Weeks Of Antidepressant Treatment Research Articles

Investigation of serum levels of sortilin in response to antidepressant treatment.

The identification of biomarkers for depression is of great clinical relevance as the diagnosis is currently subjective. Recent research points towards sortilin as a potential biomarker for depression, and the aim of the current study was to investigate the serum sortilin level in response to antidepressant treatment. The study included 56 depressed individuals of which 41 responded to treatment. Depression scores and serum levels of sortilin were measured at baseline and after 12 weeks of antidepressant treatment. Statistical analyses were performed using Stata 13. The depression score and response to treatment were not predicted by the sortilin level. Likewise, we observed no significant change in serum sortilin levels following 12 weeks of antidepressant treatment. Furthermore, no association between the serum sortilin level and depression score was observed. The results do not point towards sortilin as a state-dependent biomarker.

Early prediction of non-response to anti-depressive treatment with an easy-to-use electrophysiological index dynamics

IntroductionThe evaluation of response to pharmacological treatment in MDD requires 6–8 weeks. Therefore, the ability to predict response, and especially lack of response to treatment, as early as possible after treatment onset or change, is of major significance. Many studies demonstrated significant results regarding the ability to use EEG and ERP markers. However, these markers are derived from long EEG/ERP samples, often from multiple channels, which render them impractical for frequent sampling.MethodsWe developed a new electrophysiological attention-related marker from a single channel (2 electrodes) and 1 minute samples. This work presents an initial evaluation of the ability to harness this marker, for early differentiation between responders and non-responders to anti-depressive treatment, in 26 patients with various levels of depression and heterogeneous treatment interventions and 10 healthy controls. Subjects who initiated treatment for depression were followed clinically through their Hamilton depression scores as well as their EEG activity twice a week for a period of 8 weeks. Any acceptable anti-depressive treatment been included. The improvement in Hamilton scores at the end of 8 weeks used to discriminate responders and non-responders.ResultsWithin two weeks, we could differentiate between non-responders and responders to anti-depressive treatment, with absolute discrimination between subjects with moderate to severe depression, and with 0.71 sensitivity and 0.96 specificity within the whole depressed subjects.ConclusionsThis is a proof of concept for an easy to use, cheap and quick marker for the lack of respond to anti-depressive treatment within two weeks of anti-depressive treatment.

Effects of Escitalopram on C reactive protein in patients of depression

Objective: To study the anti-inflammatory activity of Escitalopram in newly diagnosed patients of depression. Materials and Methods: 100 Newly diagnosed patients of Depression as per ICD 10 (International classification of diseases) DCR (Diagnostic criteria for research) were selected for study after applying strict inclusion and exclusion criteria. Baseline Hamilton depression rating scale (HAMD) and baseline C reactive protein (CRP) was assessed and antidepressant treatment was started. After 8 weeks, again HAMD and CRP were assessed. Results: Mean of Baseline CRP was higher in patients in those who have no response after antidepressant treatment and it was significant. The relationship between baseline HAMD and baseline CRP was found to be significantly positively correlated. Mean HAMD was significantly reduced after 8 weeks of antidepressant treatment. Mean CRP was significantly reduced after 8 weeks of antidepressant treatment. The relationship between baseline CRP and reduction in HAM D (in baseline and after 8 weeks of treatment) found to be negatively correlated and it was significant. Conclusion: Escitalopram reduced C reactive protein in depressed patient and result was significant.

Characteristics of new depression diagnoses in patients with and without prior chronic opioid use

Chronic use (>90 Days) of opioid analgesics significantly increases the risk of development of new depression episodes (NDE). It is unclear whether depression that develops in this manner is similar to or different from NDE in persons not exposed to opioid analgesic use (OAU). MethodsVA patients were classified into two groups, those who did not receive an opioid and developed depression (non-OAU+NDE, n=4314) and those that had >90 days OAU and developed NDE (OAU+NDE, n=444). OAU+NDE patients were compared to non-OAU+NDE in terms of depression severity (PHQ-9 scores), incidence of PTSD, other anxiety disorders and substance use disorders after NDE, receipt of acute phase antidepressant treatment, dual antidepressant treatment, mood stabilizers and atypical antipsychotics. Prior to computing bivariate analysis, the prevalence of pain conditions and average maximum pain scores were equalized between the two groups using propensity scores and inverse probability of treatment weighting. ResultsControlling for pain, OAU+NDE patients had more depression symptoms (p=.012), more incident PTSD (p=.04) and opioid abuse/dependence and were more likely to receive 12 weeks of antidepressant treatment (p<.0001). Last, non-OAU+NDE were more likely to have incident diagnoses for any other anxiety disorder (p=.014). ConclusionsWithin the limitations of electronic medical record data, results indicate OAU+NDE patients have more depression symptoms, greater treatment adherence and different comorbid psychiatric conditions compared to non-OAU+NDE, independent of pain. Overall OAU related depression is as severe as non-OAU related depression and repeated depression screening in chronic opioid therapy may be warranted for pain patients, regardless of pain severity.

A Breathing-Based Meditation Intervention for Patients With Major Depressive Disorder Following Inadequate Response to Antidepressants: A Randomized Pilot Study.

To evaluate feasibility, efficacy, and tolerability of Sudarshan Kriya yoga (SKY) as an adjunctive intervention in patients with major depressive disorder (MDD) with inadequate response to antidepressant treatment. Patients with MDD (defined by DSM-IV-TR) who were depressed despite ≥ 8 weeks of antidepressant treatment were randomized to SKY or a waitlist control (delayed yoga) arm for 8 weeks. The primary efficacy end point was change in 17-item Hamilton Depression Rating Scale (HDRS-17) total score from baseline to 2 months. The key secondary efficacy end points were change in Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI) total scores. Analyses of the intent-to-treat (ITT) and completer sample were performed. The study was conducted at the University of Pennsylvania between October 2014 and December 2015. In the ITT sample (n = 25), the SKY arm (n = 13) showed a greater improvement in HDRS-17 total score compared to waitlist control (n = 12) (-9.77 vs 0.50, P = .0032). SKY also showed greater reduction in BDI total score versus waitlist control (-17.23 vs -1.75, P = .0101). Mean changes in BAI total score from baseline were significantly greater for SKY than waitlist (ITT mean difference: -5.19; 95% CI, -0.93 to -9.34; P = .0097; completer mean difference: -6.23; 95% CI, -1.39 to -11.07; P = .0005). No adverse events were reported. Results of this randomized, waitlist-controlled pilot study suggest the feasibility and promise of an adjunctive SKY-based intervention for patients with MDD who have not responded to antidepressants. ClinicalTrials.gov identifier: NCT02616549.

Association of Obstructive Sleep Apnea with Episodic Memory and Cerebral Microvascular Pathology: A Preliminary Study

To evaluate the impact of obstructive sleep apnea (OSA) on neurocognitive function and brain morphology in older adults with depression and cognitive impairment. We prospectively screened OSA with the STOP-Bang questionnaire in the last 25 patients enrolled into the Donepezil Treatment of Cognitive Impairment and Depression (DOTCODE) trial. High and low probability of OSA were defined as a STOP-Bang score of ≥5 (h-OSA) and of <5 (l-OSA), respectively. Baseline magnetic resonance imaging (MRI) was used to evaluate brain morphology. The initial 16 weeks of antidepressant treatment were part of the DOTCODE trial. After 16 weeks of antidepressant treatment, the h-OSA group performed significantly worse on the Selective Reminding Test delayed recall task than the l-OSA group, controlling for baseline performance (F = 19.1, df = 1,22, p < 0.001). In 19 of 25 participants who underwent brain MRI, the h-OSA group had significantly greater volumes of MRI hyperintensities in deep white matter, periventricular white matter, and subcortical gray matter compared with the l-OSA group. There was no significant association between OSA and hippocampal or entorhinal cortex volumes in our sample, even after controlling for intracranial volume. OSA is associated with impaired verbal episodic memory and microvascular damage in older adults with depression and cognitive impairment. One possibility is that by contributing to cerebral microvascular damage, OSA may exacerbate progressive memory decline.

Influence of temperamental and character traits on antidepressant response in patients affected by major depressive disorder

Several studies have been conducted to evaluate personality characteristics in patients affected by major depressive disorder. Temperamental and character traits may help clinicians to identify responders to antidepressive therapy. The aim of our study was to evaluate these characteristics as possible predictive indices of response to SSRIs or SNRIs. A cohort of 41 patients was included (30 F and 11 M), whose diagnosis was made according to DSM-IV criteria. Subjects were interviewed using the HAM-D and the HAM-A scale in basal condition (T0) and after 4 weeks (T1) of antidepressive treatment. Patients with a ≥ 50% reduction of HAM-D and HAM-A score, have been considered as responders, when compared to basal conditions. All subjects were in monotherapy and evaluated using the TCI-R scale. In patients affected by major depressive disorder, personality assessment was characterised, from a temperamental point of view, by high levels of Persistence and Reward Dependence and, from a character one, by high levels of Self Directiveness and Cooperativity. After 4 weeks of antidepressive treatment, responders to HAM-D had higher levels of Responsibility versus Guilt, which could be considered as a predictor of positive response to SSRIs or SNRIs. Conversely, responders to HAM-A showed higher values of Responsibility versus Guilt and of Safety versus Fear of uncertainty. These values were predictive of a recovery of anxious sintomatology associated with depressive disorder. Our results are in line with those reported in the literature, indicating that character dimensions “Self Directiveness” and “Cooperativity” could be important predictors of response to antidepressants.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Clinical status after two-weeks of antidepressant treatment: A prognostic factor in unipolar major depression?

Although most unipolar depression clinical guidelines advise against evaluating the efficacy of antidepressant pharmacological treatment until it has been administered in therapeutic doses for a minimum of 4–6 weeks, there is an increasing tendency to make therapeutic decisions after only 2 weeks of treatment. We present a study which aim is to determine whether the clinical course, following 2 weeks of antidepressant treatment, allows therapeutic decisions to be made for patients affected by a moderate/severe depressive episode. The study has an 8-week, prospective, observational design in which all consecutive in- and outpatients with moderate/severe unipolar major depression aged over 17 years received antidepressant treatment based on a standardized treatment protocol. Clinical status was assessed at baseline and at 2-, 4-, and 8-weeks. The final sample consisted of a total of 114 subjects. In our sample, the rate of remitters versus non-remitters was similar between the 2-week improvers and the 2-week non-improvers. It should also be emphasized that it was not possible to explain, based on the epidemiological and clinical characteristics assessed, which 2-week non-improvers would tend towards remission and which would show a partial or full response. Based on these results, for patients affected by a moderate/severe unipolar depressive episode, it would not be appropriate to make new therapeutic decisions following 2 weeks of anti-depressive pharmacological treatment depending on whether the patient has shown clinical improvement or not.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Role of Serum Brain Derived Neurotrophic Factor and Central N-Acetylaspartate for Clinical Response under Antidepressive Pharmacotherapy

Background: The predictive therapeutic value of brain derived neurotrophic factor (BDNF) and its changes associated with the use of specific antidepressants are still unclear. In this study, we examined BDNF as a peripheral and NAA as a central biomarker over the time course of antidepressant treatment to specify both of their roles in the response to the medication and clinical outcome. Methods: We examined serum BDNF (ELISA kit) in a sample of 76 (47 female and 29 male) depressed patients in a naturalistic setting. BDNF was assessed before medication and subsequently after two, four and six weeks of antidepressant treatment. Additionally, in fifteen patients, N-acetylaspartate (NAA) was measured in the anterior cingulate cortex (ACC) with magnetic resonance spectroscopy (MRS). Over a time course of six weeks BDNF and NAA were also examined in a group of 41 healthy controls. Results: We found significant lower serum BDNF concentrations in depressed patients compared to the sample of healthy volunteers before and after medication. BDNF and clinical symptoms decreased significantly in the patients over the time course of antidepressant treatment. Serum BDNF levels at baseline predicted the symptom outcome after eight weeks. Specifically, responders and remitters had lower serum BDNF at baseline than the nonresponders and nonremitters. NAA was slightly decreased but not significantly lower in depressed patients when compared with healthy controls. During treatment period, NAA showed a tendency to increase. Limitations: A relative high drop-out rate and possibly, a suboptimal observation period for BDNF. Conclusion: Our data confirm serum BDNF as a biomarker of depression with a possible role in response prediction. However, our findings argue against serum BDNF increase being a prerequisite to depressive symptom reduction.

Decreased Total Antioxidant Activity in Major Depressive Disorder Patients Non-Responsive to Antidepressant Treatment.

ObjectiveThis study aimed to evaluate the total antioxidant activity (TAA) in patients with major depressive disorder (MDD) and the effect of antidepressants on TAA using a novel potentiometric method.MethodsTwenty-eight patients with MDD and thirty-one healthy controls were enrolled in this study. The control group comprised 31 healthy individuals matched for gender, drinking and smoking status. We assessed symptoms of depression using the Hamilton Depression Rating Scale (HAMD) and the Beck Depression Inventory (BDI). We measured TAA using potentiometry. All measurements were made at baseline and four and eight weeks later.ResultsThere was a significant negative correlation between BDI scores and TAA. TAA was significantly lower in the MDD group than in controls. When the MDD group was subdivided into those who showed clinical response to antidepressant therapy (response group) and those who did not (non-response group), only the non-response group showed lower TAA, while the response group showed no significant difference to controls at baseline. After eight weeks of antidepressant treatment, TAA in both the response and non-response groups was similar, and there was no significant difference among the three groups.ConclusionThese results suggest that the response to antidepressant treatment in MDD patients might be predicted by measuring TAA.

Association between ABCB1 Polymorphisms and Antidepressant Treatment Response in Taiwanese Major Depressive Patients.

ObjectiveThe multidrug resistance 1 (ABCB1, MDR1) gene, encoding P-glycoprotein, is extensively distributed and expressed in various tissues, such as a blood-brain barrier transporter. P-glycoprotein plays an important role in controlling the passage of substances between the blood and brain. The current study aimed to investigate possible associations of functional ABCB1 polymorphisms (C3435T, G2677T and C1236T) with response to antidepressant treatment and serum cortisol levels in Taiwanese patients with major depressive disorder (MDD).MethodsWe recruited 112 MDD patients who were randomized to fluoxetine (n=58, mean dose: 21.4±4.5 mg/day) or venlafaxine (n=54, 80.2±34.7 mg/day) treatment for 6 weeks. The 21-item Hamilton Depression Rating Scale (HDRS) was administered initially and biweekly after treatment, and cortisol levels were assessed initially and after 6-week antidepressant treatment.ResultsThe initial HDRS scores and the HDRS scores after six weeks of antidepressant treatment were not significantly different among the different genotypes in each polymorphism of ABCB1. The percentage changes of HDRS scores over time were significantly different in the polymorphisms of ABCB1 G2677T (p=0.002). MDD patients with the G/G genotype of ABCB1 G2677T had a worse antidepressant treatment response. However, the polymorphisms of ABCB1 genotypes were not significantly associated with cortisol levels before and after antidepressant treatment in MDD patients.ConclusionThe results suggested that the variants of ABCB1 may influence the short-term antidepressant response in MDD patients. Further details of the underlying mechanisms of ABCB1 in antidepressant treatment remain to be clarified.

Salience Network Functional Connectivity Predicts Placebo Effects in Major Depression

BackgroundRecent neuroimaging studies have demonstrated resting-state functional connectivity (rsFC) abnormalities among intrinsic brain networks in major depressive disorder (MDD); however, their role as predictors of treatment response has not yet been explored. Here, we investigate whether network-based rsFC predicts antidepressant and placebo effects in MDD. MethodsWe performed a randomized controlled trial of two week-long, identical placebos (described either as having active fast-acting, antidepressant effects or as inactive) followed by a 10-week open-label antidepressant medication treatment. Twenty-nine participants underwent an rsFC functional magnetic resonance imaging scan at the completion of each placebo condition. Networks were isolated from resting-state blood oxygen level-dependent signal fluctuations using independent component analysis. Baseline and placebo-induced changes in rsFC within the default mode, salience, and executive networks were examined for associations with placebo and antidepressant treatment response. ResultsIncreased baseline rsFC in the rostral anterior cingulate within the salience network, a region classically implicated in the formation of placebo analgesia and the prediction of treatment response in MDD, was associated with greater response to 1 week of active placebo and 10 weeks of antidepressant treatment. Machine learning further demonstrated that increased salience network rsFC, mainly within the rostral anterior cingulate, significantly predicts individual responses to placebo administration. ConclusionsThese data demonstrate that baseline rsFC within the salience network is linked to clinical placebo responses. This information could be employed to identify patients who would benefit from lower doses of antidepressant medication or nonpharmacologic approaches or to develop biomarkers of placebo effects in clinical trials.

Neurotrophic factors in depression in response to treatment

BackgroundBrain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor A (VEGF) have been suggested to play a role in the pathophysiology of depression. The neurotrophic model of depression hypothesises that the serum level of e.g. BDNF is decreased during depression and increased in response to treatment. The aim of the present study was to investigate BDNF and VEGF as potential predictors of response to antidepressant treatment. MethodsWe investigated the longitudinal associations between depression scores and serum levels of these neurotrophic factors during antidepressant treatment in 90 individuals with depression of at least moderate severity. Serum levels were measured at baseline and after 8 and 12 weeks of treatment with nortriptyline or escitalopram. ResultsNo baseline or longitudinal correlations between depression scores and serum levels of BDNF and VEGF were found, and the baseline serum levels did not predict the MADRS depression score after 12 weeks of treatment or the improvement in depression scores. Interestingly, we observed a significant baseline and longitudinal correlation between serum levels of BDNF and VEGF. The two classes of antidepressant treatment did not affect the results differently. LimitationsInformation on potential factors influencing the serum levels is missing. ConclusionOur results do not support the neurotrophic model of depression, since a significant decrease in serum BDNF and VEGF levels after 12 weeks of antidepressant treatment was observed. Our study encourages future studies with large sample sizes, more observations and a longer follow-up period.

Chronobiological hypothalamic–pituitary–thyroid axis status and antidepressant outcome in major depression

We previously demonstrated that the difference between 2300h and 0800h TSH response to protirelin (TRH) tests on the same day (ΔΔTSH test) is an improved measure in detecting hypothalamic-pituitary-thyroid (HPT) axis dysregulation in depression. This chronobiological index (1) is reduced in about three quarters of major depressed inpatients, and (2) is normalized after successful antidepressant treatment. In the present study, we examined whether early changes in HPT axis activity during the first 2 weeks of antidepressant treatment could be associated with subsequent outcome. The ΔΔTSH test was performed in 50 drug-free DSM-IV euthyroid major depressed inpatients and 50 hospitalized controls. After 2 weeks of antidepressant treatment the ΔΔTSH test was repeated in all inpatients. Antidepressant response was evaluated after 6 weeks of treatment. At baseline, ΔΔTSH values were significantly lower in patients compared to controls and 38 patients (76%) showed reduced ΔΔTSH values (i.e., <2.5mU/L). After 2 weeks of antidepressant treatment, 20 patients showed ΔΔTSH normalization (among them 18 were subsequent remitters), while 18 patients did not normalize their ΔΔTSH (among them 15 were non-remitters) (p<0.00001). Among the 12 patients who had normal ΔΔTSH values at baseline, 8 out 9 who had still normal values after 2 weeks of treatment were remitters, while the 3 with worsening HPT axis function (i.e., reduced ΔΔTSH value after 2 weeks of treatment) were non-remitters (p<0.02). A logistic regression analysis revealed that ΔΔTSH levels after 2 weeks of treatment could predict the probability of remission (odds ratio [OR]=2.11, 95% confidence interval [CI]=1.31-3.41). Our results suggest that after 2 weeks of antidepressant treatment: (1) chronobiological restoration of the HPT axis activity precedes clinical remission, and (2) alteration of the HPT axis is associated with treatment resistance.

COGNITION-CHILDHOOD MALTREATMENT INTERACTIONS IN THE PREDICTION OF ANTIDEPRESSANT OUTCOMES IN MAJOR DEPRESSIVE DISORDER PATIENTS: RESULTS FROM THE iSPOT-D TRIAL.

Childhood maltreatment (CM) history has been associated with poor treatment response in major depressive disorder (MDD), but the mechanisms underlying this relationship remain opaque. Dysfunction in the neural circuits for executive cognition is a putative neurobiological consequence of CM that may contribute importantly to adverse clinical outcomes. We used behavioral and neuroimaging measures of executive functioning to assess their contribution to the relationship between CM and antidepressant response in MDD patients. Ninety eight medication-free MDD outpatients participating in the International Study to Predict Optimized Treatment in Depression were assessed at baseline on behavioral neurocognitive measures and functional magnetic resonance imaging during tasks probing working memory (continuous performance task, CPT) and inhibition (Go/No-go). Seventy seven patients completed 8 weeks of antidepressant treatment. Baseline behavioral and neuroimaging measures were assessed in relation to CM (history of childhood physical, sexual, and/or emotional abuse) and posttreatment depression outcomes. Patients with maltreatment exhibited decreased modulation of right dorsolateral prefrontal cortex (DLPFC) activity during working memory updating on the CPT, and a corresponding impairment in CPT behavioral performance outside the scanner. No between-group differences were found for imaging or behavior on the Go/No-go test of inhibition. Greater DLPFC activity during CPT significantly predicted posttreatment symptom improvement in patients without maltreatment, whereas the relationship between DLPFC activity and symptom change was nonsignificant, and in the opposite direction, in patients with maltreatment. The effect of CM on prefrontal circuitry involved in executive function is a potential predictor of antidepressant outcomes.

Mindfulness-based cognitive therapy vs. psycho-education for patients with major depression who did not achieve remission following antidepressant treatment

Mindfulness-based cognitive therapy (MBCT) showed efficacy for currently depressed patients. However, most of the available studies suffer from important methodological shortcomings, including the lack of adequate control groups. The present study aims to compare MBCT with a psycho-educational control group designed to be structurally equivalent to the MBCT program but excluding the main putative “active ingredient” of MBCT (i.e., mindfulness meditation practice) for the treatment of patients with major depression (MD) who did not achieve remission following at least 8 weeks of antidepressant treatment. Out of 106 screened subjects, 43 were randomized to receive MBCT or psycho-education and were prospectively followed for 26 weeks. MD severity was assessed with the Hamilton Rating Scale for Depression (HAM-D) and the Beck Depression Inventory-II (BDI-II). Measures of anxiety, mindfulness, and quality of life were also included. All assessments were performed at baseline, 4, 8, 17 and 26-weeks. Both HAM-D and BDI scores, as well as quality of life and mindfulness scores, showed higher improvements, which were particularly evident over the long-term period, in the MBCT group than in the psycho-education group. Although limited by a small sample size, the results of this study suggest the superiority of MBCT over psycho-education for non-remitted MD subjects.

IGF-I in major depression and antidepressant treatment response

We analyzed insulin-like growth factor I (IGF-I) in serum of 78 inpatients with depression and 92 healthy controls. Patients were selected according to remission status after 6 weeks of antidepressant treatment with remission defined by Hamilton depression rating scale (HAM-D) 21-item score <10 (39 remitters and 39 non-remitters).IGF-I was analyzed in patients at admission and after 6 weeks of psychopharmacological treatment. IGF-I levels were compared between patients and controls and between remitters and non-remitters with general linear model using age, gender, and body mass index as covariates.In patients, IGF-I levels were significantly higher at admission (p=3.29E−04) and in week 6 (p=0.002) compared to controls. Furthermore, non-remitters showed significantly higher IGF-I levels at admission (p=0.046) and a trend for higher IGF-I levels in week 6 (p=0.11) compared to remitters. In remitters change in IGF-I levels during treatment was significantly correlated with change in cortisol levels (p=0.019).A genetic association analysis of polymorphisms in 10 genes contributing to the IGF-I system (IGF1, IGF1R, IGFBP1 to IGFBP7, and IGFBPL1) in the currently largest genetic databases for major depression (Psychiatric Genomics Consortium) revealed nominal associations with susceptibility for depression and treatment response, although results did not remain significant after multiple testing correction.In our study, elevated IGF-I levels were significantly associated with depression and impaired treatment response. Based on these findings IGF-I signaling could play a role in the pathophysiology of depression and could possibly influence the response to antidepressant treatment.

No change in N-acetyl aspartate in first episode of moderate depression after antidepressant treatment: (1)H magnetic spectroscopy study of left amygdala and left dorsolateral prefrontal cortex.

BackgroundThe role of brain metabolites as biological correlates of the intensity, symptoms, and course of major depression has not been determined. It has also been inconclusive whether the change in brain metabolites, measured with proton magnetic spectroscopy, could be correlated with the treatment outcome.MethodsProton magnetic spectroscopy was performed in 29 participants with a first episode of moderate depression occurring in the left dorsolateral prefrontal cortex and left amygdala at baseline and after 8 weeks of antidepressant treatment with escitalopram. The Montgomery-Asberg Depression Rating Scale, the Hamilton Rating Scale for Depression, and the Beck Depression Inventory were used to assess the intensity of depression at baseline and at the endpoint of the study. At endpoint, the participants were identified as responders (n=17) or nonresponders (n=12) to the antidepressant therapy.ResultsThere was no significant change in the N-acetyl aspartate/creatine ratio (NAA/Cr) after treatment with antidepressant medication. The baseline and endpoint NAA/Cr ratios were not significantly different between the responder and nonresponder groups. The correlation between NAA/Cr and changes in the scores of clinical scales were not significant in either group.ConclusionThis study could not confirm any significant changes in NAA after antidepressant treatment in the first episode of moderate depression, or in regard to therapy response in the left dorsolateral prefrontal cortex or left amygdala. Further research is necessary to conclude whether NAA alterations in the first episode of depression could possibly be different from chronic or late-onset depression, and whether NAA alterations in stress-induced (reactive) depression are different from endogenous depression. The potential role of NAA as a biomarker of a treatment effect has yet to be established.

Adverse effects from antidepressant treatment: randomised controlled trial of 601 depressed individuals

RationalePremature discontinuation of antidepressant drugs is a frequent clinical problem. Adverse effects are common, occur early on in treatment and are reported to be one of the main reasons for discontinuation of antidepressant treatment.ObjectivesTo investigate the association between adverse effects occurring in the first 2 weeks of antidepressant treatment and discontinuation by 6 weeks as the outcome. To investigate the time profile of adverse effects induced by the selective serotonin reuptake inhibitor citalopram and the noradrenaline reuptake inhibitor reboxetine over 12 weeks of treatment.MethodsSix hundred and one depressed individuals were randomly allocated to either citalopram (20 mg daily) or reboxetine (4 mg twice daily). A modified version of the Toronto Side Effects Scale was used to measure 14 physical symptoms at baseline (medication free) and at 2, 6 and 12 weeks after randomisation.ResultsIndividuals randomised to reboxetine reported a greater number of adverse effects and were more likely to stop treatment than individuals receiving citalopram. Dizziness (OR 1.83; 95% CI 1.09, 3.09; p = 0.02) and the total number of adverse effects (OR 1.12; 95% CI 1.00, 1.25; p = 0.06) reported at 2 weeks were associated with discontinuation from overall antidepressant treatment by 6 weeks. Reports of adverse effects tended to reduce throughout the 12 weeks for both antidepressants.ConclusionsThe majority of adverse effects were not individually associated with discontinuation from antidepressant treatment. Reports of physical symptoms tended to reduce over time. The physical symptoms that did not reduce over time may represent symptoms of depression rather than antidepressant-induced adverse effects.Electronic supplementary materialThe online version of this article (doi:10.1007/s00213-014-3467-8) contains supplementary material, which is available to authorized users.

Influence of Genetic Polymorphisms Involved in the Hypothalamic–Pituitary–Adrenal Axis and their Interactions with Environmental Factors on Antidepressant Response

To investigate the role of genetic polymorphisms in candidate genes associated with the HPA axis and their interactions with environmental stressors in antidepressant response. The remission of depressive symptoms after 8 weeks of antidepressant treatment was tested against 21 single nucleotide polymorphisms (SNPs) in five candidate genes associated with the HPA axis in a Chinese Han sample suffering from unipolar depression (n = 273). Any history of childhood trauma and recent negative life events were measured using the Childhood Trauma Questionnaire-Short Form (CTQ-SF) (n = 206) and the Life Event Scale (48 item, LES) (n = 207), respectively. Reporter gene assays were used to evaluate the possible effects of the most significant SNP on gene expression. A functional polymorphism at 3'UTR of the corticotropin-releasing hormone receptor 1 (CRHR1) gene (rs28364032) and three haplotypes containing it showed significant relationships with antidepressant remission. Further laboratory-based genomic studies showed that the G-to-A change of rs28364032 resulted in a 10-12% decrease in the intensity of luciferase activity. However, we failed to find association of environments and their interaction with HPA system-related genes with antidepressant remission. Our results support a definite role for CRHR1 in the pharmacogenetics of antidepressant drugs. This may contribute to interpatient differences in their responses to antidepressant drugs.