Deficits of white matter axial diffusivity in bipolar disorder relative to major depressive disorder: No relationship to cerebral perfusion or body mass index.

OBJECTIVE: To compare white matter integrity (WMI) in bipolar disorder (BD) relative to healthy volunteers (HVs) and major depressive disorder (MDD). To determine the relationship of bipolar-specific differences in WMI to cerebral perfusion, body mass index (BMI), and blood pressure as indices of cardiovascular function. METHODS: Thirty-two participants with BD, 44 with MDD, and 41 HV were recruited. All BD and MDD participants were in a major depressive episode, and all but 12 BD participants were medication-free. 64-direction diffusion tensor imaging (DTI) and arterial spin labeling (ASL) sequences were obtained. Tract-based spatial statistics (TBSS) on four DTI indices were employed to distinguish patterns of DTI in BD relative to HV and MDD groups. BMI, blood pressure, and medical histories were also obtained for the BD participants. RESULTS: A cluster of lower axial diffusivity (AD) was found in BD participants in comparison to the HVs in the left posterior thalamic radiation, superior longitudinal fasciculus, inferior longitudinal fasciculus, fronto-occipital fasciculus, and internal capsule. Mean AD in the significant cluster was not associated with cerebral blood flow (CBF) in the region as measured by ASL, and was not associated with BMI or blood pressure. A cluster of lower AD was also found in the BD group when compared to MDD that had spatial overlap with the HV comparison. CONCLUSIONS: The results indicate a deficit of AD in BD when compared to MDD and HV groups. No association between AD values and either cerebral perfusion, BMI, or blood pressure was found in BD.

White matter tract integrity is associated with antidepressant response to lurasidone in bipolar depression.

OBJECTIVES: Patients with bipolar disorder spend the most time in the depressed phase, and that phase is associated with the most morbidity and mortality. Treatment of bipolar depression lacks a test to determine who will respond to treatment. White matter disruptions have been found in bipolar disorder. Previous reports suggest that white matter disruptions may be associated with resistance to antidepressant medication, but this has never been investigated in a prospective study using a Food and Drug Administration (FDA)-approved medication. METHODS: Eighteen subjects with bipolar disorder who were in a major depressive episode and off all medications were recruited. Magnetic resonance imaging was acquired using a 64-direction diffusion tensor imaging sequence on a 3T scanner. Subjects were treated with 8 weeks of open-label lurasidone. The Montgomrey-Asberg Depression Rating Scale (MADRS) was completed weekly. Tract-Based Spatial Statistics were utilized to perform a regression analysis of fractional anisotropy (FA) data with treatment outcome as assessed by percent change in MADRS as a regressor while controlling for age and sex, using a threshold of P (threshold-free cluster enhancement-corrected) <.05. RESULTS: FA was positively correlated with antidepressant treatment response in multiple regions of the mean FA skeleton bilaterally, including tracts in the frontal and parietal lobes. CONCLUSIONS: Greater disruptions in the white matter tracts in bipolar disorder were associated with poorer antidepressant response to lurasidone. The disruptions may potentially indicate treatment with a different antidepressant medication class. These results are limited by the open-label study design, sample size and lack of a healthy control group.

Behavioral activation therapy for return to work in medication-responsive chronic depression with persistent psychosocial dysfunction.

OBJECTIVE: Chronic depression is associated with significant impairment in work functioning, relationships, and health. Such impairment often persists following medication-induced remission of depressive symptoms. We adapted and tested Behavioral Activation therapy with a goal of return to work (BA-W) in subjects with chronic depression who had responded to medication treatment but remained unemployed. METHOD: Sixteen adults aged 18-65 with DSM-IV diagnosed Dysthymic Disorder or chronic Major Depression were recruited from clinical trials taking place at the New York State Psychiatric Institute between 4/2009 and 12/2012 and enrolled in 12 weeks of individual manual-driven BA-W. Functioning was measured at intake, post-treatment and at 24 week follow-up. RESULTS: Eighty-seven percent (n=14) of subjects completed the full 12 weeks of BA-W. Hours of work related activity (p<.005, d=0.83), hours of paid work (p<.0003, d=0.54), and work productivity (p<.0004, d=-0.48) increased significantly over the study period. Earned income increased post-treatment (p=.068) with significant changes by 24 week follow-up (p=.011). Secondary outcomes including behavioral avoidance (p<.004, d=-0.56), and global functioning (p<.0003, d=1.42) were also significantly improved post-treatment. Effect sizes, including for outcomes with non-significant changes, were generally in the range of 0.5-0.8. CONCLUSIONS: This pilot study provides preliminary evidence of the efficacy of a work-targeted psychotherapy to remediate vocational impairment in subjects with chronic depression. Data suggests that further testing of BA-W using a randomized controlled trial is warranted and may represent a significant advance in treatment for the residual disability present after successful pharmacotherapy.

Abnormal functional brain asymmetry in depression: evidence of biologic commonality between major depression and dysthymia.

Prior studies have found abnormalities of functional brain asymmetry in patients having a major depressive disorder (MDD). This study aimed to replicate findings of reduced right hemisphere advantage for perceiving dichotic complex tones in depressed patients, and to determine whether patients having "pure" dysthymia show the same abnormality of perceptual asymmetry as MDD. It also examined gender differences in lateralization, and the extent to which abnormalities of perceptual asymmetry in depressed patients are dependent on gender. Unmedicated patients having either a MDD (n=96) or "pure" dysthymic disorder (n=42) and healthy controls (n=114) were tested on dichotic fused-words and complex-tone tests. Patient and control groups differed in right hemisphere advantage for complex tones, but not left hemisphere advantage for words. Reduced right hemisphere advantage for tones was equally present in MDD and dysthymia, but was more evident among depressed men than depressed women. Also, healthy men had greater hemispheric asymmetry than healthy women for both words and tones, whereas this gender difference was not seen for depressed patients. Dysthymia and MDD share a common abnormality of hemispheric asymmetry for dichotic listening.

Serotonin-norepinephrine reuptake inhibitor antidepressant effects on regional connectivity of the thalamus in persistent depressive disorder: evidence from two randomized, double-blind, placebo-controlled clinical trials.

Previous neuroimaging studies have shown that serotonin-norepinephrine reuptake inhibitor antidepressants alter functional activity in large expanses of brain regions. However, it is not clear how these regions are systemically organized on a connectome level with specific topological properties, which may be crucial to revealing neural mechanisms underlying serotonin-norepinephrine reuptake inhibitor treatment of persistent depressive disorder. To investigate the effect of serotonin-norepinephrine reuptake inhibitor antidepressants on brain functional connectome reconfiguration in persistent depressive disorder and whether this reconfiguration promotes the improvement of clinical symptoms, we combined resting-state functional magnetic resonance imaging (fMRI) scans acquired in two randomized, double-blind, placebo-controlled trial studies of serotonin-norepinephrine reuptake inhibitor antidepressant treatment of patients with persistent depressive disorder. One was a randomized, double-blind, placebo-controlled trial of 10-week duloxetine medication treatment, which included 17 patients in duloxetine group and 17 patients in placebo group (ClinicalTrials.gov Identifier: NCT00360724); the other one was a randomized, double-blind, placebo-controlled trial of 12-week desvenlafaxine medication treatment, which included 16 patients in desvenlafaxine group and 15 patients in placebo group (ClinicalTrials.gov Identifier: NCT01537068). The 24-item Hamilton Depression Rating Scale was used to measure clinical symptoms, and graph theory was employed to examine serotonin-norepinephrine reuptake inhibitor antidepressant treatment effects on the topological properties of whole-brain functional connectome of patients with persistent depressive disorder. We adopted a hierarchical strategy to examine the topological property changes caused by serotonin-norepinephrine reuptake inhibitor antidepressant treatment, calculated their small-worldness, global integration, local segregation and nodal clustering coefficient in turn. Linear regression analysis was used to test associations of treatment, graph properties changes and clinical symptom response. Symptom scores were more significantly reduced after antidepressant than placebo administration (η 2 = 0.18). There was a treatment-by-time effect that optimized the functional connectome in a small-world manner, with increased global integration and increased nodal clustering coefficient in the bilateral thalamus (left thalamus η 2 = 0.21; right thalamus η 2 = 0.23). The nodal clustering coefficient increment of the right thalamus (ratio = 29.86; 95% confidence interval, -4.007 to -0.207) partially mediated the relationship between treatment and symptom improvement, and symptom improvement partially mediated (ratio = 21.21; 95% confidence interval, 0.0243-0.444) the relationship between treatment and nodal clustering coefficient increments of the right thalamus. Our study may indicate a putative mutually reinforcing association between nodal clustering coefficient increment of the right thalamus and symptom improvement from serotonin-norepinephrine reuptake inhibitor antidepressant treatments with duloxetine or desvenlafaxine.

Residual symptoms in depressed outpatients who respond by 50% but do not remit to antidepressant medication.

Little is known about the quantity or quality of residual depressive symptoms in patients with major depressive disorder (MDD) who have responded but not remitted with antidepressant treatment. This report describes the residual symptom domains and individual depressive symptoms in a large representative sample of outpatients with nonpsychotic MDD who responded without remitting after up to 12 weeks of citalopram treatment in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Response was defined as 50% or greater reduction in baseline 16-item Quick Inventory of Depressive Symptomatology--Self-Report (QIDS-SR16) by treatment exit, and remission as a final QIDS-SR16 of less than 6. Residual symptom domains and individual symptoms were based on the QIDS-SR16 and classified as either persisting from baseline or emerging during treatment. Most responders who did not remit endorsed approximately 5 residual symptom domains and 6 to 7 residual depressive symptoms. The most common domains were insomnia (94.6%), sad mood (70.8%), and decreased concentration (69.6%). The most common individual symptoms were midnocturnal insomnia (79.0%), sad mood (70.8%), and decreased concentration/decision making (69.6%). The most common treatment-emergent symptoms were midnocturnal insomnia (51.4%) and decreased general interest (40.0%). The most common persistent symptoms were midnocturnal insomnia (81.6%), sad mood (70.8%), and decreased concentration/decision making (70.6%). Suicidal ideation was the least common treatment-emergent symptom (0.7%) and the least common persistent residual symptom (17.1%). These findings suggest that depressed outpatients who respond by 50% without remitting to citalopram treatment have a broad range of residual symptoms. Individualized treatments are warranted to specifically address each patient's residual depressive symptoms.

A randomized, controlled trial assessing the acute efficacy of triple chronotherapy in unipolar depression.

BACKGROUND: Triple chronotherapy (wake night [one night without sleep], sleep phase advance, and early morning bright light exposure) demonstrated rapid efficacy primarily in bipolar depression, but has not been as well studied in unipolar depression. Our primary hypothesis is that triple chronotherapy is associated with a significantly greater Week 1 remission rate compared to the alternative protocol. METHODS: Unipolar depressed, nonpsychotic adult outpatients were randomized to triple chronotherapy or an alternative protocol (assigned sleep times without wake night, bright light exposure with blue-green wavelengths filtered out). Symptoms were assessed with Structured Interview Guide for Hamilton Depression Rating Scale with Atypical Supplement (SIGH-ADS) at each visit and a modified form (m-SIGH) daily for the first week. Response was defined as a 50% decrease in m-SIGH score, and remission as m-SIGH≤7, modified Clinical Global Impression-Improvement (m-CGI-I)≤2, and no depressed mood on m-SIGH. RESULTS: 44 patients (84.1% major depressive disorder, 75.0% persistent depressive disorder; 54.5% female; age mean±SD 38.3 ±â€¯15.2 years) were randomized to triple chronotherapy (N = 22) or an alternative protocol (N = 22). Week 1 remission rate was numerically higher but not statistically significant in the triple chronotherapy versus alternative protocol group (25.0% vs. 6.7%, Chi-square=1.76, df=1, p = 0.294). m-SIGH scores and response and remission rates on Days 2-7 were numerically improved without reaching statistical significance in the triple chronotherapy versus alternative protocol group. LIMITATIONS: Predominantly white, educated sample. CONCLUSIONS: This small pilot study demonstrated triple chronotherapy's feasibility and tolerability in unipolar depressed outpatients. Larger randomized trials are warranted to further characterize acute and long-term efficacy.

Gray matter reorganization underpinnings of antidepressant treatment of persistent depressive disorder.

Brain gray matter is organized in a manner with interconnected brain regions, resulting in a notable covariance pattern that recapitulates either the functional coactivation or structural connectivity of brain regions, which is believed to underpin psychiatric disorders such as depression. This study aimed to investigate whether and how antidepressants took effect in treating depression and reducing symptoms by altering the gray matter covariance pattern. We combined structural magnetic resonance imaging (MRI) scans acquired in two randomized, double-blind, placebo-controlled trial (RCT) studies of the treatment using serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant medications in patients with persistent depressive disorder (PDD). One was an RCT of 10-week duloxetine medication that consisted of patients who received duloxetine (N = 21) or placebo (N = 21), and the other was an RCT of 12-week desvenlafaxine medication that consisted of 19 and 17 patients respectively who received desvenlafaxine or placebo. We examined treatment effect on gray matter volume (GMV) and topological organization of GMV covariance pattern (i.e., GMV-based network). We found a treatment-by-time effect on GMV in the angular gyrus and cuneus areas, whereas the GMV change rate of the cuneus was inversely correlated with the response rate. We observed a significant increase in the local efficiency of the GMV-based network following medication treatment compared with placebo. Our findings provide preliminary evidence for a GMV-based network-specific reconfiguration caused by antidepressants compared to placebo and the cuneus may be a possible candidate region to predict antidepressant response.

Do atypical features affect outcome in depressed outpatients treated with citalopram?

Depressed patients with atypical features have an earlier onset of depression, a more chronic course of illness, several distinctive biological and familial features, and a different treatment response than those without atypical features. The efficacy and tolerability of selective serotonin reuptake inhibitors (SSRIs) have not been fully evaluated in depression with atypical features. This report evaluates data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study to determine whether depressed outpatients with and without atypical features respond differently to the SSRI citalopram. Treatment-seeking participants with non-psychotic major depressive disorder were recruited from primary- and psychiatric-care settings. The presence/absence of atypical features was approximated using baseline ratings on the 30-item Inventory of Depressive Symptomatology - Clinician-rated. Following baseline assessments, participants received citalopram up to 60 mg/d for up to 14 wk. Baseline sociodemographic and clinical characteristics, and treatment outcomes, were compared between participants with and without atypical features. Of the 2876 evaluable STAR*D participants, 541 (19%) had atypical features. Participants with atypical features were significantly more likely to be female, younger, unemployed, have greater physical impairment, a younger age of depression onset, a longer index episode, greater depressive severity, and more concurrent anxiety diagnoses. Those with atypical features had significantly lower remission rates, although this difference was no longer present after adjustment for baseline differences. Depressed patients with atypical features are less likely to remit with citalopram than those without atypical features. This finding is probably due to differences in baseline characteristics other than atypical symptom features.

Psychoticism and paranoid ideation in patients with nonpsychotic major depressive disorder: prevalence, response to treatment, and impact on short- and long-term treatment outcome.

UNLABELLED: Objective/Introduction: We sought to characterize the impact of the 90-item Symptom Checklist (SCL-90) subscales for paranoid ideation (PI) and psychoticism (P) in patients with major depressive disorder (MDD), on acute antidepressant response and on relapse prevention. METHODS: Subjects with Structured Clinical Interview for DSM Disorders-diagnosed nonpsychotic MDD were recruited into a clinical trial of open-label fluoxetine 10-60 mg/day for 12 weeks, followed by double-blind randomization of responders (n=262) to fluoxetine continuation or placebo for 12 months. PI and P were assessed with the patient-rated SCL-90. The association of these symptoms with response to treatment was assessed by logistic regression. RESULTS: We found significant decreases in PI and P during acute treatment phase for fluoxetine responders and nonresponders, although only 10.3% and 7.5% of patients experienced a >50% reduction in PI and P scores, respectively. Neither PI nor P scores significantly predicted time to relapse. P scores predicted a lower response rate to treatment with fluoxetine. DISCUSSION: The results of the present study suggest that there is a significant relationship between the presence of psychoticism in patients with nonpsychotic MDD, and the likelihood of overall depressive symptom improvement following a trial of monotherapy with fluoxetine. CONCLUSION: An increased burden of psychoticism in depressed subjects may confer poorer response to fluoxetine, but not increased risk of relapse among fluoxetine responders.

Type of residual symptom and risk of relapse during the continuation/maintenance phase treatment of major depressive disorder with the selective serotonin reuptake inhibitor fluoxetine.

UNLABELLED: Relapse of major depressive disorder (MDD) is a common clinical problem. Identifying relapse predictors could lead to strategies that reduce relapse risk. This study is designed to determine whether residual symptoms predict relapse risk during the continuation/maintenance treatment of MDD. 570 MDD patients received open-label fluoxetine for 12 weeks. Under double blind conditions, 262 patients who responded by week 12 were randomly assigned to continue fluoxetine or switch to placebo for 52 weeks or until relapse. Residual symptoms were measured using the Symptom Checklist-90 and the Symptom Questionnaire. The relationship between residual symptom severity and relapse risk was assessed. Without adjusting for overall residual symptom severity, a greater severity of residual obsessive-compulsive and phobic anxiety symptoms predicted greater relapse risk. After adjusting for overall residual symptom severity, only severity of phobic anxiety symptoms predicted relapse risk. The predictive value of phobic anxiety symptoms with respect to relapse risk was independent of treatment assignment. The results indicated that there may be a specific pattern of residual symptoms associated with depressive relapse during antidepressant continuation/maintenance, which is unrelated to treatment assignment. Future studies are needed to further explore the relationship between residual symptoms and relapse risk in MDD. CLINICAL IMPLICATIONS: (1) It is important to treat residual symptoms among antidepressant responders/remitters in order to decrease relapse risk. (2) Clinicians should target residual phobic anxiety symptoms in order to decrease relapse risk. (3) Clinicians should target residual obsessive-compulsive symptoms in order to decrease relapse risk. LIMITATIONS: (1) limited generalizability due to inclusion/exclusion criteria; (2) lack of active comparator treatment group; (3) post hoc analysis.

Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression.

BACKGROUND: After unsuccessful treatment for depression with a selective serotonin-reuptake inhibitor (SSRI), it is not known whether switching to one antidepressant is more effective than switching to another. METHODS: We randomly assigned 727 adult outpatients with a nonpsychotic major depressive disorder who had no remission of symptoms or could not tolerate the SSRI citalopram to receive one of the following drugs for up to 14 weeks: sustained-release bupropion (239 patients) at a maximal daily dose of 400 mg, sertraline (238 patients) at a maximal daily dose of 200 mg, or extended-release venlafaxine (250 patients) at a maximal daily dose of 375 mg. The study was conducted in 18 primary and 23 psychiatric care settings. The primary outcome was symptom remission, defined by a total score of 7 or less on the 17-item Hamilton Rating Scale for Depression (HRSD-17) at the end of the study. Scores on the Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR-16), obtained at treatment visits, determined secondary outcomes, including remission (a score of 5 or less at exit) and response (a reduction of 50 percent or more on baseline scores). RESULTS: Remission rates as assessed by the HRSD-17 and the QIDS-SR-16, respectively, were 21.3 percent and 25.5 percent for sustained-release bupropion, 17.6 percent and 26.6 percent for sertraline, and 24.8 percent and 25.0 percent for extended-release venlafaxine. QIDS-SR-16 response rates were 26.1 percent for sustained-release bupropion, 26.7 percent for sertraline, and 28.2 percent for extended-release venlafaxine. These treatments did not differ significantly with respect to outcomes, tolerability, or adverse events. CONCLUSIONS: After unsuccessful treatment with an SSRI, approximately one in four patients had a remission of symptoms after switching to another antidepressant. Any one of the medications in the study provided a reasonable second-step choice for patients with depression. (ClinicalTrials.gov number, NCT00021528.).

Reduced brain responses to novel sounds in depression: P3 findings in a novelty oddball task.

There have been conflicting findings as to whether the P3 brain potential to targets in oddball tasks is reduced in depressed patients. The P3 to novel distracter stimuli in a three-stimulus oddball task has a more frontocentral topography than P3 to targets and is associated with different cognitive operations and neural generators. The novelty P3 potential was predicted to be reduced in depressed patients. EEG was recorded from 30 scalp electrodes (nose reference) in 20 unmedicated depressed patients and 20 matched healthy controls during a novelty oddball task with three stimuli: infrequent target tones (12%), frequent standard tones (76%) and nontarget novel stimuli, e.g., animal or environment sounds (12%). Novel stimuli evoked a P3 potential with shorter peak latency and more frontocentral topography than the parietal-maximum P3b to target stimuli. The novelty P3 was markedly reduced in depressed patients compared to controls. Although there was a trend for patients to also have smaller parietal P3b to targets, this group difference was not statistically significant. Nor was there a group difference in the earlier N1 or N2 potentials. The novelty P3 reduction in depressed patients is indicative of a deficit in orienting of attention and evaluation of novel environmental sounds.

Does personality disorder decrease the likelihood of remission in early-onset chronic depression?

BACKGROUND: The impact of personality disorders (PD) on the course of depression has been gaining interest among clinical researchers over the past decade. Recent observational studies have found that PD was associated with impaired social functioning and reduced likelihood of depression recovery. Elevated rates of PD have been noted in early-onset and chronic forms subtypes of depression. However, scant data exist regarding the link between PD and outcome for this depression subtype. METHODS: The National Epidemiological Survey on Alcohol and Related Conditions database was analyzed. This survey included 43 093 respondents, 18 years and older, conducted in 2001 through 2002. Logistic regression was used to identify demographic and clinical predictors of remission in early-onset chronic depression. RESULTS: The absence of PD, having more years of education, and being married considerably improved the likelihood of remission. Paranoid personality disorder and obsessive-compulsive disorder were the only specific PD found to be associated with a reduced probability of remission. LIMITATIONS: Depression remission status may have biased the recollection of PD symptoms. Borderline personality disorder, narcissistic personality disorder, and schizotypal personality disorder were not assessed. CONCLUSIONS: This study suggests that PD are significant predictors of remission in early-onset chronic depression.

Desvenlafaxine vs. placebo in the treatment of persistent depressive disorder.

INTRODUCTION: Pharmacotherapy of non-major persistent depressive disorder (PDD) is little studied. We report a study of the serotonin-norepinephrine reuptake inhibitor (SNRI) desvenlafaxine (DVLX) for PDD. METHOD: Non-psychotic, non-bipolar outpatients aged 20-65 having PDD without concurrent major depression (MDD) were randomized double-blind to desvenlafaxine or placebo for 12 weeks. All had Hamilton Depression Rating Scale (HDRS-24) score ≥ 12. Open-label DVLX was offered for 12 weeks following the acute trial. RESULTS: Seventy-one subjects having mean baseline HDRS-24 20.27 ±â€¯4.77 were eligible, of whom post-RZ data was available for all 59 randomized. The primary 12 week analysis did not differentiate DVLX-treated subjects' mean HDRS scores from those on placebo (6.53 ±â€¯3.98 vs. 8.24 ±â€¯4.96, F = 3.33, df = 1, p = .07). Several secondary analyses yielded statistically significant results, including Responder, CGI and QIDS. DISCUSSION: As the primary analysis did not reach statistical significance, this is a negative study which does not support the use of DVLX for non-major PDD. Nevertheless, statistically significant secondary analyses suggest the overall negative result could be due to sample size or sampling, suggesting further studies of this medication might be appropriate in this population.

Hypomania with and without Dysphoria: comparison of comorbidity and clinical characteristics of respondents from a national community sample.

OBJECTIVE: To compare rates of comorbidity, treatment utilization, the course of illness, and past year social functioning of Hypomania with and without Dysphoria Hypomania (mixed state). METHOD: The National Epidemiological Survey on Alcohol and Related Conditions (NESARC) was a nationally representative face-to-face survey of 43,093 respondents, aged 18 years and older, conducted in 2001 through 2002. The target population of the survey is the civilian, noninstitutionalized population residing in the United States. RESULTS: Dysphoric Hypomania was associated with an increased lifetime risk for major depression, dysthymic disorder, anxiety disorders and personality disorders compared to Non-Dysphoric Hypomania. The former group had an earlier onset age of major depression, more episodes major depression and hypomania, and had a higher rate of treatment contact than the later group. Past year personal income and the frequency of full-time employment were lower in the Dysphoric Hypomania compared to Non-Dysphoric Hypomania. CONCLUSIONS: Dysphoric Hypomania is a more severe and persistent mood disorder compared to Non-Dysphoric Hypomania.

Is duloxetine effective treatment for depression with atypical features?

Depression with atypical features responds preferentially to monoamine oxidase inhibitors relative to tricyclic antidepressants. The efficacies of newer agents have been little studied in this group, although fluoxetine was more effective than placebo. Studies with newer agents seem indicated. Twenty outpatients having major depression with atypical features were treated for 8 weeks with up to 120 mg/day of duloxetine. Fifty percent responded (>50% decrease in 24-item Hamilton Rating Scale for Depression) and 35% remitted (final 24-item Hamilton Rating Scale for Depression < or =7). The small sample size results in wide confidence intervals and lack of a placebo control group limits inferences of efficacy. Response and remission rates for depressed patients with atypical depression were similar to those reported for depressed patients in general. Placebo-controlled studies are required to definitively demonstrate whether these pilot results represent the efficacy of duloxetine in treating atypical depression.

Hemispatial PCA dissociates temporal from parietal ERP generator patterns: CSD components in healthy adults and depressed patients during a dichotic oddball task.

Event-related potentials (31-channel ERPs) were recorded from 38 depressed, unmedicated outpatients and 26 healthy adults (all right-handed) in tonal and phonetic oddball tasks developed to exploit the perceptual challenge of a dichotic stimulation. Tonal nontargets were pairs of complex tones (corresponding to musical notes G and B above middle C) presented simultaneously to each ear (L/R) in an alternating series (G/B or B/G; 2-s fixed SOA). A target tone (note A) replaced one of the pair on 20% of the trials (A/B, G/A, B/A, A/G). Phonetic nontargets were L/R pairs of syllables (/ba/, /da/) with a short voice onset time (VOT), and targets contained a syllable (/ta/) with a long VOT. Subjects responded with a left or right button press to targets (counterbalanced across blocks). Target detection was poorer in patients than controls and for tones than syllables. Reference-free current source densities (CSDs; spherical spline Laplacian) derived from ERP waveforms were simplified and measured using temporal, covariance-based PCA followed by unrestricted Varimax rotation. Target-related N2 sinks and mid-parietal P3 sources were represented by CSD factors peaking at 245 and 440 ms. The P3 source topography included a secondary, left-lateralized temporal lobe maximum for both targets and nontargets. However, a subsequent hemispheric spatiotemporal PCA disentangled temporal lobe N1 and P3 sources as distinct factors. P3 sources were reduced in patients compared with controls, even after using performance as a covariate. Results are consistent with prior reports of P3 reduction in depression and implicate distinct parietal and temporal generators of P3 when using a dichotic oddball paradigm.

Predictors of attrition during initial (citalopram) treatment for depression: a STAR*D report.

OBJECTIVE: Premature attrition from treatment may lead to worse outcomes and compromise the integrity of clinical trials in major depressive disorder. The purpose of this study was to identify the pretreatment predictors of attrition during acute treatment with citalopram in a large, "real world" clinical trial. METHOD: A total of 4,041 adult outpatients with nonpsychotic major depressive disorder were enrolled in treatment with citalopram for up to 14 weeks. Attrition was defined as "immediate" (patients who attended a baseline visit only) or "later" (patients who attended at least one postbaseline visit but who dropped out before the 12-week visit). RESULTS: Overall, 26% of enrolled patients dropped out of the acute phase treatment for nonmedical reasons. Of these, 34% dropped out immediately, 59% dropped out by week 12, and 7% dropped out after 12 weeks. Immediate attrition was associated with younger age, less education, and higher perceived mental health functioning. Attrition later in treatment was associated with younger age, less education, and African American race. Experience with more than one episode of depression was associated with less attrition. CONCLUSIONS: In clinical trials and clinical practice, several time points in treatment may provide opportunities to engage and encourage populations at higher risk for attrition and populations with high-risk presentation of illness. Additionally, more aggressive forms of treatment implemented earlier in the treatment process in order to increase the likelihood of more rapid efficacy may reduce dropout rates.

Effect of age at onset on the course of major depressive disorder.

OBJECTIVE: This report assesses whether age at onset defines a specific subgroup of major depressive disorder in 4,041 participants who entered the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. METHOD: The study enrolled outpatients 18-75 years of age with nonpsychotic major depressive disorder from both primary care and psychiatric care practices. At study entry, participants estimated the age at which they experienced the onset of their first major depressive episode. This report divides the population into five age-at-onset groups: childhood onset (ages <12), adolescent onset (ages 12-17), early adult onset (ages 18-44), middle adult onset (ages 45-59), and late adult onset (ages > or =60). RESULTS: No group clearly stood out as distinct from the others. Rather, the authors observed an apparent gradient, with earlier ages at onset associated with never being married, more impaired social and occupational function, poorer quality of life, greater medical and psychiatric comorbidity, a more negative view of life and the self, more lifetime depressive episodes and suicide attempts, and greater symptom severity and suicidal ideation in the index episode compared to those with later ages at onset of major depressive disorder. CONCLUSIONS: Although age at onset does not define distinct depressive subgroups, earlier onset is associated with multiple indicators of greater illness burden across a wide range of indicators. Age of onset was not associated with a difference in treatment response to the initial trial of citalopram.