Salivary Cortisol Awakening Response as a Predictor for Depression Severity in Adult Patients with a Major Depressive Episode Performing a Daily Exercise Program.

INTRODUCTION: The hypothalamic-pituitary-adrenal axis function in depression has been the subject of considerable interest, and its function has been tested with a variety of methods. We investigated associations between saliva cortisol at awakening and the 24-h urine cortisol output, both measured at study baseline, with endpoint depression scores. METHODS: Patients were admitted to a psychiatric inpatient ward with a major depressive episode and were started on fixed duloxetine treatment. They delivered saliva samples at awakening and 15, 30, and 60 min post-awakening and sampled urine for 24 h. Subsequently, they started a daily exercise program maintained for a 9-week period. Clinician-rated depression severity was blindly assessed with the Hamilton Depression Rating 6-item subscale (HAM-D6). The cortisol awakening response was quantified by the area under the curve with respect to the ground (AUCG) and with respect to the rise (AUCI) using saliva cortisol levels in the 1-h period after awakening. Analysis of expected associations between depression severity, AUCG, AUCI, exercise, and 24-h cortisol output was performed in a general linear model. RESULTS: In all, 35 participants delivered saliva or 24-h urine samples. The mean age was 49.0 years (SD = 11.0) with 48.6% females with a mean baseline HAM-D6 score of 12.2 (SD = 2.3). In a statistical model investigating the association between HAM-D6 at week 9 as a dependent variable and AUCI, concurrent HAM-D6, gender, smoking, and exercise volume as covariates, we found a significant effect of AUCI, concurrent HAM-D6, and exercise. The following statistics were found: AUCI (regression coefficient 0.008; F value = 9.1; p = 0.007), concurrent HAM-D6 (regression coefficient 0.70; F value = 8.0; p = 0.01), and exercise (regression coefficient -0.005; F value = 5.7; p = 0.03). The model had an R2 of 0.43. The association between HAM-D6 endpoint scores and the AUCI showed that higher AUCI values predicted higher HAM-D6 endpoint values. The association between HAM-D6 endpoint scores and the exercise level showed that a high exercise level was associated with lower HAM-D6 endpoint values. CONCLUSION: The results thus showed that high AUCI values predicted less improvement of depression and high exercise levels predicted more improvement of depression. These findings need to be confirmed in larger samples to test if more covariates can improve prediction of depression severity.

The day-to-day acute effect of wake therapy in patients with major depression using the HAM-D6 as primary outcome measure: results from a randomised controlled trial.

BACKGROUND: This paper reports day-to-day data for from a one-week intervention phase, part of a 9-weeks randomised parallel study with patient having major depression (data from weekly visits have been reported). Wake therapy (sleep deprivation) has an established antidepressant effect with onset of action within hours. Deterioration on the following night's sleep is, however, common, and we used daily light therapy and sleep time stabilisation as a preventive measure. In particular, we evaluated the day-to-day acute effect of and tolerance to sleep deprivation and examined predictors of response. METHODS: Patients were assessed at psychiatric inpatient wards. In the wake group (n = 36), patients did three wake therapies in combination with light therapy each morning together with sleep time stabilisation. In the exercise group (n = 38), patients did daily exercise. Hamilton subscale scores were primary outcome (not blinded), secondary outcome was self-assessment data from the Preskorn scale and sleep. RESULTS: Patients in the wake therapy group had an immediate, large, stable, and statistically significant better antidepressant effect than patients in the exercise group with response rates at day5 of 75.0%/25.1% and remission rates of 58.6%/6.0%, respectively. The response and remission rates were diminished at day8 with response rates of 41.9%/10.1% and remission rates of 19.4%/4.7%, respectively. Patients and ward personnel found the method applicable with few side effects. Positive diurnal variation (mood better in the evening) predicted a larger response to wake therapy. In the wake group napping on days after intervention predicted greater deterioration on day8. CONCLUSIONS: The intervention induced an acute antidepressant response without relapse between wake nights but with a diminishing effect after intervention. Development is still needed to secure maintenance of response. Avoiding napping in the days after wake therapy is important. TRIAL REGISTRATION: Clinical trials.gov NCT00149110.

A 9-week randomized trial comparing a chronotherapeutic intervention (wake and light therapy) to exercise in major depressive disorder patients treated with duloxetine.

OBJECTIVE: The onset of action of antidepressants often takes 4 to 6 weeks. The antidepressant effect of wake therapy (sleep deprivation) comes within hours but carries a risk of relapse. The objective of this study was to investigate whether a new chronotherapeutic intervention combining wake therapy with bright light therapy and sleep time stabilization could induce a rapid and sustained augmentation of response and remission in major depressive disorder. METHOD: 75 adult patients with DSM-IV major depressive disorder, recruited from psychiatric wards, psychiatric specialist practices, or general medical practices between September 2005 and August 2008, were randomly assigned to a 9-week chronotherapeutic intervention using wake therapy, bright light therapy, and sleep time stabilization (n = 37) or a 9-week intervention using daily exercise (n = 38). Patients were evaluated at a psychiatric research unit. The study period had a 1-week run-in phase in which all patients began treatment with duloxetine. This phase was followed by a 1-week intervention phase in which patients in the wake therapy group did 3 wake therapies in combination with daily morning light therapy and sleep time stabilization and patients in the exercise group began daily exercise. This phase was followed by a 7-week continuation phase with daily light therapy and sleep time stabilization or daily exercise. The 17-item Hamilton Depression Rating Scale was the primary outcome measure, and the assessors were blinded to patients' treatment allocation. RESULTS: Both groups responded well to treatment. Patients in the wake therapy group did, however, have immediate and clinically significantly better response and remission compared to the exercise group. Thus, immediately after the intervention phase (week 2), response was obtained in 41.4% of wake therapy patients versus 12.8% of exercise patients (odds ratio [OR] = 4.8; 95% CI, 1.7-13.4; P = .003), and remission was obtained in 23.9% of wake therapy patients versus 5.4% of exercise patients (OR = 5.5; 95% CI, 1.7-17.8; P = .004). These superior response and remission rates obtained by the wake therapy patients were sustained for the whole study period. At week 9, response was obtained in 71.4% of wake therapy patients versus 47.3% of exercise patients (OR = 2.8; 95% CI, 1.1-7.3; P = .04), and remission was obtained in 45.6% of wake therapy patients and 23.1% of exercise patients (OR = 2.8; 95% CI, 1.1-7.3, P = .04). All treatment elements were well tolerated. CONCLUSIONS: Patients treated with wake therapy in combination with bright light therapy and sleep time stabilization had an augmented and sustained antidepressant response and remission compared to patients treated with exercise, who also had a clinically relevant antidepressant response. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00149110.