The therapeutic or prophylactic effect of exogenous melatonin against depression and depressive symptoms: A systematic review and meta-analysis

Circadian- and sleep disturbances may be central for understanding the pathophysiology and treatment of depression. The effect of melatonin on depression/depressive symptoms has been investigated previously. This systematic review assesses the current evidence of a therapeutic- and prophylactic effect of melatonin in adult patients against depression or depressive symptoms. A search was performed in The Cochrane Library, PubMed, EMBASE and PsycINFO for published trials on November 14th 2013. Inclusion criteria were English language, RCTs or crossover trials. Our outcome was measurement of depression/depressive symptoms with a validated clinician-administered or self-rating questionnaire. PRISMA recommendations were followed and the Cochrane risk-of-bias tool used. Ten studies in 486 patients were included in the final qualitative synthesis and four studies, 148 patients, were included in two meta-analyses. Melatonin doses varied from 0.5–6 mg daily and the length of follow-up varied from 2 weeks to 3.5 years. Three studies were done on patients without depression at inclusion, two studies in patients with depression and five studies included a mixture. Six studies showed an improvement in depression scores in both the melatonin and placebo groups but there was no significant difference. One study showed a significant prophylactic effect and another found a significant treatment effect on depression with melatonin compared to placebo. The two meta-analyses did not show any significant effect of melatonin. No serious adverse events were reported. Although some studies were positive, there was no clear evidence of a therapeutic- or prophylactic effect of melatonin against depression or depressive symptoms.     

Pseudoephedrine and circadian rhythm interaction on neuromuscular performance

This study analyzed the effects of pseudoephedrine (PSE) provided at different time of day on neuromuscular performance, side effects, and violation of the current doping cut‐off threshold [World Anti‐Doping Agency (WADA)]. Nine resistance‐trained males carried out bench press and full squat exercises against four incremental loads (25%, 50%, 75%, and 90% one repetition maximum [1RM]), in a randomized, double‐blind, cross‐over design. Participants ingested either 180 mg of PSE (supra‐therapeutic dose) or placebo in the morning (7:00 h; AM_PLAC and AM_PSE) and in the afternoon (17:00 h; PM_PLAC and PM_PSE). PSE enhanced muscle contraction velocity against 25% and 50% 1RM loads, only when it was ingested in the mornings, and only in the full squat exercise (4.4–8.7%; P < 0.05). PSE ingestion raised urine and plasma PSE concentrations (P < 0.05) regardless of time of day; however, cathine only increased in the urine samples. PSE ingestion resulted in positive tests occurring in 11% of samples, and it rose some adverse side effects such us tachycardia and heart palpitations. Ingestion of a single dose of 180 mg of PSE results in enhanced lower body muscle contraction velocity against low and moderate loads only in the mornings. These mild performance improvements are accompanied by undesirable side effects and an 11% risk of surpassing the doping threshold.     

The influence of shift work on cognitive functions and oxidative stress

Shift work influences health, performance, activity, and social relationships, and it causes impairment in cognitive functions. In this study, we investigated the effects of shift work on participants' cognitive functions in terms of memory, attention, and learning, and we measured the effects on oxidative stress. Additionally, we investigated whether there were significant relationships between cognitive functions and whole blood oxidant/antioxidant status of participants. A total of 90 health care workers participated in the study, of whom 45 subjects were night-shift workers. Neuropsychological tests were administered to the participants to assess cognitive function, and blood samples were taken to detect total antioxidant capacity and total oxidant status at 08:00. Differences in anxiety, depression, and chronotype characteristics between shift work groups were not significant. Shift workers achieved significantly lower scores on verbal memory, attention–concentration, and the digit span forward sub-scales of the Wechsler Memory Scale-Revised (WMS-R), as well as on the immediate memory and total learning sub-scales of the Auditory Verbal Learning Test (AVLT). Oxidative stress parameters were significantly associated with some types of cognitive function, including attention–concentration, recognition, and long-term memory. These findings suggest that night shift work may result in significantly poorer cognitive performance, particularly working memory.     

Changes in ischemic stroke occurrence following daylight saving time transitions

BackgroundCircadian rhythm disruption has been associated with increased risk of ischemic stroke (IS). Daylight saving time (DST) transitions disrupt circadian rhythms and shifts the pattern of diurnal variation in stroke onset, but effects on the incidence of IS are unknown.MethodsEffects of 2004–2013 DST transitions on IS hospitalizations and in-hospital mortality were studied nationwide in Finland. Hospitalizations during the week following DST transition (study group, n = 3033) were compared to expected hospitalizations (control group, n = 11,801), calculated as the mean occurrence during two weeks prior to and two weeks after the index week.ResultsHospitalizations for IS increased during the first two days (Relative Risk 1.08; CI 1.01–1.15, P = 0.020) after transition, but difference was diluted when observing the whole week (RR 1.03; 0.99–1.06; P = 0.069). Weekday-specific increase was observed on the second day (Monday; RR 1.09; CI 1.00–1.90; P = 0.023) and fifth day (Thursday; RR 1.11; CI 1.01–1.21; P = 0.016) after transition. Women were more susceptible than men to temporal changes during the week after DST transitions. Advanced age (>65 years) (RR 1.20; CI 1.04–1.38; P = 0.020) was associated with increased risk during the first two days, and malignancy (RR 1.25; CI 1.00–1.56; P = 0.047) during the week after DST transition.ConclusionsDST transitions appear to be associated with an increase in IS hospitalizations during the first two days after transitions but not during the entire following week. Susceptibility to effects of DST transitions on occurrence of ischemic stroke may be modulated by gender, age and malignant comorbidities.     

Seasonal variation in paroxysmal atrial fibrillation documented by 24-hour Holter electrocardiogram

BACKGROUND: The incidence of various cardiovascular diseases is known to exhibit seasonal variations, but seasonal patterns of paroxysmal atrial fibrillation (AF) have not been well characterized. OBJECTIVE: The objective of this study was to determine whether seasonal variation affects the incidence of paroxysmal AF and whether this pattern is affected by patient age. METHODS: We identified 258 paroxysmal AF episodes in 237 patients (age 65 +/- 14 years, mean +/- standard deviation; age range 16-95 years) among 12,390 consecutive 24-hour Holter electrocardiogram recordings obtained from 2001 to 2005 at our institute. Seasonal variations were analyzed by both month and by season. The relative risk (RR) of AF for each period was determined as being high or low in relation to the overall mean incidence. The association among clinical covariates and risk of paroxysmal AF was tested by logistic regression analysis. RESULTS: The incidence of paroxysmal AF was highest in September (RR = 1.40, 95% confidence interval [CI] 1.36-1.44) and lowest in June (RR = 0.52, 95% CI 0.50-0.54), with an RR difference of 63% (P < .001) among all patients. Patients aged > or =65 years demonstrated a peak incidence in September (RR = 1.46, 95% CI 1.41-1.51) and a minimum in June (RR = 0.55, 95% CI 0.52-0.58), while those aged <65 years showed a peak incidence in December (RR = 1.33, 95% CI 1.27-1.39) and a minimum in June (RR = 0.49, 95% CI 0.45-0.53). The incidence of paroxysmal AF also showed an autumn peak (RR = 1.21, 95% CI 1.16-1.27) and a summer minimum (RR = 0.66, 95% CI 0.62-0.70), with an RR difference of 53% (P < .001) among all patients. This seasonal variation in paroxysmal AF did not differ between patients of different age ranges. Clinical covariates including underlying disease or medications did not influence the monthly or seasonal variation in paroxysmal AF. There was a significant inverse relationship between the incidence of paroxysmal AF and the length of daylight in patients aged <65 years (r = -0.57, P < .05). CONCLUSION: There was a significant seasonal variation in paroxysmal AF, with maximum and minimum incidences in autumn and summer, respectively, and this pattern was not age dependent.     

Modulation of vertebral and tibial growth by compression loading: diurnal versus full-time loading.

PURPOSE: This study was designed to determine whether the amount of endochondral growth response to mechanical compression and the underlying growth mechanism differed with night-time or day-time loading, relative to full-time loading. METHODS: Mechanical compression (nominally 0.1 MPa stress) was applied across tibial and tail vertebral growth plates of growing Sprague-Dawley rats. Four groups of animals (five per group) were used: 24/24 h (full-time loading); 12/24 h (day-loading); 12/24 h (night-loading); and 0/24 h (sham instrumented). Contralateral tibiae and adjacent vertebrae served as within-animal controls. The animals were euthanized after eight days. Growth plates were processed for quantitative histology to measure 24-h growth, total and BrdU-positive proliferative zone chondrocyte counts, and hypertrophic chondrocytic enlargement in the growth direction. RESULTS: Growth as a percentage of within-animal control averaged 82% (full-time); 93% (day-loading); 90% (night-loading); 100% (sham) for vertebrae. For proximal tibiae it averaged 70% (full-time); 84% (day-loading); 86% (night-loading); 89% (sham). Reduced amount of hypertrophic chondrocytic enlargement explained about half of this effect in full-time loaded growth plates, but was not significantly altered in half-time loaded growth plates. The remaining variation in growth was apparently explained by reduced total numbers of proliferative zone chondrocytes. These findings indicate that sustained compression loading suppressed growth more than intermittent loading at both anatomical locations.     

Clinical uses of ambulatory blood pressure monitoring

Traditional office measurements of blood pressure are commonly used to initiate and monitor therapy for hypertension, but these measurements are limited in their ability to provide information from the patient's normal work or play environment and do not include data from the overnight period when the patient is asleep. Thus, much potentially important information is lost. The ambulatory blood pressure monitor offers the attractive advantage of providing multiple blood pressure measurements from a subject's normal environment during his normal activities, thereby revealing important patterns of blood pressure in health and in illness. Further, the results of ambulatory monitoring have an excellent correlation with end-organ damage and these data can be obtained in a very short time period. This review will discuss the chronobiology of blood pressure, the clinical uses of the ambulatory blood pressure monitor in health and in disease, including the patterns of blood pressure identified, correlation with end-organ damage and its uses in clinical trials of antihypertensive medications; the experience in children with this technology will also be discussed.     

Temporal aspects of glucocorticoid action and clinical implications

Summary Administration of glucocorticoids is effective and necessary in various diseases, but the appearance of side effects may compromise its results. Timing as well as dosing designed to obtain, for the highest number of patients, maximal beneficial effects with minimal undesired effects, is particularly pertinent to long-term corticosteroid therapy, in view of the rhythms exhibited by the endogenous secretion of adrenal cortical and coordinating hormones, primarily ACTH. In experimental animals, properly-timed circadian treatment can be preferred to alternate-day treatment for avoiding certain side effects. To secure the desired effect each day rather than only on alternate days, a chronobiologically correct corticosteroid therapy seeks the best compromise between timing for most of the desired and least of the undesired effects. This was the aim in the design of a chronopluricorticoid drug, with the time specification on its label. The clinical use of this preparation allowed the inferential statistical demonstration of a rhythmic circadian organization maintained during therapy, while the pharmacological results gained were similar to those obtained by the conventional administration of larger doses of corticoids. Contribution invited and delivered by the Senior Author at a Symposium coorganized by the American Society of Toxicology and the Society for Experimental Pharmacology and Therapeutics, held in Louisville, Kentucky, USA, on August 15–19, 1982.