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Cobb B.S.,University of Iowa | Coryell W.H.,University of Iowa | Cavanaugh J.,University of Iowa | Keller M.,Brown University | And 6 more authors.
Comprehensive Psychiatry | Year: 2014

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. © 2014 Elsevier Inc.


Leon A.C.,New York Medical College | Leon A.C.,Brown University | Leon A.C.,UpToDate Inc. | Leon A.C.,University of Iowa | And 31 more authors.
American Journal of Psychiatry | Year: 2012

Objective: In 2009 the U.S. Food and Drug Administration issued a warning regarding suicidality and antiepileptic drugs based on meta-analyses of 199 randomized trials (over 43,000 subjects with different illnesses) of 11 antiepileptics. The present study examines the hypothesis that the three antiepileptics approved for bipolar disorder (carbamazepine, lamotrigine, and valproate) are associated with an elevated risk of suicide attempts and suicides. Method: A prospective observational study was conducted at five U.S. academic medical centers from 1978 to 2009. Analyses included 199 participants with bipolar disorder for whom 1,077 time intervals were classified as either exposed to an antiepileptic (carbamazepine, lamotrigine, or valproate) or not exposed to an antiepileptic, an antidepressant, or lithium during 30 years of follow-up. Results: Participants who had more severe manic symptoms were more likely to receive antiepileptic drugs. Mixed-effects grouped-time survival models revealed no elevation in risk of suicide attempt or suicide during periods when participants were receiving antiepileptics relative to periods when they were not (hazard ratio= 0.93, 95% CI=0.45-1.92), controlling for demographic and clinical variables through propensity score matching. Conclusions: In this longitudinal observational study, the risk of suicide attempts or suicides was not associated with the antiepileptics approved for bipolar disorder.


Leon A.C.,New York Medical College | Fiedorowicz J.G.,University of Iowa | Solomon D.A.,Brown University | Solomon D.A.,UpToDate Inc. | And 6 more authors.
Journal of Clinical Psychiatry | Year: 2014

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. © Copyright 2014 Physicians Postgraduate Press, Inc.


Leon A.C.,New York Medical College | Solomon D.A.,Brown University | Solomon D.A.,UpToDate Inc. | Li C.,New York Medical College | And 4 more authors.
Journal of Clinical Psychiatry | Year: 2011

Objective: The 2007 revision of the black box warning for suicidality with antidepressants states that patients of all ages who initiate antidepressants should be monitored for clinical worsening or suicidality. The objective of this study was to examine the association of antidepressants with suicide attempts and with suicide deaths. Method: A longitudinal, observational study of mood disorders with prospective assessments for up to 27 years was conducted at 5 US academic medical centers. The study sample included 757 participants who enrolled from 1979 to 1981 during an episode of mania, depression, or schizoaffective disorder, each based on Research Diagnostic Criteria. Unlike randomized controlled clinical trials of antidepressants, the analyses included participants with psychiatric and other medical comorbidity and those receiving acute or maintenance therapy, polypharmacy, or no psychopharmacologic treatment at all. Over follow-up, these participants had 6,716 time periods that were classified as either exposed to an antidepressant or not exposed. Propensity score-adjusted mixed-effects survival analyses were used to examine risk of suicide attempt or suicide, the primary outcome. Results: The propensity model showed that antidepressant therapy was significantly more likely when participants' symptom severity was greater (odds ratio [OR] = 1.16; 95% CI, 1.12-1.21; z = 8.22; P .001) or when it was worsening (OR = 1.69; 95% CI, 1.50-1.89; z = 9.02; P < .001). Quintile-stratified, propensity-adjusted safety analyses using mixed-effects grouped-time survival models indicate that the risk of suicide attempts or suicides was reduced by 20% among participants taking antidepressants (hazard ratio, 0.80; 95% CI, 0.68-0.95; z = -2.54; P = .011). Conclusions: This longitudinal study of a broadly generalizable cohort found that, although those with more severe affective syndromes were more likely to initiate treatment, antidepressants were associated with a significant reduction in the risk of suicidal behavior. Nonetheless, we believe that clinicians must closely monitor patients when an antidepressant is initiated. © Copyright 2011 Physicians Postgraduate Press, Inc.


Judd L.L.,National Institute of Mental Health Collaborative Program on the Psychobiology of Depression | Judd L.L.,University of California at San Diego | Schettler P.J.,University of California at San Diego | Akiskal H.,National Institute of Mental Health Collaborative Program on the Psychobiology of Depression | And 11 more authors.
Journal of Affective Disorders | Year: 2012

Background: There is increasing evidence that subsyndromal manic symptoms occur frequently during bipolar major depressive episodes (MDEs) and may be a subtle form of 'depressive mixed state.' This paper examines the prevalence and clinical characteristics of MDEs with subsyndromal manic symptoms. The specific effects of overt irritability and psychomotor agitation are examined. Methods: Bipolar (type I or II) patients with an MDE at intake (N = 142) were compared based on the presence or absence of concurrent subsyndromal manic symptoms. The groups were further subdivided by the presence of symptoms of overt irritability and/or psychomotor agitation. Results: Subsyndromal manic symptoms during bipolar MDEs were highly prevalent (76.1%), and were associated with significantly increased severity of depression/dysphoria in the intake episode, longer episode duration, and more suicidal ideation and behavior (past, current, and during long-term follow-up). Overt irritability and psychomotor agitation were the most prevalent subsyndromal manic symptoms (co-occurring in 57% and 39% of MDEs, respectively), and accounted for most of the negative effects associated with subsyndromal manic symptoms. Limitations: The findings need to be confirmed in larger samples, which also examine the relationship to adequate antidepressant and/or mood stabilizing treatment. Conclusions: The presence of one or more subsyndromal manic symptoms appears to be the modal presentation of bipolar MDEs and a marker for a subtle form of bipolar mixed depressive state. In particular, patients with symptoms of overt irritability and/or psychomotor agitation should be monitored closely to avoid serious clinical outcomes such as longer affective episodes, exacerbation of manic symptoms syndromal mania, and heightened suicidality. © 2012 Elsevier B.V. All rights reserved.


Patent
UpToDate Inc. | Date: 2013-01-03

In a method for translation of a medical database query from a first language into a second language, a query to be translated is received from a use of the medical database. A respective translation for the query from each of several translation engines is obtained, and a respective ranking score for each of the obtained translations is determined. The determined ranking scores are then utilized to select a translations from the several obtained translations. The selected translation is then provided to the user and/or is used to search the medical database to obtain search results for the query and the obtained search results are then provided to the user.


Trademark
UpToDate Inc. | Date: 2013-07-03

computer software for use in the medical field, namely the clinical environment.


PubMed | UpToDate Inc
Type: Journal Article | Journal: Archives of general psychiatry | Year: 2010

The phenomenology of bipolar I disorder affects treatment and prognosis.To describe the duration of bipolar I mood episodes and factors associated with recovery from these episodes.Subjects with Research Diagnostic Criteria bipolar I disorder were prospectively followed up for as long as 25 years. The probability of recovery over time from multiple successive mood episodes was examined with survival analytic techniques, including a mixed-effects grouped-time survival model.Five US academic medical centers.Two hundred nineteen subjects with bipolar I disorder.Level of psychopathology was assessed with the Longitudinal Interval Follow-up Evaluation every 6 months for the first 5 years of follow-up and annually thereafter.The median duration of bipolar I mood episodes was 13 weeks. More than 75% of the subjects recovered from their mood episodes within 1 year of onset. The probability of recovery was significantly less for an episode with severe onset (psychosis or severe psychosocial impairment in week 1 of the episode) (hazard ratio [HR] = 0.746; 95% confidence interval [CI], 0.578-0.963; P = .02) and for subjects with greater cumulative morbidity (total number of years spent ill with any mood episode) (HR = 0.917; 95% CI, 0.886-0.948; P < .001). Compared with the probability of recovery from a major depressive episode, there was a significantly greater probability of recovery from an episode of mania (HR = 1.713; 95% CI, 1.373-2.137; P < .001), hypomania (HR = 4.502; 95% CI, 3.466-5.849; P < .001), or minor depression (HR = 2.027; 95% CI, 1.622-2.534; P < .001) and, conversely, a significantly reduced probability of recovery from a cycling episode (switching from one pole to the other without an intervening period of recovery) (HR = 0.438; 95% CI, 0.351-0.548; P < .001).The median duration of bipolar I mood episodes was 13 weeks, and the probability of recovery was significantly decreased for cycling episodes, mood episodes with severe onset, and subjects with greater cumulative morbidity.

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