How patients experience thyroid eye disease.

Objective: To determine the impact of thyroid eye disease (TED) on patients in various stages of the disease. Background: TED is a debilitating and potentially sight-threatening inflammatory autoimmune disease that is frequently misdiagnosed. Challenging quality-of-life (QoL) issues can persist long after the active phase of disease has subsided. Methods: A 62-question survey was designed as a hypothesis-generating instrument to identify key issues confronting patients ≥18 years old with physician-diagnosed TED. Questions focused primarily on physical and emotional status, and QoL experiences in the 2 months prior to the survey. Data for individual questions are presented as summary statistics. Correlations between questions were determined using χ2 analyses. Results: The 443 respondents were 18 to >80 years old; >90% female, and >80% from the United States. Time since TED diagnosis ranged from <1 year to >10 years. Participants provided >500 free-form responses describing experiences of living with TED. Physical signs/symptoms were experienced by 307/443 (69%) patients. Of those responding to the QoL questions (N = 394), 53 (13%) reported symptoms improving, 73 (19%) reported symptoms worsening, and 255 (65%) reported no change in the 2 months prior to the survey. The most bothersome signs/symptoms were dry/gritty eyes, light sensitivity, bulging eyes, and pressure or pain behind the eyes. Respondents <60 years were significantly (p < 0.0001) more likely to report symptomatic TED than older patients. Of 394 respondents, 179 (45%) reported feeling depressed and/or anxious, 174 (44%) reported concern about their appearance, and 73 (19%) avoided public situations; 192 (49%) reported declines in confidence or feelings of general well-being, and 78 (20%) reported an inability to achieve goals. Activities limited by TED included reading, driving, and socializing. The proportion of respondents experiencing these negative QoL measures was higher when patients reported experiencing >5 symptoms, had been diagnosed within the last 5 years, or were <60 years of age. Conclusions: Physical manifestations of TED impact QoL for patients through all phases of the disease. It is essential that physicians and healthcare professionals become more familiar with patient experiences such as those described here to better help patients manage their disease.

Adherence to antidepressant combinations and monotherapy for major depressive disorder: a CO-MED report of measurement-based care.

BACKGROUND: Non-adherence to antidepressant treatment is not routinely measured in practical clinical trials. It has not been related to outcomes in a large sample of adults with chronic and/or recurrent major depressive disorder (MDD) or any sample treated with antidepressant combinations. METHODS: Adult outpatients with chronic and/or recurrent MDD were randomized to 12 weeks of treatment with bupropion-SR plus escitalopram, venlafaxine-XR plus mirtazapine, or escitalopram plus placebo. We compared non-adherence (the frequency with which daily medications were not taken) and specifically the frequency of temporarily stopping and/or skipping medication, or reducing or increasing the dose across treatments in 567 participants using a self-report questionnaire collected at each visit. We tested the association between non-adherence, and both treatment type and outcomes. RESULTS: A non-adherence rate under 10% was reported by 77.9%, 70.9%, and 71.6% of participants during weeks 1-4, 5-12, and 1-12, respectively. Antidepressant combinations were associated with a higher non-adherence rate than monotherapy during weeks 1-4 and 1-12. During weeks 1-4, 24.1% stopped/skipped doses and 6.1% reduced the dose. During weeks 5-12, 34.7% stopped/skipped doses and 9.4% reduced the dose. Across 12 weeks, 43.2% stopped/skipped doses, and 12.9% reduced the dose. Stopping/skipping doses during all time frames and dose decreases during weeks 1-12 occurred most frequently with combination treatments. Non-adherence was unrelated to symptom remission, response, or symptom change. CONCLUSIONS: With closely monitored treatment, non-adherence is low and unrelated to depressive symptom outcome. Nonadherence is highest with antidepressant combinations. Specific non-adherent events are most often sporadic.

Increase in work productivity of depressed individuals with improvement in depressive symptom severity.

OBJECTIVE: The authors sought to identify baseline clinical and sociodemographic characteristics associated with work productivity in depressed outpatients and to assess the effect of treatment on work productivity. METHOD: Employed depressed outpatients 18-75 years old who completed the Work Productivity and Activity Impairment scale (N=1,928) were treated with citalopram (20-40 mg/day) in the Sequenced Treatment Alternatives to Relieve Depression study. For patients who did not remit after an initial adequate antidepressant trial (level 1), either a switch to sertraline, sustained-release bupropion, or extended-release venlafaxine or an augmentation with sustained-release bupropion or buspirone was provided (level 2). Participants' clinical and demographic characteristics and treatment outcomes were analyzed for associations with baseline work productivity and change in productivity over time. RESULTS: Education, baseline depression severity, and melancholic, atypical, and recurrent depression subtypes were all independently associated with lower benefit to work productivity domains. During level 1 treatment, work productivity in several domains improved with reductions in depressive symptom severity. However, these findings did not hold true for level 2 outcomes; there was no significant association between treatment response and reduction in work impairment. Results were largely confirmed when multiple imputations were employed to address missing data. During this additional analysis, an association was also observed between greater impairment in work productivity and higher levels of anxious depression. CONCLUSIONS: Patients with clinically significant reductions in symptom severity during initial treatment were more likely than nonresponders to experience significant improvements in work productivity. In contrast, patients who achieved symptom remission in second-step treatment continued to have impairment at work. Patients who have demonstrated some degree of treatment resistance are more prone to persistent impairment in occupational productivity, implying a need for additional, possibly novel, treatments.

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.

Influence of patient race and ethnicity on clinical assessment in patients with affective disorders.

CONTEXT: Rates of clinical diagnoses of schizophrenia in African American individuals appear to be elevated compared with other ethnic groups in the United States, contradicting population rates derived from epidemiologic surveys. OBJECTIVE: To determine whether African American individuals would continue to exhibit significantly higher rates of clinical diagnoses of schizophrenia, even after controlling for age, sex, income, site, and education, as well as the presence or absence of serious affective disorder, as determined by experts blinded to race and ethnicity. A secondary objective was to determine if a similar pattern occurred in Latino subjects. DESIGN: Ethnicity-blinded and -unblinded diagnostic assessments were obtained in 241 African American individuals (mean [SD] age, 34.3 [8.1] years; 57% women), 220 non-Latino white individuals (mean [SD] age, 32.7 [8.5] years; 53% women), and 149 Latino individuals (mean [SD] age, 33.5 [8.0] years; 58% women) at 6 US sites. Logistic regression models were used to determine whether elevated rates of schizophrenia in African American individuals would persist after controlling for various confounding variables including blinded expert consensus diagnoses of serious affective illness. SETTINGS: Six academic medical centers across the United States. PARTICIPANTS: Six hundred ten psychiatric inpatients and outpatients. MAIN OUTCOME MEASURE: Relative odds of unblinded clinical diagnoses of schizophrenia in African American compared with white individuals. RESULTS: A significant ethnicity/race effect (χ(2)(2)=10.4, P=.01) was obtained when schizophrenia was narrowly defined, controlling for all other predictors. The odds ratio comparing African American with non-Latino white individuals was significant (odds ratio=2.7; 95% CI, 1.5-5.1). Similar differences between African American and white individuals occurred when schizophrenia was more broadly defined (odds ratio=2.5; 95% CI, 1.4-4.5). African American individuals did not differ significantly from white individuals in overall severity of manic and depressive symptoms but did evidence more severe psychosis. CONCLUSIONS: African American individuals exhibited significantly higher rates of clinical diagnoses of schizophrenia than non-Latino white subjects, even after controlling for covariates such as serious affective disorder.

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.

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.

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.

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.

The role of complex emotions in inconsistent diagnoses of schizophrenia.

In the case of large-scale epidemiological studies, there is evidence of substantial disagreement when lay diagnoses of schizophrenia based on structured interviews are compared with expert diagnoses of the same patients. Reasons for this level of disagreement are investigated in the current study, which made use of advances in text-mining techniques and associated structural representations of language expressions. Specifically, the current study examined whether content analyses of transcribed diagnostic interviews obtained from 150 persons with serious psychiatric disorders yielded any discernable patterns that correlated with diagnostic inconsistencies of schizophrenia. In summary, it was found that the patterning or structure of spontaneous self-reports of emotion states in the diagnostic interview was associated with diagnostic inconsistencies of schizophrenia, irrespective of confounders; i.e., age of patient, gender, or ethnicity. In particular, complex emotion patterns were associated with greater disagreement between experts and trained lay interviewers than were simpler patterns.

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.

Do atypical features affect outcome in depressed outpatients treated with citalopram?

Depressed patients with atypical features have an earlier onset of depression, a more chronic course of illness, several distinctive biological and familial features, and a different treatment response than those without atypical features. The efficacy and tolerability of selective serotonin reuptake inhibitors (SSRIs) have not been fully evaluated in depression with atypical features. This report evaluates data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study to determine whether depressed outpatients with and without atypical features respond differently to the SSRI citalopram. Treatment-seeking participants with non-psychotic major depressive disorder were recruited from primary- and psychiatric-care settings. The presence/absence of atypical features was approximated using baseline ratings on the 30-item Inventory of Depressive Symptomatology - Clinician-rated. Following baseline assessments, participants received citalopram up to 60 mg/d for up to 14 wk. Baseline sociodemographic and clinical characteristics, and treatment outcomes, were compared between participants with and without atypical features. Of the 2876 evaluable STAR*D participants, 541 (19%) had atypical features. Participants with atypical features were significantly more likely to be female, younger, unemployed, have greater physical impairment, a younger age of depression onset, a longer index episode, greater depressive severity, and more concurrent anxiety diagnoses. Those with atypical features had significantly lower remission rates, although this difference was no longer present after adjustment for baseline differences. Depressed patients with atypical features are less likely to remit with citalopram than those without atypical features. This finding is probably due to differences in baseline characteristics other than atypical symptom features.

Inconsistencies in diagnosis and symptoms among bilingual and English-speaking Latinos and Euro-Americans.

OBJECTIVE: Little information is available about accuracy of diagnoses in clinical care for affective and other major mental disorders experienced by Latino patients. This study addressed two central research questions: Do Latinos have disproportionate rates of clinical diagnoses of major depression based on structured diagnostic interviews? Are diagnostic patterns consistent with patient profiles and medical record information? METHODS: A total of 259 bilingual Latino, monolingual English-speaking Latino, and Euro-American patients aged 18 to 45 years with a history of severe depression or psychotic symptoms were compared across three clinical sites by using structured interviews. RESULTS: Compared with Euro-Americans, bilingual Latinos had significantly higher rates of major depression and significantly lower levels of mania. No significant differences were found between monolingual English-speaking Latinos and Euro-Americans. CONCLUSIONS: Results suggest that the diagnostic process is affected by an apparent association with cultural-linguistic influences, notably speaking English as a second language.

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.