AUGUSTUS JOHN RUSH
Email Address
gmsajr@nus.edu.sg
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Publication Income and attrition in the treatment of depression: A STAR*D report(2009-07) Warden, D.; Rush, A.J.; Wisniewski, S.R.; Lesser, I.M.; Thase, M.E.; Balasubramani, G.K.; Shores-Wilson, K.; Nierenberg, A.A.; Trivedi, M.H.; DUKE-NUS GRADUATE MEDICAL SCHOOL S'POREBackground: Attrition, or dropping out of treatment, remains a major issue in the care of depressed outpatients. Whether different factors are associated with attrition for different socioeconomic groups is not known. This report assessed whether attrition rates and predictors of attrition differed among depressed outpatients with different income levels. Methods: Outpatients with nonpsychotic major depressive disorder treated for up to 14 weeks with citalopram in the first step of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study were divided by household incomes ofPublication Residual symptoms in depressed outpatients who respond by 50% but do not remit to antidepressant medication(2011-04) McClintock, S.M.; Husain, M.M.; Wisniewski, S.R.; Nierenberg, A.A.; Stewart, J.W.; Trivedi, M.H.; Cook, I.; Morris, D.; Warden, D.; Rush, A.J.; DUKE-NUS GRADUATE MEDICAL SCHOOL S'PORELittle 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. © 2011 Lippincott Williams & Wilkins.Publication CYP2C19 variation and citalopram response(2011-01) Mrazek, D.A.; Biernacka, J.M.; O'Kane, D.J.; Black, J.L.; Cunningham, J.M.; Drews, M.S.; Snyder, K.A.; Stevens, S.R.; Rush, A.J.; Weinshilboum, R.M.; DUKE-NUS GRADUATE MEDICAL SCHOOL S'POREObjective: Variations in cytochrome P450 (CYP) genes have been shown to be associated with both accelerated and delayed pharmacokinetic clearance of many psychotropic medications. Citalopram is metabolized by three CYP enzymes. CYP2C19 and CYP3A4 play a primary role in citalopram metabolism, whereas CYP2D6 plays a secondary role. METHODS: The Sequenced Treatment Alternatives to Relieve Depression sample was used to examine the relationship between variations in the CYP2C19 and CYP2D6 genes and remission of depressive symptoms and tolerance to treatment with citalopram. The primary analyses were of the White non-Hispanic patients adherent to the study protocol (n=1074). RESULTS: Generally, patients who had CYP2C19 genotypes associated with decreased metabolism were less likely to tolerate citalopram than those with increased metabolism, although this difference was not statistically significant (P=0.06). However, patients with the inactive 2C19*2 allele had significantly lower odds of tolerance (P=0.02). Patients with the poor metabolism CYP2C19 genotype-based category who were classified as citalopram tolerant were more likely to experience remission (P=0.03). No relationship between CYP2D6 genotype-based categories and either remission or tolerance was identified, although exploratory analyses identified a potential interaction between CYP2C19 and CYP2D6 effects. CONCLUSION: Despite several limitations including the lack of serum drug levels, this study showed that variations in CYP2C19 were associated with tolerance and remission in a large sample of White non-Hispanic patients treated with citalopram. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.Publication A randomized, double-blind, placebo-controlled trial of pramipexole augmentation in treatment-resistant major depressive disorder(2013-07) Cusin, C.; Iovieno, N.; Iosifescu, D.V.; Nierenberg, A.A.; Fava, M.; Rush, A.J.; Perlis, R.H.; DUKE-NUS GRADUATE MEDICAL SCHOOL S'POREBackground: Multiple treatments for patients with major depressive disorder (MDD) have demonstrated efficacy, but up to one-third of individuals with MDD do not achieve symptomatic remission despite various interventions. Existing augmentation or combination strategies can have substantial safety concerns that may limit their application. Method: This study investigated the antidepressant efficacy ofa flexible dose of the dopamine agonist pramipexole as an adjunct to standard antidepressant treatment in an 8-week, randomized, double-blind, placebo-controlled trial conducted in a tertiary-level depression center. We randomized 60 outpatients (aged 18 to 75 years) with treatment-resistant nonpsychotic MDD (diagnosed according to OSM-IY) to either pramipexole (n 30) or placebo (n 30).Treatment resistance was defined as continued depression (Montgomery-Asberg Depression Rating Scale [MADRS] score > 18) despite treatment with at least 1 prior antidepressant in the current depressive episode. Patients were recruited between September 2005 and April 2008. The primary outcome measure was the MADRS score. Results:The analyses that used a mixed-effects linear regression model indicated a modest but statistically significant benefit for pramipexole (P=.038). The last- observation-carried- forward analyses indicated that 40% and 33% of patients randomized to augmentation with pramipexole achieved response (x2=1.2, P=.27) and remission (x2=0.74, P=.61), respectively, compared to 27% and 23% with placebo; however, those differences were not statistically significant. Augmentation with pramipexole was well-tolerated, with no serious adverse effects identified. Conclusion: For patients who have failed to respond to standard antidepressant therapies, pramipexole is a safe and potentially efficacious augmentation strategy. © Copyright 2013 Physicians Postgraduate Press, Inc.Publication Do menopausal status and use of hormone therapy affect antidepressant treatment response? Findings from the sequenced treatment alternatives to relieve depression (STAR*D) study(2013-02-01) Kornstein, S.G.; Toups, M.; Rush, A.J.; Wisniewski, S.R.; Thase, M.E.; Luther, J.; Warden, D.; Fava, M.; Trivedi, M.H.; DUKE-NUS GRADUATE MEDICAL SCHOOL S'POREBackground: Menopausal status and use of hormonal contraception or menopausal hormone therapy (HT) may affect treatment response to selective serotonin reuptake inhibitors (SSRIs). This report evaluates whether menopausal status and use of hormonal contraceptives or menopausal HT affect outcome in women treated with citalopram. Methods: In the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, 896 premenopausal and 544 postmenopausal women were treated with citalopram for 12-14 weeks. Baseline demographic and clinical characteristics were used in adjusted analysis of the effect of menopausal status and use of hormonal contraceptives or menopausal HT on outcomes. Remission was defined as final Hamilton Rating Scale for Depression-17 (HRSD17) ≤7 or Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR16) score ≤5 and response as ≥50% decrease from the baseline QIDS-SR16 score. Results: Premenopausal and postmenopausal women differed in multiple clinical and demographic baseline variables but did not differ in response or remission rates. Premenopausal women taking hormonal contraceptives had significantly greater unadjusted remission rates on the HRSD17 and the QIDS-SR 16 than women not taking contraception. Response and remission rates were not different between postmenopausal women taking vs. not taking HT. Adjusted results showed no significant difference in any outcome measure across menopause status in women who were not taking contraception/HT. There were no significant differences in adjusted results across HT status in premenopausal or postmenopausal women. Conclusions: In this study, citalopram treatment outcome was not affected by menopausal status. Hormonal contraceptives and HT also did not affect probability of good outcome. © Copyright 2013, Mary Ann Liebert, Inc.Publication The influence of menopause status and postmenopausal use of hormone therapy on presentation of major depression in women(2010-07) Kornstein, S.G.; Young, E.A.; Harvey, A.T.; Wisniewski, S.R.; Barkin, J.L.; Thase, M.E.; Trivedi, M.H.; Nierenberg, A.A.; Rush, A.J.; DUKE-NUS GRADUATE MEDICAL SCHOOL S'POREObjective: 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. Methods: Analyses conducted with data from the Sequenced Treatment Alternatives to Relieve Depression study focused on female outpatients with nonpsychotic 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. Results: After adjusting for sociodemographic and clinical baseline differences, premenopausal women were more likely to present with irritability than were either perimenopausal or postmenopausal women and were more likely to have decreased appetite and less likely to have early-morning insomnia than were perimenopausal women. Postmenopausal women were more likely to have suicidal ideation and poorer physical functioning than were either of the other groups and were more likely to have sympathetic arousal and gastrointestinal symptoms than were 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 did women not taking hormone therapy. Conclusions: Menopause status and postmenopausal use of hormone therapy may influence the clinical presentation of major depressive episodes in women. © 2010 by The North American Menopause Society.Publication Vitalsign6: A primary care first (PCP-first) model for universal screening and measurement-based care for depression(MDPI AG, 2019) Trivedi, M.H.; Jha, M.K.; Kahalnik, F.; Pipes, R.; Levinson, S.; Lawson, T.; John Rush, A.; Trombello, J.M.; Grannemann, B.; Tovian, C.; Kinney, R.; Clark, E.W.; Greer, T.L.; DUKE-NUS MEDICAL SCHOOLMajor depressive disorder affects one in five adults in the United States. While practice guidelines recommend universal screening for depression in primary care settings, clinical outcomes suffer in the absence of optimal models to manage those who screen positive for depression. The current practice of employing additional mental health professionals perpetuates the assumption that primary care providers (PCP) cannot effectively manage depression, which is not feasible, due to the added costs and shortage of mental health professionals. We have extended our previous work, which demonstrated similar treatment outcomes for depression in primary care and psychiatric settings, using measurement-based care (MBC) by developing a model, called Primary Care First (PCP-First), that empowers PCPs to effectively manage depression in their patients. This model incorporates health information technology tools, through an electronic health records (EHR) integrated web-application and facilitates the following five components: (1) Screening (2) diagnosis (3) treatment selection (4) treatment implementation and (5) treatment revision. We have implemented this model as part of a quality improvement project, called VitalSign6, and will measure its success using the Reach, Efficacy, Adoption, Implementation, and Maintenance (RE-AIM) framework. In this report, we provide the background and rationale of the PCP-First model and the operationalization of VitalSign6 project. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.Publication Sociodemographic, clinical, and treatment characteristics associated with worsened depression during treatment with citalopram: Results of the NIMH star*D trial(2009-07) Friedman, E.S.; Wisniewski, S.R.; Gilmer, W.; Nierenberg, A.A.; Rush, A.J.; Fava, M.; Zisook, S.; Balasubramani, G.K.; Trivedi, M.H.; DUKE-NUS GRADUATE MEDICAL SCHOOL S'POREContext: Outcomes of antidepressant medication treatment for major depressive disorder include remission, response, and nonresponse. But nonresponse can include depression that worsened over the course of treatment, an outcome that has received scant attention. Objective: To describe baseline sociodemographic, clinical, and treatment characteristics associated with worsened depression during a trial of citalopram. Design, participants, and settings: Open-label clinical trial of 2,876 adult outpatients seen in 18 primary and 23 psychiatric-care settings. Intervention: Citalopram was delivered using measurement-based care and flexible dosing with the aim of achieving symptom remission. Symptom and side effect ratings were obtained at each treatment visit. Main outcome measures: Worsened depression was defined as an exit score ≥3 points above the pretreatment (baseline) score on the 16-item QIDSSR. Baseline sociodemographic, clinical, and treatment characteristics were examined for association with worsened depression. Results: Of 2,864 outpatients who returned for ≥2 post baseline visits, 150 (5.2%) had worsened depression at study exit. Baseline characteristics independently associated with increased worsened depression included African-American race (OR=2.02), having less than a college education (OR=2.36), posttraumatic stress disorder (OR=1.78), drug abuse (OR=1.97), hypochondriasis (OR=2.74). Participants with worsened depression spent less time in treatment; had fewer treatment visits; exited the study sooner; had more frequent, intense, and burdensome adverse effects; and were more intolerant of medication. Conclusions: The presence of certain baseline characteristics indicated a greater likelihood of worsened depression during antidepressant treatment. Patients with these characteristics should be monitored closely during treatment and may be candidates for more aggressive treatment.Publication Predictors of attrition during one year of depression treatment: A roadmap to personalized intervention(2009-03) Warden, D.; Rush, A.J.; Carmody, T.J.; Kashner, T.M.; Biggs, M.M.; Crismon, M.L.; Trivedi, M.H.; DUKE-NUS GRADUATE MEDICAL SCHOOL S'POREOBJECTIVE: Attrition from treatment in the short and long term for major depressive disorder (MDD) is clearly an adverse outcome. To assist in tailoring the delivery of interventions to specific patients to reduce attrition, this study reports the incidence, timing, and predictors of attrition from outpatient treatment in public mental health clinics. METHODS: Outpatients with psychotic and nonpsychotic MDD receiving measurement-based care in the Texas Medication Algorithm Project (N=179) were evaluated to determine timing and rates of attrition as well as baseline sociodemographic, clinical, and attitu-dinal predictors of attrition. RESULTS: Overall, 23% (42/179) of the patients left treatment by 6 months, and 47% (84/179) left by 12 months. Specific beliefs about the impact of medication, such as its perceived harmfulness, predicted attrition at both 6 and 12 months. Younger age (P=0.0004) and fewer side effects at baseline (P=0.0376) were associated with attrition at 6 months. Younger age (P=0.0013), better perceived physical functioning (P=0.0007), and more negative attitudes about psychiatric medications at baseline (P=0.0075) were associated with attrition at 12 months. CONCLUSIONS: Efforts to elicit attitudes about medications and tailoring educational and other retention interventions for patients with negative beliefs about antidepressants both when initiating a new medication and throughout treatment may reduce attrition. Particular focus on younger patients and those requiring frequent visits may be helpful. © 2009 Lippincott Williams & Wilkins Inc.Publication Clinical and sociodemographic characteristics associated with suicidal ideation in depressed outpatients(2013-02) Trivedi, M.H.; Morris, D.W.; Wisniewski, S.R.; Nierenberg, A.A.; Gaynes, B.N.; Kurian, B.T.; Warden, D.; Stegman, D.; Shores-Wilson, K.; Rush, A.J.; DUKE-NUS GRADUATE MEDICAL SCHOOL S'POREObjective: To identify clinical and sociodemographic characteristics associated with suicidal ideation (SI) among patients seeking care for depression in routine primary and psychiatric care settings. Methods: We examined data from 4041 treatment-seeking outpatients with major depressive disorder (MDD) to compare baseline sociodemographic and clinical characteristics of those with and without SI, and the presence or absence of baseline depressive symptoms and psychiatric comorbidities in those with SI. Results: SI was significantly (P < 0.01) associated with numerous sociodemographic characteristics (that is, lower level of education, Caucasian or African American, male, unemployed, and treated in psychiatric care) and clinical features (that is, previous suicide attempt, younger age of MDD onset, greater baseline depressive symptom severity, greater number of depressive symptoms, and presence of agoraphobia and [or] generalized anxiety disorder). Elevated levels of SI at baseline were associated with decreased remission rates. Conclusions: Consistent with past findings, increased rates of SI were associated with greater depressive symptom severity as well as other features suggestive of severity of illness. Our results confirm previous findings of associations between SI and panic and (or) phobic symptoms and anxiety, but did not confirm previous findings of an association between SI and alcohol or drug use and (or) dependence. While selective serotonin reuptake inhibitor monotherapy appeared significantly helpful in reducing SI during the course of treatment, the presence of SI at baseline was found to be a associated with decreased treatment response, with patients reporting SI at the start of treatment being less likely to achieve remission. Clinical Trial Registration Number: Sequenced Treatment Alternatives to Relieve Depression, NCT00021528.