Weeks Of Antidepressant Therapy Research Articles

A Randomized Controlled Trial Comparing Efficacy and Safety of Antidepressant Monotherapy.

The majority of mainstream antidepressants lack the promise of complete amelioration of symptoms. Other pitfalls include the latency period and side effects. These issues prompted investigations concerning thevarious roles of serotonin (5-HT) neurotransmissions in the etiology of depression. In this study, each study participant received vilazodone, vortioxetine, and escitalopram monotherapy for major depressive disorder (MDD)for 16 weeks. After that, the subject's scores on the Hamilton Depression Rating Scale (HDRS)-17 item version and the Montgomery Åsberg Depression Rating Scale (MADRS) were evaluated. In the study population, we kept track of the incidence of adverse events. Ninety-six patients with MDD participated in this open-label, randomized, three-arm study. Participants were allotted into three groups according to a 1:1:1 ratio and given vilazodone (20-40 mg/day), vortioxetine (5-20 mg/day), or escitalopram (10-20 mg/day) for 16 weeks. Vortioxetine and vilazodone are test medications, with escitalopram serving as the control. After the baseline visit, follow-up appointments were scheduled every four weeks. Per-protocol (PP) and intent-to-treat (ITT) populations served as means for efficacy and safety evaluations, respectively. We prospectively registered this research in the Clinical Trial Registry, India (CTRI) (2022/07/043808). Out of the 134 patients we screened, 109 (81.34%) were eligible. Ninety-six (88.07%) of them completed the 16-week trial. In the PP population (n = 96), we analyzed efficacy. They had a mean age of 46.3 ± 6.2 years. At baseline, each group's median HDRS score was 30.0 (p = 0.964). Following 16 weeks of antidepressant therapy, these scores dropped to 15.0, 14.0, and 13.0 (p = 0.002). Baseline MADRS scores for all groups were 36.0 (p = 0.741). They had corresponding values of 20.0, 18.0, and 17.0 at 16 weeks (p < 0.001). Regarding both efficacy endpoints, the post-hoc analysis with the Bonferroni correction demonstrated statistically significant differences (p < 0.001). We performed the safety assessments within our ITT population (n = 109). Ninety-six adverse events were recorded. Nonetheless, none of them seemed serious. Still, five participants opted out because of their side effects. Vomiting and nausea were the most frequent side effects. Compared to escitalopram and vilazodone, vortioxetine demonstrated a statistically significant reduction in HDRS and MADRS scores. It also had fewer and milder side effects. We recommend conducting studies involving a broader population to investigate the antidepressant effects of these medications further.

Recognition of Facial Emotion Expressions in Patients with Depressive Disorders: A Functional MRI Study

The present study evaluated the cortical activation during emotional information recognition. The study group included 16 patients with depression, and 16 healthy subjects were enrolled as a control group. Patients received eight weeks of antidepressant therapy. Functional MRI evaluated the cortical activation twice in the patient group and once in the control group. The fMRI task processed the emotional information with face demonstration from the PennCNP test battery. During the processing of emotional information, patients showed activation in the middle and the inferior frontal gyri, the fusiform gyrus, and the occipital cortex. After treatment, patients showed a significant decrease in the frontal cortex activation for negative face demonstration and no frontal activation for positive emotion recognition. The left superior temporal gyrus activation zone appeared in patients after treatment and in the control group. Healthy subjects showed more intense frontal cortex activation when processing neutral emotions and less when showing happy and sad faces. Activation zones in the amygdala and the insula and deactivation zones in the posterior cingulate cortex were revealed in the controls. This study confirms the hypothesis that anomalies in the processing of emotional stimuli can be a sign of a depressive disorder.

Early Response to Antidepressant Medications in Adults With Major Depressive Disorder: A Naturalistic Study and Odds of Remission at 14 Weeks.

Early response after 2 to 4 weeks of antidepressant therapy has been shown to predict remission by 8 to 12 weeks. Most of the work to date on early response has been done using data from randomized controlled trials. This naturalistic study uses archival data from a national tele-mental health company. The positive and negative predictive values as well as sensitivity and specificity were calculated using different drops in baseline Patient Health Questionnaire 9 scores at various periods. Demographic and clinical characteristics were compared between early responders versus those lacking early response. Binary logistic regression analyses determined if early response was predictive of remission, response, and greater than minimal improvement at 14 weeks. For those who do not show early improvement, treatments were investigated using binary logistic regression to see if changes predicted later outcomes. Positive predictive values for all endpoints improved with the strength of early response but did not improve much with the time allowed for that response to occur. In contrast, negative predictive values increased substantially with time. Using a definition of 30% drop in Patient Health Questionnaire 9 score at week 4, 56.5% of patients were early responders. Early responders were ~3.2 times more likely to achieve remission than those lacking early response. Of nonresponders by week 4, those prescribed atypical antipsychotics (+SSRI) had significantly reduced odds of response at week 14, whereas those prescribed a norepinephrine and dopamine reuptake inhibitor had increased odds. Early response may be associated with better outcomes at 14 weeks. In those with lack of response by week 4, patients prescribed a norepinephrine and dopamine reuptake inhibitor may achieve superior outcomes.

Clinical dynamics of anhedonia symptom in mood disorder and in alcohol use disorder

IntroductionAnhedonia is an important transdiagnostic phenotypic characteristic of schizophrenia, mood disorders (MD), alcohol use disorder (AUD) and other mental diseases. This Symptom could reflect the neurochemical abnormalities in addictive and affective disorders when the function of reward system is dysregulated (Koob G.F., 2017).ObjectivesTo compare the severity of Anhedonia in clinic of MD and AUD in dynamic of antidepressant therapyMethods The study enrolled 93 patients under treatment in MHRI Clinics: 45 AUD (F10.2; ICD-10) and 48 MD patients (F31-F34; ICD-10). The evaluation of Anhedonia was provided with the SHAPS modified for clinician administration (SHAPS-C) (Rezvan A., 2014).ResultsDue to statistical analysis, we found the level of anhedonia in the MD group was higher than in the AUD group before the treatment. After four weeks of antidepressant therapy the scrutiny of score difference shows less changes in severity of the Symptom in the AUD group (Table 1) Table 1. Dynamics of Anhedonia in MD and AUD groups by SHAPS-C GroupTotal score upon admissionTotal score after four weeks therapyTotal score upon admission and after four weeks therapyAUD (n=45)24 (22; 27,5)22 (20,25; 28)1 (-3; 4)MD (n=48)30 (23; 38)25 (20; 28)4 (1; 8)р (Mann-Whitney test)0,0030,3730,002ConclusionsAnhedonia in the structure of AUD is less pronounced than in MD, but responds less to antidepressant therapy. The study is supported by RSF Grant no. 19-15-00023 “Clinical features and search of potential biomarkers of comorbidity of alcoholism and affective disorders”.

Recognition of Facial Emotion Expressions in Patients with Depressive Disorders: A Prospective, Observational Study.

IntroductionProcessing of emotional stimuli is altered in patients with depression. The present feasibility study investigated the features of emotional information recognition in people with depressive disorders and how these differ from individuals without depression to determine whether response times could potentially be used as a diagnostic marker to identify individuals at high risk of depression and as an indicator of antidepressant medication response.MethodsThe study recruited 32 individuals, 16 with single or recurrent depressive episodes and 16 control subjects without depression. Patients with depression received 8 weeks of antidepressant therapy. The severity of depressive symptoms at baseline and their changes on prescribed therapy were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS). The processing of emotional information was assessed using the computerized Penn Emotion Recognition Task (ER-40).ResultsThe two groups were well matched in terms of age and gender. There was no difference between the groups in their ability to correctly recognize happy or sad emotional facial expressions, but the average time patients with depression took to recognize a happy face was significantly longer than controls. In addition, they were more likely to misinterpret facial expressions as non-emotional. In patients with depression, the mean MADRS total score decreased from 26.3 ± 4.4 at baseline to 11.1 ± 8.9 at 8 weeks, a reduction of 57.8%. The proportion of responders with greater than 50% reduction in their baseline MADRS total score was 64.3%. Antidepressive treatment was associated with a reduction in the mean time required for recognition of a happy face (P < 0.05).ConclusionsPatients with depression are slower to identify positive emotions but have a similar time to recognition of negative emotions as patients without depression. The greater time required for recognition of happiness distinguished the patients with depression from control subjects, and was also the only parameter that showed an improvement with antidepressant therapy, suggesting a specific relationship of this parameter with the depressive state.

Associations between Self-Reported Daily Affect Ratings and Sleep Duration during the First Two Weeks of Antidepressant Therapy

ABSTRACT Background: In the context of a randomized controlled trial evaluating the efficacy of augmenting fluoxetine treatment in young adults with major depressive disorder (MDD) using a modified repeated partial sleep deprivation protocol contrasting 2 weeks of restricted time in bed (i.e., 6 h TIB) to no time in bed restriction (i.e., 8 h TIB) the study examines whether sleep duration and the timing of repeated partial sleep deprivation predicts patient-reported affect ratings. Participants: Participants included 58 young adults with DSM-IV-diagnosed MDD. Methods: Daily ratings of affect and sleep were collected during the first 2 weeks of initiating fluoxetine treatment, yielding 630 person-days. Actigraphy monitoring was employed to assess compliance with time in bed condition. Results: Negative affect ratings and positivity ratios in the morning were more improved among participants assigned to the 6 h TIB condition compared to the 8 h TIB group. Participants whose bedtime was delayed by 2-h nightly demonstrated the most significant improvement in negative affect and positivity ratio during the first 2 weeks of fluoxetine therapy. Moreover, the trajectory of morning negative affect ratings in the first 2 weeks was predictive of remission after 4 weeks of fluoxetine therapy. Conclusions: These findings suggest that monitoring changes in daily affect may be a valuable marker of early treatment response in young adults with MDD.

Sexual Dysfunction in Women with Depressive Disorder: A Prospective, Hospital Based Study

Background: Depression causes emotional and physical disturbances which impacts biological functions such as sleep, appetite, libido, and disinterest in sexual function. Since discussing sexual problems is considered a taboo, there is limited data available concerning the prevalence of sexual dysfunction in women with depression and its response to treatment. Aim: To assess the prevalence of sexual dysfunction in females with depressive disorder and the effects of treatment. Material and Methods: A total of 53 females with recurrent depression and age and sex matched normal control group were included in the study with their informed consent. All the subjects were assessed with the Hamilton Rating Scale for Depression (HAM-D), Arizona sexual experience scale (ASEX), and female sexual functioning index (FSFI), which were re-administered after 6 weeks of treatment. Results: There was a significant difference in the HAM-D, ASEX, and FSFI scores between index and control groups at baseline. There was a significant correlation between the scores of HAM-D, ASEX, and FSFI before treatment. The correlation between the HAM-D and ASEX scores after treatment was not significant. A significant correlation was found between the HAM-D scores and the scores of arousal, lubrication, orgasm, satisfaction, pain, total domains of FSFI after treatment. No correlation was found between the HAM-D scores and desire domain score of FSFI after treatment. Conclusion: Women with depression have a high prevalence of sexual dysfunction. A highly significant improvement in depression and sexual functioning was observed at the end of 6 weeks of antidepressant therapy. Despite the improvement in sexual dysfunctions, the individual domains of sexual functions were not comparable to the normal subjects at the end of 6 weeks suggesting the need for longer treatment.

Cost per successfully treated patient for vortioxetine versus duloxetine in adults with major depressive disorder: an analysis of the complete symptoms of depression and functional outcome

Objective: To determine the cost-effectiveness of vortioxetine vs duloxetine in adults with moderate-to-severe major depressive disorder (MDD) in Norway using a definition of a successfully treated patient (STP) that incorporates improvement in both mood symptoms and functional capacity.Methods: Using the population of patients who completed the 8-week CONNECT study, the cost-effectiveness of vortioxetine (n = 168) (10–20 mg/day) vs duloxetine (n = 176) (60 mg/day) was investigated for the treatment of adults in Norway with moderate-to-severe MDD and self-reported cognitive dysfunction over an 8-week treatment period. Cost-effectiveness was assessed in terms of cost per STP, defined as improvement in mood symptoms (≥50% decrease from baseline in Montgomery-Åsberg Depression Rating Scale total score) and change in UCSD [University of California San Diego] performance-based skills assessment [UPSA] score of ≥7. The base case analysis utilized pharmacy retail price (apotek utsalgspris (AUP)) for branded vortioxetine (Brintellix) and branded duloxetine (Cymbalta).Results: After 8 weeks of antidepressant therapy, there were more STPs with vortioxetine than with duloxetine (27.4% vs 22.5%, respectively). The mean number needed to treat for each STP was 3.6 for vortioxetine and 4.4 for duloxetine, resulting in a lower mean cost per STP for vortioxetine (NOK [Norwegian Kroner] 3264) than for duloxetine (NOK 3310) and an incremental cost per STP of NOK 3051. The use of a more challenging change in the UPSA score from baseline (≥9) resulted in a mean cost per STP of NOK 3822 for vortioxetine compared with NOK 3983 for duloxetine and an incremental cost per STP of NOK 3181.Conclusions: Vortioxetine may be a cost-effective alternative to duloxetine, owing to its superior ability to improve functional capacity. The dual-response STP concept introduced here represents a more comprehensive analysis of the cost-effectiveness of antidepressants.

Alterations in leukocyte transcriptional control pathway activity associated with major depressive disorder and antidepressant treatment.

Major depressive disorder (MDD) is associated with a significantly elevated risk of developing serious medical illnesses such as cardiovascular disease, immune impairments, infection, dementia and premature death. Previous work has demonstrated immune dysregulation in subjects with MDD. Using genome-wide transcriptional profiling and promoter-based bioinformatic strategies, we assessed leukocyte transcription factor (TF) activity in leukocytes from 20 unmedicated MDD subjects versus 20 age-, sex- and ethnicity-matched healthy controls, before initiation of antidepressant therapy, and in 17 of the MDD subjects after 8 weeks of sertraline treatment. In leukocytes from unmedicated MDD subjects, bioinformatic analysis of transcription control pathway activity indicated an increased transcriptional activity of cAMP response element-binding/activating TF (CREB/ATF) and increased activity of TFs associated with cellular responses to oxidative stress (nuclear factor erythroid-derived 2-like 2, NFE2l2 or NRF2). Eight weeks of antidepressant therapy was associated with significant reductions in Hamilton Depression Rating Scale scores and reduced activity of NRF2, but not in CREB/ATF activity. Several other transcriptional regulation pathways, including the glucocorticoid receptor (GR), nuclear factor kappa-B cells (NF-κB), early growth response proteins 1–4 (EGR1–4) and interferon-responsive TFs, showed either no significant differences as a function of disease or treatment, or activities that were opposite to those previously hypothesized to be involved in the etiology of MDD or effective treatment. Our results suggest that CREB/ATF and NRF2 signaling may contribute to MDD by activating immune cell transcriptome dynamics that ultimately influence central nervous system (CNS) motivational and affective processes via circulating mediators.

Zinc in the Glutamatergic Theory of Depression.

Depression is a serious psychiatric illness that affects millions of people worldwide. Weeks of antidepressant therapy are required to relieve depressive symptoms, and new drugs are still being extensively researched. The latest studies have shown that in depression, there is an imbalance between the main excitatory (glutamatergic) and inhibitory (GABAergic) systems. Administration of antagonists of the glutamatergic system, including zinc, has shown an antidepressant effect in preclinical as well as clinical studies. Zinc inhibits the NMDA receptor via its binding site located on one of its subunits. This is thought to be the main mechanism explaining the antidepressant properties of zinc. In the present review, a link between zinc and the glutamatergic system is discussed in the context of depressive disorder.

Reward, memory and prediction of treatment response in affective disorders

The reward system has been reported to be affected in patients with major depression or anhedonia and has been viewed as a symptom expressed by deficits in experiencing proper reward. In a sample of first-episode and multipleepisode patients with major depression plus healthy controls, Hall et al. [1] for the first time compared functional magnetic resonance imaging (fMRI) during performance of a contingency reversal reward paradigm. They detected group differences in orbitofrontal and medial prefrontal regions. Additionally, nucleus accumbens, anterior cingulate and ventral prefrontal cortices were most activated in healthy controls, less in patients with one-episode and least in multiple-episode patients. Those brain areas may be sensitive to neurobiological alterations during repeated episodes of depression. While impaired cognition and decreased volumes of the hippocampus repeatedly have been reported for patients with major depression, bipolar patients present inconsistent structural imaging data possibly due to lithium therapy. Using a transitive inference (TI) paradigm suitable for assessing relational memory performance and fMRI, Avery et al. [2] examined hippocampal activity and hippocampal volumes via manual segmentation in patients with bipolar disorder compared to healthy controls. They found no differences in any of these parameters between both groups but very well a positive correlation between hippocampal volume and relational memory performance. These results possibly distinguish bipolar disorder from schizophrenia without consulting a common neurogenetic background, which confirms recent genome-wide association studies. Low-resolution brain electromagnetic tomography is a neuroelectric brain imaging technique based on electroencephalography (EEG), which Rentzsch et al. [3] used in combination with assessing symptoms improvement after 4 weeks of antidepressant therapy in patients with major depression to predict treatment response. Responders showed more slow-frequency power in the right anterior cingulate cortex compared to non-responders which the authors attribute to antidepressant treatment response. In a

Antidepressant response to aripiprazole augmentation associated with enhanced FDOPA utilization in striatum: A preliminary PET study

Several double blind, prospective trials have demonstrated an antidepressant augmentation efficacy of aripiprazole in depressed patients unresponsive to standard antidepressant therapy. Although aripiprazole is now widely used for this indication, and much is known about its receptor-binding properties, the mechanism of its antidepressant augmentation remains ill-defined. In vivo animal studies and in vitro human studies using cloned dopamine dopamine D2 receptors suggest aripiprazole is a partial dopamine agonist; in this preliminary neuroimaging trial, we hypothesized that aripiprazole's antidepressant augmentation efficacy arises from dopamine partial agonist activity. To test this, we assessed the effects of aripiprazole augmentation on the cerebral utilization of 6-[18F]-fluoro-3,4-dihydroxy-l-phenylalanine (FDOPA) using positron emission tomography (PET). Fourteen depressed patients, who had failed 8 weeks of antidepressant therapy with selective serotonin reuptake inhibitors, underwent FDOPA PET scans before and after aripiprazole augmentation; 11 responded to augmentation. Whole brain, voxel-wise comparisons of pre- and post-aripiprazole scans revealed increased FDOPA trapping in the right medial caudate of augmentation responders. An exploratory analysis of depressive symptoms revealed that responders experienced large improvements only in putatively dopaminergic symptoms of lassitude and inability to feel. These preliminary findings suggest that augmentation of antidepressant response by aripiprazole may be associated with potentiation of dopaminergic activity.

Hypothalamus-Anchored Resting Brain Network Changes before and after Sertraline Treatment in Major Depression

Sertraline, one of the oldest antidepressants, remains to be the most efficacious treatment for depression. However, major depression disorder (MDD) is characterized by altered emotion processing and deficits in cognitive control. In cognitive interference tasks, patients with MDD have shown excessive hypothalamus activity. The purpose of this study was to examine the effects of antidepressant treatment (sertraline) on hypothalamus-anchored resting brain circuitry. Functional magnetic resonance imaging was conducted on depressed patients (n=12) both before and after antidepressant treatment. After eight weeks of antidepressant treatment, patients with depression showed significantly increased connectivity between the hypothalamus and dorsolateral prefrontal cortex, orbitofrontal cortex, anterior cingulate cortex, insula, putamen, caudate, and claustrum. By contrast, decreased connectivity of the hypothalamus-related areas was primarily located in the inferior frontal gyrus, medial frontal gyrus, cingulated gyrus, precuneus, thalamus, and cerebellum. After eight weeks of antidepressant therapy, 8 out of the 12 depressed subjects achieved 70% reduction or better in depressive symptoms, as measured on the Hamilton depression rating scale. Our findings may infer that antidepressant treatment can alter the functional connectivity of the hypothalamus resting brain to achieve its therapeutic effect.

Adjunctive Pregabalin in Partial Responders With Major Depressive Disorder and Residual Anxiety

Anxiety symptoms in depression result often in treatment resistance, residual symptoms, and persistent functional impairment. To assess the effectiveness and safety of adjunctive pregabalin to antidepressants for residual anxiety in patients with major depressive disorder (MDD). A retrospective chart review was conducted to identify partial responders among patients with MDD with residual anxiety. Twenty such patients (age, 58.4 ± 11.2 years; 15 women; baseline Hamilton Depression Rating Scale [HDRS], 17.1 ± 3.5) who received adjunctive pregabalin for residual anxiety were included. Antidepressants augmented were the selective serotonin reuptake inhibitors (n = 12), mirtazapine (n = 2), and selective serotonin-norepinephrine reuptake inhibitors (n = 6). Twenty patients received at least 4 weeks of pregabalin treatment after 8 weeks of antidepressant therapy. At week 1 (9 weeks after initiating treatment), pregabalin was prescribed at a mean ± SD dose of 71.2 ± 31.7 mg, and the mean maximum pregabalin dose prescribed was 156.2 ± 76.5 mg (range, 75-300 mg). At week 8, there were 13 responders (13/20 [65%]), and 7 of these 13 patients achieved remission (HDRS17 < 8). There were significant decreases in HDRS scores (13.5 ± 3.1 vs 9.1 ± 2.9, P < 0.000), and HDRS anxiety/somatization subscale scores (6.3 ± 2 to 3.6 ± 1.7, P < 0.000). Adverse effects included somnolence (n = 7), weight gain (n = 3), dizziness (n = 4), dry mouth (n = 6), edema (n = 3), blurred vision (n = 3), difficulty with concentration/attention (n = 8), headache (n = 6), and diarrhea (n = 5). The results suggest a possible augmentation role for pregabalin when used in conjunction with conventional antidepressants for residual anxiety in MDD.

Impact of antidepressant treatment: a study from The Netherlands

Impact of antidepressant treatment: a study from The Netherlands Nadine van Dongen,1 Scott Mason21PIP Health Ltd, London, United Kingdom; 2London Metropolitan University, London, United KingdomBackground: The purpose of the study was to identify the extent and severity of treatment-related side effects experienced by patients with depression. The study was designed to identify the extent of the different antidepressant side effects to gain an understanding of their impact on the lives of patients suffering from depression.Methods: A total of 303 patients from The Netherlands with physician-diagnosed depression completed an online questionnaire. All participating patients were receiving antidepressants and were members of the Patient Intelligence Panel (PIP). Participants answered questions about their antidepressant medication, degree of personal research into antidepressant medication, and about any side effects they had experienced as a result of their current antidepressant therapy, the severity of any such side effects, and the impact on their daily lives.Results: Over two-thirds (69%) of patients were receiving antidepressant therapy for the first time. Forty-two percent (42%) of patients felt it took 2&ndash;6 weeks of antidepressant therapy before their depressive mood improved. More than half of participating patients (60%) had experienced side effects from their antidepressant therapy, the most common being &lsquo;somnolence, drowsiness, or fatigue&rsquo; (14%). Of the 60% of patients who had experienced side effects, 46% admitted to absenteeism as a consequence.Conclusion: Central to the effective management of depression is an understanding of the effects of antidepressant therapy on patients&rsquo; lives. Treatment-related side effects, and their potential influence on treatment discontinuation, need to be recognized and assessed on an individual patient basis to optimize management and minimize potential relapse.Keywords: depression, antidepressants, SSRI, side effects, The Netherlands

P-469 - Investigation of the functional activity of autonomic nervous system and endogenous opioid system in endogenomorphic depression

Introduction Investigation of the pathogenesis mechanisms in depression remains an actual task of modern psychiatry. Objectives The analysis of clinical-psychopathological characteristics, functional activity of autonomic nervous system and endogenous opioid system in endogenomorphic depression. The main group included 72 patients diagnosed with depressive episode. Methods Clinico- psychopathological, clinico-anamnestic, Hamilton Depression Rating Scale (HDRS-17), the analysis of heart rate variability (HRV) for evaluation of autonomic regulation. In 9 patients plasma levels of beta-endorphin were obtained. Patients were investigated 3 times - at baseline, and then during 2nd–3d and 4th–6th weeks of antidepressant therapy. Results The reduction of total HRV was observed at rest and in orthostatic test during evaluation of autonomic regulation in depressive patients. The hyperactivation of suprasegmental ergotropic systems was observed in depressive patients before treatment. In responders subgroup despite on positive dynamics of clinico-psychopathological and psychometric characteristics, in the 2nd–3d week of therapy increase in general HRV was observed, in the 4th–6th week parameters come back to baseline level. The balance of sympathetic, parasympathetic and suprasegmental parts of autonomic nervous system did not change. The plasma endorphin levels were rising to 2nd–3d treatment week, and come back to baseline level at the 4th–6th treatment week. Conclusion Obtained data confirm evidence that the therapeutic dynamics of depression is characterized by a faster reduction of clinical symptoms, whereas changes in functional activity of stress-realizing and stress-limiting mechanisms can be kept much longer. Acknowledgments This research is supported by grant provided by Russian Humanitarian Research Foundation project 11-06-00869а

Residual Anxiety Symptoms in Depressed Primary Care Patients

The goal of this study was to characterize the burden of anxiety among residual depressive symptoms in naturalistic primary care settings. A post-hoc analysis of a database comprised of naturalistically treated depressed patients across Canada was done. This bilingual (English and French), multi-center, randomized validation study was conducted in 47 primary care settings in four provinces of Canada. Patients who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text-Revision (DSM-IV-TR) criteria for a major depressive episode, in the context of a major depressive disorder (N=454) were enrolled. Eligible patients received open-label, flexible-dose antidepressant treatment. The analysis reported here was limited to patients whose depression severity was evaluated using the Hamilton Depression Rating Scale (HAMD-17) (n=205). Patients completing 8 weeks of open-label antidepressant treatment (n=157) were considered evaluable. As a proxy for anxiety symptoms, scores on 6 items from the HAMD-17 (psychological anxiety, somatic anxiety, gastrointestinal distress, fatigue, hypochondriasis, and insight into illness) were summed to arrive at a composite anxiety score, which was then used to calculate an anxiety ratio (with the composite anxiety score as the numerator and the total HAMD-17 score as the denominator). The composite anxiety ratio at baseline did not correlate with the probability of remitting at endpoint (p=0.534). After 8 weeks of antidepressant therapy, remitting patients evinced a statistically significant decrease in anxiety ratio (p=0.041). Moreover, an inverse correlation was noted between severity of anxious symptoms at endpoint and probability of remission (p=0.026). The burden of anxiety, presented as the anxiety ratio, was higher in non-remitting patients at endpoint (p=0.828). Residual depressive symptoms represent ongoing illness activity in depression. Sharpening the focus of therapeutic interventions in the clinical environment calls for tracking and managing residual anxiety symptoms.

Complementary, Holistic, and Integrative Medicine: St. John's Wort

1. Theresa L. Charrois, BScPharm, MSc* 2. Candace Sadler* 3. Sunita Vohra, MD, MSc* 1. *Complementary and Alternative Research and Education (CARE) Program, Department of Pediatrics, University of Alberta, Canada, on behalf of the American Academy of Pediatrics Provisional Section on Complementary, Holistic, and Integrative Medicine St. John’s wort, derived from the Hypericaceae family, has played a medicinal role for thousands of years. (1) Although it has been used empirically for a wide range of ailments in the past, including skin conditions, nerve problems, and muscle pain, the primary uses currently are for depression and nervous conditions, (2)(3)(4)(5)(6)(7) due to its ability to inhibit the reuptake of dopamine, serotonin, and norepinephrine within the brain. (2) Although promising evidence is emerging for the clinical use of St. John’s wort, data specific to pediatrics are still limited, warranting additional research. Surveys in the United States and Britain of herbal use for the treatment of pediatric depression (8)(9) demonstrate that St. John’s wort is used commonly by children (22% and 9% in the two surveys, respectively). Formal evaluation of efficacy in pediatric populations is preliminary but shows some promise. Presently, no systematic reviews or randomized, controlled trials have been published regarding the use of St. John’s wort in children. An open-label pilot study conducted by Findling and associates (10) analyzed the use of St. John’s wort in children between the ages of 6 and 16 years for treatment of major depressive disorder. The starting dose was 150 mg 3 times daily for 4 weeks. Exclusion criteria included failure to respond to 4 weeks of antidepressant therapy. Patients considered clinically nonresponsive to St. John’s wort (as per a priori criteria) after 4 weeks had their dosage increased to 300 mg 3 times daily. A total of 33 patients were enrolled in the study, with a mean age of 10.5 years (SD, 2.9 y). At the end of the 8-week trial, 25 patients met the criteria of clinical response (76%). Also, 93% of the study population decided to …

Circadian blood pressure regulation in hospitalized depressed patients and non-depressed comparison subjects.

Neuroendocrine dysregulation and disturbed sleep, frequently seen in major depression, may interfere with circadian blood pressure regulation. Using a portable device, 24 h blood pressure profiles were registered in 69 depressed in-patients and 26 hospitalized, non-depressed comparison subjects. The use of antihypertensive medication was considered to be indicative of known arterial hypertension. Mean systolic and diastolic blood pressure levels were compared between the group of depressed patients not taking antihypertensive medication and the healthy comparison subjects, both for the entire 24 h of measurement, and for the daytime and night-time periods. In a subgroup of patients, circadian blood pressure follow-up data were obtained after 5 weeks of antidepressant therapy. Depressed patients not receiving antihypertensive medication (n=52) had higher mean 24 h systolic blood pressure levels than non-depressed comparison subjects (125.5+/-14.7 versus 119.6+/-13.3 mmHg, P<0.05). Subgroup analysis revealed that this difference could be almost exclusively attributed to patients on hypnotic medication; this subgroup also had a high day/night blood pressure change ('dip'). In depressed patients using antihypertensive agents (n=17), circadian blood pressure levels pointed to a suboptimal control of hypertension. In the subgroup with follow-up measurements, circadian blood pressure levels had not changed after 5 weeks of antidepressant therapy. Circadian blood pressure monitoring identified a subgroup of depressed patients characterized by higher mean systolic blood pressure levels, the use of hypnotics and a high day/night blood pressure change.

Substance P serum levels are increased in major depression: preliminary results

Background Substance P (SP) is thought to have an impact in the pathophysiology of depression and the mechanism of action of antidepressant drugs. The aim of this study was to analyze the serum SP levels in healthy control subjects and in depressed patients before and after antidepressant treatments. Methods Twenty-three patients with major depression and 33 control subjects participated in the study. Using an enzyme immunoassay, the SP serum levels were determined in patients at baseline (before treatment) and after 2 and 4 weeks of antidepressant therapy. Determinations of SP in control subjects were carried out twice, at baseline and after 4 weeks. Results The mean baseline SP serum concentration was significantly higher in depressed patients as compared with control subjects ( p < .001). Repeated measurements in control subjects showed that SP remains relatively constant over a period of 4 weeks. Although in depressed patients there was no overall change in the mean SP levels between baseline and 4 weeks’ treatment, 37% of them exhibited a decrease of SP (15%–50%), which can be correlated to a better drug response than an increase in SP concentration after treatment ( p = .001). Conclusions Our data show that serum SP levels are increased in a proportion of patients with major depression and might thus indicate a subgroup of the disorder in which neuropeptides have a key position. Future studies are needed to clarify whether the observed SP decrease in treatment responders can be attributed to a specific class of drugs.