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Artificial intelligence is currently being used to facilitate early disease detection, better understand disease progression, optimize medication/treatment dosages, and uncover promising novel treatments and potential outcomes.Utilizing the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) dataset, we built a machine learning model to predict depression remission rates using same clinical data as features for each of the first three antidepressant treatment steps in STAR*D. We only used early treatment data (baseline and first follow up) in each STAR*D step to temporally analyze predictive features of remission at the end of the step.Our model showed significant prediction performance across the three treatment steps, At step 1, Model accuracy was 66 %; sensitivity-65 %, specificity-67 %, positive predictive value (PPV)-65.5 %, and negative predictive value (NPV)-66.6 %. At step 2, model accuracy was 71.3 %, sensitivity-74.3 %, specificity-69 %, PPV-64.5 %, and NPV-77.9 %. At step 3, accuracy reached 84.6 %; sensitivity-69 %, specificity-88.8 %, PPV-67 %, and NPV-91.1 %. Across all three steps, the early Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR) scores were key elements in predicting the final treatment outcome. The model also identified key sociodemographic factors that predicted treatment remission at different steps.The retrospective design, lack of replication in an independent dataset, and the use of "a complete case analysis" model in our analysis.This proof-of-concept study showed that using early treatment data, multi-step temporal prediction of depressive symptom remission results in clinically useful accuracy rates. Whether these predictive models are generalizable deserves further study.

BACKGROUND: Many depressed patients are not able to achieve or sustain symptom remission despite serial treatment trials - often termed "treatment resistant depression". A broader, perhaps more empathic concept of "difficult-to-treat depression" (DTD) was considered. METHODS: A consensus group discussed the definition, clinical recognition, assessment and management implications of the DTD heuristic. RESULTS: The group proposed that DTD be defined as "depression that continues to cause significant burden despite usual treatment efforts". All depression management should include a thorough initial assessment. When DTD is recognized, a regular reassessment that employs a multi-dimensional framework to identify addressable barriers to successful treatment (including patient-, illness- and treatment-related factors) is advised, along with specific recommendations for addressing these factors. The emphasis of treatment, in the first instance, shifts from a goal of remission to optimal symptom control, daily psychosocial functional and quality of life, based on a patient-centred approach with shared decision-making to enhance the timely consideration of all treatment options (including pharmacotherapy, psychotherapy, neurostimulation, etc.) to optimize outcomes when sustained remission is elusive. LIMITATIONS: The recommended definition and management of DTD is based largely on expert consensus. While DTD would seem to have clinical utility, its specificity and objectivity may be insufficient to define clinical populations for regulatory trial purposes, though DTD could define populations for service provision or phase 4 trials. CONCLUSIONS: DTD provides a clinically useful conceptualization that implies a search for and remediation of specific patient-, illness- and treatment obstacles to optimizing outcomes of relevance to patients. ispartof: Journal of Affective Disorders vol:267 pages:264-282 ispartof: location:Netherlands status: published

Background While childhood maltreatment (CMT) is associated with higher rates of chronicity and recurrence in depression, whether CMT results in poorer outcomes with antidepressant medication remains unclear. Methods We performed secondary analyses with data from the large, representative, multisite trial Combining Medications to Enhance Depression Outcomes (CO-MED). CO-MED was a randomized, single-blinded, placebo-controlled study with 665 individuals (663 assessed for CMT) with chronic and/or recurrent Major Depressive Disorder (MDD). CMT was determined by a brief self-reported questionnaire assessing the four types of CMT defined by the Centers for Disease Control and Prevention: sexual abuse, emotional abuse, physical abuse, and neglect. Repeated measures and logistic regression analyses were used. Results Individuals with CMT did not have a differential improvement of depressive symptoms when compared to those without CMT (adjusted p=.203 for continuous analysis; adjusted p=.320 for remission rates). Neither type of antidepressant medication (adjusted p=.302) nor the age at which CMT occurred (adjusted p=.509) affected depressive symptom outcomes. There was no difference in functional improvement between individuals with and without CMT (adjusted p=.228). A history of CMT was associated with greater antidepressant side effects (p=.009). Limitations This study investigated treatment-seeking individuals with chronic and/or recurrent MDD. Intensity and duration of CMT were not assessed. Conclusion In a sample of treatment-seeking outpatients with chronic and/or recurrent MDD, a history of CMT was not associated with differential symptomatic or functional response to pharmacological treatment. However, those with CMT reported greater antidepressant side effect burden.

Objective : To identify data-driven subgroups in Major Depressive Disorder (MDD) in order to elucidate underlying neural correlates and determine if these subgroups have utility in predicting response to antidepressant versus placebo. Methods : Using 27 clinical measures at baseline of Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care for Depression (EMBARC) study, participants with MDD (n=244) were sub grouped using principal component (PC) analysis. Baseline-to-week-8 changes in depression severity with sertraline versus placebo were compared in these subgroups. Resting-state functional connectivity of these subgroups were compared to those of healthy controls (n=38). Results : Eight subgroups were identified from four PCs: (PC1) severity of depression-associated symptoms, (PC2) sub-threshold mania and anhedonia, (PC3) childhood trauma, medical comorbidities, and sexual dysfunction, and (PC4) personality traits of openness and agreeableness. Participants with high childhood trauma experienced greater improvement with sertraline (Cohen's d=0.87), whereas those with either higher levels of subthreshold hypomanic symptoms (Cohen's d=0.67) or with lower levels of agreeableness and openness experienced greater improvement with placebo (Cohen's d=0.71). Participants with high childhood trauma had greater connectivity between salience and dorsal attention networks, whereas those with higher levels of subthreshold hypomanic symptoms and lower levels of agreeableness and openness had greater connectivity within limbic network and that of visual network with hippocampus and dorsal attention network. Conclusion : Assessing history of childhood trauma, presence of subthreshold hypomanic symptoms and personality traits may help to identify subgroups of patients with MDD who respond differentially to sertraline or placebo and have distinct neural signatures.

Several self-report rating scales have been developed to assess suicidal ideation, yet few examine other factors related to increased suicidal risk, and even fewer have been validated in both adolescents and adults. We evaluate the 14-item Concise Health Risk Tracking - Self Report (CHRT-SR), a measure previously validated in adults, in a sample of adolescents at risk for suicide.Data are from a retrospective chart review of adolescents treated in an intensive outpatient program for youth with severe suicidality. Teens completed the CHRT-SR and Quick Inventory of Depressive Symptomatology - Adolescents (QIDS-A) at baseline and discharge. The CHRT-SR was evaluated to determine the factor validity, internal consistency, construct validity, and sensitivity to change.Adolescents (n = 271) completed the CHRT-SR prior to treatment, and 231 completed the CHRT-SR at discharge. Three factors were identified with excellent model fit: Propensity, Impulsivity, and Suicidal Thoughts. Internal consistency reliability coefficients were good-to-excellent for the total score and all three factors at baseline (a = 0.774-0.915) and exit (a = 0.849-0.941). The total score and all three factors significantly correlated with overall depression severity and suicidal ideation as rated by teens and parent (p = .704-0.756, all p .001). The CHRT-SR was sensitive to change, with moderate to large effect sizes (Cohen's d = 0.599-1.062).Study limitations include generalizability, lack of a control group, and retrospective data from a sample of opportunity.The CHRT-SR is a reliable and valid measure for examining severity of suicidal thoughts and associated risk factors, and is sensitive to change following an intervention in adolescents.

Background Although normal Quality of Life (QoL) is the outcome desired by patients, it is unclear if QoL changes early in course of antidepressant treatments are independent of depression severity, and can predict subsequent remission. Methods The Quality of Life Inventory was obtained repeatedly in the Combining Medications to Enhance Depression Outcomes trial. Mixed model analyses assessed QoL change. Using population-based norms, participants were grouped as very low, low, or normal QoL at week 4, and association with remission was evaluated. Results Overall baseline to week 4 QoL improved significantly (p=0.0015) even after controlling for change in depression severity and baseline variables (gender, age, education, race, ethnicity, income, employment status, anxious features, depression onset before age 18, suicidal ideations, and treatment-arm). At week 4, participants with low and normal QoL had higher unadjusted odds ratio (OR) for remission at 3 months (low QoL OR=2.36, 95% confidence interval (CI)=1.25,4.44; normal QoL OR=2.59, 95% CI=1.53,4.39) and 7 months (low QoL OR=2.07, 95% CI=1.00,4.31; normal QoL OR=3.98, 95% CI=2.06,7.69) compared to those with very low QoL. Remission rates, adjusted for baseline variables, were higher only for participants with normal QoL (3 months OR=2.83, 95% CI=1.42,5.68; 7 months OR=6.10, 95% CI=2.40,15.63). Limitations Secondary analysis, short period of assessment for QoL change, remission instead of functional recovery as long-term outcome. Conclusion Quality of life improves early, independent of depression severity. Normal QoL at week 4 is associated with 2–6 times higher remission rates. Findings support QoL beyond symptomatic change as a potential mediator of remission.

Immune system dysfunction is implicated in the pathophysiology of major depression, and is hypothesized to normalize with successful treatment. We aimed to investigate immune dysfunction in melancholic depression and its response to ECT.55 melancholic depressed patients and 26 controls participated. 33 patients (60%) were referred for ECT. Blood samples were taken at baseline, one hour after the first ECT session, and 48h after ECT series completion.At baseline, melancholic depressed patients had significantly higher levels of the pro-inflammatory cytokine IL-6, and lower levels of the regulatory cytokine TGF-β than controls. A significant surge in IL-6 levels was observed one hour after the first ECT session, but neither IL-6 nor TGF-β levels normalized after completion of ECT series. Seventy per cent (n=23) of ECT recipients showed clinical response and 42% (n=10) reached remission. Neither IL-6 nor TGF-β changes correlated with clinical improvement following ECT. No significant changes in IL-10, TNF-α and CRP levels were found in relation to melancholia or response to ECT.As a naturalistic study, some potential confounders could not be eliminated or controlled, including medication use.Melancholic depressed patients demonstrated a peripheral increase in IL-6 and reduction in TGF-β, which did not normalize despite clinical response to ECT. These findings may be consistent with emerging hypotheses of the role of inflammation in mediating neurotrophin expression. The implications of chronic inflammation in the melancholic depressed population for future medical health, particularly cardiovascular risk, are largely unknown and warrant further investigation.

Objective To develop and evaluate a new brief self-report measure of satisfaction/quality of life in depressed outpatients. Methods Using the Quality of Life Enjoyment and Satisfaction Questionnaire Short-Form (Q-LES-Q-SF) self-report from Step-1 (n = 2181) of the STAR*D trial, items were selected based on their magnitude of change with treatment and correlation with 16-item Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16). Psychometric analyses were conducted. Replication of scale performance was assessed with STAR*D Step-2 data (n = 250). Results The 7 items selected (“Mini-Q-LES-Q”) rated satisfaction with work, household activities, social and family relations, leisure time activities, daily function and sense of well-being in the past week. This uni-dimensional scale captured 83–94% variance in Q-LES-Q-SF and had acceptable Item Response and Classical Test Theory characteristics. Baseline to exit percent changes in the Mini-Q-LES-Q and the QIDS-SR16 were significantly, modestly related (r = -0.552) (Step-1) and replicated (r = -0.562) (Step-2). The Mini-Q-LES-Q detected the expected improvement in satisfaction/quality of life in acute treatment, yet also identified residual deficits expected in many at acute-phase exit. Limitations Population norms are yet undefined. Concurrent validity with detailed, well-validated scales that assess the seven Quality of Life domains incorporated in the Mini-Q-LES-Q remains unestablished. Sensitivity to symptom changes induced by psychotherapy or somatic therapies or sensitive to the effects of therapies aimed at enhancing quality of life enjoyment and function is unknown. Conclusion The 7-item Mini-Q-LES-Q self-report measure satisfaction/quality of life has acceptable psychometric properties, reflects change with depressive symptom reduction, and detects residual deficits in this key clinical outcome.

Background Substantial research progress can be achieved if available clinical datasets can be mapped to the National Institute of Mental Health Research-Domain-Criteria (RDoC) constructs. This mapping would allow investigators to both explore more narrowly defined clinical phenotypes and the relationship of these phenotypes to biological markers and clinical outcomes approximating RDoC criteria. Methods Using expert review and consensus, we defined four major depression phenotypes based on specific RDoC constructs. Having matched these constructs to individual items from the Hamilton Depression Rating Scale and Quick Inventory of Depressive Symptomatology, we identified subjects meeting criteria for each of these phenotypes from two large clinical trials of patients treated for major depression. In a post hoc analysis, we evaluated the overall treatment response based on the phenotypes: Core Depression (CD), Anxiety (ANX), and Neurovegetative Symptoms of Melancholia (NVSM) and Atypical Depression (NVSAD). Results The phenotypes were prevalent (range 10.5–52.4%, 50% reduction range 51.9–82.9%) and tracked with overall treatment response. Although the CD phenotype was associated with lower rates of remission in both cohorts, this was mainly driven by baseline symptom severity. However, when controlling for baseline severity, patients with the ANX phenotype had a significantly lower rate of remission. Limitations The lack of replication between the studies of the phenotypes’ treatment prediction value reflects important variability across studies that may limit generalizability. Conclusion Further work evaluating biological markers associated with these phenotypes is needed for further RDoC concept development.

Background: This study seeks to provide a comprehensive and systematic evaluation of baseline clinical and psychological features and treatment response characteristics that differentiate Major Depressive Disorder (MDD) outpatients with and without melancholic features. Reflecting the emphasis in DSM-5, we also include impairment and distress. Methods: Participants were assessed pre-treatment on clinical features (severity, risk factors, comorbid conditions, illness course), psychological profile (personality, emotion regulation), functional capacity (social and occupational function, quality of life) and distress/coping (negativity bias, emotional resilience, social skills, satisfaction with life). Participants were randomized to sertraline, escitalopram or venlafaxine extended-release and re-assessed post-treatment at 8 weeks regarding remission, response, and change in impairment and distress. Results: Patients with melancholic features (n¼339; 33.7%) were distinguished clinically from nonmelancholics by more severe depressive symptoms and greater exposure to abuse in childhood. Psychologically, melancholic patients were defined by introversion, and a greater use of suppression to regulate negative emotion. Melancholics also had poorer capacity for social and occupational function, and physical and psychological quality of life, along with poorer coping, reflected in less emotional resilience and capacity for social skills. Post-treatment, melancholic patients had lower remission and response, but some of this effect was due to the more severe symptoms pre-treatment. The distress/ coping outcome measure of capacity for social skills remained significantly lower for melancholic participants. Limitations: Due to the cross-sectional nature of this study, causal pathways cannot be concluded. Conclusions: Findings provide new insights into a melancholic profile of reduced ability to function interpersonally or effectively deal with one's emotions. This distinctly poorer capacity for social skills remained post-treatment. The pre-treatment profile may account for some of the difficulty in achieving remission or response with treatment. & 2014 Published by Elsevier B.V.

Background Untreated major depressive disorder (MDD) is a major risk factor for suicide, but some data suggest antidepressants may be associated with increased suicidal ideation (SI) in some depressed patients. The purpose of this study was to determine whether, and in whom, treatment of MDD is associated with increased or emergent SI. Methods Patients were treated with Citalopram, 10–60 mg/day for 12–14 weeks. A score > 0 on Item 12 of the Quick Inventory of Depressive Symptomatology — Self-Report indicated the presence of SI. Worsening was defined by a ≥ 1 point increase. Emergent SI was defined by an increase from 0 at baseline to ≥ 1 during treatment. Results Of the 1909 participants with baseline SI, 57% experienced improvement in SI by their first post-baseline visit and 5% worsened. By the final visit, 74% experienced improvement and 4% worsened. Of 1721 participants without baseline SI, 7% experienced emergence by the first postbaseline visit. Of these, 63% had no SI at their final visit. Major risk factors for treatment-emergent SI at the first treatment visit were drug abuse, severe depression and melancholic features. Limitations Main limitations are lack of a comparison group to help pinpoint whether citalopram treatment added risk or protection, a placebo group to determine whether changes in SI were related to illness factors, medication effects or other factors, and more detailed and validated measures of SI. Conclusions SI and behaviors, core features of MDD, wax and wane in intensity before, during, and perhaps after treatment. It is clinically important to understand risk factors, maintain careful surveillance and treat as vigorously as necessary to attain remission.

Background Patients with major depressive disorder (MDD) have high rates of medical comorbidities which can impair MDD treatment. Yet little is known regarding associations between the presence of a serious comorbidity and MDD treatment. The purpose of this study was to examine the baseline sociodemographic and clinical characteristics of MDD outpatients with and without diabetes mellitus to evaluate possible associations between these characteristics and the presence of comorbid diabetes. Methods We gathered baseline sociodemographic and clinical data for 4041 participants with non-psychotic MDD who enrolled in the STAR ⁎ D, a large-scale depression treatment protocol, and made comparisons between participants with and without diabetes. Results Participants with diabetes were more likely to be male, older, black, Hispanic, unemployed, and have less education, a lower income, higher mental functioning, lower physical functioning, atypical features, increased appetite, psychomotor slowing and leaden paralysis, and were less likely to have concurrent alcohol abuse/dependence, mood reactivity or problems with concentration. We found no significant differences between groups regarding depression severity. Limitations The primary limitation is the lack of a clinical diagnosis of diabetes. Conclusions We found no difference in depression severity between participants with and without diabetes. Diabetes was associated with physical symptoms of depression. Thus treatments for these participants should be directed toward these symptoms.

Background Strategies to compute benefits from continuing cognitive therapy for patients with recurrent major depression do not take into account whether discontinuing treatments may induce temporary increases in the risk that symptoms return (discontinuation-effect). Methods We apply varying-effects analyses and compare findings with traditional methods to assess the effects of continuation-phase cognitive therapy. Two years of data came from 79 patients with recurrent major depression who responded to acute cognitive therapy. Patients were randomized to either an experimental cohort (n = 39) who received 10-session, protocol continuation-phase therapy for 8 months, or a control cohort (n = 40) who stopped protocol treatment after the acute-phase. Symptoms were assessed using the Longitudinal Interval Follow-up Evaluation (LIFE). Symptom risk rates were computed weekly by cohort as the proportion of patients at risk who were suffering from a major depressive episode. Results Significant discontinuation-effects occurred when protocol treatments stopped for both experimental and control cohorts. Following acute-phase care, traditional computation methods (week 1–35) revealed treated patients had 18% of the risk for symptoms as controls. Expanding the observation period (week 1–74) to include these discontinuation-effects revealed more modest initial effect sizes (43%), but significant long-term effects (54% for week 75–101). Limitations Limitations include limited sample size, one-site study, confounds from patient-level interactions, and off-protocol use of depression-related care. Conclusions Varying-effects analyses can describe how outcomes from cognitive therapy may unfold over time for patients with major depression. These analyses reveal complex longitudinal patterns that otherwise are not detectable with traditional time-to-event methods. Specifically, we observed discontinuation-effects, or temporary spikes in symptom risks that occur after treatment ends. Further research is needed to identify the mechanisms driving these effects. Future studies are needed to determine if higher risks result from the patients' anxiety as they attempt to maintain gains independent of ongoing therapy, or reflect residual symptoms previously suppressed by treatment. We also observed longer-term preventive effects from therapy. Again, further research is recommended to determine the extent to which lower risks result from coping and compensatory skills learned during cognitive therapy. These findings suggest that varying-effects analyses may provide an appealing paradigm for understanding treatment-related effects in episodic illness.

Background Premature termination is common among patients treated for depression with either pharmacotherapy or psychotherapy. Yet little is known about factors associated with premature treatment termination among depressed patients. Methods This study examines predictors of, time to, and reasons for dropout from the 12-week acute phase treatment of nonpsychotic adult outpatients, age 18–75, with chronic major depression who were randomly assigned to nefazadone alone (MED), cognitive behavioral analysis system of psychotherapy alone (CBASP) or both treatments (COMB). Results Of 681 randomized study participants, 156 were defined as dropouts. Dropout rates were equivalent across the three treatments. Among dropouts, those in COMB remained in treatment (Mean = 40 days) significantly longer than those in either MED (Mean = 27 days) or CBASP (Mean = 28 days). Dropouts attributed to medication side-effects were significantly lower in COMB than in MED, suggesting that the relationship with the psychotherapist may increase patient willingness to tolerate side-effects associated with antidepressant medications. Ethnic or racial minority status, younger age, lower income, and co-morbid anxiety disorders significantly predicted dropout in the full sample. Within treatments, differences between completers and dropouts in minority status and the prevalence of anxiety disorders were most pronounced in MED. Among those receiving CBASP, dropouts had significantly lower therapeutic alliance scores than completers. Limitations The sample included only individuals with chronic depression. Conclusions Predictors of dropout included baseline patient characteristics, but not early response to treatment. Ethnic and racial minorities and those with comorbid anxiety are at higher risk of premature termination, particularly in pharmacotherapy, and may require modified treatment strategies.

This study sought to determine whether a history of suicide attempts among outpatients diagnosed with nonpsychotic major depressive disorder (MDD) is correlated with any difference in clinical presentation that should influence patient care.Baseline data from the Sequenced Treatment Alternatives to Relieve Depression (STAR()D) trial on outpatients with MDD treated in primary and specialty care settings were used to model significant demographic and clinical correlates of suicide attempter status.Altogether, 16.5% of participants (n=667) reported prior suicide attempts. Controlling for age, gender, and depressive symptom severity, previous attempters had more current general medical conditions (micro=3.2 vs. 2.9, p.0001), more current alcohol/substance abuse (p.0001), and more work hours missed in the past week (26.2% vs. 18.2%, p.0001) than non-attempters. On average, for the previously suicidal, the onset of MDD occurred 8.9 years earlier in life (p.0001) and had included 1.2 additional depressive episodes (p=0.001) compared to those without prior suicidal behavior. Previous attempters also reported more current suicidal ideation (61.3% of previous attempters, adjusted OR 1.6, vs. 45.5% of nonattempters, p.0001).Presence or absence of a history of suicide attempts was determined only through self report.Those with a history of suicidal behavior suffer a greater burden of depressive illness. Earlier intervention and ongoing, aggressive care, including maintenance-phase pharmacotherapy, may be critical to mitigating the long-term consequences associated with this increased disease burden.

Background Bipolar disorder (BPD) is associated with high rates of substance abuse. We previously reported favorable results with lamotrigine in 30 patients with BPD and cocaine dependence. This report examines lamotrigine therapy in an additional 32 cocaine dependent patients. Data on these 32 participants are presented as a replication study. In addition, we extend the previous findings by combining data from both groups, and by exploring predictors of response. Method Participants received a baseline evaluation and assessment for up to 36 weeks with the 17-item Hamilton Rating Scale for Depression (HRSD 17 ), Young Mania Rating Scale (YMRS), Brief Psychiatric Rating Scale (BPRS 18 ), and Cocaine Craving Questionnaire (CCQ). Urine samples were obtained, and participants reported drug use during the previous week. Results In the replication sample ( n = 32), significant improvements were observed in HRSD 17 , YMRS, BPRS 18 , and CCQ (baseline to exit), as well as on dollars/week spent on cocaine. In the extension study, the original sample ( n = 30) and the replication sample ( n = 32) were combined for a total of 62 participants in the intent-to-treat sample. HRSD 17 , YMRS, BPRS 18 , and CCQ scores, as well as dollars spent on cocaine, decreased significantly. Limitations The study has an open-label, uncontrolled design. Conclusion Lamotrigine treatment was associated with significant improvements in mood, drug craving, and drug use. Controlled trials are needed.

Background Epidemiologic research consistently reports gender differences in the rates and course of major depressive disorder (MDD). The STAR*D (Sequenced Treatment Alternatives to Relieve Depression) multicenter trial provides a unique opportunity to explore gender differences in outpatients with nonpsychotic MDD. Methods This sample included the first 1500 outpatients with MDD who enrolled in STAR*D. Nearly two-thirds of the sample (62.8%) were women. Baseline sociodemographic factors, comorbidities, and illness characteristics were analyzed by gender. Results Women (62.8% of the sample) had a younger age at onset of the first major depressive episode. They commonly reported concurrent symptoms consistent with anxiety disorders, somatoform disorder, and bulimia as well as atypical symptoms. Alcohol and drug abuses were more common in men. Limitations This report is a subpopulation of the entire STAR*D sample. These exploratory analyses aimed to identify potential gender differences for further hypothesis testing. Conclusions The gender-specific rate of MDD in this study population is proportional to rates found in community samples with a 1.7:1 prevalence of MDD in women vs. men which argues against increased treatment seeking in women.

Background This study evaluated the clinical and sociodemographic features associated with various degrees of concurrent comorbidity in adult outpatients with nonpsychotic major depressive disorder (MDD). Methods Outpatients enrolled in the STAR*D trial completed the Psychiatric Diagnostic Screening Questionnaire (PDSQ). An a priori 90% specificity threshold was set for PDSQ responses to ascertain the presence of 11 different concurrent DSM-IV Axis I disorders. Results Of 1376 outpatients, 38.2% had no concurrent comorbidities, while 25.6% suffered one, 16.1% suffered two, and 20.2% suffered three or more comorbid conditions. Altogether, 29.3% met threshold for social anxiety disorder, 20.8% for generalized anxiety disorder, 18.8% for posttraumatic stress disorder, 12.4% for bulimia, 11.9% for alcohol abuse/dependence, 13.4% for obsessive–compulsive disorder, 11.1% for panic disorder, 9.4% for agoraphobia, 7.3% for drug abuse/dependence, 3.7% for hypochondriasis, and 2.2% for somatoform disorder. Those with more concurrent Axis I conditions had earlier ages at first onset of MDD, longer histories of MDD, greater depressive symptom severity, more general medical comorbidity (even though they were younger than those with fewer comorbid conditions), poorer physical and mental function, health perceptions, and life satisfaction; and were more likely to be seen in primary care settings. Limitations Participants had to meet entry criteria for STAR*D. Ascertainment of comorbid conditions was not based on a structured interview. Conclusions Concurrent Axis I conditions (most often anxiety disorders) are very common with MDD. Greater numbers of concurrent comorbid conditions were associated with increased severity, morbidity, and chronicity of their MDD.

Few medically acceptable treatments for depression during pregnancy are available. The aim of this randomized controlled pilot study was to determine whether acupuncture holds promise as a treatment for depression during pregnancy.Sixty-one pregnant women with major depressive disorder and a 17-item Hamilton Rating Scale for Depression (HRSD17) scoreor=14 were randomly assigned to one of three treatments, delivered over 8 weeks: an active acupuncture (SPEC, N=20), an active control acupuncture (NSPEC, N=21), and massage (MSSG, N=20). Acupuncture treatments were standardized, but individually tailored, and were provided in a double-blind fashion. Responders to acute phase treatment (HRSD17 score14 andor=50% reduction from baseline) continued the treatment they were initially randomized to until 10 weeks postpartum.Response rates at the end of the acute phase were statistically significantly higher for SPEC (69%) than for MSSG (32%), with an intermediate NSPEC response rate (47%). The SPEC group also exhibited a significantly higher average rate of reduction in BDI scores from baseline to the end of the first month of treatment than the MSSG group. Responders to the acute phase of all treatments combined had significantly lower depression scores at 10 weeks postpartum than nonresponders.Generalizability is limited by the small sample and its relative homogeneity.Acupuncture holds promise for the treatment of depression during pregnancy.

The NIMH-Stanley Foundation Bipolar Treatment Outcome Network, a multisite clinical trials network, has been established to address many of the neglected areas of research in bipolar illness. The Network was designed so that it would be able to conduct randomized clinical trials at several different levels of methodologic rigor (blinded and open-label) both in academic and community practice settings in order to better assess long-term efficacy of existing treatments and develop new ones. In this fashion, large numbers of representative patients with bipolar disorder have been enrolled with an additional focus of elucidating possible clinical and biological predictors of treatment response. The unique focus of the Network is its systematic longitudinal approach to illness so that patients can be assessed comprehensively over the long-term in sequential randomized clinical trials at critical clinical decision points where data on relative efficacy are inadequate. Bipolar I and bipolar II patients with a range of illness variants and comorbidities are included. Daily prospective ratings of severity of mania and depression and associated degree of functional impairment are completed on the NIMH-Life Chart Method and a modified Clinical Global Impressions Scale for Bipolar Illness (CGI-BP) is utilized. More detailed cross-sectional ratings for depression (Inventory of Depressive Symptomatology), mania (Young Mania Rating Scale), and psychosis (Positive and Negative Syndrome Scale) are additionally used at academic centers. This article describes the rationale for the Network, its guiding principles, methods, and study design to systematically assess the highly variable course of bipolar illness and its response to current and future treatments.

Background Since recent NIMH Bipolar Disorder Workshops highlighted the dearth of longitudinal and controlled studies of bipolar illness, the Stanley Foundation Bipolar Network (SFBN) has recruited a large cohort of patients with bipolar disorder to begin to address these issues. This report describes the demographics and course of illness characteristics of this study population. Methods The first 261 outpatients to be diagnosed by the Structured Clinical Interview for DSM-IV (SCID) and complete a detailed patient and a brief clinician questionnaire are described. All patients met DSM-IV criteria for bipolar I (n=211), bipolar II (n=42), or NOS (n=5) or schizoaffective (n=3), bipolar type. Chi-square and t-tests were used to examine statistically significant associations among important demographic and descriptive items. Results The general demographic and illness characteristics were similar to those in many bipolar clinical samples and not dissimilar from those reported in epidemiological surveys. The majority of patients had been hospitalized, with almost half reporting a worsening of illness over time, and two-thirds were not asymptomatic between episodes. First treatment for patients had been delayed by an average of 10 years from illness onset (by SCID). Almost a third of patients had attempted suicide at least once, and 30% reported current suicidal ideation at study entry. A total of 62% reported moderate to severe impact of the illness on occupational functioning. Early onset bipolar illness ( Conclusion The SFBN represents a sample of predominantly BP I patients largely recruited from the community who will be followed in detail longitudinally, participate in clinical trials, and thus help advance our understanding and treatment of this life-threatening medical disorder. While there is a broad range of illness characteristics and severity, the majority of patients have been severely impacted by their illness despite the availability of multiple conventional treatment approaches in the community. These data further underscore the need for development of new and earlier treatment interventions. Limitation The SFBN population is limited by the lack of random selection and represents a cohort willing to be treated and followed intensively in academic tertiary referral centers. While its characteristics are similar to many clinical study populations, the generalizability to non-clinic populations remains uncertain.

Background : The clinical and etiological significance of the early–late onset distinction in chronic major depressive disorder was explored. Method : Subjects were 289 outpatients with DSM-III-R chronic major depression drawn from a multi-site study comparing the efficacy of sertraline and imipramine in the acute and long-term treatment of chronic depression. Patients received comprehensive evaluations using semi-structured interviews and rating scales. Results : Early-onset chronic major depression was associated with a longer index major depressive episode and higher rates of recurrent major depressive episodes, comorbid personality disorders, lifetime substance use disorders, depressive personality traits, and a history of psychiatric hospitalization. In addition, more early-onset patients tended to have a family history of mood disorders. The early-late onset distinction was not associated with differences in symptom severity, functional impairment, or treatment response. Limitations : Family members were not interviewed directly; there were a large number of statistical comparisons; and interrater reliability of the assessments was not evaluated. Conclusions : Early-onset chronic major depression has a more malignant course and is associated with greater comorbidity than late-onset chronic major depression.

Background: The results of multivariate analyses to identify potential predictors of response to fluoxetine or placebo separately in 96 child and adolescent outpatients with major depressive disorder from a recent controlled trial are presented. Methods: A variety of clinical, demographic and laboratory factors were examined as possible predictors of response to fluoxetine or placebo using logistic regression models. Results: No single variable or combination of variables strongly predicted response to fluoxetine. For the placebo group, a younger age, a shorter duration of depressive episode, and a lower socioeconomic status predicted response with an overall predictive power of 81%. Conclusions: This study is limited by the small sample size and should be considered hypothesis generating rather than confirming.

Sex differences in period-amplitude-analysed (PAA) sleep EEG activity were evaluated in 20 symptomatic, unmedicated, unipolar, depressed outpatients. 19 20 PAA measures showed significant gender main effects or interactions. Overall, depressed females showed a higher incidence and amplitude of fast frequency, beta activity than males, particularly in the right hemisphere. Moreover, gender effects were also evident in sleep-stage-independent analysis of PAA measures. These findings are in striking contrast to normal controls for whom only slow-frequency activity differentiates males from females. These findings suggest that sex differences are stronger in depressed patients than those observed in normals and that these effects are more pronounced than age-related changes in sleep EEG activity.

A cross-sectional evaluation of 243 unipolar, nonpsychotic outpatients with major depression was conducted. All subjects were diagnosed by RDC with SADS-L structured interviews. Diagnoses included RDC primary/secondary, RDC endogenous/nonendogenous and Winokur's family-history subtypes. Symptom severity was assessed by the 17-item Hamilton Rating Scale for Depression. Chronic depression was defined as the current episode of major depression lasting at least 2 years, corresponding to DSM-III-R and -IV criteria. Patients with chronic depression ( n = 64) were compared with those with nonchronic depression ( n = 179). Chronicity was not related to gender, symptom severity, prior length of illness, age at onset of illness, RDC endogenous/nonendogenous, RDC primary/secondary or Winokur's family-history subtypes. Those with chronic depression were older and had fewer major depressive episodes than the nonchronic group. That the chronic group had fewer total episodes of depression than the nonchronic group, but a similar age at onset, is consistent with the notion that patients in a current chronic episode have characteristically longer depressive episodes throughout the course of their illness. Those with chronic episodes may be subject to psychological, biological and/or sociocultural factors that preclude an earlier episode remission for these individuals.