Sleep disturbance is a common feature during mood episodes in bipolar disorder. The aim of this study was to investigate the prevalence of such symptoms among euthymic bipolar patients, and their association with risk for mood episode recurrence.
A cohort of bipolar I and II subjects participating in the Systematic Treatment Enhancement Program for Bipolar Disorder who were euthymic for at least eight weeks were included in this analysis. Survival analysis was used to examine the association between sleep disturbance on the Montgomery-Asberg Depression Rating Scale (MADRS) and recurrence risk.
73/483 bipolar I and II subjects reported at least mild sleep disturbance (MADRS sleep item ≥ 2) for the week prior to study entry. The presence of sleep problems was associated with a history of psychosis, number of previous suicide attempts, and anticonvulsant use. Sleep disturbance at study entry was significantly associated with risk for mood episode recurrence.
Sleep disturbance is not uncommon between episodes for individuals with bipolar disorder and may be associated with a more severe course of illness. This suggests that sleep disturbance is an important prodromal symptom of bipolar disorder and should be considered a target for pharmacologic or psychosocial maintenance treatment.
Bipolar disorder; sleep disturbance; relapse prevention; treatment
Little is known about predictors of recovery from bipolar depression or moderators of treatment response. In the present study we investigated attributional style (a cognitive pattern of explaining the causes of life events) as a predictor of recovery from episodes of bipolar depression and as a moderator of response to psychotherapy for bipolar depression.
106 depressed outpatients with DSM-IV bipolar I or II disorder enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) were randomized to intensive psychotherapy for depression (n=62), or collaborative care (n=44), a minimal psychoeducational intervention. The primary outcome was recovery status at each study visit as measured by the Clinical Monitoring Form. Attributional style was measured at baseline using the Attributional Style Questionnaire. Data were collected between 1998 and 2005.
All analyses were by intention to treat. Extreme attributions predicted a lower likelihood of recovery (p=.01, OR=0.93, 95% CI=.88-.98) and longer time until recovery (p<.01, OR=0.96, 95% CI=.93-.99), independent of the effects of initial depression severity. Among individuals with more pessimistic attributional styles, initial depression severity predicted a lower likelihood of recovery (p=.01, OR=0.64, 95% CI=.45-.91) and longer time until recovery (p<.001, OR=0.76, 95% CI=.66-.88). There was no difference in recovery rates between intensive psychotherapy and collaborative care (OR=0.90, 95% CI=0.40-2.01) in the full sample.
These results suggest that extreme, rigid attributions may be associated with a more severe course of depression, and that evaluating attributional style may help clinicians to identify patients who are at risk for experiencing a more severe course of depression.
Bipolar disorder is characterized by recurrent episodes of depression and/or mania along with inter-episodic mood symptoms that interfere with psychosocial functioning. Despite periods of symptomatic recovery, many individuals with bipolar disorder continue to experience substantial residual mood symptoms that often lead to the recurrence of mood episodes.
The present study explored whether a new mindfulness-based cognitive therapy (MBCT) for bipolar disorder would increase mindfulness, reduce residual mood symptoms, and increase emotion regulation abilities, psychological well-being, positive affect and psychosocial functioning. Following a baseline clinical assessment, 12 individuals with DSM-IV bipolar disorder were treated with 12 group sessions of MBCT.
At the end of treatment, as well as at the 3-months follow-up, participants showed increased mindfulness, lower residual depressive mood symptoms, less attentional difficulties, and increased emotion regulation abilities, psychological well-being, positive affect and psychosocial functioning.
These findings suggest that treating residual mood symptoms with MBCT may be another avenue to improving mood, emotion regulation, well-being and functioning in individuals with bipolar disorder.
Bipolar Disorder; Residual Symptoms; Well-being; Mindfulness-based Cognitive Therapy; Cognitive-Behavior Therapy
High attrition rates which occur frequently in longitudinal clinical trials of interventions for bipolar disorder limit the interpretation of results.
The aim of this article is to present design approaches that limited attrition in the Lithium Use for Bipolar Disorder (LiTMUS) Study.
LiTMUS was a 6-month randomized, longitudinal multi-site comparative effectiveness trial that examined bipolar participants who were at least mildly ill. Participants were randomized to either low to moderate doses of lithium or no lithium, in addition to other treatments needed for mood stabilization administered in a guideline-informed, empirically supported, and personalized fashion (N=283).
Components of the study design that may have contributed to the low attrition rate of the study included use of: (1) an intent-to-treat design; (2) a randomized adjunctive single-blind design; (3) participant reimbursement; (4) intent-to-attend the next study visit (includes a discussion of attendance obstacles when intention is low); (5) quality care with limited participant burden; and (6) target windows for study visits.
Site differences and the effectiveness and tolerability data have not been analyzed yet.
These components of the LiTMUS study design may have reduced the probability of attrition which would inform the design of future randomized clinical effectiveness trials.
Attrition; Randomized Clinical Trial Design; Bipolar disorder; Lithium
Little is known about the quantity or quality of residual depressive symptoms in patients with major depressive disorder (MDD) who have responded but not remitted with antidepressant treatment. This report describes the residual symptom domains and individual depressive symptoms in a large representative sample of outpatients with nonpsychotic MDD who responded without remitting after up to 12 weeks of citalopram treatment in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Response was defined as 50% or greater reduction in baseline 16-item Quick Inventory of Depressive Symptomatology—Self-Report (QIDS-SR16) by treatment exit, and remission as a final QIDS-SR16 of less than 6. Residual symptom domains and individual symptoms were based on the QIDS-SR16 and classified as either persisting from baseline or emerging during treatment. Most responders who did not remit endorsed approximately 5 residual symptom domains and 6 to 7 residual depressive symptoms. The most common domains were insomnia (94.6%), sad mood (70.8%), and decreased concentration (69.6%). The most common individual symptoms were midnocturnal insomnia (79.0%), sad mood (70.8%), and decreased concentration/decision making (69.6%). The most common treatment-emergent symptoms were midnocturnal insomnia (51.4%) and decreased general interest (40.0%). The most common persistent symptoms were midnocturnal insomnia (81.6%), sad mood (70.8%), and decreased concentration/decision making (70.6%). Suicidal ideation was the least common treatment-emergent symptom (0.7%) and the least common persistent residual symptom (17.1%). These findings suggest that depressed outpatients who respond by 50% without remitting to citalopram treatment have a broad range of residual symptoms. Individualized treatments are warranted to specifically address each patient's residual depressive symptoms.
depression; STAR*D; residual; symptoms; treatment response
For many disorders, patient heterogeneity requires physicians to customize their treatment to each patient’s needs. We test for the existence of customization in physicians’ prescribing for bipolar disorder, using data from a naturalistic clinical effectiveness trial of bipolar disorder treatment (STEP-BD), which did not constrain physician prescribing. Multinomial logit is used to model the physician’s choice among five combinations of drug classes. We find that our observed measure of the patient’s clinical status played only a limited role in the choice among drug class combinations, even for conditions such as mania that are expected to affect class choice. However, treatment of a patient with given characteristics differed widely depending on which physician was seen. The explanatory power of the model was low. There was variation within each physician’s prescribing, but the results do not suggest a high degree of customization in physicians’ prescribing, based on our measure of clinical status.
Bipolar disorder; pharmaceuticals; prescribing decisions; personalization
We developed an integrated psychosocial treatment for bipolar disorder to decrease the disproportionate medical burden associated with this illness. Three treatment modules, Nutrition/weight loss, Exercise, and Wellness Treatment (NEW Tx) were administered in twelve 60-minute group sessions over 14 weeks. After the first group (N = 4) had completed the treatment, it was revised, and then a second group (N = 6) completed the revised treatment. Participants completed all of the study assessments and attended 82% of the sessions. Both groups added over 100 minutes of weekly exercise to their baseline duration. Participants in the second group showed improvements in their quality of life, depressive symptoms, and weight. It appears that NEW Tx may be a feasible intervention with promising pilot data for reducing the medical burden in bipolar disorder, but future research is needed to further evaluate the efficacy of NEW Tx.
bipolar disorder; psychosocial treatment; diet; exercise; cognitive-behavioral therapy
Psychosocial interventions have been shown to enhance pharmacotherapy outcomes in bipolar disorder.
To examine the benefits of 4 disorder-specific psychotherapies in conjunction with pharmacotherapy on time to recovery and the likelihood of remaining well after an episode of bipolar depression.
Randomized controlled trial.
Fifteen clinics affiliated with the Systematic Treatment Enhancement Program for Bipolar Disorder.
A total of 293 referred outpatients with bipolar I or II disorder and depression treated with protocol pharmacotherapy were randomly assigned to intensive psychotherapy (n=163) or collaborative care (n=130), a brief psychoeducational intervention.
Intensive psychotherapy was given weekly and biweekly for up to 30 sessions in 9 months according to protocols for family-focused therapy, interpersonal and social rhythm therapy, and cognitive behavior therapy. Collaborative care consisted of 3 sessions in 6 weeks.
Main Outcome Measures
Outcome assessments were performed by psychiatrists at each pharmacotherapy visit. Primary outcomes included time to recovery and the proportion of patients classified as well during each of 12 study months.
All analyses were by intention to treat. Rates of attrition did not differ across the intensive psychotherapy (35.6%) and collaborative care (30.8%) conditions. Patients receiving intensive psychotherapy had significantly higher year-end recovery rates (64.4% vs 51.5%) and shorter times to recovery than patients in collaborative care (hazard ratio, 1.47; 95% confidence interval, 1.08–2.00; P=.01). Patients in intensive psychotherapy were 1.58 times (95% confidence interval, 1.17–2.13) more likely to be clinically well during any study month than those in collaborative care (P=.003). No statistically significant differences were observed in the outcomes of the 3 intensive psychotherapies.
Intensive psychosocial treatment as an adjunct to pharmacotherapy was more beneficial than brief treatment in enhancing stabilization from bipolar depression. Future studies should compare the cost-effectiveness of models of psychotherapy for bipolar disorder.
clinicaltrials.gov Identifier: NCT00012558
Some studies suggest that depressive subtypes, defined by groups of symptoms, have predictive or diagnostic utility. These studies make the implicit assumption of stability of symptoms across episodes in mood disorders, which has rarely been investigated.
We examined prospective data from a cohort of 3,750 individuals with bipolar I or II disorder participating in the Systematic Treatment Enhancement Program for Bipolar Disorder study, selecting a subset of individuals who experienced two depressive episodes during up to two years of follow-up. Across-episode association of individual depressive or hypomanic/mixed symptoms was examined using the weighted kappa measure of agreement as well as logistic regression.
A total of 583 subjects experienced two prospectively observed depressive episodes, with 149 of those subjects experiencing a third. Greatest evidence of stability was observed for neurovegetative features, suicidality, and guilt/rumination. Loss of interest and fatigue were not consistent across episodes. Structural equation modeling suggested that the dimensional structure of symptoms was not invariant across episodes.
While the overall dimensional structure of depressive symptoms lacks temporal stability, individual symptoms including suicidality, mood, psychomotor, and neurovegetative symptoms are stable across major depressive episodes in bipolar disorder and should be considered in future investigations of course and pathophysiology in bipolar disorder.
bipolar disorder; factor analysis; major depression; mixed state; psychosis; subtype; suicide; symptom stability
Bipolar disorder is associated with impairments in cognition, including difficulties in executive functioning, even when patients are euthymic (neither depressed nor manic). The purpose of this study was to assess changes in self-reported cognitive functioning in patients with bipolar disorder who participated in an open pilot trial of mindfulness-based cognitive therapy (MBCT). Following MBCT, patients reported significant improvements in executive functioning, memory, and ability to initiate and complete tasks, as measured by the Behavior Rating Inventory of Executive Function (BRIEF) and the Frontal Systems Behavior Scale (FrSBe). Changes in cognitive functioning were correlated with increases in mindful, nonjudgmental observance and awareness of thoughts, feelings, and sensations, and were not associated with decreases in depression. Improvements tended to diminish after termination of treatment, but some improvements, particularly those in executive functioning, persisted after 3 months. These results provide preliminary evidence that MBCT may be a treatment option that can be used as an adjunct to medication to improve cognitive functioning in bipolar disorder.
bipolar disorder; executive functioning; cognitive functioning; mindfulness; mindfulness-based cognitive therapy (MBCT); psychosocial treatment
Published studies suggest associations between circadian gene polymorphisms and bipolar I disorder (BPI), as well as schizoaffective disorder (SZA) and schizophrenia (SZ). The results are plausible, based on prior studies of circadian abnormalities. As replications have not been attempted uniformly, we evaluated representative, common polymorphisms in all three disorders.
We assayed 276 publicly available ‘tag’ single nucleotide polymorphisms (SNPs) at 21 circadian genes among 523 patients with BPI, 527 patients with SZ/SZA, and 477 screened adult controls. Detected associations were evaluated in relation to two published genome-wide association studies (GWAS).
Using gene-based tests, suggestive associations were noted between EGR3 and BPI (p = 0.017), and between NPAS2 and SZ/SZA (p = 0.034). Three SNPs were associated with both sets of disorders (NPAS2: rs13025524 and rs11123857; RORB: rs10491929; p < 0.05). None of the associations remained significant following corrections for multiple comparisons. Approximately 15% of the analyzed SNPs overlapped with an independent study that conducted GWAS for BPI; suggestive overlap between the GWAS analyses and ours was noted at ARNTL.
Several suggestive, novel associations were detected with circadian genes and BPI and SZ/SZA, but the present analyses do not support associations with common polymorphisms that confer risk with odds ratios greater than 1.5. Additional analyses using adequately powered samples are warranted to further evaluate these results.
association; bipolar disorder; circadian; gene; schizoaffective disorder; schizophrenia
This paper presents new data addressing two important controversies in psychiatry: the construct of Minor Depression (MinD) and the efficacy of St. John’s Wort for milder forms of depressive disorders. Data are from a three-arm, 12 week, randomized clinical trial of investigating the efficacy of St. John’s Wort (810 mg/day), citalopram (20 mg/day), or placebo for acute treatment of MinD. Due to a high placebo response on all outcome measures, neither St. John’s Wort nor citalopram separated from placebo on change in depressive symptom severity, quality of life, or well-being. However, systematic assessment of potential adverse effects (AEs) led to three important observations: (1) prior to the administration of study compound, 60% of subjects endorsed items that would be characterized as AEs once study compound was administered, (2) St. John’s Wort and citalopram were each associated with a significant number of new or worsening AEs during treatment, and (3) using a structured interview for identifying AEs at baseline and during treatment is informative. MinD was not responsive to either a conventional antidepressant or a nutraceutical, and both compounds were associated with a notable side effects burden. Other treatment approaches for MinD should be investigated.
Bipolar Disorder is characterized by recurrent episodes of depression and/or mania along with interepisodic mood symptoms that interfere with psychosocial functioning. Despite periods of symptomatic recovery, individuals with bipolar disorder often continue to experience impairments in psychosocial functioning, particularly occupational functioning. Two determinants of psychosocial functioning of euthymic (neither fully depressed nor manic) individuals with bipolar disorder are residual depressive symptoms and cognitive impairment (i.e. difficulties with executive functioning, attention and memory).
The present study explored whether a new cognitive remediation (CR) treatment designed to treat residual depressive symptoms and, for the first time to the best of our knowledge, address cognitive impairment would be associated with improvement in psychosocial functioning in individuals with bipolar disorder. Following a neuropsychological and clinical assessment 18 individuals with DSM-IV bipolar disorder were treated with 14 individual sessions of CR.
Results indicated that at the end of treatment, as well as at the 3-months follow-up, patients showed lower residual depressive symptoms, and increased occupational, as well as overall psychosocial functioning. Pre-treatment neuropsychological impairment predicted treatment response. Improvements in executive functioning were associated with improvements in occupational functioning.
These findings suggest that treating residual depressive symptoms and cognitive impairment may be an avenue to improving occupational and overall functioning in individuals with bipolar disorder.
Bipolar Disorder; Occupational Functioning; Psychosocial Functioning; Cognitive Impairment; Cognitive-Behavior Therapy
The purpose of this study was to determine whether there are differences in depression characteristics among premenopausal, perimenopausal, and postmenopausal women with major depressive disorder. This study also evaluated these differences between postmenopausal women with major depressive disorder who are taking and not taking hormone therapy.
Analyses conducted with data from the Sequenced Treatment Alternatives to Relieve Depression study focused on female outpatients with non-psychotic major depressive disorder seeking treatment in 41 primary or psychiatric care settings across the United States. Baseline demographic and clinical characteristics were compared among women not taking hormone therapy who were premenopausal (N=950), perimenopausal (N=380), or postmenopausal (N=562). These comparisons were also made between postmenopausal women (n=768) taking (N=171) or not taking (N=562) hormone therapy.
After adjusting for sociodemographic and clinical baseline differences, premenopausal women were more likely to present with irritability than either peri- or postmenopausal women, and were more likely to have decreased appetite and less likely to have early morning insomnia than perimenopausal women. Postmenopausal women were more likely to have suicidal ideation and poorer physical functioning than either of the other groups, and were more likely to have sympathetic arousal and gastrointestinal symptoms than premenopausal women. After adjusting for baseline differences, postmenopausal women taking hormone therapy had better physical functioning, fewer melancholic features, less sympathetic arousal, and more lack of involvement in activities than women not taking hormone therapy.
Menopausal status and postmenopausal use of hormone therapy may influence the clinical presentation of major depressive episodes in women.
menopause; hormone therapy; depression; major depressive disorder
Virtually nothing is known about the epidemiology of rapid cycling bipolar disorder (BPD) in community samples. Nationally representative data are reported here for the prevalence and correlates of a surrogate measure of DSM-IV rapid cycling BPD from the National Comorbidity survey Replication (NCS-R), a national survey of the US household population. DSM-IV disorders were assessed in the NCS-R with the WHO Composite International Diagnostic Interview (CIDI). Although the CIDI did not assess rapid cycling, it did assess the broader category of 12-month BPD with frequent mood episodes (FME), having at least four episodes of mania/hypomania or major depression in the 12 months before interview. Roughly one-third of NCS-R respondents with lifetime DSM-IV BPD and half with 12-month BPD met criteria for FME. FME was associated with younger age-of-onset (of BP-I, but not BP-II) and higher annual persistence (73% of the years since first onset of illness with an episode) than non-FME BPD. No substantial associations of FME vs. non-FME BPD were found with socio-demographics, childhood risk factors (parental mental disorders, other childhood adversities), or comorbid DSM-IV disorders. However, FME manic episodes had greater clinical severity than non-FME episodes (assessed with a fully-structured version of the Young Mania Rating Scale) and FME hypomanic episodes had greater role impairment than non-FME episodes (assessed with the Sheehan Disability Scales). Whether these indicators of severity merely reflect attenuated effects of rapid cycling or independent effects of sub-threshold rapid cycling warrants further study given the high proportion of lifetime cases that met criteria for FME.
Bipolar Disorder; Rapid-cycling bipolar disorder; Mania; Hypomania; National Comorbidity Survey Replication (NCS-R); Comorbidity; Treatment
Nine DSM-IV-TR criterion symptom domains are evaluated to diagnose major depressive disorder (MDD). The Quick Inventory of Depressive Symptomatology (QIDS) provides an efficient assessment of these domains and is available as a clinician rating (QIDS-C16), a self-report (QIDS-SR16), and in an automated, interactive voice response (IVR) (QIDS-IVR16) telephone system. This report compares the performance of these three versions of the QIDS and the 17-item Hamilton Rating Scale for Depression (HRSD17).
Data were acquired at baseline and exit from the first treatment step (citalopram) in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial. Outpatients with nonpsychotic MDD who completed all four ratings within ±2 days were identified from the first 1500 STAR*D subjects. Both item response theory and classical test theory analyses were conducted.
The three methods for obtaining QIDS data produced consistent findings regarding relationships between the nine symptom domains and overall depression, demonstrating interchangeability among the three methods. The HRSD17, while generally satisfactory, rarely utilized the full range of item scores, and evidence suggested multidimensional measurement properties.
In nonpsychotic MDD outpatients without overt cognitive impairment, clinician assessment of depression severity using either the QIDS-C16 or HRSD17 may be successfully replaced by either the self-report or IVR version of the QIDS.
Quick Inventory of Depressive Symptomatology; Inventory of Depressive Symptomatology; item response theory; Samejima graded response model; depressive symptoms
Cigarette smoking in individuals with bipolar disorder has been associated with suicidal behavior, although the precise relationship between the two remains unclear.
In this prospective observational study of 116 individuals with bipolar disorder, we examined the association between smoking and suicidality as measured by Linehan’s Suicide Behaviors Questionnaire (SBQ) and prospective suicide attempts over a nine-month period. Impulsivity was measured by the Barratt Impulsiveness Scale.
Smoking was associated with higher baseline SBQ scores in univariate and adjusted analyses, but was not significant after statistical adjustment for impulsivity in a regression model. A higher proportion of smokers at baseline made a suicide attempt during the follow-up period (5/31, 16.1%) compared to nonsmokers (3/85, 3.5%); p = 0.031, odds ratio = 5.25 (95% confidence interval: 1.2–23.5). Smoking at baseline also significantly predicted higher SBQ score at nine months.
In this study, current cigarette smoking was a predictor of current and nine-month suicidal ideation and behavior in bipolar disorder, and it is likely that impulsivity accounts for some of this
bipolar disorder; impulsivity; nicotine; smoking; substance abuse; suicidality
Bipolar disorder is highly comorbid with substance use disorders, and this comorbidity may be associated with a more severe course of illness, but the impact of comorbid substance abuse on recovery from major depressive episodes in these patients has not been adequately examined. The authors hypothesized that comorbid drug and alcohol use disorders would be associated with longer time to recovery in patients with bipolar disorder.
Subjects (N=3,750) with bipolar I or bipolar II disorder enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) were followed prospectively for up to 2 years. Prospectively observed depressive episodes were identified for this analysis. Subjects with a past or current drug or alcohol use disorder were compared with those with no history of drug or alcohol use disorders on time to recovery from depression and time until switch to a manic, hypomanic, or mixed episode.
During follow up, 2,154 subjects developed a new-onset major depressive episode; of these, 457 subjects switched to a manic, hypomanic, or mixed episode prior to recovery. Past or current substance use disorder did not predict time to recovery from a depressive episode relative to no substance use comorbidity. However, those with current or past substance use disorder were more likely to experience switch from depression directly to a manic, hypomanic, or mixed state.
Current or past substance use disorders were not associated with longer time to recovery from depression but may contribute to greater risk of switch into manic, mixed, or hypomanic states. The mechanism conferring this increased risk merits further study.
We examined the efficacy and tolerability of ethyl-eicosapentaenoate (EPA-E) monotherapy for major depressive disorder (MDD) in a double-blind, randomized controlled pilot study.
57 adults with DSM-IV MDD were randomized from 1/2003-6/2006 to receive 1 gram/day of EPA or placebo (PBO) for 8 weeks. Response criteria were based on the Hamilton-D-17 scale. Subjects' plasma lipid profiles were examined by gas chromatography.
35 subjects (63% female; mean age 45+/-13 yrs) were eligible for the intent to treat (ITT) analysis. In the ITT sample, mean HAM-D-17 scores decreased from 21.6+/-2.7 to 13.9+/-8.9 for the EPA group (n=16) and from 20.5+/-3.6 to 17.5+/-7.5 for the PBO group (n=19) (p=0.123); the effect size for EPA was 0.55. ITT response rates were 38% (6/16) for EPA, and 21% (4/19) for PBO (p=0.45). Among the 24 study completers, mean HAM-D-17 scores decreased from 21.3+/-3.0 to 11.1+/-8.1 for the EPA group and from 20.5+/-3.8 to 16.3+/-6.9 for the PBO group (p=0.087); the effect size for EPA was 0.73. Completer response rates were 45% (5/11) for EPA, and 23% (3/13) for PBO (p=0.39). Among EPA subjects, baseline n-6/n-3 ratio was associated with decrease in HAM-D-17 score (r= -0.686, p=0.030) and with treatment response (p=0.032); change in n-6/n-3 ratio was associated with change in HAM-D-17 score (r=0.784, p=0.032). Side effects, reported in 2 EPA subjects and 5 PBO subjects, were exclusively gastrointestinal, mild, and not associated with discontinuation.
EPA demonstrated an advantage over placebo that did not reach statistical significance, possibly due to the small sample and low completer rates, which were the major study limitations.
eicosapentaenoic acid; docosahexaenoic acid; DHA; EPA; omega-3; n-3; depression
To summarize points for consideration generated in an NIMH workshop convened to provide an opportunity for reviewers from different disciplines – specifically clinical researchers and statisticians – to discuss how their differing and complementary expertise can be well integrated in the review of intervention related grant applications.
A one day workshop was convened in October, 2004. The workshop featured panel presentations on key topics followed by interactive discussion. This manuscript summarizes the workshop and subsequent discussions, which centered on topics including: weighting the statistics/data analysis elements of an application in the assessment of the application’s overall merit; the level of statistical sophistication appropriate to different stages of research and for different funding mechanisms; some key considerations in the design and analysis portions of applications; appropriate statistical methods for addressing essential questions posed by an application; and the role of the statistician in the application’s development, study conduct, and interpretation and dissemination of results.
A number of key elements crucial to the construction and review of grant applications were identified. It was acknowledged that intervention related studies unavoidably involve trade-offs. Reviewers are helped when applications acknowledge such trade-offs and provide good rationale for choices made. Clear linkage among the design, aims, hypotheses and data analysis plan and avoidance of disconnections among these elements also strengthens applications.
Multiple points to consider when constructing intervention related grant applications were identified. The points are presented here as questions and do not reflect institute policy or comprise a list of best practices, but rather represent points for consideration.
While epidemiologic research consistently reports greater prevalence of major depressive disorder in women, small sample sizes in many studies do not allow for full elaboration of illness characteristics. This paper examines gender differences in terms of illness attributes in a cohort of 2541 outpatients from across the United States who enrolled in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study.
Confirmatory analyses were performed in 2541 outpatients comparing men and women with regard to socio-demographic features, comorbid Axis I and Axis III conditions, and illness characteristics. Results were compared to those of our previous report on the initial population of the first 1500 individuals enrolled in STAR*D.
In both samples, nearly two-thirds of the sample (62.5%) were women. Women had greater symptom severity, but men had more episodes of major depression, despite no difference in the length of illness. No differences in age of onset emerged. As in the first cohort, women showed greater rates of an anxiety disorder, bulimia and somatoform disorder, as well as more past suicide attempts, while men showed more alcohol and substance abuse. Women reported more appetite, weight, hypersomnia, interpersonal sensitivity, gastrointestinal and pain complaints, and less suicidal ideation. Irritability was equally common in men and women.
This large analysis confirmed most of the clinical features and co-morbidities found to be more prevalent in the first cohort of women. Additionally, this analysis corroborated previous research suggesting higher rates of atypical and anxious depression in women, but refuted the notion of an “irritable depression” found in men. The report confirmed the 1.7:1 ratio for depression seen across genders in the National Comorbidity Survey.
Women; Depression; Prevalence; Gender
Whether the acute outcomes of major depressive disorder (MDD) treated in primary (PC) or specialty care (SC) settings are different is unknown.
To compare the treatment and outcomes for depressed outpatients treated in primary versus specialty settings with citalopram in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study (www.star-d.org), a broadly inclusive effectiveness trial.
Open clinical trial with citalopram for up to 14 weeks at 18 primary and 23 specialty sites. Participants received measurement-based care with 5 recommended treatment visits, manualized pharmacotherapy, ongoing support and guidance by a clinical research coordinator, the use of structured evaluation of depressive symptoms and side effects at each visit, and a centralized treatment monitoring and feedback system.
A total of 2,876 previously established outpatients in primary (n = 1091) or specialty (n = 1785) with nonpsychotic depression who had at least 1 post-baseline measure.
Measurements and Main Results
Remission (Hamilton Depression Rating Scale for Depression [Hamilton] or 16-item Quick Inventory of Depressive Symptomatology-Self-Rated [QIDS-SR16]); response (QIDS-SR16); time to first remission (QIDS-SR16). Remission rates by Hamilton (26.6% PC vs 28.0% SC, p = .40) and by QIDS-SR16 (32.5% PC vs 33.1% SC, p = .78) and response rates by QIDS-SR16 (45.7% PC vs 47.6% SC, p = .33) were not different. For those who reached remission or response at exit, the time to remission (6.2 weeks PC vs 6.9 weeks SC, p = .12) and to response (5.5 weeks PC vs 5.4 weeks SC, p = .97) did not differ by setting.
Identical remission and response rates can be achieved in primary and specialty settings when identical care is provided.
primary care; depression; clinical trial; outcomes