Anxiety Symptom Severity and Long-term Risk for Suicidal Behavior in Depressive Disorders.

OBJECTIVE: We have previously shown that the severity of anxiety symptoms during major depressive episodes is associated in a linear fashion with the proportion of weeks in depressive episodes during a subsequent 25 years of follow-up. Here, we test whether the negative prognostic implications of anxiety comorbidity extend to higher likelihoods of suicidal behavior. METHODS: We used the NIMH Collaborative Depression Study (CDS) cohort to test both the severity of eight anxiety symptoms and the presence or absence of four anxiety disorders as risk factors for suicide attempts or completions over a mean (SD) follow-up of 16.6 (8.5) years. Separate analyses tested potential predictors of events that occurred within 2 years and those that occurred later. RESULTS: None of the baseline anxiety manifestations were significantly associated with overall risks for past or future suicide attempts. Only the diagnosis of phobic disorder was overrepresented in the 36 who committed suicide. Psychic anxiety was a risk factor for suicide attempts beyond 2 years of follow-up, and phobic anxiety was protective of suicides within this period. CONCLUSIONS: These results did not show anxiety comorbidity to be an important risk factor for suicide attempts or completions.

Mixed state and suicide: Is the effect of mixed state on suicidal behavior more than the sum of its parts?

OBJECTIVE: To assess whether suicidal behavior during mixed states exceeds that expected from the manic or depressive components alone. METHODS: This study included 429 participants with bipolar disorder from the National Institute of Mental Health Collaborative Depression Study (CDS). Mood and suicidal behavior were captured using the Longitudinal Interval Follow-up Evaluation and the Schedule of Affective Disorders and Schizophrenia. Suicidal behavior during each mood state, relative to euthymia, was analyzed using Cox regression to allow for repeated events, with a frailty term to account for intra-participant correlation. Mixed states were modeled as a depression-by-mania interaction. RESULTS: Individuals with a history of mixed states were at higher risk of suicidal behavior and spent more time depressed, compared to subjects with no such history. In bipolar I disorder, risk increased during episodes of mania (hazard ratio [HR]: 1.96, 95% confidence interval [CI]: 1.28-2.99, P = .0019) and depression (HR: 5.49, 95% CI: 4.01-7.51, P < .0001) and there was a less than additive effect of mixed states. In bipolar II disorder, risk was increased during episodes of depression (HR: 3.66, 95% CI: 2.51-5.35, P < .0001) and there was no excess risk during mixed states beyond that attributable to the depressed component. Most of the excess risk (71%) among those with a history of mixed states was attributable to a depression predominant course of illness. CONCLUSIONS: Individuals with mixed states are at high risk of suicidal behavior, largely due to more time spent depressed. Clinicians should aggressively treat depression to mitigate suicide risk for patients with or without mixed states.

Fourth consensus of the International Society for Premenstrual Disorders (ISPMD): auditable standards for diagnosis and management of premenstrual disorder.

Whilst professional bodies such as the Royal College and the American College of Obstetricians and Gynecologists have well-established standards for audit of management for most gynaecology disorders, such standards for premenstrual disorders (PMDs) have yet to be developed. The International Society of Premenstrual Disorders (ISPMD) has already published three consensus papers on PMDs covering areas that include definition, classification/quantification, clinical trial design and management (American College Obstetricians and Gynecologists 2011; Brown et al. in Cochrane Database Syst Rev 2:CD001396, 2009; Dickerson et al. in Am Fam Physician 67(8):1743-1752, 2003). In this fourth consensus of ISPMD, we aim to create a set of auditable standards for the clinical management of PMDs. All members of the original ISPMD consensus group were invited to submit one or more auditable standards to be eligible in the inclusion of the consensus. Ninety-five percent of members (18/19) responded with at least one auditable standard. A total of 66 auditable standards were received, which were returned to all group members who then ranked the standards in order of priority, before the results were collated. Proposed standards related to the diagnosis of PMDs identified the importance of obtaining an accurate history, that a symptom diary should be kept for 2 months prior to diagnosis and that symptom reporting demonstrates symptoms in the premenstrual phase of the menstrual cycle and relieved by menstruation. Regarding treatment, the most important standards were the use of selective serotonin reuptake inhibitors (SSRIs) as a first line treatment, an evidence-based approach to treatment and that SSRI side effects are properly explained to patients. A set of comprehensive standards to be used in the diagnosis and treatment of PMD has been established, for which PMD management can be audited against for standardised and improved care.

Reanalysis of efficacy of interpersonal psychotherapy for antepartum depression versus parenting education program: initial severity of depression as a predictor of treatment outcome.

OBJECTIVE: Interpersonal psychotherapy (IPT) is supported by substantial empirical evidence as a treatment for depression. Surprisingly, our recently reported randomized, single-blind, controlled clinical trial found no significant difference between interpersonal psychotherapy for antepartum depression (IPT-P) and a parenting education program (PEP) control condition for the treatment of prenatal depression. Because depression severity has been found to influence treatment response in antidepressant treatment trials, the current study reassessed IPT-P outcomes, limiting analyses to women with moderate depressive symptoms. METHOD: For this reanalysis, 75 of the 110 study participants who met DSM-IV criteria for major depressive disorder and scored ≥ 16 on the 17-item Hamilton Depression Rating Scale (HDRS-17) from 2005 through 2011 were classified as moderately depressed. Linear mixed models were used to examine the longitudinal treatment response on the HDRS-17, the Edinburgh Postnatal Depression Scale (EPDS), and the Clinical Global Impressions Improvement (CGI-I) and Severity (CGI-S) scales. RESULTS: Although the longitudinal analysis did not reveal a significant interaction of treatment group and visit (ie, treatment response variation), the IPT-P group had significantly lower HDRS-17 and EPDS depression ratings than the PEP group at week 8 (respectively, P = .008 and P = .046); these scores remained low but lost significance versus those for the PEP group at week 12 due to attrition and smaller sample size. For the CGI ratings, the longitudinal analysis revealed significant interaction of treatment groups and visits for the CGI-I (P = .021) and CGI-S (P = .005) ratings. Post hoc analysis showed significant illness improvement and less illness severity for the IPT-P group as measured by the CGI ratings at weeks 8 (P = .007 and P = .003, respectively) and 12 (P = .003 and P = .012, respectively), whereas the PEP group remained relatively unchanged during the study. CONCLUSIONS: The results of this reanalysis indicate that among women with moderate levels of depression severity, IPT-P is markedly more effective than PEP. The significance of baseline severity level in depression is important in treatment trial outcomes and considerably more important in determining treatment decisions for pregnant depressed women. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00251043.

Disagreement between therapist raters and independent evaluators in a controlled clinical trial of interpersonal psychotherapy for depressed pregnant women.

BACKGROUND: The randomized controlled trial in which both the patient and the treating clinician are kept blinded to the treatment is the "gold standard" for treatment research assignment. However, in psychotherapy research, evaluations can only be single blind; thus, such studies are inherently more limited. METHODS: A 12-week, bilingual, parallel-design, controlled clinical treatment trial compared interpersonal psychotherapy for antepartum depression (IPT-P) with a parenting education program (PEP) provided to a control group. An outpatient sample of 142 women who met DSM-IV criteria for major depressive disorder was randomly assigned to IPT-P or PEP between September 2005 and May 2011. Only 110 cases were assessed at baseline and had at least 1 other treatment week of paired ratings by a therapist and a blinded independent evaluator (IE). The 17-item Hamilton Depression Rating Scale and the Clinical Global Impressions Scale were administered weekly by a therapist and every 4 weeks by a blinded IE. We examined cross-informant agreement on ratings of mood and global improvement and severity. RESULTS: Nonblinded therapists consistently rated the IPT-P treatment group as more improved than the PEP control group throughout treatment, whereas the ratings by the blinded IE were significantly higher than the therapist ratings, indicating less improvement in the IPT-P group compared with the control group. The ratings suggest that rater bias may have caused the therapist raters to perceive subjects as more improved because of the expectation that IPT-P would be more effective than the PEP control condition. CONCLUSION: Ratings in psychotherapy research must be made by anonymous participation in treatment and an independent clinical evaluator who is blind to all therapy.

Seasonal variation of depressive symptoms in unipolar major depressive disorder.

OBJECTIVES: Retrospective and cross-sectional studies of seasonal variation of depressive symptoms in unipolar major depression have yielded conflicting results. We examined seasonal variation of mood symptoms in a long-term prospective cohort - the Collaborative Depression Study (CDS). METHODS: The sample included 298 CDS participants from five academic centers with a prospectively derived diagnosis of unipolar major depression who were followed for at least ten years of annual or semi-annual assessments. Generalized linear mixed models were utilized to investigate the presence of seasonal patterns. In a subset of 271 participants followed for at least 20 years, the stability of a winter depressive pattern was assessed across the first two decades of follow-up. RESULTS: A small increase in proportion of time depressed was found in the months surrounding the winter solstice, although the greatest symptom burden was seen in December through April with a peak in March. The relative burden of winter depressive symptoms in the first decade demonstrated no relationship to that of the second decade. The onset of new episodes was highest October through January, peaking in January. CONCLUSIONS: There exists a small but statistically significant peak in depressive symptoms from the month of the winter solstice to the month of the spring equinox. However, the predominance of winter depressive symptoms did not appear stable over the long-term course of illness.

Risk of suicidal behavior with antidepressants in bipolar and unipolar disorders.

OBJECTIVE: To examine the risk of suicidal behavior (suicide attempts and deaths) associated with antidepressants in participants with bipolar I, bipolar II, and unipolar major depressive disorders. DESIGN: A 27-year longitudinal (1981-2008) observational study of mood disorders (Research Diagnostic Criteria diagnoses based on Schedule for Affective Disorders and Schizophrenia and review of medical records) was used to evaluate antidepressants and risk for suicidal behavior. Mixed-effects logistic regression models examined propensity for antidepressant exposure. Mixed-effects survival models that were matched on the propensity score examined exposure status as a risk factor for time until suicidal behavior. SETTING: Five US academic medical centers. RESULTS: Analyses of 206 participants with bipolar I disorder revealed 2,010 exposure intervals (980 exposed to antidepressants; 1,030 unexposed); 139 participants with bipolar II disorder had 1,407 exposure intervals (694 exposed; 713 unexposed); and 361 participants with unipolar depressive disorder had 2,745 exposure intervals (1,328 exposed; 1,417 unexposed). Propensity score analyses confirmed that more severely ill participants were more likely to initiate antidepressant treatment. In mixed-effects survival analyses, those with bipolar I disorder had a significant reduction in risk of suicidal behavior by 54% (HR = 0.46; 95% CI, 0.31-0.69; t = -3.74; P < .001) during periods of antidepressant exposure compared to propensity-matched unexposed intervals. Similarly, the risk was reduced by 35% (HR = 0.65; 95% CI, 0.43-0.99; t = -2.01; P = .045) in bipolar II disorder. By contrast, there was no evidence of an increased or decreased risk with antidepressant exposure in unipolar disorder. CONCLUSIONS: Based on observational data adjusted for propensity to receive antidepressants, antidepressants may protect patients with bipolar disorders but not unipolar depressive disorder from suicidal behavior.

Improvements in quality of life with desvenlafaxine 50mg/d vs placebo in employed adults with major depressive disorder.

BACKGROUND: Diminished quality of life (QOL) is associated with major depressive disorder (MDD). METHODS: QOL was assessed in a post-hoc analysis of a double-blind, placebo-controlled trial. Employed adult outpatients with MDD were randomly assigned to 12 weeks of treatment with desvenlafaxine 50mg/d or placebo. Changes from baseline in the Short Form of the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) item scores at week 12 were analyzed using analysis of covariance with treatment, region, and baseline in the model. Correlations between change from baseline in the 17-item Hamilton Rating Scale for Depression (HAM-D17) total score and Q-LES-Q scores were computed. RESULTS: The intent-to-treat population included 427 patients. There were statistically significant improvements from baseline for desvenlafaxine vs placebo in 10 of 16 Q-LES-Q item scores (P values ≤0.0441). The percentage of patients with severe QOL impairment (≥2 SD below community norm) at week 12 was significantly lower for desvenlafaxine (46%) vs placebo (62%; P=0.0024; baseline: 95% and 94%, respectively). Change in Q-LES-Q total score was highly correlated with change in HAM-D17 score at week 12, LOCF (P<0.0001), and improvement in HAM-D17 total score at week 2 predicted change in Q-LES-Q total score at week 12 for the desvenlafaxine group (F=24.89; P<0.0001) but not placebo. LIMITATIONS: This analysis excluded patients who were unemployed, had severe comorbidities, and those taking multiple, concomitant medications. CONCLUSION: Improvement in QOL and depressive symptoms was significantly greater for employed depressed patients treated with desvenlafaxine vs placebo.

Predictors of functional improvement in employed adults with major depressive disorder treated with desvenlafaxine.

We carried out a secondary analysis of a double-blind, placebo-controlled trial of desvenlafaxine for major depressive disorder (MDD) to explore the associations between depressive symptoms and subtypes, and functional outcomes, including work functioning. Employed outpatients with MDD were assigned randomly in a 2 : 1 ratio to receive desvenlafaxine 50 mg/day or placebo for 12 weeks. Analyses were carried out post-hoc with the intent-to-treat (ITT) sample (N=427) and a prospectively defined modified ITT sample (N=310), composed of patients with baseline 17-item Hamilton Rating Scale for Depression score of at least 20. Functional outcomes at week 12 included items and factors from the Montgomery-Åsberg Depression Rating Scale, Sheehan Disability Scale, and the Work Productivity and Activity Impairment questionnaire. In the modified ITT sample, but not in the ITT sample, desvenlafaxine-treated patients showed significantly greater improvement in several functional outcomes in the responder, nonanxious, and normal-energy patient subgroups. Improvement in the 17-item Hamilton Rating Scale for Depression total score at week 2 predicted change at week 12 in several functional outcomes. Functional improvement at 12 weeks was greater in subgroups of patients and was also significantly predicted by early improvement in depressive symptoms in employed patients with MDD treated with desvenlafaxine.

Predictors of functional response and remission with desvenlafaxine 50 mg/d in patients with major depressive disorder.

BACKGROUND: The predictive value of early functional improvement for treatment success at week 8 was assessed in a pooled analysis in patients with major depressive disorder (MDD). METHODS: Data were pooled from 7 double-blind studies in adult patients with MDD randomly assigned to desvenlafaxine 50 mg/d or placebo. Four levels of treatment success were determined at week 8 for patients with baseline Sheehan Disability Scale (SDS) score > 12 (N = 2156): functional response (SDS ≤12 and ≥50% improvement in SDS), functional/depression response (SDS ≤12 and ≥50% improvement in both SDS and 17-item Hamilton Rating Scale for Depression [HAM-D17] score), functional remission (SDS < 7), and functional/depression remission (SDS < 7 and HAM-D17 ≤7). Week 2 improvement in SDS was evaluated as a predictor of later functional response/remission using receiver operating characteristic analysis. Odds ratios (ORs) of the predictability of improvement thresholds were computed from a logistic regression model. RESULTS: The proportion of patients achieving each level of treatment success was significantly greater for patients treated with desvenlafaxine (40%, 32%, 23%, 15%, respectively) vs placebo (31%, 22%, 17%, 10%; all P ≤ 0.002). Early change in SDS was a highly significant predictor of functional response/remission (ORs, 0.958-0.970; all P < 0.0001). Discussion Patients' early functional response to desvenlafaxine 50 mg/d is predictive of treatment success.

Increased breastfeeding rates in black women after a treatment intervention.

There has been a considerable increase in rates of breastfeeding in the United States. Despite these trends, black women continue to fall below medical recommendations. Impoverished and poorly educated women also have a comparatively lower rate of breastfeeding. Provider encouragement and supportive interventions increase breastfeeding initiation among women of all backgrounds. The data presented come from a three-site randomized controlled bilingual depression treatment trial from 2005 to 2011 that examined the comparative effectiveness of interpersonal psychotherapy and a parenting education program. Breastfeeding education and support were provided for the majority of participants in each intervention. Breastfeeding status was queried at postpartum week 4. We found higher rates of breastfeeding in black women compared with those reported in national surveys. The black breastfeeding rate did not significantly differ from that of white or Hispanic women. American-born black women were just as likely to breastfeed as American-born white women, both at significantly greater rates than American-born Hispanic women. We also found no differences in breastfeeding rate in poorly educated and impoverished women. These data must be seen against the backdrop of a significant intervention to treat depression. Because breastfeeding interventions have been shown to increase breastfeeding rates, the support provided in our study likely increased rates in groups that lag behind.

A controlled clinical treatment trial of interpersonal psychotherapy for depressed pregnant women at 3 New York City sites.

OBJECTIVE: While treatment decisions for antepartum depression must be personalized to each woman and her illness, guidelines from the American Psychiatric Association and the American College of Obstetrics and Gynecology include the recommendation of psychotherapy for mild-to-moderate depression in pregnant women. Although we previously demonstrated the efficacy of interpersonal psychotherapy for antepartum depression in a sample of Hispanic women, this study provides a larger, more diverse sample of African American, Hispanic, and white pregnant women from 3 New York City sites in order to provide greater generalizability. METHOD: A 12-week bilingual, parallel-design, controlled clinical treatment trial compared interpersonal psychotherapy for antepartum depression to a parenting education program control group. An outpatient sample of 142 women who met DSM-IV criteria for major depressive disorder was randomly assigned to interpersonal psychotherapy or the parenting education program from September 2005 to May 2011. The 17-item Hamilton Depression Rating Scale (HDRS-17) was the primary outcome measure of mood. Other outcome scales included the Edinburgh Postnatal Depression Scale (EPDS) and the Clinical Global Impressions scale (CGI). The Maternal Fetal Attachment Scale (MFAS) assessed mother's interaction with the fetus. RESULTS: Although this study replicated previous findings that interpersonal psychotherapy is a beneficial treatment for antepartum depression, the parenting education program control condition showed equal benefit as measured by the HDRS-17, EPDS, CGI, and MFAS. CONCLUSIONS: This study supports the recommendation for the use of interpersonal psychotherapy for mild-to-moderate major depressive disorder in pregnancy. The parenting education program may be an alternative treatment that requires further study. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00251043

Effects of once-daily extended release quetiapine fumarate (quetiapine XR) on quality of life and sleep in elderly patients with major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) is frequently associated with reduced quality of life (QoL) and sleep disturbance. We investigated the effects of once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy on QoL and sleep in elderly patients with MDD. METHODS: Prospectively planned analysis of patient-reported data from an 11-week (9-week randomized; 2-week post-treatment), double-blind, placebo-controlled, Phase III study. Elderly patients (≥66 years; DSM-IV MDD; Hamilton Rating Scale for Depression [HAM-D] total score ≥22, HAM-D Item 1 score ≥2) were randomized to quetiapine XR (flexible dosing 50-300 mg/day) or placebo. PRIMARY OUTCOME: MADRS total score change from randomization at Week 9. Patient-reported outcomes: Quality of Life, Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF) % of maximum total score (Items 1-14), Q-LES-Q-SF Item 15 ('satisfaction with medication'), Q-LES-Q-SF Item 16 ('overall life satisfaction'), and Pittsburgh Sleep Quality Index (PSQI) global score. RESULTS: In total, 338 patients were randomized (166 quetiapine XR; 172 placebo). At Week 9, quetiapine XR significantly reduced MADRS total score (-16.33; difference: -7.54; 95% CI: -9.23, -5.85; p<0.001) versus placebo (-8.79). Quetiapine XR significantly improved Q-LES-Q-SF % of maximum total score (16.86; difference: 7.69; 95% CI: 4.99, 10.39; p<0.001) versus placebo (9.17), with numerical improvement in Q-LES-Q-SF Item 15 and improvement in Item 16. Improvement in PSQI global score was observed with quetiapine XR (-6.42; difference: -3.52; 95% CI: -4.26, -2.79; p<0.001) versus placebo (-2.89). LIMITATIONS: Lack of active-comparator arm, flexible-dose design, acute treatment period. CONCLUSIONS: Quetiapine XR monotherapy improved QoL and sleep in elderly patients with MDD.

Recovery from multiple episodes of bipolar I depression.

OBJECTIVE: To describe the duration of bipolar I major and minor depressive episodes and factors associated with time to recovery. METHOD: As part of the National Institute of Mental Health Collaborative Depression Study, 219 participants with bipolar I disorder based on Research Diagnostic Criteria analogs to DSM-IV-TR criteria were recruited at 5 academic medical centers from 1978 to 1981 and followed for up to 25 years with the Longitudinal Interval Follow-Up Evaluation. The probability of recovery over time from depressive episodes, the primary outcome measure, was examined with mixed-effects grouped-time survival models. RESULTS: The median duration of major depressive episodes was 14 weeks, and over 70% of participants recovered within 12 months of episode onset. The median duration of minor depressive episodes was 8 weeks, and approximately 90% of participants recovered within 6 months of onset of the episode. Aggregated data demonstrated similar durations of the first 3 major depressive episodes. However, for each participant with multiple episodes of major depression or minor depression, the duration of each episode was not consistent (intraclass correlation coefficient = 0.07 and 0.25 for major and minor depression, respectively). The total number of years in episode over follow-up with major plus minor depression prior to onset of a major depressive episode was significantly associated with a decreased probability of recovery from that episode; with each additional year, the likelihood of recovery was reduced by 7% (hazard ratio = 0.93; 95% CI, 0.89-0.98; P = .002). CONCLUSIONS: Bipolar I major depression generally lasts longer than minor depression, and the duration of multiple episodes within an individual varies. However, the probability of recovery over time from an episode of major depression appears to decline with each successive episode.

ISPMD consensus on the management of premenstrual disorders.

The second consensus meeting of the International Society for Premenstrual Disorders (ISPMD) took place in London during March 2011. The primary goal was to evaluate the published evidence and consider the expert opinions of the ISPMD members to reach a consensus on advice for the management of premenstrual disorders. Gynaecologists, psychiatrists, psychologists and pharmacologists each formally presented the evidence within their area of expertise; this was followed by an in-depth discussion leading to consensus recommendations. This article provides a comprehensive review of the outcomes from the meeting. The group discussed and agreed that careful diagnosis based on the recommendations and classification derived from the first ISPMD consensus conference is essential and should underlie the appropriate management strategy. Options for the management of premenstrual disorders fall under two broad categories, (a) those influencing central nervous activity, particularly the modulation of the neurotransmitter serotonin and (b) those that suppress ovulation. Psychotropic medication, such as selective serotonin reuptake inhibitors, probably acts by dampening the influence of sex steroids on the brain. Oral contraceptives, gonadotropin-releasing hormone agonists, danazol and estradiol all most likely function by ovulation suppression. The role of oophorectomy was also considered in this respect. Alternative therapies are also addressed, with, e.g. cognitive behavioural therapy, calcium supplements and Vitex agnus castus warranting further exploration.

Age of onset and the prospectively observed course of illness in bipolar disorder.

BACKGROUND: To test the validity of age-of-onset grouping in bipolar disorder through the use of prospectively observed time in mood episodes. METHODS: Age-of-onset ranges from prior admixture analyses were used to divide 427 individuals with bipolar I or bipolar II disorders into early-, middle- and late- onset groups. These were compared by the proportions of weeks depressed and manic or hypomanic during a mean (SD) prospective follow-up of 17.4 (8.4) years. RESULTS: As predicted, the group with the earliest onsets reported at intake more previous episodes, suicide attempts and panic attacks. An early age of onset, but not current age, was predictive of significantly more time in depressive episodes during follow-up but was not predictive of time in manic or hypomanic episodes. LIMITATIONS: This was a naturalistic study with no control of treatment so variability in treatment may have obscured relationships between predictors and outcomes. Age of onset was retrospectively determined and subject to inaccuracies in recall. CONCLUSIONS: An early age of onset conveys, to a modest degree, a poorer prognosis as expressed in more depressive morbidity.

Effects of once-daily extended release quetiapine fumarate on patient-reported outcomes in patients with generalized anxiety disorder.

BACKGROUND: We evaluated the effects of once-daily extended-release quetiapine fumarate (quetiapine XR) on patient-reported outcomes in generalized anxiety disorder (GAD). METHODS: This is a report of a pooled analysis from three acute 8-week, randomized, placebocontrolled, fixed-dose (50, 150, 300 mg/day) studies and a 52-week maintenance flexible dose (50-300 mg/day) study of quetiapine XR monotherapy in patients with GAD. Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF) percent maximum total scores (items 1-14), item 15 ("satisfaction with medication"), item 16 ("overall life satisfaction"), and Pittsburgh Sleep Quality Index (PSQI) global scores are reported. Sheehan Disability Scale (SDS) total scores were also assessed (maintenance study only). RESULTS: The acute studies showed significant improvements at week 8 in Q-LES-Q-SF percent maximum total score with quetiapine XR 150 mg/day (P < 0.001) and item 16 with quetiapine XR 50 (P < 0.05) and 150 mg/day (P < 0.001) versus placebo; PSQI global scores significantly improved with quetiapine XR 50, 150, and 300 mg/day versus placebo (P < 0.001). The maintenance study showed significant benefits versus placebo with quetiapine XR 50-300 mg/day in Q-LES-Q-SF percent total score, item 15 and item 16 scores, PSQI global score, and SDS total score. CONCLUSION: Quetiapine XR 150 mg/day (acute studies) and 50-300 mg/day (maintenance study) improved quality of life, overall functioning, and sleep quality in patients with GAD.

Course of illness following prospectively observed mania or hypomania in individuals presenting with unipolar depression.

OBJECTIVES: In a well-defined sample, we sought to determine which clinical variables, some of potential nosological relevance, influence subsequent course following prospectively observed initial episodes of hypomania or mania (H/M). METHODS: We identified 108 individuals in the National Institute of Mental Health Collaborative Depression Study diagnosed with unipolar major depression at intake who subsequently developed H/M. We assessed time to repeat H/M based on whether one had been started on an antidepressant or electroconvulsive therapy within eight weeks of developing H/M, had longer episodes, or had a family history of bipolar disorder. RESULTS: Modeling age of onset, treatment-associated H/M, family history of bipolar disorder, duration of index H/M episode, and psychosis in Cox regression analysis, family history of bipolar disorder (n=21) was strongly associated with repeat episodes of H/M [hazard ratio (HR)=2.01, 95% confidence interval (CI): 1.06-3.83, p=0.03]. Those with treatment-associated episodes (n=12) were less likely to experience subsequent episodes of H/M, although this was not significant in the multivariate model (HR=0.25, 95% CI: 0.06-1.05, p=0.06). These individuals also had a later age of onset for affective illness and were more likely to be depressed. Duration of illness with a temporal resolution of one week, psychosis, and age of onset were not associated with time to repeat H/M episode. CONCLUSIONS: A family history of bipolar disorder influences the course of illness, even after an initial H/M episode. In this select sample, treatment-associated H/M did not appear to convey the same risk for a course of illness characterized by recurrent H/M episodes.

A 16-year prospective study of prodromal features prior to BPI onset in well Amish children.

BACKGROUND: Longitudinal research of well Amish children over 16 years to identify the pattern and frequency of prodromal symptoms/behaviors associated with onset of BPI disorder during childhood or adolescence. METHODS: Parental informants were interviewed annually using structured and semi-structured interviews to record medical, developmental and behavioral/symptomatic data for their children in two samples. The bipolar sample had 115 children with a BPI parent. The control sample had 106 children of well parents, with and without a positive family history for mood disorders. A panel of clinicians assigned risk ratings independently and blind to family relations. RESULTS: Eight children, age 13 or older, onset with BPI in the bipolar sample compared with one in the control sub-sample (well parent of a BPI sibling). The specific "pre-school" behaviors/symptoms that most identified children with BPI from well children in control samples were: sensitivity, crying, hyper-alertness, anxiety/worry and somatic complaints. During school years, parents reported mood (sad) and energy changes (low not high) decreased sleep and fearfulness as key symptoms. LIMITATIONS: The sample of 9 BPI onsets is small. However, a variable age of onset means many children remain at risk. Although not statistically significant, 34.6% of the bipolar sample youngsters carry risk ratings compared to 15.2% among controls. CONCLUSIONS: The miniclusters of prodromal features that emerged pre-school (ages 1-6), were "episodic" through childhood (7-12) and appeared to mimic adult recurrent illness. Prepubertal onset with mania did not occur. The pattern of prodromal symptoms has clinical relevance for its potential predictive value for onset with BPI disorder and early intervention.