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Light Treatment Effective for Nonseasonal Major Depressive Disorder

JAMA Psychiatry

 1 Expert Comment

TAKE-HOME MESSAGE

  • Adults with moderate to severe non-seasonal major depressive disorder (MDD) were randomized to receive light monotherapy, antidepressant monotherapy (fluoxetine hydrochloride), combination light and antidepressant, or placebo for 8 weeks. Light monotherapy and combination therapy were both significantly better than placebo for response and remission, but fluoxetine was not superior to placebo. The number needed to treat with combination therapy for a response was 2.4 and for remission was 3.5. There were no adverse effects reported in any of the groups.
  • Light therapy, both alone and combined with fluoxetine, was safe and effective for the treatment of non-seasonal MDD, with combination therapy being the most effective.

Primary Care

Written by
David Rakel MD, FAAFP

Turn towards the light

As we approach winter, the days get shorter and we find ourselves going to work and coming home in the dark. Research supports the use of therapeutic light for seasonal affective disorder (SAD), but what about using it to treat major depression when it is not winter? This study wanted to see if light therapy is beneficial in any season.

This study was a double-dummy design, which means that each participant in all four groups received both a pill (fluoxetine or placebo) and sat in front of a box (light or a negative ion generator). This controls for the nonspecific variables that can influence outcomes if everyone does not go through the procedure of taking a pill or sitting in front of a box.

The four groups consisted of placebo (placebo pill + ion generator), fluoxetine (med + ion generator), light (light box + placebo), and combination (fluoxetine + light) for 8 weeks. The 121 participants were randomized with only about 30 in each group, which was a limitation of this study. The light therapy consisted of 30 minutes daily between 7 and 8 AM, sitting within 14 inches (35.56 cm) inches of the box. The fluoxetine was dosed at 20 mg daily.

The light therapy was more effective than fluoxetine, and combining both was best for inducing remission, with a NNT of just 3.5.

Light Therapy for Depression

Light therapy is thought to benefit depression by resynchronizing circadian rhythms and improving neurotransmitter dysfunction, but the underlying mechanism still remains entirely unclear.

I like it when there is good evidence for therapies that are effective while presenting low cost and minimal to no harm. The individuals in this study were instructed to avoid spending time outdoors, so natural light therapy did not interfere with the results. Ideally, this is the ultimate light therapy. Spending time in the sun is likely better than fluoxetine, and, when used with fluoxetine, may have added benefit in treating major depression no matter the season.

Abstract

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IMPORTANCE

Bright light therapy is an evidence-based treatment for seasonal depression, but there is limited evidence for its efficacy in nonseasonal major depressive disorder (MDD).

OBJECTIVE

To determine the efficacy of light treatment, in monotherapy and in combination with fluoxetine hydrochloride, compared with a sham-placebo condition in adults with nonseasonal MDD.

DESIGN, SETTING, AND PARTICIPANTS

Randomized, double-blind, placebo- and sham-controlled, 8-week trial in adults (aged 19-60 years) with MDD of at least moderate severity in outpatient psychiatry clinics in academic medical centers. Data were collected from October 7, 2009, to March 11, 2014. Analysis was based on modified intent to treat (randomized patients with ≥1 follow-up rating).

INTERVENTIONS

Patients were randomly assigned to (1) light monotherapy (active 10 000-lux fluorescent white light box for 30 min/d in the early morning plus placebo pill); (2) antidepressant monotherapy (inactive negative ion generator for 30 min/d plus fluoxetine hydrochloride, 20 mg/d); (3) combination light and antidepressant; or (4) placebo (inactive negative ion generator plus placebo pill).

MAIN OUTCOMES AND MEASURES

Change score on the Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to the 8-week end point. Secondary outcomes included response (≥50% reduction in MADRS score) and remission (MADRS score ≤10 at end point).

RESULTS

A total of 122 patients were randomized (light monotherapy, 32; fluoxetine monotherapy, 31; combination therapy, 29; placebo, 30). The mean (SD) changes in MADRS score for the light, fluoxetine, combination, and placebo groups were 13.4 (7.5), 8.8 (9.9), 16.9 (9.2), and 6.5 (9.6), respectively. The combination (effect size [d] = 1.11; 95% CI, 0.54 to 1.64) and light monotherapy (d = 0.80; 95% CI, 0.28 to 1.31) were significantly superior to placebo in the MADRS change score, but fluoxetine monotherapy (d  = 0.24; 95% CI, −0.27 to 0.74) was not superior to placebo. For the respective placebo, fluoxetine, light, and combination groups at the end point, response was achieved by 10 (33.3%), 9 (29.0%), 16 (50.0%), and 22 (75.9%) and remission was achieved by 9 (30.0%), 6 (19.4%), 14 (43.8%), and 17 (58.6%). Combination therapy was superior to placebo in MADRS response (β = 1.70; df = 1; P = .005) and remission (β = 1.33; df = 1; P  = .02), with numbers needed to treat of 2.4 (95% CI, 1.6 to 5.8) and 3.5 (95% CI, 2.0 to 29.9), respectively. All treatments were generally well tolerated, with few significant differences in treatment-emergent adverse events.

CONCLUSIONS AND RELEVANCE

Bright light treatment, both as monotherapy and in combination with fluoxetine, was efficacious and well tolerated in the treatment of adults with nonseasonal MDD. The combination treatment had the most consistent effects.

 

Exercise Can Reduce Heart Failure Risk at Any Age

Starting to exercise later in life can still reduce risk of heart failure, and even modest increases in activity could provide some protection, researchers say. The study was presented earlier this month at the annual meeting of the American Heart Association, held from Nov. 7 to 11 in Orlando, Fla.

 

FRIDAY, Nov. 20, 2015 (HealthDay News) — Starting to exercise later in life can still reduce risk of heart failure, and even modest increases in activity could provide some protection, researchers say. The study was presented earlier this month at the annual meeting of the American Heart Association, held from Nov. 7 to 11 in Orlando, Fla.

Chiadi Ndumele, M.D., M.H.S., a preventive cardiologist and assistant professor of medicine at the Johns Hopkins University School of Medicine in Baltimore, and colleagues studied the exercise habits of about 11,000 American men and women in a 20-year government study on aging and heart disease. All were between the ages of 45 and 64. None had heart disease at the start of the study. Activity levels were assessed on two consecutive visits over six years.

The researchers found that, compared to those who were inactive at both visits, people who met or exceeded recommended physical activity levels of 150 minutes of moderate exercise or 75 minutes of vigorous exercise per week at both visits were 33 percent less likely to develop heart failure. Those who were consistently getting modest amounts of exercise — less than 149 minutes of moderate activity or less than 74 minutes of vigorous activity a week — had a 20 percent lower risk. But the researchers also found that inactive people who got moving to reach recommended physical activity levels at some point during the study reduced their risk of heart failure — by 22 percent. Inactive people who increased their activity levels to about 30 minutes of walking four times a week reduced their risk by 12 percent.

“Many people get discouraged if they don’t have the time or ability to exercise vigorously, but our findings demonstrate that every little bit of movement matters and that picking up exercise later in life is decidedly better than not moving at all,” first author Roberta Florido, M.D., a cardiology fellow at Hopkins, said in a university news release.

Press Release

Sweetened Beverage Consumption and Risk of Heart Failure

Heart (British Cardiac Society)

 

TAKE-HOME MESSAGE

  • The authors of this prospective, population-based cohort study assessed the association between consumption of sweetened beverages and risk of heart failure (HF) in men. Over a mean follow-up period of 11.7 years, drinking sweetened beverages was associated with increased risk of HF. Compared with men who did not consume sweetened beverages, men who consumed two or more servings per day had a significantly higher risk.
  • Consumption of sweetened beverages was associated with increased risk of HF. Additional prospective studies will be required.

Abstract

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OBJECTIVES

To investigate whether sweetened beverage consumption is associated with risk of heart failure (HF) in a large prospective population-based study of men.

METHODS AND RESULTS

A population-based cohort comprising 42 400 men, 45-79 years of age, was followed from 1998 through 2010. Sweetened beverage consumption was assessed by utilising a food frequency questionnaire. Incident events of HF were identified through linkage to the Swedish National Patient Register and the Cause of Death Register. Cox regression analyses were implemented to investigate the association between sweetened beverage consumption and HF. During a mean follow-up time of 11.7 years, a total of 4113 HF events were identified. We observed a positive association between sweetened beverage consumption and risk of HF after adjustment for other risk factors (p for trend <0.001). Men who consumed two or more servings of sweetened beverages per day had a statistically significant higher risk of developing HF (23%, 95% CI 1.12 to 1.35) compared to men who were non-consumers.

CONCLUSIONS

Our finding that sweetened beverage consumption is associated with higher risk of HF could have implications for HF prevention strategies. Additional prospective studies investigating the link between sweetened beverage consumption and HF are therefore needed.

Newborn Probiotic Use Tied to Lower Risk of Type 1 Diabetes

Adding probiotics to an infant’s feedings in the first month of life may reduce the risk of type 1 diabetes for those genetically predisposed to the disease, according to research published online Nov. 9 in JAMA Pediatrics.

THURSDAY, Nov. 12, 2015 (HealthDay News) — Adding probiotics to an infant’s feedings in the first month of life may reduce the risk of type 1 diabetes for those genetically predisposed to the disease, according to research published online Nov. 9 in JAMA Pediatrics.

Researchers looked at an ongoing prospective study from six medical centers — three in the United States and three in Europe. The final study sample included 7,473 children between 4 and 10 years old. Blood samples were taken every three months from age 3 months to 48 months to detect signs of type 1 diabetes. Samples were taken every six months after that. Parents completed questionnaires and food diaries to detail infant feeding and probiotic supplement use from birth to 3 months. Mothers provided information on their diets during pregnancy as well.

The researchers found that probiotic use in the first 27 days was linked to reduced odds of type 1 diabetes by 60 percent for children with the highest risk of developing the disease. These children had the DR3/4 genotype, the researchers said. Children without that genetic makeup didn’t benefit from the early probiotics. And no one seemed to benefit from later probiotic use.

“Early probiotic exposure during the first 27 days is associated with a decreased risk of type 1 diabetes among those who have the highest genetic risk of type 1 diabetes,” lead researcher Ulla Uusitalo, Ph.D., an associate professor in the department of pediatric epidemiology at the University of South Florida in Tampa, told HealthDay. However, Uusitalo noted that because of the study’s design, the researchers “cannot make a conclusion about causality.” But she stressed that because the association was so strong, these findings warrant further study.

Abstract
Full Text
Editorial

Curcumin Modulates Colonic Microbiota During Colitis and May Prevent Colon Cancer

Published in Gastroenterology

Journal Scan / Research · November 17, 2015

TAKE-HOME MESSAGE

  • In this study, wild-type or Il10 (a model for colorectal cancer associated with colitis) mice that received six injections of azoxymethane (or a negative control) were fed curcumin-supplemented or control food to investigate its effect on the microbiota. The diet with curcumin prolonged survival, lowered colon weight/length ratio, and completely eliminated tumors (at 0.5% curcumin).
  • The positive impact of curcumin on tumorigenesis was linked to the maintenance of a greater diversity in colonic microbiota.

Abstract

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BACKGROUND

Intestinal microbiota influences the progression of colitis-associated colorectal cancer. With diet being a key determinant of the gut microbial ecology, dietary interventions are an attractive avenue for the prevention of colitis-associated colorectal cancer. Curcumin is the most active constituent of the ground rhizome of the Curcuma longa plant, which has been demonstrated to have anti-inflammatory, antioxidative, and antiproliferative properties.

METHODS

Il10 mice on 129/SvEv background were used as a model of colitis-associated colorectal cancer. Starting at 10 weeks of age, wild-type or Il10 mice received 6 weekly intraperitoneal injections of azoxymethane (AOM) or phosphate-buffered saline (PBS) and were started on either a control or a curcumin-supplemented diet. Stools were collected every 4 weeks for microbial community analysis. Mice were killed at 30 weeks of age.

RESULTS

Curcumin-supplemented diet increased survival, decreased colon weight/length ratio, and, at 0.5%, entirely eliminated tumor burden. Although colonic histology indicated improvement with curcumin, no effects of mucosal immune responses have been observed in PBS/Il10 mice and limited effects were seen in AOM/Il10 mice. In wild-type and in Il10 mice, curcumin increased bacterial richness, prevented age-related decrease in alpha diversity, increased the relative abundance of Lactobacillales, and decreased Coriobacterales order. Taxonomic profile of AOM/Il10 mice receiving curcumin was more similar to those of wild-type mice than those fed control diet.

CONCLUSIONS

In AOM/Il10 model, curcumin reduced or eliminated colonic tumor burden with limited effects on mucosal immune responses. The beneficial effect of curcumin on tumorigenesis was associated with the maintenance of a more diverse colonic microbial ecology.

 

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