Implementation and scalability of a digital intervention to reduce depressive symptoms in people with diabetes, hypertension or both in Brazil and Peru: a qualitative study of health system's stakeholders' perspectives.

Two randomized controlled trials (RCTs) in Brazil and Peru demonstrated the effectiveness of CONEMO, a digital intervention supported by trained nurses or nurse assistants (NAs), to reduce depressive symptoms in people with diabetes and/or hypertension. This paper extends the RCTs findings by reflecting on the conditions needed for its wider implementation in routine care services. A qualitative study using semi-structured interviews and content analysis was conducted with nurses/NAs, clinicians, healthcare administrators, and policymakers. Informants reported that CONEMO would be feasible to implement in their health services, but some conditions could be improved before its scale-up: reducing workloads of healthcare workers; raising mental health awareness among clinicians and administrators; being able to inform, deliver and accompany the intervention; assuring appropriate training and supervision of nurses/NAs; and supporting the use of technology in public health services and by patients, especially older ones. We discuss some suggestions on how to overcome these challenges.

Predictors of engagement with remote sensing technologies for symptom measurement in Major Depressive Disorder.

BACKGROUND: Remote sensing for the measurement and management of long-term conditions such as Major Depressive Disorder (MDD) is becoming more prevalent. User-engagement is essential to yield any benefits. We tested three hypotheses examining associations between clinical characteristics, perceptions of remote sensing, and objective user engagement metrics. METHODS: The Remote Assessment of Disease and Relapse - Major Depressive Disorder (RADAR-MDD) study is a multicentre longitudinal observational cohort study in people with recurrent MDD. Participants wore a FitBit and completed app-based assessments every two weeks for a median of 18 months. Multivariable random effects regression models pooling data across timepoints were used to examine associations between variables. RESULTS: A total of 547 participants (87.8% of the total sample) were included in the current analysis. Higher levels of anxiety were associated with lower levels of perceived technology ease of use; increased functional disability was associated with small differences in perceptions of technology usefulness and usability. Participants who reported higher system ease of use, usefulness, and acceptability subsequently completed more app-based questionnaires and tended to wear their FitBit activity tracker for longer. All effect sizes were small and unlikely to be of practical significance. LIMITATIONS: Symptoms of depression, anxiety, functional disability, and perceptions of system usability are measured at the same time. These therefore represent cross-sectional associations rather than predictions of future perceptions. CONCLUSIONS: These findings suggest that perceived usability and actual use of remote measurement technologies in people with MDD are robust across differences in severity of depression, anxiety, and functional impairment.

Remote assessment of disease and relapse in major depressive disorder (RADAR-MDD): a multi-centre prospective cohort study protocol.

BACKGROUND: There is a growing body of literature highlighting the role that wearable and mobile remote measurement technology (RMT) can play in measuring symptoms of major depressive disorder (MDD). Outcomes assessment typically relies on self-report, which can be biased by dysfunctional perceptions and current symptom severity. Predictors of depressive relapse include disrupted sleep, reduced sociability, physical activity, changes in mood, prosody and cognitive function, which are all amenable to measurement via RMT. This study aims to: 1) determine the usability, feasibility and acceptability of RMT; 2) improve and refine clinical outcome measurement using RMT to identify current clinical state; 3) determine whether RMT can provide information predictive of depressive relapse and other critical outcomes. METHODS: RADAR-MDD is a multi-site prospective cohort study, aiming to recruit 600 participants with a history of depressive disorder across three sites: London, Amsterdam and Barcelona. Participants will be asked to wear a wrist-worn activity tracker and download several apps onto their smartphones. These apps will be used to either collect data passively from existing smartphone sensors, or to deliver questionnaires, cognitive tasks, and speech assessments. The wearable device, smartphone sensors and questionnaires will collect data for up to 2-years about participants' sleep, physical activity, stress, mood, sociability, speech patterns, and cognitive function. The primary outcome of interest is MDD relapse, defined via the Inventory of Depressive Symptomatology- Self-Report questionnaire (IDS-SR) and the World Health Organisation's self-reported Composite International Diagnostic Interview (CIDI-SF). DISCUSSION: This study aims to provide insight into the early predictors of major depressive relapse, measured unobtrusively via RMT. If found to be acceptable to patients and other key stakeholders and able to provide clinically useful information predictive of future deterioration, RMT has potential to change the way in which depression and other long-term conditions are measured and managed.

Occupational medicine specialist referral triggers: Mixed-methods analysis of teleconsult cases.

Background: Qualitative analyses can yield critical lessons for learning organizations in healthcare. Few studies have applied these techniques in the field of occupational and environmental medicine (OEM). Aims: To describe the characteristics of complex cases referred for OEM subspecialty evaluation and variation by referring provider's training. Methods: Using a mixed methods approach, we conducted a content analysis of clinical cases submitted to a national OEM teleconsult service. Consecutive cases entered between April 2014 and July 2015 were screened, coded and analysed. Results: 108 cases were available for analysis. Local Veterans Health Administration (VHA) non-specialist providers entered a primary medical diagnosis in 96% of cases at the time of intake. OEM speciality physicians coded significant medical conditions based on free text comments. Coder inter-rater reliability was 84%. The most frequent medical diagnosis types associated with tertiary OEM referral by non-specialists were endocrine (19%), cardiovascular (18%) and mental health (16%). Concern for usage of controlled and/or sedating medications was cited in 1% of cases. Compared to referring non-specialists, OEM physicians were more likely to attribute case complexity to musculoskeletal (OR: 2.3, 1.68-3.14) or neurological (OR: 1.69, 1.28-2.24) conditions. Medication usage (OR: 2.2, 1.49-2.26) was more likely to be a source of clinical concern among referring providers. Conclusions: The findings highlight the range of triggers for OEM physician subspecialty referral in clinical practice with employee patients. The results of this study can be used to inform development of provider education, standardized clinical practice pathways, and quality review activities for occupational medicine practitioners.

Predictors of outcome for telephone and face-to-face administered cognitive behavioral therapy for depression.

BACKGROUND: Cognitive behavioral therapy (CBT) can be delivered efficaciously through various modalities, including telephone (T-CBT) and face-to-face (FtF-CBT). The purpose of this study was to explore predictors of outcome in T-CBT and FtF-CBT for depression. METHOD: A total of 325 depressed participants were randomized to receive eighteen 45-min sessions of T-CBT or FtF-CBT. Depression severity was measured using the Hamilton Depression Rating Scale (HAMD) and the Patient Health Questionnaire-9 (PHQ-9). Classification and regression tree (CART) analyses were conducted with baseline participant demographics and psychological characteristics predicting depression outcomes, HAMD and PHQ-9, at end of treatment (week 18). RESULTS: The demographic and psychological characteristics accurately identified 85.3% and 85.0% of treatment responders and 85.7% and 85.0% of treatment non-responders on the HAMD and PHQ-9, respectively. The Coping self-efficacy (CSE) scale predicted outcome on both the HAMD and PHQ-9; those with moderate to high CSE were likely to respond with no other variable influencing that prediction. Among those with low CSE, depression severity influenced response. Social support, physical functioning, and employment emerged as predictors only for the HAMD, and sex predicted response on the PHQ-9. Treatment delivery method (i.e. telephone or face-to-face) did not impact the prediction of outcome. CONCLUSIONS: Findings suggest that the predictors of improved depression are similar across treatment modalities. Most importantly, a moderate to high level of CSE significantly increases the chance of responding in both T-CBT and FtF-CBT. Among patients with low CSE, those with lower depressive symptom severity are more likely to do well in treatment.

Blood transcriptomic biomarkers in adult primary care patients with major depressive disorder undergoing cognitive behavioral therapy.

An objective, laboratory-based diagnostic tool could increase the diagnostic accuracy of major depressive disorders (MDDs), identify factors that characterize patients and promote individualized therapy. The goal of this study was to assess a blood-based biomarker panel, which showed promise in adolescents with MDD, in adult primary care patients with MDD and age-, gender- and race-matched nondepressed (ND) controls. Patients with MDD received cognitive behavioral therapy (CBT) and clinical assessment using self-reported depression with the Patient Health Questionnaire-9 (PHQ-9). The measures, including blood RNA collection, were obtained before and after 18 weeks of CBT. Blood transcript levels of nine markers of ADCY3, DGKA, FAM46A, IGSF4A/CADM1, KIAA1539, MARCKS, PSME1, RAPH1 and TLR7, differed significantly between participants with MDD (N=32) and ND controls (N=32) at baseline (q< 0.05). Abundance of the DGKA, KIAA1539 and RAPH1 transcripts remained significantly different between subjects with MDD and ND controls even after post-CBT remission (defined as PHQ-9 <5). The ROC area under the curve for these transcripts demonstrated high discriminative ability between MDD and ND participants, regardless of their current clinical status. Before CBT, significant co-expression network of specific transcripts existed in MDD subjects who subsequently remitted in response to CBT, but not in those who remained depressed. Thus, blood levels of different transcript panels may identify the depressed from the nondepressed among primary care patients, during a depressive episode or in remission, or follow and predict response to CBT in depressed individuals.

Do positive or negative stressful events predict the development of new brain lesions in people with multiple sclerosis?

BACKGROUND: Stressful life events have long been suspected to contribute to multiple sclerosis (MS) disease activity. The few studies examining the relationship between stressful events and neuroimaging markers have been small and inconsistent. This study examined whether different types of stressful events and perceived stress could predict the development of brain lesions. METHOD: This was a secondary analysis of 121 patients with MS followed for 48 weeks during a randomized controlled trial comparing stress management therapy for MS (SMT-MS) to a waitlist control (WLC). Patients underwent magnetic resonance imaging (MRI) scans every 8 weeks. Every month, patients completed an interview measure assessing stressful life events and self-report measures of perceived stress, anxiety and depressive symptoms, which were used to predict the presence of gadolinium-enhancing (Gd+) and T2 lesions on MRI scans 29-62 days later. Participants classified stressful events as positive or negative. Negative events were considered 'major' if they involved physical threat or threat to the patient's family structure, and 'moderate' otherwise. RESULTS: Positive stressful events predicted decreased risk for subsequent Gd+ lesions in the control group [odds ratio (OR) 0.53 for each additional positive stressful event, 95% confidence interval (CI) 0.30-0.91] and less risk for new or enlarging T2 lesions regardless of group assignment (OR 0.74, 95% CI 0.55-0.99). Across groups, major negative stressful events predicted Gd+ lesions (OR 1.77, 95% CI 1.18-2.64) and new or enlarging T2 lesions (OR 1.57, 95% CI 1.11-2.23) whereas moderate negative stressful events, perceived stress, anxiety and depressive symptoms did not. CONCLUSIONS: Major negative stressful events predict increased risk for Gd+ and T2 lesions whereas positive stressful events predict decreased risk.

Comparison of psychotherapies for adult depression to pill placebo control groups: a meta-analysis.

BACKGROUND: The effects of antidepressants for treating depressive disorders have been overestimated because of selective publication of positive trials. Reanalyses that include unpublished trials have yielded reduced effect sizes. This in turn has led to claims that antidepressants have clinically insignificant advantages over placebo and that psychotherapy is therefore a better alternative. To test this, we conducted a meta-analysis of studies comparing psychotherapy with pill placebo. METHOD: Ten 10 studies comparing psychotherapies with pill placebo were identified. In total, 1240 patients were included in these studies. For each study, Hedges' g was calculated. Characteristics of the studies were extracted for subgroup and meta-regression analyses. RESULTS: The effect of psychotherapy compared to pill placebo at post-test was g = 0.25 [95% confidence interval (CI) 0.14-0.36, I² = 0%, 95% CI 0-58]. This effect size corresponds to a number needed to treat (NNT) of 7.14 (95% CI 5.00-12.82). The psychotherapy conditions scored 2.66 points lower on the Hamilton Depression Rating Scale (HAMD) than the placebo conditions, and 3.20 points lower on the Beck Depression Inventory (BDI). Some indications for publication bias were found (two missing studies). We found no significant differences between subgroups of the studies and in meta-regression analyses we found no significant association between baseline severity and effect size. CONCLUSIONS: Although there are differences between the role of placebo in psychotherapy and pharmacotherapy research, psychotherapy has an effect size that is comparable to that of antidepressant medications. Whether these effects should be deemed clinically relevant remains open to debate.

Behavioral interventions in multiple sclerosis: a biopsychosocial perspective.

Managing uncertainty is a major challenge associated with the diagnosis of multiple sclerosis (MS). In addition to physical symptoms, neuropsychiatric symptoms are highly prevalent in this disease. Depression in particular is more common in MS than in other chronic diseases. While substantial achievements have been made in the therapy of MS and an increasing number of immunomodulatory treatments are now available, the long-term benefits of these are still a matter of debate. Importantly, while the approved therapies show good efficacy on inflammatory lesions and relapse rate, and may slow certain aspects of disease progression, improvements in function have rarely been reported. On the other hand, behavioral interventions have recently been shown to significantly improve fatigue and depression as well as motor function. In addition, recent evidence suggests that group education or face-to-face behavioral interventions may decrease inflammatory disease activity (such as relapse rate or lesion formation measured by MRI). Therefore, behavioral interventions not only ameliorate symptoms but may have the potential to modify the disease process itself.

Stress and the risk of multiple sclerosis.

OBJECTIVE: Several studies have shown that stressful life events are associated with a subsequent significant increase in risk of multiple sclerosis (MS) exacerbations. We wanted to study prospectively whether stress can increase the risk of developing the disease itself. METHODS: We studied 2 cohorts of female nurses: the Nurses' Health Study (NHS) (n = 121,700) followed from 1976 and the Nurses' Health Study II (NHS II) (n = 116,671) followed from 1989. The risk of MS after self-report on general stress at home and at work in the NHS in 1982 was studied prospectively using Cox regression. Logistic regression was used to retrospectively estimate the effects of physical and sexual abuse in childhood and adolescence collected in the NHS II 2001. We identified 77 cases of MS in the NHS by 2005 and 292 in the NHS II by 2004. All analyses were adjusted for age, ethnicity, latitude of birth, body mass index at age 18, and smoking. RESULTS: We found no increased risk of MS associated with severe stress at home in the NHS (hazard ratio 0.85 [95% confidence interval (CI)] 0.32-2.26). No significantly increased risk of MS was found among those who reported severe physical abuse during childhood (odds ratio [OR] 0.68, 95% CI 0.41-1.14) or adolescence (OR 0.77, 95% CI 0.46-1.28) or those having been repeatedly forced into sexual activity in childhood (OR 1.47, 95% CI 0.87-2.48) or adolescence (OR 1.21, 95% CI 0.68-2.17). CONCLUSIONS: These results do not support a major role of stress in the development of the disease, but repeated and more focused measures of stress are needed to firmly exclude stress as a potential risk factor for MS.

MS quality of life, depression, and fatigue improve after mindfulness training: a randomized trial.

OBJECTIVE: Health-related quality of life (HRQOL) is often much reduced among individuals with multiple sclerosis (MS), and incidences of depression, fatigue, and anxiety are high. We examined effects of a mindfulness-based intervention (MBI) compared to usual care (UC) upon HRQOL, depression, and fatigue among adults with relapsing-remitting or secondary progressive MS. METHODS: A total of 150 patients were randomly assigned to the intervention (n = 76) or to UC (n = 74). MBI consisted of a structured 8-week program of mindfulness training. Assessments were made at baseline, postintervention, and 6 months follow-up. Primary outcomes included disease-specific and disease-aspecific HRQOL, depression, and fatigue. Anxiety, personal goal attainment, and adherence to homework were secondary outcomes. RESULTS: Attrition was low in the intervention group (5%) and attendance rate high (92%). Employing intention-to-treat analysis, MBI, compared with UC, improved nonphysical dimensions of primary outcomes at postintervention and follow-up (p < 0.002); effect sizes, 0.4-0.9 posttreatment and 0.3-0.5 at follow-up. When analyses were repeated among subgroups with clinically relevant levels of preintervention depression, fatigue, or anxiety, postintervention and follow-up effects remained significant and effect sizes were larger than for the total sample. CONCLUSIONS: In addition to evidence of improved HRQOL and well-being, these findings demonstrate broad feasibility and acceptance of, as well as satisfaction and adherence with, a program of mindfulness training for patients with MS. The results may also have treatment implications for other chronic disorders that diminish HRQOL. CLASSIFICATION OF EVIDENCE: This trial provides Class III evidence that MBI compared with UC improved HRQOL, fatigue, and depression up to 6 months postintervention.

ApoE alleles, depression and positive affect in multiple sclerosis.

BACKGROUND: The role of apolipoprotein E (ApoE) alleles has received recent attention in depressive disorders, the ApoE epsilon4 conferring greater risk for poorer outcomes, and the ApoE epsilon2 allele providing some protective effects. Depression is common in multiple sclerosis (MS) and the role of ApoE alleles is unknown. AIMS: To evaluate ApoE alleles in relation to symptoms of depression in a cohort of patients with MS participating in the Sonya Slifka Longitudinal Multiple Sclerosis Study (Slifka Study). To examine risk and protection, depressed mood and positive affect were each investigated with respect to the ApoE epsilon4 and ApoE epsilon2 alleles, respectively. RESULTS: Of the total 101 participants, 22.8% were ApoE epsilon2 carriers and 21.8% were ApoE epsilon4 carriers. Hierarchical linear regression analyses suggested that after controlling for demographics, disease duration, and disability, ApoE epsilon2 significantly predicted increased positive affect (R2Delta=0.05, F(1,94)=5.44, P=0.02) and was associated with decreased severity of depressive symptoms, although this did not reach statistical significance (R2Delta=0.03, F(1,94)=3.44, P=0.06). ApoE epsilon4 did not significantly predict depression status. CONCLUSION: The presence of the ApoE epsilon2 allele in this study is suggested to be protective against depressive symptoms in our subsample of patients recruited from the Slifka Study. These findings are consistent with reports in psychiatric populations linking ApoE epsilon2 with decreased incidence of depressive disorders. Further investigation would be warranted to understand the role of ApoE genotypes and risk for depressive symptoms.

Stress regulation in multiple sclerosis: current issues and concepts.

Since its first description by Charcot, psychological stress has been considered a triggering factor for exacerbations in multiple sclerosis, but until recently the clinical evidence for a causal relation was weak. Over the past years, a growing number of studies have started to elucidate this association and highlight potential mechanisms, including brain-immune communication. On 5 June 2005, a panel of international researchers discussed the current evidence. This article summarizes the observational, animal experimental, as well as human experimental findings on stress regulation in MS, as well as studies on the functioning of the major stress response systems, ie, the hypothalamo-pituitary-adrenal (HPA) axis and the autonomous nervous system (ANS) in MS. Consensus statements from the group to these aspects are given. Research objectives and strategies are delineated, as well as clinical implications.

Screening for depression among patients with multiple sclerosis: two questions may be enough.

BACKGROUND: Depression among patients with multiple sclerosis (MS) is common and has a significant impact on quality of life. As many as two-thirds of depressed MS patients receive no treatment for their depression. While guidelines for depression management suggest screening, the only validated screening tools are questionnaires, which have not been widely implemented in practice. This is the first study on the effectiveness of using two questions assessing mood and anhedonia (loss of interest or pleasure) in screening for major depressive disorder (MDD) in MS. METHODS: MS patients under the care of neurologists were recruited from a large health maintenance organization (HMO). The MDD module of the Structured Clinical Interview for the DSM-IV and screening questions was administered. RESULTS: Of the 260 participants, 26% met the criteria for MDD. Among patients with MDD, 67% received no anti-depressant medication. The MDD screen identified 99% (95% CI: 91-100%) of cases. DISCUSSION: A brief, two question screen is reliable in identifying MS patients with MDD. This suggests that asking these two brief questions could identify almost all MS patients meeting MDD criteria, with minimal numbers of false positives.

The relationship among depression, subjective cognitive impairment, and neuropsychological performance in multiple sclerosis.

The aim of this study was to examine, within the context of a treatment study, the relative contributions of depression and neuropsychological performance on patient ratings of cognitive functioning in a cohort of 58 moderately-depressed multiple sclerosis (MS) patients. All participants were randomized to one of three 16-week conventional treatments for depression. Assessments were conducted pre- and post-treatment using: (1) Cognitive Function subscale of the Multiple Sclerosis Quality of Life-54 (MSQOL-54) to evaluate subjective cognitive impairment (SC), (2) Beck Depression Inventory (BDI), and (3) a neuropsychological index score (NP). Prior to treatment, 8% of the variance in SC was explained by NP, whereas 14% of the variance was explained by BDI, above and beyond NP. At post-treatment, patients were classified as 'responders' (BDI < 11) and 'non-responders' (BDI > or = 11). Among those participants classified as 'responders', NP accounted for 39% of the variance in SC, and BDI did not significantly predict SC. The results of this study suggest that depression may influence subjective reports of cognitive impairment, but these reports may not be reliably related to objective neuropsychological performance. Furthermore, patients may be more accurate reporters of their cognitive impairment after successful treatment for depression, suggesting that depression decreases the accuracy of patient reported cognitive impairment.

Treatment of depression for patients with multiple sclerosis in neurology clinics.

UNLABELLED: The objective of this study was to examine the adequacy of antidepressant pharmacotherapy in a sample of patients with multiple sclerosis (MS) treated by neurologists. METHODS: MS patients under the care of neurologists were recruited from a large health maintenance organization. Major depressive disorder (MDD) was diagnosed using a structured telephone interview. Antidepressant treatment data were obtained from the HMO pharmacy database. RESULTS: Study participants included 260 patients with MS treated by 35 neurologists. A total of 67 (25.8%) patients met the criteria for MDD. Among the patients with MDD, 65.6% received no antidepressant medication, 4.7% received subthreshold doses from their neurologists, 26.6% received doses at threshold, and 3.1% received doses exceeding threshold. DISCUSSION: Depression was undertreated by the neurologists treating this sample of patients with comorbid MS and MDD. Potential solutions are discussed.

The relationship between social support, depression and treatment for depression in people with multiple sclerosis.

BACKGROUND: Studies have been fairly consistent in finding a relationship between social support and depression. However, little is known about the relationship between depression and social support in the context of treatment for depression. This study examined the effects of treatment for depression on social support among patients with multiple sclerosis (MS). METHOD: Sixty-three moderately depressed MS patients received 16 weeks of cognitive behaviour therapy (CBT), supportive expressive group psychotherapy (SEGP) or sertraline. Depression was measured using the Beck Depression Inventory and social support was measured using Arizona Social Support Interview Schedule. RESULTS: Treatment for depression was associated with significant increases in perceived social support, utilized social support and satisfaction with support, as well as reduction in need for emotional support. There were no significant changes in structural support or need for physical support. There were also no differences in change in social support across treatments. All changes in social support were fully explained by depression. Improvements in utilized social support and satisfaction with social support were fully mediated by improvements in depression. Baseline depression predicted improvements in perceived support and need for emotional support. CONCLUSIONS: These findings suggest that improvements in social support among MS patients during treatment for depression can be explained by depression. However, different domains of social support may be differentially sensitive to changes in depression.

Peer support groups in multiple sclerosis: current effectiveness and future directions.

Peer support programs have become a common method of providing support for patients with chronic illness. Utilizing peers as resources has been proposed as an effective means for coping with a stressful life experience and for gaining support from others who share a common factor, although data are somewhat mixed on the efficacy of peer support. The aim of the present study was to evaluate the effectiveness of eight weeks of a standard form of peer support in improving quality of life and reducing depressive symptoms in 44 patients with multiple sclerosis (MS). One person from each of six groups participated in a training course in order to learn basic principles of peer support. Eight weekly sessions were held and patients completed self-administered questionnaires pre- and post-treatment assessing quality of life and depression. Results showed that support groups do not provide consistent improvement in quality of life or depression in patients with MS and suggest that patients who have better mental health functioning could be at risk for deterioration in support groups.

Treatment of depression is associated with suppression of nonspecific and antigen-specific T(H)1 responses in multiple sclerosis.

OBJECTIVE: To examine the relationship between depression, treatment of depression, and interferon gamma (IFN-gamma) production by peripheral blood mononuclear cells in patients with comorbid diagnoses of relapsing-remitting multiple sclerosis (MS) and major depressive disorder. DESIGN: A randomized comparative outcome trial of three 16-week treatments for depression. Assessments were conducted at baseline, week 8, and treatment cessation. SETTING: An academic outpatient treatment and clinical research center. PATIENTS: Fourteen patients who met the criteria for relapsing-remitting MS and major depressive disorder. INTERVENTIONS: Individual cognitive behavioral therapy, group psychotherapy, or sertraline therapy. MAIN OUTCOME MEASURES: Depression was assessed using the Beck Depression Inventory. Interferon gamma production by peripheral blood mononuclear cells was measured following stimulation with OKT3 or recombinant human myelin oligodendrocyte glycoprotein (MOG). Variability in immune assays was controlled using 8 nondepressed healthy subjects who were enrolled at times corresponding with the enrollment of MS patients. RESULTS: Results of the Beck Depression Inventory were significantly related to IFN-gamma production stimulated with OKT3 or MOG at baseline (P< or = .03 for all). Level of depression, OKT3-stimulated IFN-gamma production, and MOG-stimulated IFN-gamma production all declined significantly over the 16-week treatment period (P< or = .03 for all). Among controls, there were no significant changes over time in OKT3- or MOG-stimulated IFN-gamma, or in depression (P> or = .25 for all). CONCLUSIONS: These findings suggest that the production of the proinflammatory cytokine IFN-gamma by autoaggressive T cells in relapsing-remitting MS is related to depression and that treatment of depression may decrease IFN-gamma production. Thus, treatment of depression may provide a novel disease-modifying therapeutic strategy as well as a symptomatic treatment for patients with MS.

Injectable medication for the treatment of multiple sclerosis: the influence of self-efficacy expectations and injection anxiety on adherence and ability to self-inject.

The management of many chronic illnesses involves medications that must be injected on a frequent basis. With fewer support resources available, patients are increasingly being obliged to manage injectable medications themselves. Interferon beta-1a (IFNbeta-1a), recommended for the treatment of multiple sclerosis (MS), must be injected intramuscularly on a weekly basis. Patients are generally advised and taught to self-inject, if possible. This longitudinal study examined cognitive and affective contributions to the ability to self-inject and adherence to IFNbeta-1a over 6 months following initiation of medication. Participants were 101 patients with a relapsing form of MS. Injection self-efficacy expectations, injection anxiety, adherence expectations, method of injection administration, and 6-month adherence to IFNbeta-1a were fitted to a path analytic model. Pretreatment injection self-efficacy expectations were significantly related to 6-month adherence. This relation was mediated by the patient's ability to self-inject. Patients 'experienced level of injection anxiety was related to adherence but not to method of injection.