Association between inflammatory joint disease and severe or treatment-resistant depression: population-based cohort and case-control studies in Sweden.

OBJECTIVE: To investigate whether the association between depression and inflammatory joint disease (IJD; rheumatoid arthritis [RA], psoriatic arthritis [PsA], ankylosing spondylitis/spondyloarthropathies [AS], and juvenile idiopathic arthritis [JIA]) is affected by the severity or treatment-resistance of depression. METHOD: Parallel cohort studies and case-control studies among 600,404 patients with a depressive episode identified in Swedish nationwide administrative registers. Prospective and retrospective risk for IJD in patients with depression was compared to matched population comparators, and the same associations were investigated in severe or treatment-resistant depression. Analyses were adjusted for comorbidities and sociodemographic covariates. RESULTS: Patients with depression had an increased risk for later IJD compared to population comparators (adjusted hazard ratio (aHR) for any IJD 1.34 [95% CI 1.30-1.39]; for RA 1.27 [1.15-1.41]; PsA 1.45 [1.29-1.63]; AS 1.32 [1.15-1.52]). In case-control studies, patients with depression more frequently had a history of IJD compared to population controls (adjusted odds ratio (aOR) for any IJD 1.43 [1.37-1.50]; RA 1.39 [1.29-1.49]; PsA 1.59 [1.46-1.73]; AS 1.49 [1.36-1.64]; JIA 1.52 [1.35-1.71]). These associations were not significantly different for severe depression or TRD. CONCLUSION: IJD and depression are bidirectionally associated, but this association does not seem to be influenced by the severity or treatment resistance of depression.

Resistance Training Behavior Is Enhanced With Digital Behavior Change Coaching: A Randomized Controlled Trial With Novice Adults.

BACKGROUND: Approximately a third of US adults meet the physical activity guidelines of engaging in resistance training 2 times per week, yet few studies have examined how to increase participation rates. The present randomized control trial compared a remotely delivered coaching intervention with an education only control group. METHODS: Eligible participants completed 2 remotely delivered Zoom-based personal training sessions during a 1-week run-in period. Participants randomized to the intervention group received synchronous weekly behavioral video coaching sessions over Zoom, whereas the control group received no further contact. Days of resistance training completed were assessed at baseline (pre), 4 weeks (post), and 8 weeks (follow-up). Linear mixed models were used to examine group differences at each time point and within-group differences over time. RESULTS: There were significant between-group differences favoring the intervention, at posttest for both the previous week (b = 0.71, SE = 0.23; P = .002) and the previous 4 weeks (b = 2.54, SE = 0.87; P = .003) but not at the follow-up period for either the last week (b = 0.15, SE = 0.23; P = .520) or the last 4 weeks (b = 0.68, SE = 0.88; P = .443). CONCLUSION: The present study showed that by providing participants with equipment, skill, and in the case of the intervention group, a remote coaching intervention, resistance training participation increased.

How responding in Spanish affects CAHPS results.

BACKGROUND: The most widely used surveys for assessing patient health care experiences in the U.S. are the Consumer Assessment of Healthcare Providers and Systems (CAHPS) surveys. Studies examining the associations of language and ethnicity with responses to CAHPS surveys have yielded inconsistent findings. More research is needed to assess the effect of responding to CAHPS surveys in Spanish. METHODS: Subjects were patients who had received care at a study community health center in Connecticut within 6 or 12 months of being sent a CAHPS survey that asks about care experiences. The survey included four multi-item measures of care plus an overall rating of the provider. Sampled patients were mailed dual language (English and Spanish) cover letters and questionnaires. Those who did not respond after follow-up mailings were contacted by bilingual interviewers to complete the survey by telephone. We tested three hypotheses for any observed differences by ethnicity and language: 1. Spanish speakers are more likely than others to choose extreme response options. 2. The semantic meaning of the Spanish translation is not the same as the English version of the questions, resulting in Spanish speakers giving different answers because of meaning differences. 3. Spanish speakers have different expectations regarding their health care than those who answer in English. Analyses compared the answers on the survey measures for three groups: non-Hispanics answering in English, Hispanics answering in English, and Hispanics answering in Spanish. RESULTS: The overall response rate was 45%. After adjusting for differences in demographic characteristics and self-rated health, those answering in Spanish gave significantly more positive reports than the other two groups on three of the five measures, and higher than the non-Hispanic respondents on a fourth. CONCLUSIONS: Those answering in Spanish gave more positive reports of their medical experiences than Hispanics and non-Hispanics answering in English. Whether these results reflect different response tendencies, different standards for care, or better care experiences is a key issue in whether CAHPS responses in Spanish need adjustment to make them comparable to responses in English.

Patient perceptions of in-home urgent care via mobile integrated health.

OBJECTIVES: Emergency department (ED) crowding poses a severe public health threat, and identifying acceptable means of treating medical conditions in alternative sites of care is imperative. We compared patients' experiences with in-home urgent care via mobile integrated health (MIH) vs urgent care provided in EDs. STUDY DESIGN: Survey, completed on paper, online, or by telephone. We surveyed all patients who received MIH care for an urgent health problem (n = 443) and consecutive patients who visited EDs for urgent care (n = 1436). METHODS: Study participants were members of a managed care plan who were dually eligible for Medicare and Medicaid, 21 years or older, and treated either by MIH or in an ED for nonemergent conditions around Boston, Massachusetts, between February 2017 and June 2018. The survey assessed patients' perceptions of their urgent care experiences. RESULTS: A total of 206 patients treated by community paramedics and 718 patients treated in EDs completed surveys (estimated 66% and 62% response rates, respectively). Patients treated by MIH perceived higher-quality care, more frequently reporting "excellent" (54.7%) or "very good" (32.4%) care compared with ED patients (40.7% and 24.3%, respectively; P < .0001), and were significantly more likely to report that decisions made about their care were "definitely right" compared with patients treated in the ED (66.1% vs 55.6%; P = .02). CONCLUSIONS: Patients appear satisfied with receiving paramedic-delivered urgent care in their homes rather than EDs, perceiving higher-quality care. This suggests that in-home urgent care via MIH may be acceptable for patients with nonemergent conditions.

Health care utilisation in treatment-resistant depression: a Swedish population-based cohort study.

OBJECTIVE: To investigate the health care utilisation (HCU) among patients with treatment-resistant depression (TRD) compared to patients with depression not meeting TRD criteria. METHODS: Nationwide Swedish registers were used to identify patients 18-69 years old with incident depression and antidepressant treatment. Patients were followed prospectively and defined as having TRD at start of the third distinct consecutive treatment episode. Each of the 16,329 identified TRD patients were matched with five comparators with depression not meeting criteria for TRD. Main outcome measure was total number of inpatient days and outpatient visits, and secondary outcome was HCU in connection with a main diagnosis of depression or suicide attempt. RESULTS: TRD patients had a significantly higher risk of all-cause inpatient care than comparators (first year adjusted risk ratio [aRR] 3.03 [95%CI 3.01-3.05], years 1-3 aRR 2.15 [2.13-2.16]). This was more pronounced when the main diagnosis was depression (first year aRR 4.41 [4.36-4.45]), and after suicide attempt (first year aRR 4.43 [4.26-4.60]). Outpatient visits were also markedly more frequent for patients with TRD (first year aRR 2.05 [2.03-2.07]). Higher HCU among TRD patients persisted throughout follow-up. CONCLUSIONS: Patients with TRD may have a twofold to fourfold higher HCU than other patients with depression.KEYPOINTSThis register-based prospective study investigated health care utilisation (HCU) among patients with treatment-resistant depression (TRD) compared to other patients with depression.Patients with TRD had a two to fourfold higher HCU regarding all measured outcomes, including inpatient hospital days and outpatient visits.The elevated HCU persisted for more than three years, although decreasing gradually. This should correspond to increased costs and individual burden for patients with TRD.

Comparing Web and Mail Protocols for Administering Hospital Consumer Assessment of Healthcare Providers and Systems Surveys.

OBJECTIVE: The objective of this study was to compare results of using web-based and mail (postal) Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) data collection protocols. RESEARCH DESIGN: Patients who had been hospitalized in a New England Hospital were surveyed about their hospital experience. Patients who provided email addresses were randomized to 1 of 3 data collection protocols: web-alone, web with postal mail follow-up, and postal mail only. Those who did not provide email addresses were surveyed using postal mail only. Analyses compared response rates, respondent characteristics, and patient-reported experiences. SUBJECTS: For an 8-week period, patients were discharged from the study hospital to home. MEASURES: Measures included response rates, characteristics of respondents, 6 composite measures of their patient experiences, and 2 ratings of the hospital. RESULTS: Response rates were significantly lower for the web-only protocol than the mail or combined protocols, and those who had not provided email addresses had lower response rates. Those over 65 were more likely than others to respond to all protocols, especially for the mail-only protocols. Respondents without email addresses were older, less educated, and reported worse health than those who provided email addresses. After adjusting for respondent differences, those in the combined protocol differed significantly from the mail (postal) only respondents on 2 measures of patient experience; those in the web-only protocol differed on one. Those not providing an email address differed from those who did on one measure. CONCLUSION: If web-based protocols are used for HCAHPS surveys, adjustments for a mode of data collection are needed to make results comparable.

Excess deaths in treatment-resistant depression.

BACKGROUND: Patients with treatment-resistant depression (TRD) have an increased mortality risk compared with other patients with depression, but it is not known how this translates into absolute numbers of excess deaths. METHODS: Swedish national registers were used to identify a cohort of 118,774 antidepressant initiators 18-69 years old with a depression diagnosis. Patients who initiated a third consecutive treatment trial were classified as having TRD. Flexible parametric survival models were used to estimate the mortality risk due to all causes and external causes (suicides and accidents), comparing TRD patients with patients with other depression while adjusting for clinical and sociodemographic covariates and including interactions with TRD, age, and Charlson comorbidity index (CCI) for a number of somatic comorbidities. Standardized survival was estimated, as were numbers of excess deaths among TRD patients within each age and comorbidity category. RESULTS: Compared with the mortality risk of other depressed patients, patients with TRD experienced excess deaths in most age and comorbidity categories in the range of 7-16 deaths per 1000 patients during 5 years. Highest numbers for all-cause excess deaths were found among patients 18-29 years old with CCI 1, where 16 [95% confidence interval 5-28] of the expected 37 [25-48] deaths per 1000 patients were excess deaths. The majority of the excess deaths were due to external causes. CONCLUSION: Patients with TRD experience significant numbers of excess deaths compared with other patients with depression.

Risk Factors for Suicide and Suicide Attempts Among Patients With Treatment-Resistant Depression: Nested Case-Control Study.

The risk of suicide is elevated among patients with treatment-resistant depression (TRD). Risk factors for suicide and suicide attempts among cases and controls with TRD were investigated using data from nationwide Swedish registers. Among 119,407 antidepressant initiators with a diagnosis of depression, 15,631 patients who started a third sequential treatment trial during the same depressive episode were classified with TRD. A nested case-control study compared cases with suicide and suicide attempts with up to three closely matched controls. Sociodemographic and clinical risk factors were assessed using conditional logistic regression analyses. In all, 178 patients died by suicide and 1,242 experienced a suicide attempt during follow-up. History of suicide attempts, especially if <1 year after the attempt, was a significant independent risk factor for suicide (adjusted odds ratio [aOR], 8.9; 95% confidence interval [CI], 5.1-15.7) as were 10 to 12 years of education compared to lower education (aOR, 1.69; 95% CI, 1.02-2.81). For attempted suicide, the strongest independent risk factors were history of suicide attempts (<1 year aOR, 5.1; 95% CI, 4.0-6.5), substance abuse (aOR, 2.6; 95% CI, 2.2-3.1), personality disorders (aOR, 1.9; 95% CI, 1.5-2.3), and somatic comorbidity (aOR, 2.0; 95% CI, 1.04-3.9). Suicide attempts, especially if recent, are strong risk factors for completed suicide among patients with TRD. Established risk factors for suicide attempts were confirmed for patients with TRD.

A register-based approach to identifying treatment-resistant depression-Comparison with clinical definitions.

BACKGROUND: Several definitions of treatment-resistant depression (TRD) are used for clinical research, but no verified model for use in register data exists. We aimed to compare a novel model created for use in register data-the Karolinska Institutet Model (KIM)-to the clinical definitions regarding the proportion of patients identified with TRD, their characteristics and clinical outcomes. METHODS: All patients in Sweden initiating antidepressant treatment with a diagnosis of depression in specialized healthcare 2006-2014 were identified and followed in national registers. In KIM, patients who initiated a third sequential, >28-day antidepressant treatment trial were defined as having TRD. Proportion of TRD and patient characteristics were compared with register adaptations of the European Staging Model (ESM), Massachusetts General Hospital Staging Method (MGH-s), and Maudsley Staging Model (MSM). Differences in patient characteristics were assessed with Chi-square tests and one-way ANOVAs. Hazard ratios for psychiatric hospitalization and for death from external causes were estimated by Cox proportional hazard regressions. RESULTS: Out of 127,108 antidepressant initiators with depression, the highest proportion of TRD was found using the MGH-s (19.0%), followed by MSM (15.3%), KIM (12.9%), and ESM (9.5%). Clinical characteristics were similar across the models. Compared with TRD patients identified by KIM, those identified by ESM had a marginally higher risk for psychiatric hospitalization (adjusted hazard ratio [aHR] 1.03, 95%CI 1.00-1.05), whereas those identified by MGH-s (aHR 0.92; 0.90-0.94) and MSM (aHR 0.95; 0.94-0.97) had a slightly reduced risk. Patients identified by MGH-s showed a reduced mortality compared with KIM (aHR 0.84; 0.72-0.98). CONCLUSIONS: This study provides insight into the differing characteristics of patients captured by various TRD models when used for register research. Models yielding lower proportions of TRD seemed to identify patients with greater morbidity. The KIM may be useful for register based research in TRD.

Risk and risk factors for disability pension among patients with treatment resistant depression- a matched cohort study.

BACKGROUND: Treatment resistant depression (TRD) is common among patients with depression, and is associated with clinical and functional disability. However, the risk and risk factors for being granted disability pension (DP) among patients with TRD have not been investigated. METHODS: All antidepressant initiators in Sweden with a diagnosis of depression in specialized care were identified in nationwide registers 2006-2013 and followed regarding treatment trials. TRD was defined as the start of a third sequential trial. Patients with TRD who were not on DP (N = 3204) were matched by age, sex, history of depression, calendar year, and time for treatment start with 3204 comparators with depression and ongoing antidepressant treatment. A proportional Cox Regression was performed with DP as outcome, adjusted for various sociodemographic and clinical covariates. RESULTS: Compared to the comparison cohort, TRD was associated with a doubled risk for all-cause DP (aHR 2.07; 95%CI 1.83-2.35), DP due to depression (2.28; 1.82-2.85) and to any mental disorder (2.24; 1.95-2.57) but not due to somatic diagnoses (1.25; 0.84-1.86). Among significant risk factors for DP in TRD were female sex, being > 29 years of age, unemployment and a diagnosis of comorbid personality disorder (ICD-10 codes F60.0-9). CONCLUSION: TRD is associated with an elevated risk for DP compared to other patients with depression, with large potential costs for the affected patients and for society. Clinical and therapeutic implications for patients with TRD who are granted DP should be further investigated. LIMITATION: No clinical data, e.g. type of depression or reason for treatment switch, was available for this study.

Use of antidepressants and benzodiazepine-related hypnotics before and after initiation of TNF-α inhibitors or non-biological systemic treatment in patients with rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis.

BACKGROUND: Rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) are autoimmune disorders associated with an increased risk for depression, anxiety and sleeping problems. The objective of this study was to analyze use of antidepressants and benzodiazepine-related hypnotics (BRH) in Sweden before and after first time treatment with anti-TNF and non-biological systemic (NBS) treatments among patients with the above diagnoses, and to correlate such use with that of randomly selected population controls. METHODS: Patients and dispensed drugs were identified in nationwide Swedish healthcare registers. Proportions of subjects filling prescriptions of antidepressants and BRH from 2 years before start of treatment (index-date), and 2 years after index date were assessed. Using the period -6 months to index-date as reference, prevalence rate ratios were computed for 6 months' intervals before and after index. For up to ten randomly selected population controls per patient, the same measures were calculated. RESULTS: A total of 6256 patients started anti-TNF treatment, and 13,241 NBS treatment. The mean age at index was 52.0 for the anti-TNF group and 56.1 for NBS. Use of antidepressants and BRH was similar in both treatment groups (10.4-12.8%), significantly more common than in the controls (6.6 to 7.6%). For all patients, proportions filling prescriptions for antidepressants and BRH decreased directly or soon after the index; no such changes were seen in the controls, who all showed a slow but steady increase in use over time. Starters of anti-TNF treatment did not show clearer decreases in use of psychotropics than those initiating NBS. CONCLUSIONS: Decreased rates of dispensed psychotropic drugs after the time of anti-TNF and NBS treatment initiation were seen among patients with autoimmune disorders but not population controls. This may correspond to treatment effects of anti-TNF and NBS also on psychiatric symptoms among these patients.

Substance use disorders and risk for treatment resistant depression: a population-based, nested case-control study.

BACKGROUND AND AIMS: Treatment-resistant depression (TRD), defined as inadequate treatment response after at least two adequate treatment trials, is common among patients initiating antidepressant treatment. Current or previous substance use disorders (SUD) are common among patients with depression and often lead to worse treatment outcomes. However, in clinical studies, SUD have not been found to increase the risk for TRD. The aim of this study was to investigate the association between SUD and TRD. DESIGN: Nested case-control study. SETTING: Nation-wide governmental health-care registers in Sweden. CASES AND CONTROLS: Data on prescribed drugs and diagnoses from specialized health care were used to establish a prospectively followed cohort of antidepressant initiators with depression (n = 121 669) from 2006 to 2014. Of these, 15 631 patients (13%) were defined as TRD cases, with at least three treatment trials within a single depressive episode. Each case with TRD was matched on socio-demographic data with five controls with depression. MEASUREMENTS: Crude and adjusted odds ratios (aOR) with 95% confidence intervals (CI) estimated the association between TRD and SUD diagnosis and/or treatment in five different time intervals until the time for fulfillment of TRD definition for the case. The analysis was adjusted for clinical and socio-demographic covariates. FINDINGS: Having any SUD during, or ≤ 180 days before start of, antidepressant treatment was associated with almost double the risk for TRD [≤ 180 days before: adjusted OR (aOR) = 1.86, CI = 1.70-2.05]. Increased risks for TRD were found ≤ 180 days before treatment start for the subcategories of sedative use (aOR = 2.37; 1.88-2.99), opioids (aOR = 2.02; 1.48-2.75), alcohol (aOR = 1.77; CI = 1.59-1.98) and combined substance use (aOR = 2.31; 1.87-2.99). CONCLUSIONS: Recent or current substance use disorders is positively associated with treatment resistance among patients initiating treatment for depression.

A Post-Authorization Safety Study of Quetiapine as Antidepressant Treatment in Sweden: Nested Case-Control Analyses of Select Outcomes.

INTRODUCTION: This post-authorization safety study (PASS) was a commitment to the European Medicines Agency. OBJECTIVE: This PASS investigated quetiapine as antidepressant treatment in Swedish registers with regard to the risk for all-cause mortality, self-harm and suicide, acute myocardial infarction, stroke, diabetes mellitus, extrapyramidal disorders, and somnolence. METHODS: Users of quetiapine and antidepressants (2011‒2014) who had changed treatment in the past year were included. Conditional logistic regression models were used to calculate odds ratios (ORs) and their 95% confidence intervals (CIs) for each outcome in nested case-control studies for quetiapine as combination therapy and monotherapy, monotherapy with antidepressants, and no medication, versus the use of combinations of antidepressants (reference group). RESULTS: Overall, 7421 quetiapine users and 281,303 antidepressant users were included. For quetiapine in combination, risks were increased for all-cause mortality [adjusted OR (aOR) 1.31, 95% CI 1.12-1.54] compared with combinations of antidepressants; however, when stratified by age, only patients ≥ 65 years of age had an increased mortality, and, in a post hoc analysis excluding patients with Parkinson's disease, no mortality increase remained. Furthermore, the risk for self-harm and suicide was increased (aOR 1.53, 95% CI 1.31-1.79), but when stratified by age, the risk increase was found only among patients aged 18-64 years. Risks were also increased for stroke among patients ≥ 65 years of age (aOR 1.47, 95% CI 1.01-2.12), for extrapyramidal disorder (aOR 6.15, 95% CI 3.57-10.58), and for somnolence (aOR 2.41, 95% CI 1.42-4.11). CONCLUSION: Risks for all-cause mortality, self-harm and suicide, and stroke in older patients may be higher among patients treated with quetiapine and antidepressant combination therapy.

Disability worsening among persons with multiple sclerosis and depression: A Swedish cohort study.

OBJECTIVE: Depression is common in multiple sclerosis (MS), but its impact on disability worsening has not yet been determined. We explored the risk of disability worsening associated with depression in a nationwide longitudinal cohort. METHODS: This retrospective cohort study used linked data from 3 Swedish nationwide registries: the MS Register, National Patient Register, and Prescribed Drug Register. Two incident cohorts were developed: cohort 1 included all registered cases of MS in the MS Registry (2001-2014) with depression defined as ≥1 ICD-10 code for depression; and cohort 2 comprised all cases of MS in the MS Registry (2005-2014) with depression defined as ≥1 prescription filled for an antidepressant. Cox regression models were used to compare the risk of reaching sustained disability milestone scores of 3.0, 4.0, and 6.0 on the Expanded Disability Status Scale (EDSS) between persons with MS with and without depression. RESULTS: Cohort 1 included 5,875 cases; 502 (8.5%) had depression. Cohort 2 had 3,817 cases; 1,289 (33.8%) were prescribed an antidepressant. Persons with depression were at a significantly higher risk of reaching sustained EDSS scores of 3.0, 4.0, and 6.0, with hazard ratios of 1.50 (95% confidence interval [CI] 1.20-1.87), 1.79 (95% CI 1.40-2.29), and 1.89 (95% CI 1.38-2.57), respectively. A similar increased risk among persons exposed to antidepressants was observed, with hazard ratios of 1.37 (95% CI 1.18-1.60), 1.93 (95% CI 1.61-2.31), and 1.86 (95% CI 1.45-2.40) for sustained EDSS scores of 3.0, 4.0, and 6.0, respectively. CONCLUSION: Persons with MS and comorbid depression had a significantly increased risk of disability worsening. This finding highlights the need for early recognition and appropriate treatment of depression in persons with MS.

All-cause mortality in patients with treatment-resistant depression: a cohort study in the US population.

BACKGROUND: Treatment-resistant depression (TRD) may represent a substantial proportion of major depressive disorder (MDD); however, the risk of mortality in TRD is still incompletely assessed. METHODS: Data were obtained from Optum Clinformatics™ Extended, a US claims database. Date of the first antidepressant (AD) dispensing was designated as the index date for study entry and 6 months prior to that was considered the baseline period. Patients with MDD aged ≥ 18 years, index date between January 1, 2008 and September 30, 2015, no AD claims during baseline, and continuous enrollment in the database during baseline were included. Patients who started a third AD regimen after two regimens of appropriate duration were included in the TRD cohort. All-cause mortality was compared between patients with TRD and non-TRD MDD using a proportional hazards model and Kaplan-Meier estimate with TRD status being treated as a time-varying covariate. The model was adjusted for study year, age, gender, depression diagnosis, substance use disorder, psychiatric comorbidities, and Charlson comorbidity index. RESULTS: Out of 355,942 patients with MDD, 34,176 (9.6%) met the criterion for TRD. TRD was associated with a significantly higher mortality compared with non-TRD MDD (adjusted HR: 1.29; 95% CI 1.22-1.38; p < 0.0001). Survival time was significantly shorter in the TRD cohort compared with the non-TRD MDD cohort (p < 0.0001). CONCLUSIONS: Patients with TRD had a higher all-cause mortality compared with non-TRD MDD patients.

Treatment-resistant depression as risk factor for substance use disorders-a nation-wide register-based cohort study.

BACKGROUND AND AIMS: Treatment-resistant depression (TRD) is common among patients with major depressive disorder (MDD). MDD may increase the risk for developing substance use disorders (SUD). The aim of this study was to investigate the risk for developing SUD among patients with TRD compared with other depressed patients. DESIGN: Observational cohort study. SETTING: Nation-wide governmental health registers in Sweden. PARTICIPANTS: All patients aged 18-69 years with an MDD diagnosis in specialized health care who had received at least one antidepressant prescription during 2006-14 were identified. Patients with at least three treatment trials within a single depressive episode were classified with TRD. MEASUREMENTS: Patients with TRD were compared with the whole MDD cohort regarding risk for obtaining a SUD diagnosis or medication using survival analyses adjusted for socio-demographics and comorbidities. FINDINGS: Of 121 669 MDD patients, 13% were classified with TRD. Among the patients without any history of SUD, patients with TRD had a risk increase for any SUD both ≤ 1 and > 1 year after antidepressant initiation [> 1 year hazard ratio (HR) = 1.4; 95% confidence interval (CI) = 1.3-1.5]. Risks were elevated for the subcategories of opioid (HR = 1.9, 95% CI = 1.4-2.5) and sedative SUD (HR = 2.7, 95% CI = 2.2-3.2). Patients with a history of SUD had a risk increase for any SUD ≤ 1 year after start of treatment (HR = 1.2, 95% CI = 1.1-1.4), and both ≤ 1 year and > 1 year for sedative (> 1 year HR = 2.0, 95% CI = 1.3-3.0) and multiple substance SUD (HR = 1.9, 95% CI = 1.4-2.5). CONCLUSIONS: Patients with treatment-resistant depression may be at greater risk for substance use disorders compared with other patients with major depressive disorder. Patterns may differ for patients with and without a history of substance use disorders, and for different categories of substance use disorder.

Telephone health survey estimates: Effects of nonresponse and sample limitations.

OBJECTIVE: The objective of this study was to assess nonresponse error in telephone health survey data based on an address-based sample. DATA SOURCES: Telephone and in-person interviews in Greater Boston. STUDY DESIGN/DATA COLLECTION: Interviewers attempted telephone interviews at addresses that were matched to telephone numbers using questions drawn from federal health surveys. In-person household interviews were carried out with telephone nonrespondents and at addresses without matching telephone numbers. PRINCIPAL FINDINGS: After adjusting for demographic differences, only eight of 15 estimates based on the telephone interviews lay within two standard errors of the estimates when data from all three groups were included. CONCLUSIONS: For health surveys of address-based samples, many estimates based on telephone respondents differ from the total population in ways that cannot be corrected with simple demographic adjustments.

Humanistic outcomes in treatment resistant depression: a secondary analysis of the STAR*D study.

BACKGROUND: In the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, a third of patients did not achieve remission or adequate response after two treatment trials, fulfilling requirements for treatment resistant depression (TRD). The present study is a secondary analysis of the STAR*D data conducted to compare the humanistic outcomes in patients with TRD and non-TRD MDD. METHODS: Patients with major depressive disorder who entered level 3 of the STAR*D were included in the TRD group, while patients who responded to treatment and entered follow-up from level 1 or 2 were included in the non-TRD group. The first visit in level 1 was used for baseline assessments. The time-point of assessments for comparison was the first visit in level 3 for TRD patients (median day: 141), and the visit closest to 141 ± 60 days from baseline for non-TRD patients. Outcomes were assessed by the 12-item Short Form Health Survey (SF12), 16-item Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), Work and Social Adjustment Scale (WSAS), and Work Productivity and Activity Impairment scale (WPAI). Scores were compared in a linear model with adjustment for covariates including age, gender, and depression severity measured by the 17-item Hamilton Rating Scale for Depression (HDRS17) and Quick Inventory of Depressive Symptomatology (QIDS). RESULTS: A total of 2467 (TRD: 377; non-TRD: 2090) patients were studied. TRD patients were slightly older (mean age 44 vs 42 years), had a higher proportion of men (49% vs 37%, p < .0001), and baseline depression severity (HDRS17: 24.4 vs 22.0, p < .0001) vs non-TRD patients. During follow-up, TRD patients had lower health-related quality of life (HRQOL) scores on mental (30 vs 45.7) and physical components (47.7 vs 48.9) of the SF12, and lower Q-LES-Q scores (43.6 vs 63.7), greater functional and work impairments and productivity loss vs non-TRD patients (all p < 0.05). CONCLUSION: Patients with TRD had worse HRQOL, work productivity, and social functioning than the non-TRD patients.

Mortality in treatment-resistant unipolar depression: A register-based cohort study in Sweden.

BACKGROUND: The impact of treatment resistant depression (TRD) on mortality is not established. METHODS: Using Swedish national registers, 118,774 patients between 18-69 years of age who had been prescribed an antidepressant and been diagnosed with depression in specialized care were identified. Patients with at least two additional treatment trials during the same depressive episode were classified as having TRD. Data on the covariates of sex, age, history of depression, self-harm, substance use disorders, and other psychiatric and somatic comorbidities was also used. Relative risks comparing TRD patients with other depressed patients were calculated as hazard ratios (HR) for all-cause mortality and for external and non-external causes of death, as well as excess mortality rate ratios (EMRR), with 95% confidence intervals (CI). RESULTS: In total 15,013 patients (13%) were classified with TRD. Adjusted HR for all-cause mortality was 1.35 (95% CI 1.21-1.50). Mortality from external causes (including suicides and accidents) was markedly higher in TRD patients than in other depressed patients (HR 1.97; 1.69-2.29), while mortality from non-external causes was similar. The adjusted EMRR was 1.52 (1.31-1.76), highest among patients 18-29 years old (EMRR 2.03; 1.31-1.76) and patients without somatic comorbidity (EMRR 1.99; 1.63-2.43). LIMITATIONS: Severity of depression and adherence to treatment were not available in the data. CONCLUSIONS: Patients with TRD may have an increased all-cause mortality compared to other depressed patients, mainly for external causes of death. The relative mortality is highest among young and physically healthy patients.

Depression and fatigue in multiple sclerosis: Relation to exposure to violence and cerebrospinal fluid immunomarkers.

Multiple sclerosis (MS) is a neuroinflammatory condition characterized by chronic dysregulation of immune responses leading to repeated episodes of inflammation in the central nervous system. Depression and fatigue are common among MS patients, even in early disease phases, and the disease course can be negatively affected by stressful events. IL-6 and IL-8 have been associated with depression and stressful life events in non-MS patients. The aim of this study was to examine the relationships between depression, fatigue, and exposure to violence, with IL-6 and IL-8 levels in the cerebrospinal fluid (CSF) of MS patients. Levels of IL-6 and -8 were analyzed in the CSF of 47 patients with relapsing-remitting MS. Correlations between IL-6 and IL-8 levels and self-rated depression and fatigue symptoms, as well as clinician-rated history of being exposed to interpersonal violence, were analyzed with correction for age, sex and MS disability status. IL-6 correlated significantly (p < 0.05) with depressive symptoms (adjusted Spearman's ρ = 0.39), fatigue (ρ = 0.39), and exposure to violence in adult life (ρ = 0.35). Depression correlated with both fatigue and being exposed to violence. Associations were not present among patients exposed to disease modifying drugs. In exploratory analyses, the relationship between exposure to violence and IL-6 was non-significant when controlled for depression. Further research should focus on replication of these results, as well as exploring the impact of stressful life events on immune regulation and the clinical characteristics and prognosis of MS patients.