Adjunct modafinil for the short-term treatment of fatigue and sleepiness in patients with major depressive disorder: a preliminary double-blind, placebo-controlled study

BACKGROUND: Fatigue and sleepiness are primary symptoms of depression that may not resolve with antidepressant therapy. Modafinil is a novel agent that has been shown to improve wakefulness and lessen fatigue in a variety of conditions. In this study, we examined the utility of modafinil as an adjunct therapy to treat fatigue and sleepiness in patients with major depression who are partial responders to antidepressants. METHOD: Patients with partial response to anti-depressant therapy given for at least a 6-week period for a current major depressive episode (DSM-IV criteria) were enrolled in this 6-week, randomized, double-blind, placebo-controlled, parallel-group, multicenter study. Patients received once-daily doses (100-400 mg) of modafinil or matching placebo as adjunct treatment to ongoing antidepressant therapy. The effects of modafinil were evaluated using the Hamilton Rating Scale for Depression (HAM-D), the Fatigue Severity Scale (FSS), the Epworth Sleepiness Scale (ESS), the Clinical Global Impression of Change (CGI-C), and the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). Adverse events were monitored throughout the study. RESULTS: One hundred thirty-six patients were randomized to treatment, with 118 patients (87%) completing the study. Most patients (82%) were fatigued, and one half of patients (51%) were sleepy. Modafinil rapidly improved fatigue and daytime wakefulness, with significantly greater mean improvements from baseline than placebo in fatigue (FSS) scores at week 2 (p < .05) and sleepiness (ESS) scores at week 1 (p < .01); the differences between modafinil and placebo at week 6 were not statistically significant. Assessment of the augmentation effects of modafinil (HAM-D, CGI-C, and SF-36) did not significantly distinguish modafinil from placebo. Modafinil was well tolerated in combination with a variety of antidepressants. CONCLUSION: Modafinil may be a useful adjunct therapy for the short-term management of residual fatigue and sleepiness in patients who are partial responders to antidepressant therapy.     

Do family physicians and internists differ in knowledge,attitudes, and self-reported approaches for depression?

OBJECTIVES: The purpose of this investigation was to assess the relationship of primary care specialty training with self-assessed skill, knowledge, attitudes, and behavior toward depression recognition and management. METHOD: A baseline self-report questionnaire was administered to 184 internists and 138 family physicians participating in a multisite depression intervention study. RESULTS: There were no marked differences in knowledge of internists and family physicians regarding depression, in attitudes about the effectiveness of specific therapies, or in barriers to providing optimum treatment for depression. However, compared to internists, family physicians rated themselves as more skilled in the management of depression. When considering management of patients with moderate to severe depression, family physicians were more likely to report that they prescribed a selective serotonin-reuptake inhibitor (relative odds (RO) = 3.51, 95 percent Confidence interval (CI) [2.19, 5.60] and to personally counsel patients (RO = 1.97, 95 percent CI [1.16, 3.38]) more than half the patients, but were less likely to refer to a specialist in mental health (RO = 0.52, 95 percent CI [0.33, 0.82]) than were internists. Additional potentially influential characteristics did not wholly account for the reported differences in practice according to specialty. Physicians of both specialties expressed considerable uncertainty in their knowledge of psychotherapy and in their evaluation of the effectiveness of other strategies for the prevention of recurrence of depression. CONCLUSION: Strategies to improve mental health care should account for the orientation of primary care physicians to mental health issues.     

Effect of Hypericum perforatum (St John's wort) in major depressive disorder: a randomized controlled trial

Context  Extracts of Hypericum perforatum (St John's wort) are widely used for the treatment of depression of varying severity. Their efficacy in major depressive disorder, however, has not been conclusively demonstrated. Objective  To test the efficacy and safety of a well-characterized H perforatum extract (LI-160) in major depressive disorder. Design and Setting  Double-blind, randomized, placebo-controlled trial conducted in 12 academic and community psychiatric research clinics in the United States. Participants  Adult outpatients (n = 340) recruited between December 1998 and June 2000 with major depression and a baseline total score on the Hamilton Depression Scale (HAM-D) of at least 20. Interventions  Patients were randomly assigned to receive H perforatum, placebo, or sertraline (as an active comparator) for 8 weeks. Based on clinical response, the daily dose of H perforatum could range from 900 to 1500 mg and that of sertraline from 50 to 100 mg. Responders at week 8 could continue blinded treatment for another 18 weeks. Main Outcome Measures  Change in the HAM-D total score from baseline to 8 weeks; rates of full response, determined by the HAM-D and Clinical Global Impressions (CGI) scores. Results  On the 2 primary outcome measures, neither sertraline nor H perforatum was significantly different from placebo. The random regression parameter estimate for mean (SE) change in HAM-D total score from baseline to week 8 (with a greater decline indicating more improvement) was –9.20 (0.67) (95% confidence interval [CI], –10.51 to –7.89) for placebo vs –8.68 (0.68) (95% CI, –10.01 to –7.35) for H perforatum (P = .59) and –10.53 (0.72) (95% CI, –11.94 to –9.12) for sertraline (P = .18). Full response occurred in 31.9% of the placebo-treated patients vs 23.9% of the H perforatum–treated patients (P = .21) and 24.8% of sertraline-treated patients (P = .26). Sertraline was better than placebo on the CGI improvement scale (P = .02), which was a secondary measure in this study. Adverse-effect profiles for H perforatum and sertraline differed relative to placebo. Conclusion  This study fails to support the efficacy of H perforatum in moderately severe major depression. The result may be due to low assay sensitivity of the trial, but the complete absence of trends suggestive of efficacy for H perforatum is noteworthy.      

Antidepressant pharmacotherapy in the treatment of depression in the very old: a randomized, placebo-controlled trial

OBJECTIVE: This study determined the efficacy of antidepressant medication for the treatment of depression in the "old-old." METHOD: This randomized 8-week medication trial compared citalopram, 10-40 mg/day, to placebo in the treatment of patients 75 and older with unipolar depression. RESULTS: A total of 174 patients who were 58% women with a mean age of 79.6 years (SD=4.4) and a mean baseline Hamilton Depression Rating Scale score of 24.3 (SD=4.1) were randomly assigned to treatment at 15 sites. There was a main effect for site but not for treatment condition. The remission rate, defined as a final Hamilton depression scale score <10, was 35% for the citalopram and 33% for the placebo groups. However, patients with severe depression (baseline Hamilton depression scale score >24) tended to have a higher remission rate with medication than with placebo (35% versus 19%). CONCLUSIONS: In the oldest group of community-dwelling patients to be studied to date, medication was not more effective than placebo for the treatment of depression. However, given the considerable psychosocial support received by all patients, the placebo condition represents more than the ingestion of an inactive pill. Across sites, there was considerable range in response to medication, 18% to 82%, and to placebo, 16% to 80%.     

Community-based treatment of late life depression an expert panel-informed literature review

OBJECTIVES: To present findings from an expert panel-informed literature review on community-based treatment of late-life depression. METHODS: A systematic literature review was conducted to appraise publications on community-based interventions for depression in older adults. The search was conducted between March and October 2005. An expert panel of mental health, aging, health services, and epidemiology researchers guided the review and voted on quality and effectiveness of these interventions. RESULTS: A total of 3,543 articles were found with publication dates from 1967 to October 2005; of these, 116 were eligible for inclusion. Adequate data existed to determine effectiveness for the following interventions: depression care management, group and individual psychotherapy for depression, psychotherapy targeting mental health, psychotherapy for caregivers, education and skills training (to manage health problems besides depression; and for caregivers), geriatric health evaluation and management, exercise, and physical rehabilitation and occupational therapy. After reviewing the data, panelists rated the depression care management interventions as effective. Education and skills training, geriatric health evaluation and management, and physical rehabilitation and occupational therapy received ineffective ratings. Other interventions received mixed effectiveness ratings. Insufficient data availability and poor study quality prevented the panelists from rating several reviewed interventions. CONCLUSIONS: While several well-described interventions were found to treat depression effectively in community-dwelling older adults, significant gaps still exist. Interventions that did not target depression specifically may be of benefit to older adults, but they should not be presumed to treat depression by themselves. Treating depressed elders may require a multifaceted approach to ensure effectiveness. More research in this area is needed.     

Measurement of cytokines in sweat patches and plasma in healthy women: validation in a controlled study

Cytokines have been detected by ELISA in a variety of body fluids. Recycling immunoaffinity chromatography (RIC) coupled with laser-induced fluorescence detection is a highly sensitive and specific method, which allows simultaneous measurements of many analytes in small volumes of biological fluids. This method has been applied to plasma, cervical secretions and other body fluids, but has not previously been applied to sweat. The aim of this study was to validate the RIC methodology in sweat for measurements of IL-1alpha, IL-1beta, IL-6, TNF-alpha, IL-8 and TGF-beta. Two sweat patches were applied for 24 h on the torso, and blood was collected at one time point during this period in nine healthy women. Cytokines were measured in paired samples of plasma and sweat. Cytokines were detected in sweat in similar concentrations to plasma. Linear regression analysis confirmed that sweat levels of these cytokines accounted for a large percentages of variance in plasma levels: IL-1alpha (R2 = 0.70, p = 0.005), IL-1beta (R2 = 0.79, p = 0.003), IL-6 (R2 = 0.52, p = 0.03), TNF-alpha (R2 = 0.95, p < 0.0001), IL-8 (R2 = 0.81, p = 0.001) and TGF-beta (R2 = 0.94, p = 0.0003). These findings indicate that cytokine levels measured in sweat are informative of circulating levels and that sweat patches combined with RIC represents a viable non-invasive method to measure cytokines in ambulatory settings over time. This method is unobtrusive and requires minimal active compliance on the part of the subjects being studied, without pain or stress. This approach can open a new generation of studies to address the effects of environmental factors on immune responses in a wide range of different settings.     

Recommendations for treating depression in community-based older adults

OBJECTIVE: To present recommendations for community-based treatment of late-life depression to public health and aging networks. METHODS: An expert panel of mental health and public health researchers and community-based practitioners in aging was convened in April 2006 to form consensus-based recommendations. When making recommendations, panelists considered feasibility and appropriateness for community-based delivery, as well as strength of evidence on program effectiveness from a systematic literature review of articles published through 2005. RESULTS: The expert panel strongly recommended depression care management-modeled interventions delivered at home or at primary care clinics. The panel recommended individual cognitive behavioral therapy. Interventions not recommended as primary treatments for late-life depression included education and skills training, comprehensive geriatric health evaluation programs, exercise, and physical rehabilitation/occupational therapy. There was insufficient evidence for making recommendations for several intervention categories, including group psychotherapy and psychotherapies other than cognitive behavioral therapy. CONCLUSIONS: This interdisciplinary expert panel determined that recommended interventions should be disseminated throughout the public health and aging networks, while acknowledging the challenges and obstacles involved. Interventions that were not recommended or had insufficient evidence often did not treat depression primarily and/or did not include a clinically depressed sample while attempting to establish efficacy. These interventions may provide other benefits, but should not be presumed to effectively treat depression by themselves. Panelists also identified primary prevention of depression as a much under-studied area. These findings should aid individual clinicians as well as public health decision makers in the delivery of population-based mental health services in diverse community settings.     

Improving the Diagnostic Accuracy of Depression in Older Persons: The Depression in the Aged Female National Evaluation Cluster Randomized Trial

OBJECTIVES: To evaluate whether a training intervention can improve the ability of geriatricians to recognize depression in older persons.
DESIGN: Multicenter, cluster randomized clinical trial.
SETTING: Fourteen geriatric outpatient clinics in Italy, each representing the unit of randomization.
PARTICIPANTS: After training, a total of 1,914 outpatients aged 65 years and older in both arms, not on antidepressant at entry, were blindly evaluated by the clinic geriatrician, in charge of routine clinical management, and by a field researcher, who formally diagnosed depression by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), taken as the criterion standard.
INTERVENTION: After randomization, geriatricians belonging to the intervention arm were assigned to receive a residential 3-day educational program on depression. Those in the control arm received a generic course on disease management in elderly people.
MEASUREMENTS: Sensitivity and specificity of the diagnosis of depression made by geriatricians, compared with the DSM-IV diagnosis.
RESULTS: Sensitivity and specificity were significantly higher in trained than in untrained geriatricians (49 vs 35% and 91 vs 88%, respectively; P =.002 in marginal regression models). Effectiveness of training was confirmed, adjusting for age, sex, and cognitive performance ( P =.02).
CONCLUSION: The ability of geriatricians to diagnose depression in older outpatients can be improved with a specific training intervention. Improvement of diagnostic performance might translate into more-appropriate clinical management.     

Prediction of recurrence in recurrent depression and the influence of consecutive episodes on vulnerability for depression: a 2-year prospective study

OBJECTIVE: Depression is a recurring disease. Identifying risk factors for recurrence is essential. The purpose of this study was to identify factors predictive of recurrence and to examine whether previous depressive episodes influence vulnerability for subsequent depression in a sample of remitted recurrently depressed patients. METHOD: Recurrence was examined prospectively using the Structured Clinical Interview for DSM-IV Axis I Disorders in 172 euthymic patients with recurrent depression (DSM-IV) recruited from February 2000 through September 2000. Illness-related characteristics, coping, and stress (life events and daily hassles) were examined as predictors. RESULTS: Risk factors for recurrence were a high number of previous episodes, more residual depressive symptomatology and psychopathology, and more daily hassles. Factors with both an increasing and decreasing pathogenic effect with increasing episode number were detected. CONCLUSION: We found some support for dynamic vulnerability models that posit a change of vulnerability with consecutive episodes. Preventive interventions should be considered in patients with multiple recurrences, focusing on residual symptomatology and specific coping styles.