Response to citalopram is not associated with SLC6A4 genotype in African-Americans and Caucasians with major depression.

AIMS: Ethnic differences in genotype frequency provide a natural condition for assessing the contribution of gene variations to the causes and treatments of disease. Accordingly, the purpose of this study was to determine whether ethnic variations in allele frequencies of the serotonin transporter gene-linked polymorphic region (5-HTTLPR) of the SLC6A4 gene were related to the response to the treatment of depression. MAIN METHODS: African-Americans (n=101) and Caucasians (n=100) with major depressive disorder were treated with the antidepressant citalopram (20-60mg/day) for 8weeks. Genotyping for the long (L) and short (s) alleles (LL, Ls, and ss) of the SLC6A4 gene was performed and the association between genotype and treatment response was assessed. KEY FINDINGS: Subjects in both ethnic groups showed a significant reduction in depression scores over time (p<.0001). However, in spite of a significantly greater frequency of the L allele in African-Americans as compared to Caucasians, a comparable clinical response between the two groups was found with 5-HTTLPR polymorphism not significantly associated with clinical response in either ethnic group. SIGNIFICANCE: The results are consistent with a previous finding and in accord with most of the results obtained in Caucasian subjects that SLC6A4 genotype is not related, at least by itself, to a response to treatment in either ethnic group to any clinically significant degree.

Effect of antidepressant medication treatment on suicidal ideation and behavior in a randomized trial: an exploratory report from the Combining Medications to Enhance Depression Outcomes Study.

OBJECTIVE: To explore relationships between baseline sociodemographic and clinical features and baseline suicidal ideation, and treatment effects on suicidal ideation and behavior, in depressed outpatients. METHOD: From March 2008 to September 2009, the Combining Medications to Enhance Depression Outcomes study, a single-blind, 7-month randomized trial, enrolled outpatients with nonpsychotic chronic and/or recurrent major depressive disorder (DSM-IV-TR criteria) in primary and psychiatric care (N = 665). Participants received escitalopram plus placebo, bupropion sustained release (SR) plus escitalopram, or venlafaxine extended release (XR) plus mirtazapine. The primary outcome measure for this report is presence of suicidal ideation assessed by the Concise Health Risk Tracking Self-Report, which measures suicidal ideation and behaviors over the last 24 hours. Sociodemographic and clinical features were compared in those with versus without baseline ideation. At 4, 12, and 28 weeks, treatment effects on suicidality were assessed, and unadjusted and adjusted outcomes were compared among those with and without baseline ideation using linear, logistic, ordinal logistic, and negative binomial regression models. RESULTS: Baseline suicidal ideation was associated with greater depressive severity, childhood neglect, childhood abuse, early major depressive disorder onset, greater psychiatric comorbidity, and worse functioning and quality of life. After adjustment for treatment, gender, age at first depressive episode, obsessive-compulsive symptoms, and depressive severity, depressive symptom outcomes did not differ between ideation groups at 12 or 28 weeks or between treatments. Overall, 79% of participants with baseline suicidal ideation had none at week 4, 83% had none at week 12, and 86% had none at week 28. All treatments reduced ideation, with bupropion-SR plus escitalopram the most effective at week 12 (P < .01). In participants without baseline ideation, emergent ideation did not differ between treatments: 2.5% had ideation at 4 weeks, 1.3% had ideation at 12 weeks, and only 1.7% had ideation at 28 weeks. Four patients (all receiving venlafaxine-XR plus mirtazapine) attempted suicide (P = .0162). CONCLUSION: Baseline ideation did not affect depressive symptom outcome. Bupropion-SR plus escitalopram most effectively reduced ideation. Ideation emergence was uncommon. Venlafaxine-XR plus mirtazapine may pose a higher risk of suicide attempts. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00590863.

Effects of race and ethnicity on depression treatment outcomes: the CO-MED trial.

OBJECTIVE: The investigators examined whether outcomes differ by race-ethnicity for patients with major depressive disorder in acute- (12 weeks) and continuation-phase (weeks 12-28) treatment with one of two antidepressant combinations or one selective serotonin reuptake inhibitor. METHODS: This single-blind, seven-month prospective, randomized trial enrolled 352 non-Hispanic white (59%), 169 black (28%), and 79 white Hispanic (13%) participants from six primary and nine psychiatric care U.S. sites. Patients had nonpsychotic chronic or recurrent major depressive disorder (or both) of at least moderate severity. Escitalopram plus placebo, bupropion sustained-release plus escitalopram, or venlafaxine extended-release plus mirtazapine were delivered according to measurement-based care. The primary outcome was remission (last two consecutive 16-item Quick Inventory of Depressive Symptomatology-Self-Report ratings <8 and <6); secondary outcomes included side effects, adverse events, quality of life, function, and attrition. RESULTS: Black participants had greater baseline psychiatric and medical comorbidity. Baseline depression severity did not significantly differ between groups. In both phases more blacks than those in other groups exited the trial early. There were only minor differences in side effects, no significant differences in remission rates, and no significant differences between groups in other outcomes for each treatment. CONCLUSIONS: Despite differences in sociodemographic characteristics and comorbidities, when measurement-based care was used, members of different minority groups had similar outcomes when treated with one antidepressant or a combination of two antidepressants. Black participants had the highest attrition rate, an important issue to address in clinical care.

Support and undermining in interpersonal relationships are associated with symptom improvement in a trial of antidepressant medication.

The purpose of this study was to investigate the relationships of chronic stress, social undermining, and social support with symptom reduction and remission in depressed patients treated with antidepressant medication (citalopram), and to determine whether these relationships were moderated by ethnicity. A sample of 301 treatment-seeking adult patients with non-psychotic depression, including 169 African American and 132 Caucasian men and women, were enrolled in an eight week, dose-escalation clinical trial. Intent-to-treat analyses indicated that, consistent with expectations, more baseline social support was associated with greater symptom reduction and higher likelihood of remission, especially at higher levels of social undermining. Additionally, increases in social support from baseline to last visit were associated with more symptom reduction and higher likelihood of remission. However, contrary to expectations, higher levels of baseline social undermining were associated with more symptom reduction in Caucasians, but not in African Americans. Results supported the treatment-enhancing effect of available social support at the beginning of treatment and over the course of treatment. Efforts to enhance social support for patients on antidepressants should be considered as part of comprehensive treatment.

Randomized comparison of selective serotonin reuptake inhibitor (escitalopram) monotherapy and antidepressant combination pharmacotherapy for major depressive disorder with melancholic features: a CO-MED report.

BACKGROUND: The clinical effects of antidepressant combinations vs. monotherapy as initial treatment for major depression with melancholic features (MDD-MF) are unknown. METHODS: Outpatients with chronic or recurrent major depression (MDD) were randomized to initial treatment with escitalopram+placebo (the MONO condition), bupropion-sustained release+escitalopram, or venlafaxine-extended release+mirtazapine (the COMB conditions) in the Combining Medications to Enhance Depression Outcomes (CO-MED) trial. Secondary data analyses were conducted to compare demographic and clinical characteristics, and contrast clinical responses according to drug treatment, in patients with MDD-MF (n=124) and non-melancholic MDD (n=481). RESULTS: While numerically lower, remission rates in MDD-MF did not differ significantly from those with non-melancholic MDD either at 12 (33.1% vs. 41.0%, aOR 1.16, p=0.58) or 28 (39.5% vs. 46.8%, aOR=1.02, p=0.93) weeks of treatment. Remission rates did not differ significantly between combination and monotherapy groups in either MDD-MF or non-melancholic MDD patients at either time point. Similar conclusions were reached for response rates, premature study discontinuation, and self-rated depression symptom severity. LIMITATIONS: This is a secondary analysis of data from the CO-MED trial, which was not designed to address differential treatment response in melancholic and non-melancholic MDD. CONCLUSIONS: We found no evidence of differential remission or response rates to antidepressant combination or monotherapy between melancholic/non-melancholic MDD patients, or according to antidepressant treatment group, after 12 and 28 weeks. Melancholic features may not be a valid predictor of more favorable response to antidepressant combination therapy as initial treatment.

Combining medications to enhance depression outcomes (CO-MED): acute and long-term outcomes of a single-blind randomized study.

OBJECTIVE: Two antidepressant medication combinations were compared with selective serotonin reuptake inhibitor monotherapy to determine whether either combination produced a higher remission rate in first-step acute-phase (12 weeks) and long-term (7 months) treatment. METHOD: The single-blind, prospective, randomized trial enrolled 665 outpatients at six primary and nine psychiatric care sites. Participants had at least moderately severe nonpsychotic chronic and/or recurrent major depressive disorder. Escitalopram (up to 20 mg/day) plus placebo, sustained-release bupropion (up to 400 mg/day) plus escitalopram (up to 20 mg/day), or extended-release venlafaxine (up to 300 mg/day) plus mirtazapine (up to 45 mg/day) was delivered (1:1:1 ratio) by using measurement-based care. The primary outcome was remission, defined as ratings of less than 8 and less than 6 on the last two consecutive applications of the 16-item Quick Inventory of Depressive Symptomatology--Self-Report. Secondary outcomes included side effect burden, adverse events, quality of life, functioning, and attrition. RESULTS: Remission and response rates and most secondary outcomes were not different among treatment groups at 12 weeks. The remission rates were 38.8% for escitalopram-placebo, 38.9% for bupropion-escitalopram, and 37.7% for venlafaxine-mirtazapine, and the response rates were 51.6%-52.4%. The mean number of worsening adverse events was higher for venlafaxine-mirtazapine (5.7) than for escitalopram-placebo (4.7). At 7 months, remission rates (41.8%-46.6%), response rates (57.4%-59.4%), and most secondary outcomes were not significantly different. CONCLUSIONS: Neither medication combination outperformed monotherapy. The combination of extended-release venlafaxine plus mirtazapine may have a greater risk of adverse events.

Religiosity and treatment response to antidepressant medication: A prospective multi-site clinical trial.

The present study examined the relationship between religiosity/spirituality and treatment response to antidepressant medication (citalopram). One-hundred and forty-eight Caucasian and African-American adults with uncomplicated major depression were treated with citalopram (20-60mg/day) over an 8-week period in a prospective multi-site clinical trial. Treatment response was assessed weekly with the Hamilton Rating Scale for Depression. Religiosity (i.e., religious behaviours) and spirituality (i.e., spiritual well-being) were assessed at Week 3. No significant associations between spirituality and treatment response were found; however, there was a strong curvilinear relationship between religiosity and treatment response. Compared to lower or higher levels of religiosity, a moderate level of religiosity was significantly associated with a higher likelihood of remission and greater reduction in severity of depression. This association was independent of social support, ethnicity, gender, education, and baseline depression severity. A moderate amount of religiosity appears to be independently associated with an enhanced treatment response to citalopram.

Ethnic differences in antidepressant response: a prospective multi-site clinical trial.

BACKGROUND: Although depression is a highly prevalent condition that occurs in all ethnic groups, the influence of ethnicity on treatment response still remains unclear. METHODS: A prospective 8-week, open-label clinical trial comparing the efficacy and side effects of citalopram (CIT) with dose escalation (20-60 mg/day) was performed in African-Americans and Caucasians with nonpsychotic major depression. The intent-to-treat sample consisted of 301 participants (169 African-Americans and 132 Caucasians). RESULTS: Although African-Americans were more socially disadvantaged and had a more severe depression, outcomes between the groups were similar. Remission rates were approximately 50% in both groups and about 2/3 of participants met response criteria. Retention was greater than 75% in both groups, with no differences in dropout rate. There were no differences in the number of completers, number of visits made, final dose of CIT, or in side effect profiles. CONCLUSIONS: These results confirm the growing body of evidence, including recent studies using measurement-based care, that patients from minority groups have outcomes that are similar to those of Caucasians. The provision of measurement-based care and encouragement of patient participation can reduce ethnic differences in response to treatment for depression.

Identifying risk for attrition during treatment for depression.

BACKGROUND: Understanding patients' ambivalence about treatment persistence may be useful in tailoring retention interventions for individual patients with major depressive disorder. METHODS: Participants (n = 265) with major depressive disorder were enrolled into an 8-week trial with a selective serotonin reuptake inhibitor. At baseline and week 2, the participants were asked about their intent to return for the next visit, complete the study and continue in the study should they experience side effects or no improvement. Dropouts were defined as participants who discontinued attending clinic visits before completing the trial. RESULTS: Participants who at baseline reported an uncertain/negative intent to continue if they experienced side effects or no improvement dropped out at a significantly higher rate by weeks 6 and 8. Uncertain/negative intent at week 2 predicted attrition at all following visits. Dropouts without side effects were more likely to have reported an uncertain/negative intent to attend at both baseline and week 2, while dropouts who experienced side effects were more likely to have reported an uncertain/negative intent to attend only at baseline. Positive intent to continue was associated with greater symptom improvement in both dropouts and completers despite the possibility of lack of efficacy. CONCLUSIONS: Participants' pretreatment concerns about continuing antidepressant treatment in the presence of side effects signals challenges to the completion of a full 8-week acute phase treatment, even if the participant does not develop side effects. Individualized review of concerns and tailoring appropriate interventions may be necessary to reduce attrition.

Income and attrition in the treatment of depression: a STAR*D report.

BACKGROUND: 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 of <$20,000, $20,000-<$40,000, and >or=$40,000. Attrition rates and sociodemographic and clinical correlates of attrition were identified for each group. RESULTS: Regardless of income level, remission rates were lower for participants who dropped out of treatment. Attrition rates increased as income decreased. For all income levels, younger age was independently associated with attrition. For the lowest income level, less education, better mental health functioning, being on public insurance, and having more concurrent Axis I conditions were associated with a greater likelihood of attrition. For the middle income group, less education, better mental health functioning, being Black or of another non-White race, and treatment in a psychiatric versus primary-care setting predicted greater attrition. For the highest income group, being Hispanic, having a family history of drug abuse, and melancholic features predicted attrition. Atypical symptom features (middle income group) and recurrent depression (highest income group) were associated with retention. CONCLUSIONS: Efforts to retain patients in antidepressant treatment should focus especially on less educated patients with lower household incomes and younger patients.

What predicts attrition in second step medication treatments for depression?: a STAR*D Report.

Attrition rates are high during treatment for major depressive disorder (MDD), and patients who drop out are less likely to reach remission. This report evaluates the incidence, timing, and predictors of attrition during second-step medication treatment. Outpatients in the multisite Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study receiving a medication augmentation (n=563) or medication switch (n=723) for non-psychotic MDD after an unsatisfactory outcome with citalopram were evaluated to determine attrition rates and pretreatment sociodemographic or clinical predictors of attrition. Twenty percent of participants receiving a medication augmentation and 27% receiving a medication switch dropped out before 12 wk in the second treatment step. Remission rates were lower for dropouts [7% vs. 43% (medication augmentation); 12% vs. 31% (medication switch)]. For medication augmentation, Black and other non-Caucasian races, Hispanic ethnicity, younger age, family history of drug abuse, concurrent drug abuse, sociodemographic disadvantage, less symptom improvement with initial citalopram treatment, and greater symptom severity when beginning augmentation were associated with attrition. For medication switch, Black and other non-Caucasian races, younger age, more melancholic features, and lower exit doses but more severe side-effects with citalopram treatment were associated with attrition. Minority status, younger age, and greater difficulty with the first treatment step are risk factors for attrition in the second treatment step. Focus on patients with attrition risk factors for medication augmentation or switch strategies may enhance retention and improve outcomes.

An open pilot study of the combination of escitalopram and bupropion-SR for outpatients with major depressive disorder.

OBJECTIVE: Monotherapy with a selective serotonin reuptake inhibitor (SSRI) is the most common initial treatment for major depressive disorder (MDD), but this monotherapy leads to remission in fewer than a third of patients. The combination of the SSRI escitalopram and bupropion-SR is commonly used for treating patients with MDD who have had an inadequate response to antidepressant monotherapy. This pilot study was conducted to evaluate this combination in the treatment of MDD in patients with chronic or recurrent MDD to estimate safety, tolerability, and remission rates. METHOD: In this study, 51 outpatients with chronic or recurrent non-psychotic MDD were treated with a combination of escitalopram and bupropion-SR for up to 12 weeks. Participants were started on escitalopram at 10 mg/day, and bupropion-SR was then added at week 1, starting at 150 mg/day. The maximum dose of escitalopram was 20 mg/day and the maximum dose of bupropion-SR was 400 mg/day. RESULTS: Rates of response (62%) and remission (50%) at study exit (based on participants for whom at least one post-baseline measure was collected) were significantly higher than is typical for SSRI monotherapy. The level of treatment emergent adverse events was low, and only 3 participants (6%) discontinued treatment due to side effects. The mean maximum dose of escitalopram was 18 mg/day, which was achieved by week 6, and the mean dose at study exit was also 18 mg/day. The mean maximum dose of bupropion-SR was 329 mg/day, which was achieved by week 8, and the mean dose at study exit was 327 mg/day. CONCLUSIONS: These results suggest that the combination of escitalopram and bupropion-SR is effective and well tolerated. Further controlled trials comparing this combination with monotherapy are needed.

Ethnicity/race and outcome in the treatment of depression: results from STAR*D.

OBJECTIVES: This secondary analysis of data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study compared rates of remission and response for blacks (n = 495), whites (n = 1853), and Hispanics (n = 327) with nonpsychotic major depressive disorder who were treated with citalopram. METHODS: STAR*D included representative outpatients treated in 23 psychiatric and 18 primary care centers. Participants received flexible doses of citalopram for up to 14 weeks, with dosage adjustments based on routine clinical assessments. Efforts were made to achieve remission, using a measurement-based care approach with adjustments based on symptoms and side effects assessed at each visit. RESULTS: There were significant differences among groups on many baseline demographic, sociocultural, and clinical variables. Blacks and Hispanics were more socially disadvantaged and had more comorbidity than whites. Before adjusting for differences, blacks had lower remission rates than whites, with Hispanics intermediate between the 2. After adjustments, remission rates for groups were not significantly different on the 17-item Hamilton Rating Scale for Depression (HRSD), but remained lower for blacks compared with whites with the 16-item Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR). Blacks took longer to achieve remission or response, though this did not remain after adjusting for baseline differences. CONCLUSIONS: Overall, black and to a lesser extent Hispanic participants had a poorer response to citalopram. After adjusting for baseline differences, the remission rates seemed to be more similar on the HRSD, but remained worse for blacks on the QIDS-SR. We discuss the possible biologic and sociocultural factors that may underlie these findings.

Insured and non-insured depressed outpatients: how do they compare?

BACKGROUND: The purpose of this study was to examine associations between clinical and demographic characteristics of depressed patients and source of payment for care. We attempted to confirm and extend findings from a previous study regarding the first 1500 participants enrolled in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study with 2541 participants enrolled in later stages of the trial. METHODS: Demographic, clinical, and presenting symptom features were compared among participants with public, private or no insurance. RESULTS: Compared to those having private or no insurance, participants with public insurance were older; more likely to be women, Hispanic, widowed or divorced, unemployed, and less educated; were more frequently seen in primary care; had greater medical comorbidity and functional impairment, and a later age of depression onset. The publicly insured also had a longer current episode, but fewer episodes over their lifetime. Both the publicly insured and the uninsured had poorer life satisfaction compared to those with private insurance. Participants without insurance were intermediate between those with public and private insurance regarding several demographic characteristics and measures of severity. CONCLUSIONS: Depressed outpatients with public insurance demonstrated greater functional impairment, though they did not have a more severe depression per se. Participants without insurance seemed to be a heterogeneous group with a presentation intermediate between those with public and private insurance. Those with public insurance were overrepresented in primary care clinics; therefore, clinicians in these settings need to be particularly vigilant in recognizing depression and offering appropriate treatments.

Has the rolling uterus finally gathered moss? Somatization and malingering of cognitive deficit in six cases of "toxic mold" exposure.

This article reports six cases of litigants claiming neuropsychiatric impairment due to toxic mold exposure. In spite of recent growth in personal injury claims due to mold, numerous reviews of the literature have failed to find an association between environmental exposure to mold and neuropsychiatric and/or neuropsychological damage. We report data on six patients claiming harm, 4 of whom revealed a long history of somatization by history and psychological testing, and 2 of whom were shown to be malingering based on multiple indicators of non-credible performance. Of the 6 patients, only the 2 somatoform patients who were also depressed showed credible evidence of neuropsychological dysfunction. We review two other studies that have examined the link between mold exposure and cognitive impairment and discuss their limitations in view of the presenting behaviors of these 6 patients. Until the literature has established a credible link between mold and neuropsychiatric/neuropsychological impairment, jurists and clinicians must consider the ethics and potential harm of exposing somatoform patients to multiple unwarranted medical evaluations. Principles for forensic evaluations in this special population are reviewed.

Characteristics of insured and noninsured outpatients with depression in STAR(*)D.

OBJECTIVE: This study examined data from the first 1,500 patients with major depressive disorder who were entered into the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) and compared baseline characteristics of outpatients on the basis of their insurance status. METHODS: We compared the demographic and clinical characteristics and the features of the presenting symptoms of outpatients with private insurance, public insurance, Medicaid and Medicare, or no insurance who were seeking treatment for depression. RESULTS: Valid insurance data were available for 1,452 patients. Compared with patients with private insurance, patients with public or no insurance were more likely to be members of a racial or ethnic minority group, unmarried, less educated, and unemployed. Patients were more likely to attend primary care clinics if they had public insurance (46 percent) compared with private insurance (34 percent) or no insurance (30 percent). Compared with the other groups, patients with public insurance had the greatest number and severity of comorbid medical conditions. In general, compared with patients with private insurance, those with public or no insurance had greater severity of depression, more comorbid psychiatric symptoms, lower life satisfaction scores, and greater functional impairment. These findings remained after the analyses adjusted for gender, employment, comorbid medical conditions, race, and duration of illness. CONCLUSIONS: Compared with patients with private insurance, those with public or no insurance had a more chronic, more severe, and more disabling form of depression.