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BACKGROUND: Psilocybin is being studied for use in treatment-resistant depression.METHODS: In this phase 2 double-blind trial, we randomly assigned adults with treatment-resistant depression to receive a single dose of a proprietary, synthetic formulation of psilocybin at a dose of 25 mg, 10 mg, or 1 mg (control), along with psychological support. The primary end point was the change from baseline to week 3 in the total score on the Montgomery-Åsberg Depression Rating Scale (MADRS; range, 0 to 60, with higher scores indicating more severe depression). Secondary end points included response at week 3 (≥50% decrease from baseline in the MADRS total score), remission at week 3 (MADRS total score ≤10), and sustained response at 12 weeks (meeting response criteria at week 3 and all subsequent visits).RESULTS: A total of 79 participants were in the 25-mg group, 75 in the 10-mg group, and 79 in the 1-mg group. The mean MADRS total score at baseline was 32 or 33 in each group. Least-squares mean changes from baseline to week 3 in the score were -12.0 for 25 mg, -7.9 for 10 mg, and -5.4 for 1 mg; the difference between the 25-mg group and 1-mg group was -6.6 (95% confidence interval [CI], -10.2 to -2.9; PCONCLUSIONS: In this phase 2 trial involving participants with treatment-resistant depression, psilocybin at a single dose of 25 mg, but not 10 mg, reduced depression scores significantly more than a 1-mg dose over a period of 3 weeks but was associated with adverse effects. Larger and longer trials, including comparison with existing treatments, are required to determine the efficacy and safety of psilocybin for this disorder. (Funded by COMPASS Pathfinder; EudraCT number, 2017-003288-36; ClinicalTrials.gov number, NCT03775200.).

Purpose Depression is among the most common comorbid psychiatric disorders for patients with breast cancer. Depression can decrease patient quality of life and adversely affect cancer treatment if untreated. We sought to identify treatment barriers to women with breast cancer treated with psychotherapy for depression. Findings may help policy makers and researchers determine funding and design of future studies involving this population, especially in communities with high rates of health disparities. Methods We used data from a randomized trial for women with breast cancer and current DSM-IV non-psychotic unipolar major depressive disorder (MDD). Patients were randomly assigned to 12 weeks of one of three psychotherapies and attrition was assessed by whether subjects completed 12 weekly treatment sessions. Descriptive analyses and logistic regression were used to identify treatment barriers. R shiny was used to determine the residence of study participants. Results Of 134 randomized patients, 84 (62.7%) were Hispanic. Fifty-nine (44%) either did not start or dropped out of treatment, 49 (83.1%) of them Hispanic. Being a Hispanic woman, less educated, and living geographically distant significantly predicted attrition. Single Hispanic mothers had significantly higher attrition risk than married and/or childless women. Conclusion Identifying barriers to treatment is important to improve treatment adherence for women with concurrent diagnoses of breast cancer and MDD, especially for traditionally underserved minorities. Additional support, such as affordable tele-medicine, multi-language assistance, financial aid for transportation and child-care, and allocating more funds to assist some identified barriers should be considered to improve treatment adherence and outcomes.

BACKGROUND: COMP360 is a proprietary, synthetic formulation of psilocybin being developed for treatment-resistant depression (TRD), a burdensome, life-threatening illness with high global impact. Here, we expand upon the previous report of primary outcomes from a phase 2 study of COMP360 in individuals with TRD-the largest randomised controlled clinical trial of psilocybin-to discuss findings of the exploratory efficacy endpoints.METHODS: In this phase 2, double-blind trial, 233 participants with TRD were randomised to receive a single dose of psilocybin 25 mg, 10 mg, or 1 mg (control), administered alongside psychological support from trained therapists. Efficacy measures assessed patient-reported depression severity, anxiety, positive and negative affect, functioning and associated disability, quality of life, and cognitive function.RESULTS: At Week 3, psilocybin 25 mg, compared with 1 mg, was associated with greater improvements from Baseline total scores in all measures. The 10 mg dose produced smaller effects across these measures.LIMITATIONS: Interpretation of this trial is limited by the absence of an active comparator and the possibility of functional unblinding in participants who received a low dose of psilocybin.CONCLUSIONS: Three weeks after dosing, psilocybin 25 mg and, to a lesser degree, 10 mg improved measures of patient-reported depression severity, anxiety, affect, and functioning. These results extend the primary findings from the largest randomised clinical trial of psilocybin for TRD to examine other outcomes that are of importance to patients.

Background: Therapeutic administration of psychedelic drugs has shown significant potential in historical accounts and in recent clinical trials in the treatment of depression and other mood disorders. A recent randomized double-blind phase-IIb study demonstrated the safety and efficacy of COMP360, COMPASS Pathways’ proprietary synthetic formulation of psilocybin, in participants with treatment resistant depression. While promising, the treatment works for a portion of the population and early prediction of outcome is a key objective.Methods: Transcripts were made from audio recordings of the psychological support session between participant and therapist one day post COMP360 administration. A zero-shot machine learning classifier based on the BART large language model was used to compute two-dimensional sentiment (valence and arousal) for the participant and therapist from the transcript. These scores, combined with the Emotional Breakthrough Index (EBI) and treatment arm were used to predict treatment outcome as measured by MADRS scores. Code and data are available at https://github.com/compasspathways/Sentiment2DResults: Two multinomial logistic regression models were fit to predict responder status at week 3 and through week 12. Cross-validation of these models resulted in 85% and 88% accuracy and AUC values of 88% and 85%.Conclusions: A machine learning algorithm using NLP and EBI accurately predicts long term patient response, allowing rapid prognostication of personalized response to psilocybin treatment and insight into therapeutic model optimization. Further research is required to understand if language data from earlier stages in the therapeutic process hold similar predictive power.

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.

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 (η2 = 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 η2 = 0.21; right thalamus η2 = 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.

A broad reassessment of the potential benefits of psychedelic drugs has led to the initiation of multiple major clinical trials in an effort to advance their status to become FDA-approved medications, as well as local legislative efforts to legalize or decriminalize their use.To use recently published data to assess potential risks and benefits of psychedelic drugs as therapeutics, as well as to synthesize what is currently known in order to generate fruitful future research directions.A review of studies conducted since 1991 identified 14 clinical trials of classical psychedelics, including 11 of psilocybin (N = 257 participants), 1 of lysergic acid diethylamide (N = 12 participants), and 2 of ayahuasca (N = 46 participants). Other published studies (e.g., of healthy volunteers, survey studies, case reports, neuroimaging) were also considered for review.Published studies since 1991 largely support the hypothesis that small numbers of treatments with psychedelic-assisted psychotherapy can offer significant and sustained alleviation to symptoms of multiple psychiatric conditions. No serious adverse events attributed to psychedelic therapy have been reported. Existing studies have several limitations, including small sample sizes, inherent difficulty in blinding, relatively limited follow-up, and highly screened treatment populations.Substantial data have been gathered in the past 30 years suggesting that psychedelics are a potent treatment for a variety of common psychiatric conditions, though the ideal means of employing these substances to minimize adverse events and maximize therapeutic effects remains controversial. Unique factors related to study design are vital for clinical researchers in the field to address.

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.

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 ± 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.

PURPOSE: Breast cancer (BC) is a risk factor for major depressive disorder (MDD), yet little research has tested the efficacy of different psychotherapies for depressed women with BC. This study, the largest to date, compared outcomes of three evidence-based, twelve-week therapies in treating major depressive disorder among women with breast cancer. METHODS: This randomized trial compared interpersonal psychotherapy (IPT), problem solving therapy (PST), and brief supportive psychotherapy (BSP). Conducted at the outpatient clinic of the New York State Psychiatric Institute/Columbia University, the trial offered bilingual treatment by treatment-specific psychotherapists supervised by treatment experts. The primary outcome was change in the Hamilton Depression Rating Scale (HAM-D) at 12 weeks. Secondary outcomes included other validated patient-reported outcomes for depression and quality of life. RESULTS: Of 179 women with breast cancer screening positive for depression at the Columbia Cancer Center, 134 eligible patients signed informed treatment consent. Half of patients were Hispanic and economically disadvantaged. Most women had stage I (35.2%) or II (36.9%) BC; 9% had stage IV. The three brief psychotherapies showed similar improvements on the HAM-D, with large pre-post effect sizes (d~ 1.0); a priori defined response rates were 35% for IPT, 50% for PST and 31% for BSP, and remission rates 25%, 30% and 27%, respectively. The three treatments also showed similar improvements in the Quality of Life Enjoyment and Satisfaction Questionnaire. Dropout was high, ranging from 37–52% across treatments. Predictors of dropout included having

Patients with mood disorders often can benefit from psychotherapy, whether as a primary treatment for depression or as an adjunct to medications or other biological treatments. Today, therapeutic approaches such as cognitive–behavioral therapy and interpersonal therapy are commonly thought of as first-line evidence-based treatments of depression, yet there is also evidence that psychodynamic psychotherapy (PDT) and supportive psychotherapy (SPT) can be effective treatments of depression. Both PDT and SPT are commonly used in clinical practice, by a wide range of clinicians and in many different settings. This chapter describes the theoretical background of each of these therapies, therapeutic techniques, how they can be adapted for treatment of depression, and patient populations for which they may be indicated.

BACKGROUND: Antidepressant medications offer an effective treatment for depression, yet nearly 50% of patients either do not respond or have side-effects rendering them unable to continue the course of treatment. Mechanistic studies might help advance the pharmacology of depression by identifying pathways through which treatments exert their effects. Toward this goal, we aimed to identify the effects of antidepressant treatment on neural connectivity, the relationship with symptom improvement, and to test whether these effects were reproducible across two studies. METHODS: We completed two double-blind, placebo-controlled trials of SNRI antidepressant medications with MRI scans obtained before and after treatment. One was a 10-week trial of duloxetine (30–120 mg daily; mean 92·1 mg/day [SD 30·00]) and the other was a 12-week trial of desvenlafaxine (50–100 mg daily; 93·6 mg/day [16·47]). Participants consisted of adults with persistent depressive disorder. Adjusting for sex and age, we examined the effect of treatment on whole-brain functional connectivity. We also examined correlations between change in functional connectivity and improvement in symptoms of depression (24-item Hamilton Depression Rating Scale) and pain symptom severity (Symptom Checklist-90-Revised). FINDINGS: Participants were enrolled between Jan 26, 2006, and Nov 22, 2011, for the duloxetine RCT and Aug 5, 2012, and Jan 28, 2016, for the desvenlafaxine RCT. Before and after treatment MRI scans were collected in 32 participants for the duloxetine RCT and 34 participants for the desvenlafaxine RCT. In both studies, antidepressants decreased functional connectivity compared with placebo (duloxetine study: β = −0·06; 95% CI −0·08 to −0·03; p < 0·0001, η(p)(2) = 0·44; desvenlafaxine study: −0·06, −0·09 to −0·03; p < 0·0001, η(p)(2) = 0·35) within a thalamo-cortico-periaqueductal network that has previously been associated with the experience of pain. Within the active drug groups, reductions in functional connectivity within this network correlated with improvements in depressive symptom severity in both studies (duloxetine study: r = 0·38, 95% CI 0·01–0·65; p = 0·0426; desvenlafaxine study: 0·44, 0·10–0·69; p = 0·0138) and pain symptoms in the desvenlafaxine study (0·39, 0·04 to 0·65; p = 0·0299). INTERPRETATION: The findings suggest the thalamo-cortico-periaqueductal network associated with the experience of pain is a new and potentially important target for novel antidepressant therapeutics. FUNDING: National Mental Health Institute, Eli Lilly and Company, Pfizer Pharmaceuticals, and the Edwin S Webster Foundation.

Background Bipolar Disorder (BD) cannot be reliably distinguished from Major Depressive Disorder (MDD) until the first manic or hypomanic episode. Consequently, many patients with BD are treated with antidepressants without mood stabilizers, a strategy that is often ineffective and carries a risk of inducing a manic episode. We previously reported reduced cortical thickness in right precuneus, right caudal middle-frontal cortex and left inferior parietal cortex in BD compared with MDD. Methods This study extends our previous work by performing individual level classification of BD or MDD in an expanded, currently unmedicated, cohort using gray matter volume (GMV) based on Magnetic Resonance Imaging and a Support Vector Machine. All patients were in a Major Depressive Episode and a leave-two-out analysis was performed. Results Nineteen out of 26 BD subjects and 20 out of 26 MDD subjects were correctly identified, for a combined accuracy of 75%. The three brain regions contributing to the classification were higher GMV in bilateral supramarginal gyrus and occipital cortex indicating MDD, and higher GMV in right dorsolateral prefrontal cortex indicating BD. Limitations This analysis included scans performed with two different headcoils and scan sequences, which limited the interpretability of results in an independent cohort analysis. Conclusions Our results add to previously published data which suggest that regional gray matter volume should be investigated further as a clinical diagnostic tool to predict BD before the appearance of a manic or hypomanic episode.

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

Drugs lifted Frank's depression, but he had to find meaningful activity to relaunch his life

Psychotherapy of borderline personality disorder (BPD) has often focused on specialized and putatively more effective treatments such as dialectical behavioral therapy. In recent years, accumulating evidence suggests that many BPD patients benefit equally well from well-structured but less specialized care designed to meet their needs. Supportive psychotherapy (SPT) and various forms of clinical management, such as structured clinical management (SCM) and general psychiatric management (GPM), have been successfully adapted for treatment of BPD. This chapter describes the theoretical backgrounds for these approaches, main treatment techniques, and how they can be implemented to provide good outcomes for individuals diagnosed with BPD.

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)

OBJECTIVE: This work tested the hypothesis that patients with high negative affectivity (NA) would have a better response to a serotonergic agent (escitalopram) than to one not thought to act directly on serotonin (bupropion). METHOD: Data from a study conducted between August 2007 and July 2011 were reanalyzed retrospectively. Patients (N = 245) meeting criteria for major depressive disorder (MDD), diagnosed with DSM-IV-TR, were randomly assigned to double-blind treatment with bupropion extended-release, escitalopram, or the combination. Negative affectivity score was estimated using the guilt, hostility/irritability, and fear/anxiety items of the Hamilton Depression Rating Scale, the Montgomery-Asberg Depression Rating Scale, the Quick Inventory of Depressive Symptoms, and the Social Adjustment Scale. We felt that these items captured published descriptions of the NA construct. A Clinical Global Impressions-Severity of Illness (CGI-S) score ≤ 2 defined response. Because combined treatment addressed both serotonin and non-serotonin systems, patients treated with both medications did not test the hypothesis and so were excluded from the analyses. RESULTS: Analysis of covariance with treatment as a grouping variable, NA as covariate, and CGI-S as dependent variable showed a significant 2-way interaction between treatment and NA (F₁,₁₅₆ = 4.82, P < .03). In the low-NA group, response rates were similar between treatments (escitalopram: 28/42 [67%]; bupropion: 23/40 [58%]; NS), while there was a significant advantage for escitalopram in patients with high NA (escitalopram: 24/40 [60%]; bupropion = 14/41 [34%]; P = .017). CONCLUSIONS: These data suggest that patients with high negative affectivity respond preferentially to antidepressants that selectively enhance serotonin neurotransmission. Although patients with low NA appear to benefit from serotonin enhancement as well, they also improved with bupropion, an antidepressant not thought to directly affect serotonin neurotransmission. These findings come from retrospective analyses using unproven approximation of NA, so no clinical inferences should be made before independent replication utilizing accepted NA measurement. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00519428.

Background Executive dysfunction and psychomotor slowing in depressed patients have been associated with poor antidepressant clinical response, but little is known about the value of neurocognitive tests for differential prediction of response. Methods This report presents new findings for 70 depressed patients tested on neurocogntive tests before receiving treatment with a SSRI (escitalopram or citalopram), NDRI (bupropion) or dual mechanism therapy including a serotonergic agent, and for 57 healthy controls. Results As predicted from previous research, patients who did not respond to a SSRI or dual therapy showed poorer word fluency than responders, whereas this was not seen for patients treated with bupropion alone. Longer choice reaction time (RT) was also found in nonresponders to a SSRI or dual therapy, but the opposite trend was seen for bupropion. Using a combined index of word fluency and RT (with normative performance as a cutoff) yielded differential predictions of response. Equal to or above normal performance predicted good response to a SSRI or dual therapy, with high positive predictive value (90%) and specificity (78%) but lower sensitivity (53%). In contrast, less than normal performance predicted good response to bupropion alone (positive predictive value=82%; specificity=67%; sensitivity=90%). Limitations Relatively small sample size, no placebo control, and combining across SSRI alone and dual treatments. Conclusions Although findings are preliminary due to small sample size, brief tests of word fluency and psychomotor speed may help identify depressed patients who are unresponsive to a serotonergic agent, but who may respond to bupropion alone.

BackgroundTo assess whether patients with Persistent Depressive Disorder (PDD) have abnormal levels of N-acetyl-aspartate (NAA) and whether those levels normalize following treatment with the antidepressant medication duloxetine. Furthermore, we conducted post hoc analyses of other important brain metabolites to understand better the cellular and physiological determinants for changes in NAA levels.MethodsWe acquired proton (1H) magnetic resonance spectroscopic imaging (MRSI) data on a 3 Tesla (3T), GE Magnetic Resonance Imaging (MRI) scanner in 41 patients (39.9±10.4 years, 22 males) with PDD at two time points: before the start and at the end of a 10-week, placebo-controlled, double-blind, randomized controlled trial (RCT) of the antidepressant medication duloxetine. Patients were randomized such that 21 patients received the active medication and 20 patients received placebo during the 10 week period of the trial. In addition, we acquire 1H MRSI data once in 29 healthy controls (37.7±11.2 years, 17 males).FindingsPatients had significantly higher baseline concentrations of NAA across white matter (WM) pathways and subcortical gray matter, and in direct proportion to the severity of depressive symptoms. NAA concentrations declined in duloxetine-treated patients over the duration of the trial in the direction toward healthy values, whereas concentrations increased in placebo-treated patients, deviating even further away from healthy values. Changes in NAA concentration did not mediate medication effects on reducing symptom severity, however; instead, changes in symptom severity partially mediated the effects of medication on NAA concentration, especially in the caudate and putamen.InterpretationThese findings, taken together, suggest that PDD is not a direct consequence of elevated NAA concentrations, but that a more fundamental pathophysiological process likely causes PDD and determines the severity of its symptoms. The findings also suggest that although duloxetine normalized NAA concentrations in patients, it did so by modulating the severity of depressive symptoms. Medication presumably reduced depressive symptoms through other, as yet unidentified, brain processes.Trial registrationClinicalTrials.gov NCT00360724.

Internet-based technologies, such as email and social media, are being increasingly used by mental health providers. The authors created a survey to better understand mental health providers' practices and attitudes regarding these platforms.Psychiatrists and psychologists at Columbia and the New York State Psychiatric Institute completed a 24-item multiple choice and free-text survey about their use of and attitudes toward Internet technologies.One hundred and thirty faculty responded to the survey: 70% percent of respondents reported that they were somewhat or more familiar with social media; 20% reported that they sometimes or often searched for information about their patients online; and 60% said that searching for patients online could have a positive role in ongoing psychiatric care. Respondents with fewer years of practice were significantly more likely to use Facebook/Google Plus, texting, and instant messenger in their personal lives, while those with more years of practice were more likely to use Skype professionally. Practitioners who worked in hospital settings were more likely to search online for information about their patients. Practitioners working in outpatient clinics, private practices, and research settings were more likely to use websites, email, and Skype in their practices.Mental health care professionals are starting to incorporate Internet technologies into their professional lives, but they remain divided on the ethics and utility of using these technologies in clinical care. There appear to be differences in practices and attitudes toward the Internet among clinicians with different levels of experience and in different practice settings.

Objective To determine efficacy of continued treatment with the serotonin norepinephrine reuptake inhibitor duloxetine on symptom reduction and functional improvement in outpatients with dysthymia. Method Fifty outpatients with DSM-IV-TR diagnosed dysthymia who had participated in a 10 week double-blind, placebo-controlled study of duloxetine received open treatment for three months. Nineteen duloxetine responders continued duloxetine, 24 patients initially treated with placebo started open duloxetine treatment, and 7 duloxetine non-responders were treated with desvenlafaxine or bupropion, selected by clinician choice. Results Patients continuing duloxetine maintained symptom improvement, 84% meeting response and 63% remission criteria at week 22. Patients initially treated with placebo showed similarly high levels of response (83%) and remission (62%) at week 22, and most duloxetine non-responders subsequently responded to other antidepressants. Duloxetine-continuation patients improved modestly between weeks 10 and 22 on measures of social and cognitive functioning and temperament. Despite this improvement concurrently across several functional domains, 66.7% of patients continuing duloxetine remained in the impaired range of functioning according to the Social Adjustment Scale (SAS). Conclusions Continued duloxetine treatment appears to be effective in maintaining symptom response in dysthymic disorder, and has positive effects on social functioning. However, the majority of patients do not show normalization of functioning, even when controlling for remission status. Additional treatments should be considered to target residual impairments in social functioning in mood remitted patients with persistent depressive disorder.

Objective Numerous double-blind studies have assessed the efficacy of antidepressants in treating chronic depressive disorder, including dysthymic disorder, low-grade chronic depression. However, there are no double-blind, placebo-controlled studies of serotonin-norepinephrine reuptake inhibitors in chronic depressive disorder. Method Outpatients with chronic depressive disorder, but without concurrent major depressive disorder (MDD), were randomly assigned to prospective double-blind duloxetine (beginning at 30 mg/d, increased to a maximum dose of 120 mg/d) versus placebo for 10 weeks. Inclusion criteria were current DSM-IV-TR diagnosis of dysthymic disorder or depression not otherwise specified, age 18-75 years, and a Hamilton Depression Rating Scale (HDRS) score ≥ 12. Exclusion criteria included current major depression. The study was conducted between August 2006 and December 2011. HDRS, Cornell Dysthymia Rating Scale (CDRS), Clinical Global Impressions (CGI), Beck Depression Inventory (BDI), Global Assessment of Functioning (GAF), Social Adjustment Scale (SAS), and other assessments were administered at each visit. We hypothesized that duloxetine would be superior to placebo in (1) 24-item HDRS total score, (2) the percentage of subjects classified as responders and remitters, and (3) secondary measures (CDRS, BDI, CGI). Response was defined as > 50% decrease in 24-item HDRS and CGI-Improvement scale score of 1 or 2 ("very much improved" or "much improved"). Remission was defined as HDRS-17 item score ≤ 4 and 0 on item 1 of the HDRS (depressed mood). Results 65 subjects were enrolled, of whom 57 began medication. They ranged in age from 19 to 70 years (mean ± SD = 41.63 ± 11.22) and included 24 women and 33 men. Baseline 24-item HDRS score (mean ± SD) for both groups was 20.75 ± 4.92. After 10 weeks, duloxetine-treated subjects had significantly lower 24-item HDRS scores than placebo-treated subjects (time-by-drug group effect on analysis of variance: F1,55 = 9.43, P = .003). Responder and remitter analyses significantly favored duloxetine treatment. The response rate was 65.5% for duloxetine versus 25.0% for placebo (χ(2)(1) = 9.43, P = .003); and the remitter rate was 55.2% for duloxetine versus 14.3% for placebo (χ(2)(1) = 10.46, P = .002). After 10 weeks, duloxetine-treated subjects did not differ significantly better from placebo-treated subjects on the SAS (time-by-drug group effect on analysis of variance: F(1,46) = 0.35, P = .555) or on the GAF (time-by-drug group effect on analysis of variance: F(1,51) = .01, P = .922). Conclusions Results on the 24-item HDRS, CGI, and CDRS suggest that duloxetine is efficacious in acute treatment of chronic nonmajor depressive disorder. Response and remission rates also differed significantly, favoring duloxetine treatment, but BDI, GAF, and social functioning (Social Adjustment Scale) did not. Duloxetine appears to be effective in acute treatment of nonmajor chronic depression. Trial registration ClinicalTrials.gov identifier: NCT00360724.

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.

The purpose of this article is to explore the use of behavioral activation therapy in patients with medication-responsive chronic depression who continue to experience social and occupational deficits. The classification of chronic depression includes a variety of disorders that are both common and debilitating and that frequently leave patients socially impaired even after remission of mood symptoms. Medication is often only partially effective in remedying these social impairments. As a result, other interventions, including forms of psychotherapy, may be justified as an adjunct to medication to improve residual social impairment. Behavioral activation therapy is one such treatment that may be especially appropriate for such individuals. The authors offer a brief description of behavioral activation therapy and examine how to adapt this therapy for use in patients with medication-responsive chronic depression. Preliminary evidence suggests that the therapy can be easily implemented with few modifications to improve social and occupational difficulties.

Background Chronic depression is associated with impaired functioning. The National Epidemiologic Survey of Alcoholism and Related Conditions (NESARC) is a representative sample ( N = 43,093) of the United States non-institutionalized population aged 18 years and older. We hypothesized that individuals with chronic low-grade depression, dysthymic disorder, would have more impaired functioning than individuals with acute major depression or the general population. Method Diagnoses were generated by the NIAAA Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV Version (AUDADIS-IV). The dysthymic disorder (DD) sample ( N = 328) consisted of DD diagnosis without current MDD. The dysthymic group was not chosen on the basis of alcohol use or abuse. Individuals with MDD with duration ≦24 months, without lifetime DD constituted the acute depression (AD) sample ( N = 712). All other respondents were classified as general population (GP) ( N = 42,052). Past year functioning was assessed by Supplemental Social Security Income (SSI), employment, and Medicaid statuses. Past month functioning was assessed by Short-form 12-Item Health Survey (SF-12), with scores for social functioning, role emotional functioning, and mental health, using odds ratios. Results Over the past year, compared to AD, persons with DD were less likely to work full-time (36.2% vs. 44%; OR = 0.70, CI = .54,.92) and more often received SSI (13.9% vs. 4.5%; OR = 3.4, CI = 2.0,5.9) and Medicaid (20.2% vs. 13%; OR = 1.7 , CI = 1.1,2.6). Dysthymics reported accomplishing less over the past month due to emotional problems, and that emotional or physical problems interfered with social activities. Relative to GP, respondents with DD were more likely to receive SSI (13.9% vs. 2.9%; OR = 4.6, CI 3.4,6.2) and Medicaid (20.2% vs. 5.9%; OR = 2.9, CI 2.0,4.1). Compared to GP, dysthymics reported accomplishing less due to emotional problems, and that emotional or physical problems interfered with social activities and work functioning. Conclusions DD-associated psychosocial impairment in the community setting comprises a significant public health burden.

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.

Background: Research on the relationship between depression and alcohol use disorder in remission has been scarce. The authors examined whether a lifetime history of alcohol use disorder affected response to antidepressant treatment of dysthymic disorder (DD) in adult outpatients. Methods: This is a secondary analysis of data from previous prospective medication trials. Data from 123 subjects with DD were included. Subjects were categorized into 2 groups: (1) no lifetime alcohol use disorder (NLAUD) (n = 99) and (2) lifetime alcohol use disorder (LAUD) (n = 24). None of the subjects met criteria for alcohol use disorder for 6 months prior to intake. Rating scales from baseline and after 8 weeks of pharmacotherapy were collected. Results: After 8 weeks of treatment, the NLAUD and LAUD groups did not differ in rates of response or remission, despite significantly higher baseline Hamilton Depression Rating Scale (HDRS)-24 scores in the LAUD group. We also found a greater decrease in symptoms in the ...

Aripiprazole may be an effective adjunctive treatment in outpatients with unipolar depression that has been refractory to treatment with SSRI or SNRI medication.Fifteen subjects with a current DSM-IV diagnosis of MDD which had not responded to SSRI or SNRI treatment were enrolled in a 12 week open-label study of aripiprazole with a maximum dose of 30 mg/day. Patients' current episode averaged 10.4+/-16.6 years, with a range of 3 months to 54 years. Baseline severity averaged 30.1+/-7.1 on HDRS-24, and 19.7+/-8.4 on BDI. Patients had been treated with a mean dose of 79.2+/-28.2 mg/day of fluoxetine equivalents for an average of 1 year prior to starting the study. Five subjects were on SNRI medications and 10 on SSRIs.Seven of 14 (50.0%) subjects were classified as treatment responders, as defined by at least 50% reduction in the HDRS-24 at week 12. Four subjects (28.6%) achieved remission, based on STAR D criteria (HDRS-17 scoreor=7). 26.7% (4/15) of subjects discontinued participation due to side effects. Two (40%) of 5 SNRI-treated subjects responded to aripiprazole augmentation.These findings support previous studies for the effectiveness of aripiprazole in augmenting SSRIs or SNRIs in treatment-resistant major depression.

We describe a hospital-wide effort to decrease restraint and seclusion of psychiatric inpatients. Our hypotheses were that interventions could reduce the number of patients as well as patient hours in restraint and seclusion, without an increase in adverse outcomes (fights/assaults, staff injuries, and elopements).This study was performed at an urban academic psychiatric hospital (New York State Psychiatric Institute) with 3 inpatient units totaling 58 beds. Interventions included 1) decreasing initial time in restraint or seclusion from 4 to 2 hours before a new order was required; 2) education of staff concerning identification of patients at risk of restraint or seclusion and early interventions to avoid crises; and 3) use of a coping questionnaire to assess patient preferences for dealing with agitation. Data were assessed 20 months before and 67 months following the implementation of these interventions.The mean number of patients restrained went from 0.35 +/- 0.6 to 0.32 +/- 0.5 patients/month; mean hours of restraint decreased from 1.7 +/- 5.2 to 1.0 +/- 2.4 hours/month. The mean number of patients secluded decreased significantly from 3.1 +/- 1.4 to 1.0 +/- 1.1 patients/month. The mean hours of seclusion decreased markedly, from 41.6 +/- 52 to 2.7 +/- 4.5 hours/month. Adverse outcomes (elopements and fights/assaults) also decreased significantly over the follow-up period.Interventions were successful in decreasing use of restraint and seclusion on both clinical and research units over more than 5 years of follow-up. Such interventions may be adapted to other settings.

This paper describes the role of an agency Clinical Director in developing a project to assess and begin to address obesity-related health problems of patients treated in a community-based mental health clinic in New York City. After a five year review of outpatient deaths revealed a high rate of deaths from cardiovascular and diabetes-related issues, the Clinical Director assembled a group of clinicians, researchers, and administrative staff to design a pilot project to assess health and nutrition status of primarily Hispanic day treatment patients with severe and persistent mental illness.About 69 of the 105 patients at the clinic were assessed by chart review, interview about nutritional habits and medical care, and somatic measurements for blood pressure, weight, girth, body mass index (BMI), glucose and lipid levels.Patients were predominantly between the ages of 25 and 64 years, 51% were female, and 78% were Hispanic. Around 57% were diagnosed with schizophrenia-spectrum disorders, 86% were receiving antipsychotic medications, and 25% were on two or more antipsychotics. Only 11% of the women and 41% of the men had normal weight. A total of 29% of the women and 18% of the men were overweight (BMI = 25-29.9); and an additional 60% of the women and 41% of the men were obese (BMIor = 30). Atypical antipsychotic treatment was significantly associated with obesity (BMIor = 30) (chi sq = 5.5, df = 1, P0.025). Using American Heart Association criteria, waist measurements showed significant abdominal obesity among female patients. Blood pressure was elevated in 77% of the patients: 45% were pre-hypertensive with BP 120-139/80-89 and 32% were hypertensive with BPor = 140/90. About 53% had elevated random blood glucoses (110 mg/dl). On the positive side, patients generally had had recent medical follow-up, and most had adequate cooking facilities.This project revealed that these predominantly Hispanic, severely mentally ill individuals were at high risk for cardiac illness, highlighting the need for developing culturally-sensitive interventions in urban outpatient psychiatric settings. Findings were disseminated in educational presentations and clinical discussions, and have mobilized an institutional effort to significantly improve medical monitoring for these patients.

Over the past decade, several studies have attempted to determine whether integrating psychiatric and substance abuse treatment leads to better outcome for patients with comorbid schizophrenia and substance use disorders. A recent (1999) Cochrane Review (1) analyzed the effectiveness of prospective randomized studies of integrated treatment approaches, and concluded that there was no clear evidence for superiority of integrated treatment. This paper describes one such integrated treatment approach, in Beth Israel Medical Center's COPAD (Combined Psychiatric and Addictive Disorders) program. We summarize findings from an initial outcome study and a recent replication study; and describe clinical and research issues relevant to this population. Our data suggests the benefits of integrated treatment for patients with addictive disorders and schizophrenia, at least with regard to treatment retention. Clinical issues for such patients include identification of patients at risk, proper assessment and treatment planning, decision-making about mainstreaming vs. referral to specialized programs, and the importance of initial engagement and ongoing reengagement in successful treatment.

RAW MATERIALS I work in a psychiatric clinic, an "outpatient mental health center" at a hospital on the Lower East Side of Manhattan, in a neighborhood which has traditionally been, and remains, the meeting ground of a hundred world cultures. Our neighborhood is a place of artists and bohemians and outcasts and addicts, and its streets are filled with the music of innumerable languages. At case conferences, in patient sessions, I am continually astonished by what I hear. I observe both as a psychiatrist and as a writer. A bipolar patient explains that he has been treated with "lithium carburetor"—the psychiatrist hears "neologisms" (creation of new words) or the phenomenon we call "flight of ideas" (runaway thoughts common in mania), the writer hears poetry. Another patient claims to be assaulted by "forces of magnetism released by construction in the city," or "caused by echoes from satellite dishes." A man comes to our Walk In Clinic convinced he has wings sprouting out of his feet. He wears a rubber suit studded with tiny blinking electric lights, and he regales the second year resident with tales of his girlfriend, a woman with twenty-two personalities. One morning in Teaching Case Conference, a man offhandedly reveals that "the whispering of demons make me choose the wrong Lotto numbers." Another day, a shy Caribbean woman describes being raped for hours each night by a phantom lover. Even our staff talks poetry—reporting on a crack-abusing schizophrenic man who is "ripping and running, dashing and scheming, and copping and hiding." On my way to lunch, walking down 15th Street, I pass by a bedraggled man who is singing: "If that don't get my woman, I'm sure my sho-sho-shotgun will!" At Grand Rounds, one of

Introduction Only about a third of patients with an episode of major depressive disorder remit with a given treatment and few remissions occur within the first weeks of treatment. This study tested whether combining escitalopram and bupropion as initial treatment would result in quicker remission and a higher remission rate than monotherapy with either drug. Method Two hundred forty-five outpatients aged 18–65 having non-psychotic, non-bipolar major depression were randomly assigned to double-blind treatment with bupropion or escitalopram or the combination dosed to a maximum of bupropion 450 mg/d and/or escitalopram 40 mg/d for 12 weeks. A Montgomery–Asberg Depression Rating Scale score of 22 was required for randomization, while a Hamilton Rating Scale for Depression score ≤ 7 defined remission. We hypothesized that bupropion plus escitalopram would outperform both monotherapies in both earlier onset of remission and higher rate of remission. Results Primary analyses did not demonstrate that dual therapy outperformed both monotherapies in either timing of remission or remission rate. All three treatments were well tolerated. Discussion These results do not support initial use of bupropion plus escitalopram to speed or enhance antidepressant response. Clinical trials registration NCT00519428 .

Importance The default mode network (DMN) is a collection of brain regions that reliably deactivate during goal-directed behaviors and is more active during a baseline, or so-called resting, condition. Coherence of neural activity, or functional connectivity, within the brain's DMN is increased in major depressive disorder relative to healthy control (HC) subjects; however, whether similar abnormalities are present in persons with dysthymic disorder (DD) is unknown. Moreover, the effect of antidepressant medications on DMN connectivity in patients with DD is also unknown. Objective To use resting-state functional-connectivity magnetic resonance imaging (MRI) to study (1) the functional connectivity of the DMN in subjects with DD vs HC participants and (2) the effects of antidepressant therapy on DMN connectivity. Design After collecting baseline MRI scans from subjects with DD and HC participants, we enrolled the participants with DD into a 10-week prospective, double-blind, placebo-controlled trial of duloxetine and collected MRI scans again at the conclusion of the study. Enrollment occurred between 2007 and 2011. Setting University research institute. Participants Volunteer sample of 41 subjects with DD and 25 HC participants aged 18 to 53 years. Control subjects were group matched to patients with DD by age and sex. Main Outcome Measures We used resting-state functional-connectivity MRI to measure the functional connectivity of the brain's DMN in persons with DD compared with HC subjects, and we examined the effects of treatment with duloxetine vs placebo on DMN connectivity. Results Of the 41 subjects with DD, 32 completed the clinical trial and MRI scans, along with the 25 HC participants. At baseline, we found that the coherence of neural activity within the brain's DMN was greater in persons with DD compared with HC subjects. Following a 10-week clinical trial, we found that treatment with duloxetine, but not placebo, normalized DMN connectivity. Conclusions and Relevance The baseline imaging findings are consistent with those found in patients with major depressive disorder and suggest that increased connectivity within the DMN may be important in the pathophysiology of both acute and chronic manifestations of depressive illness. The normalization of DMN connectivity following antidepressant treatment suggests an important causal pathway through which antidepressants may reduce depression.

In recent years, the frequency with which patients present with 'double depression', i.e. coexisting chronic depression (dysthymia) and acute major depression, has become increasingly evident. A growing research literature demonstrates that patients with double depression are at increased risk for poor outcome, including poor psychosocial functioning, high usage of medical services, high rates of suicide attempts, and increased recurrence of major depression. Furthermore, naturalistic studies have shown that when these patients are treated in the community, they often do not receive adequate antidepressant medication to treat their acute or chronic depressive disorders.In this article, we introduce a typology that is designed to assist clinicians in determining useful strategies in the short and long term treatment of double depression. This differentiates between those patients with double depression who present primarily with acute depression; those presenting primarily with chronic depression (where treatment can focus on the single, more severe disorder, and may be time-limited or episodic); and those presenting with severe acute depression and severe chronic depression, in whom lifelong medication is often required. Aggressive treatment is recommended for all patients with double depression, but refined treatment strategies based on depressive typology may help to increase compliance, consolidate therapeutic gains and forestall relapse.A growing psychopharmacology literature shows that several different classes of medication [tricyclic antidepressants, monamine oxidase inhibitors, selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors and others] are effective in the treatment of double depression, although perhaps somewhat less effective than in the treatment of acute major depression.

Forty-seven psychiatric inpatients with concurrent RDC-diag-nosed schizophrenia and psychoactive substance use disorders were randomly assigned to one of two outpatient treatment programs: 1) integrated psychiatric and substance abuse treatment; or 2) non-integrated treatment. Patients abused cocaine, alcohol, and marijuana, with over two-thirds using all three drugs. At 4 months, 16 of 23 patients (69.6%) in integrated treatment remained in treatment vs. 9 of 24 (3 7.5%) in the nonintegrated treatment. Rehospitalization did not differ between groups, but treatment nonstarters had significantly more days in the hospital than those who began treatment. At 8 months, addiction and psychiatric severity decreased significantly for patients remaining in treatment. Engagement in integrated outpatient treatment may decrease rehospitalization, and lessen psychiatric and substance abuse severity.

Background: Several meta- or mega-analyses suggest antidepressant medications should be given only to severely depressed patients. In our experience, mild depression benefits from medication. We reanalyzed 1 clinic's randomized placebo-controlled antidepressant studies, limiting analyses to patients with major depressive disorder (MDD) without severe illness, to determine whether nonsevere depression responds to antidepressant medication. Data Sources: Archives of the Depression Evaluation Service outpatient clinic of the New York State Psychiatric Institute were searched for randomized, placebo-controlled antidepressant studies that were conducted between 1977 and 2009 and included patients having MDD and pretreatment Hamilton Depression Rating Scale (HDRS) scores < 23. StudySelection: Six placebo-controlled studies were found, including 8 active treatment arms and 1,440 patients. 825 patients were randomized and had MDD and an HDRS score < 23. DSM-III, DSM-III-R, or DSM-IV diagnostic criteria contemporary to each study were employed. Data Extraction: Treatments were compared within study and via a patient-level meta-analysis using analysis of covariance (ANCOVA) of HDRS end point scores adjusted for pretreatment score. The number needed to treat (NNT) was calculated from remission rates (HDRS end point score ≤ 7), which were compared by χ 2 . Effect sizes were calculated from change in HDRS scores. Secondary analyses investigated the effect of chronicity and atypical features on treatment response. Data Synthesis: Three of 6 studies showed significant (P