransmitters) that nerves in the brain use to communicate with one another. The neurotransmitters affected by antidepressants are nor epinephrine, serotonin and dopamine. The different classes of antidepressants differ in the neurotransmitters they affect. This determines some of their side effects and potential drug interactions. All available antidepressants are effective and for most cases of depression there is no good evidence that any antidepressant is more effective than another. Side effects and potential drug interactions are major factors that influence selection of antidepressants. This article highlights some forensic aspects, their types, side effects and potential drug interactions of the major antidepressants classes.

A Review of Novel Antidepressants: A Guide for Clinicians.

This review article aims to provide insight into the mechanisms of action, pharmacokinetics, clinical efficacy, safety and tolerability of four novel antidepressants including desvenlafaxine, vortioxetine, vilazodone, and levomilnacipran. Following keywords are used in PubMed and Scopus to search for relevant articles: (depression) AND (psychopharmacology OR desvenlafaxine OR levomilnacipran OR vortioxetine OR vilazodone). Patients with a lack of effectiveness or tolerability to certain antidepressants may get benefit from selecting a new antidepressant with different mechanism of action. These medications can be an option in the selection of newer antidepressants. Depression may not be caused by the simple deficiency of serotonin in the brain, but rather a complex interplay of various neurotransmitters including serotonin, norepinephrine, glutamate, and histamine at certain brain areas. The above-mentioned novel antidepressants exert their therapeutic benefits by acting on multiple neurotransmitters. The complexity of underlying the neurobiological mechanism should be considered while formulating a plan of care.

Genetic Testing to Improve Antidepressant Selection, Redux

The utility of genetic testing in depression is still in question (NEJM JW Psychiatry Oct 2017). In a multisite study funded by the manufacturer of the

Влияние кратковременного и длительного неконтролируемого стресса на животных доминантного и субординантного социального статуса с различным типом стрессорной реакции

The aim of this study was to explore the effects of the short-term and subchronic uncontrolled stress on the behavior of animals with different of coping styles and social status. The short-term stress (forced 5-minute swimming) inhibits locomotion in subordinate rats with passive coping style, while dominants with active coping style exhibit only a slight stress reaction (grooming). Under subchronic uncontrolled stress (4-hour immobilization in confined cases for 5 days), active dominants, but not passive subordinate rats, develop the signs of a depression-like state, such as decreased body weight, increased anhedonia and anxiety, increased locomotory and research activity, and increased pain threshold, on the 5-th day of exposure, compared to the background. The subordinate rats with passive coping style show the stress reaction marked by the decreased locomotory and research activity and increased anxiety on the 5-th day of exposure. Thus, short-term and subchronic uncontrolled stress have different effects on animals with opposite social status and coping styles. These data can be useful for individual selection of appropriate antidepressants based on psychophysiological characteristics.

Anti-inflammatory treatment of depression: study protocol for a randomised controlled trial of vortioxetine augmented with celecoxib or placebo

BackgroundIn patients with major depressive disorder (MDD), antidepressant response and remission rates are low, highlighting the need for new treatment approaches. Recently, the abundant literature linking inflammatory processes and depressive symptoms have led to the hypothesis that selecting treatment for MDD based on the patient’s inflammatory status could be a promising strategy to improve outcomes in patients suffering from MDD. The aim of the randomised control trial we propose is to investigate the antidepressant efficacy of the combined treatment of MDD with antidepressant medication plus anti-inflammatory medication in individuals with raised inflammation levels. For the first time, this study will prospectively test the efficacy of an antidepressant plus anti-inflammatory augmentation based on baseline inflammatory maker levels in MDD using a randomised controlled trial design.MethodsThis study proposes to measure blood C-reactive protein (CRP) levels before the initiation of treatment in 200 participants with MDD. Study participants are then assigned into one of two study strata: either into the ‘Depression with inflammation’ stratum (CRP levels > 3 mg/L); or into the ‘Depression without inflammation’ stratum (CRP levels ≤ 3 mg/L). Within each of the two study strata, participants randomly receive either antidepressant medication alone (vortioxetine) plus anti-inflammatory medication (celecoxib) or vortioxetine plus placebo for six weeks. At the end of the treatment period, participants have the opportunity to continue vortioxetine alone for a six-month post-trial period. Clinical outcomes are measured at baseline, fortnightly during the treatment period and at the three-month and six-month post-trial visits. The primary outcome is change in MADRS score, with a primary endpoint of a score reduction by 50% from baseline to six weeks (end of augmentation treatment with celecoxib). Secondary clinical outcomes are changes in the cognitive dimensions of depression (cognitive function, emotion processing and social cognition). Biological outcome measures (levels of CRP and other inflammatory markers) are measured at baseline, after six weeks of treatment and at the six-month post-trial visit.DiscussionThe current study will generate novel evidence for biomarker-based personalised antidepressant treatment selection based on patient inflammatory status before treatment.Trial registrationAustralian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12617000527369p. Registered on 11 April 2017.

Tailoring antidepressant therapy based on genetic profiles

Background: Depression is a substantial public health concern that impacts millions of individuals globally. The wide range of symptoms and manifestations of depression emphasizes the need of tailoring treatment methods to each individual, which includes adapting antidepressant prescriptions accordingly. Genetic factors contribute to depression and its association with other psychiatric and non-psychiatric illnesses, highlighting the need of a thorough assessment that encompasses psychopathology, physical health, and genetic variables. Aim of Work: This research aims to highlight the significance of customized therapy in the management of depression, taking into account hereditary variables, metabolic abnormalities, and inflammatory indicators. The research also seeks to emphasize the potential use of genotyping in directing the selection of antidepressants and making dose changes for people with altered metabolism. Methods: The research entails examining previously published works on the genetic factors related to depression, the influence of inflammatory and metabolic abnormalities in its development, and the possible advantages of genotyping in the treatment of antidepressants. The research also examines the incorporation of genetic information, such as the tendency to develop cardio-metabolic illnesses due to several genes, together with non-genetic risk factors to improve treatment results.

Personalized Antidepressant Selection and Pathway to Novel Treatments: Clinical Utility of Targeting Inflammation.

Major depressive disorder (MDD) is a chronic condition that affects one in six adults in the US during their lifetime. The current practice of antidepressant medication prescription is a trial-and-error process. Additionally, over a third of patients with MDD fail to respond to two or more antidepressant treatments. There are no valid clinical markers to personalize currently available antidepressant medications, all of which have similar mechanisms targeting monoamine neurotransmission. The goal of this review is to summarize the recent findings of immune dysfunction in patients with MDD, the utility of inflammatory markers to personalize treatment selection, and the potential of targeting inflammation to develop novel antidepressant treatments. To personalize antidepressant prescription, a c-reactive protein (CRP)-matched treatment assignment can be rapidly implemented in clinical practice with point-of-care fingerstick tests. With this approach, 4.5 patients need to be treated for 1 additional remission as compared to a CRP-mismatched treatment assignment. Anti-cytokine treatments may be effective as novel antidepressants. Monoclonal antibodies against proinflammatory cytokines, such as interleukin 6, interleukin 17, and tumor necrosis factor α, have demonstrated antidepressant effects in patients with chronic inflammatory conditions who report significant depressive symptoms. Additional novel antidepressant strategies targeting inflammation include pharmaceutical agents that block the effect of systemic inflammation on the central nervous system. In conclusion, inflammatory markers offer the potential not only to personalize antidepressant prescription but also to guide the development of novel mechanistically-guided antidepressant treatments.

The effects of using the PReDicT Test to guide the antidepressant treatment of depressed patients: study protocol for a randomised controlled trial

BackgroundAntidepressant medication is commonly used to treat depression. However, many patients do not respond to the first medication prescribed and improvements in symptoms are generally only detectable by clinicians 4–6 weeks after the medication has been initiated. As a result, there is often a long delay between the decision to initiate an antidepressant medication and the identification of an effective treatment regimen.Previous work has demonstrated that antidepressant medications alter subtle measures of affective cognition in depressed patients, such as the appraisal of facial expression. Furthermore, these cognitive effects of antidepressants are apparent early in the course of treatment and can also predict later clinical response. This trial will assess whether an electronic test of affective cognition and symptoms (the Predicting Response to Depression Treatment Test; PReDicT Test) can be used to guide antidepressant treatment in depressed patients and, therefore, hasten treatment response compared to a control group of patients treated as usual.Methods/designThe study is a randomised, two-arm, multi-centre, open-label, clinical investigation of a medical device, the PReDicT Test. It will be conducted in five European countries (UK, France, Spain, Germany and the Netherlands) in depressed patients who are commencing antidepressant medication. Patients will be randomised to treatment guided by the PReDicT Test (PReDicT arm) or to Treatment as Usual (TaU arm). Patients in the TaU arm will be treated as per current standard guidelines in their particular country. Patients in the PReDicT arm will complete the PReDicT Test after 1 (and if necessary, 2) weeks of treatment. If the test indicates non-response to the treatment, physicians will be advised to immediately alter the patient’s antidepressant therapy by dose escalation or switching to another compound. The primary outcome of the study is the proportion of patients showing a clinical response (defined as 50% or greater decrease in baseline scores of depression measured using the Quick Inventory of Depressive Symptoms – Self-Rated questionnaire) at week 8. Health economic and acceptability data will also be collected and analysed.DiscussionThis trial will test the clinical efficacy, cost-effectiveness and acceptability of using the novel PReDicT Test to guide antidepressant treatment selection in depressed patients.Trial registrationClinicalTrials.gov, ID: NCT02790970. Registered on 30 March 2016.

Selection and measurement of control antidepressants in clinical tests for Chinese: A systematic review.

Objective:The study aims to help domestic application units and research institutions improve their research quality of antidepressant clinical tests by studying and analyzing the current status and problems in selecting control drugs during domestic antidepressant clinical tests and illustrating some key problems that should be noted when selecting the control drug in such researches.Methods:Considering the current domestic and overseas status of control drug selection in antidepressant clinical tests, various considerations, and misunderstandings on control drug selection in domestic antidepressant clinical tests were clarified and described, and possible factors that may influence the absolute effect of antidepressants were analyzed. Furthermore, problems that should be noted in selecting control drugs for the antidepressant clinical test, especially the placebo control, were stated.Results:During the antidepressant clinical research, selecting placebo controls conform to moral philosophy and safety requirements. To verify the absolute effect of a test drug, a placebo control should be set or 3-arm tests should be conducted as far as possible. Possible factors that may affect the absolute effect of the test drug, including illness severity of the subject at baseline and research scale, should be given consideration.Conclusions:Application units and research institutions should consider the selection of subjects, control the failure rate, strengthen safety risks, and control and intensify quality control to further improve the overall quality and research level of domestic antidepressant clinical tests.

Does Pharmacogenomic Testing Improve Clinical Outcomes for Major Depressive Disorder? A Systematic Review of Clinical Trials and Cost-Effectiveness Studies.

Pharmacogenomic testing has become scalable and available to the general public. Pharmacogenomics has shown promise for predicting antidepressant response and tolerability in the treatment of major depressive disorder (MDD). In theory, pharmacogenomics can improve clinical outcomes by guiding antidepressant selection and dosing. The current systematic review examines the extant literature to determine the impact of pharmacogenomic testing on clinical outcomes in MDD and assesses its cost-effectiveness. The MEDLINE/PubMed and Google Scholar databases were systematically searched for relevant articles published prior to October 2015. Search terms included various combinations of the following: major depressive disorder (MDD), depression, mental illness, mood disorder, antidepressant, response, remission, outcome, pharmacogenetic, pharmacogenomics, pharmacodynamics, pharmacokinetic, genetic testing, genome wide association study (GWAS), CYP450, personalized medicine, cost-effectiveness, and pharmacoeconomics. Of the 66 records identified from the initial search, relevant clinical studies, written in English, assessing the cost-effectiveness and/or efficacy of pharmacogenomic testing for MDD were included. Each publication was critically examined for relevant data. Two nonrandomized, open-label, 8-week, prospective studies reported overall greater improvement in depressive symptom severity in the group of MDD subjects receiving psychiatric care guided by results of combinatorial pharmacogenomic testing (GeneSight) when compared to the unguided group. One industry-sponsored, randomized, double-blind, 10-week prospective study reported a trend for improved outcomes for the GeneSight-guided group; however, the trend did not reach statistical significance. Another industry-sponsored, randomized, double-blind, 12-week prospective study reported a 2.5-fold increase in remission rates in the CNSDose-guided group (P < .0001). One naturalistic, unblinded, industry-sponsored study showed clinical improvement when pharmacogenomics testing guided prescribing; however, this study lacked a control group. A single cost-effectiveness study concluded that single gene testing was not cost-effective. Conversely, a separate study reported that combinatorial pharmacogenomic testing is cost-effective. A limited number of studies have shown promise for the clinical utility of pharmacogenomic testing; however, cost-effectiveness of pharmacogenomics, as well as demonstration of improved health outcomes, is not yet supported with replicated evidence.

Reevaluating Antidepressant Selection in Patients With Bruxism and Temporomandibular Joint Disorder

Temporomandibular joint disorder (TMD) is a broad pain disorder that refers to several conditions affecting the temporomandibular joint of the jaw and the muscles of mastication. As with most pain disorders, a high prevalence of depression and anxiety is associated with TMD. Research has shown that selective serotonin reuptake inhibitors (SSRIs), the first-line drug therapy for major depressive disorder, may not be suitable for TMD patients because SSRIs can induce teeth-grinding, otherwise known as bruxism. This is problematic because bruxism is believed to further exacerbate TMD. Therefore, the purpose of this literature review is to better understand the mechanism of SSRI-induced bruxism, as well as discuss alternative antidepressant options for treating depression and anxiety in patients with bruxism and TMD. Alternative classes of antidepressants reviewed include serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, atypical antidepressants, and monoamine oxidase inhibitors. Findings indicate that dopamine agonists and buspirone are currently the most effective medications to treat the side effects of SSRI-induced bruxism, but results regarding the effectiveness of specific antidepressants that avoid bruxism altogether remain inconclusive.

Genetic tests for controlling treatment with antidepressants

In clinical practice, there is aneed for amore individualized selection of antidepressants and adequate dosage. The investigation of pharmacokinetically relevant genes is a promising approach to assist this selection. In the past 2 years, two commercially available tests have been subject of advertisement, a test from Stada, which analyses variants of the cytochrome P450 isoenzymes CYP2D6 and CYP2C19 and a test from HMNC Brain Health, which analyses variants of the ABCB1 gene. The costs for both kits are not covered by the statutory health insurance and it is therefore proposed that the patients are invoiced directly in the form of individual healthcare payment. The companies claim that by applying the tests antidepressant treatment failure can be avoided and that patients will respond faster to the antidepressant used. These claims are not based on appropriate clinical trials, which are either lacking or reveal conflicting results. Hence, the routine use of these tests is not recommended. In accordance with the German S3 Guideline for unipolar depression, therapeutic drug monitoring (TDM) of serum levels should be carried out in cases of non-response to an antidepressant with adequate dosage and duration. As arule the costs for TDM are covered by the statutory health insurance. Cytochrome P450 genotyping is only indicated when the serum level is not within the expected range and other reasons to explain this discrepancy are excluded. Many laboratories provide these analyses and in individual cases the costs are reimbursed by the statutory health insurance. Further research should be carried out to investigate the importance of the ABCB1 gene for the treatment with antidepressants.

Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 3. Pharmacological Treatments.

The Canadian Network for Mood and Anxiety Treatments (CANMAT) conducted a revision of the 2009 guidelines by updating the evidence and recommendations. The scope of the 2016 guidelines remains the management of major depressive disorder (MDD) in adults, with a target audience of psychiatrists and other mental health professionals. Using the question-answer format, we conducted a systematic literature search focusing on systematic reviews and meta-analyses. Evidence was graded using CANMAT-defined criteria for level of evidence. Recommendations for lines of treatment were based on the quality of evidence and clinical expert consensus. "Pharmacological Treatments" is the third of six sections of the 2016 guidelines. With little new information on older medications, treatment recommendations focus on second-generation antidepressants. Evidence-informed responses are given for 21 questions under 4 broad categories: 1) principles of pharmacological management, including individualized assessment of patient and medication factors for antidepressant selection, regular and frequent monitoring, and assessing clinical and functional outcomes with measurement-based care; 2) comparative aspects of antidepressant medications based on efficacy, tolerability, and safety, including summaries of newly approved drugs since 2009; 3) practical approaches to pharmacological management, including drug-drug interactions and maintenance recommendations; and 4) managing inadequate response and treatment resistance, with a focus on switching antidepressants, applying adjunctive treatments, and new and emerging agents. Evidence-based pharmacological treatments are available for first-line treatment of MDD and for management of inadequate response. However, given the limitations of the evidence base, pharmacological management of MDD still depends on tailoring treatments to the patient.

Evidence-Based Selection and Use of Antidepressants in Psychiatric Practice

Depressive disorders (DD) have a high risk of recurrence and involve impairments to patients’ daily and social functioning and quality of life; these factors result in a high socioeconomic burden. Optimization of antidepressant use on the basis of the risk: benefit ratio and evidence-based resource-sparing potential is important for lightening of the load of DD, along with targeted psychosocial intervention and monitoring of compliance with the long-term therapy regime. Various aspects of the evidence-based selection of antidepressants for the treatment of DD on the basis of combined pharmacoepidemiological and pharmacoeconomic assessments of state-of-the-art agents (including SSRI and SNRI) are discussed.

Review on EEG and ERP predictive biomarkers for major depressive disorder

Abstract The selection of suitable antidepressants for Major Depressive Disorder (MDD) has been challenging and is mainly based on subjective assessments that include minimal scientific evidence. Objective measures that are extracted from neuroimaging modalities such as electroencephalograms (EEGs) could be a potential solution to this problem. This approach is achieved by the successful prediction of antidepressant treatment efficacy early in the patient's care. EEG-based relevant research studies have shown promising results. These studies are based on derived measures from EEG and event-related potentials (ERPs), which are called neurophysiological predictive biomarkers for MDD. This paper seeks to provide a detailed review on such research studies along with their possible limitations. In addition, this paper provides a comparison of these methods based on EEG/ERP common datasets from MDD and healthy controls. This paper also proposes recommendations to improve these methods, e.g., EEG integration with other modalities such as functional magnetic resonance imaging (fMRI) and magnetoencephalograms (MEG), to achieve better evidence of the efficacy than EEG alone, to eventually improve the treatment selection process.

Biomarkers for Antidepressant Selection: iSPOT-D Study

The International Study to Predict Optimized Treatment in Depression (iSPOT-D) is a randomized clinical trial conducted at 22 sites across 5 countries, looking at biomarkers of improvement in depressive symptoms to treatment with SSRIs escitalopram and sertraline, and the SNRI venlafaxine-XR. It is the first to take an integrative neuroscience approach to biomarker discovery, looking across the disciplines of structural and functional MRI, EEG, cognitive performance, and genomics, all in the same patients. The initial biomarkers from within each of these disciplines have now been reported. Symptom improvement has been found to be predicted by markers relating to greater structural connectivity in the cingulate and less connectivity in hippocampal and amygdala axonal projections, along with less amygdala engagement in processing facial emotion. Non-remission has additionally been predicted by markers relating to less attention and cognitive control, including less engagement of the dorsolateral prefrontal cortex during inhibitory control and smaller medial frontal volume, greater frontal EEG theta activity, and poorer cognitive performance. Specific biomarkers of response to SSRIs have been identified that include the rs10245483 SNP major allele and better performance on the cognitive assessment, and in females, more left lateralized resting brain activity. Symptom improvement to the SNRI has been found to be predicted by rs10245483 SNP minor allele, less amygdala engagement to sad facial expressions and less frontal EEG theta. The next step in this study will be to integrate these findings across disciplines so as to explore how this integration can enhance prediction accuracy and improve our understanding of the key drivers underlying these relationships, and whether integration into a single biomarker or a more stepwise approach is a more feasible approach from a real-world clinical perspective. The replicability of these biomarkers will also be evaluated in a new sample of patients.