Healthy Living Not a Panacea for Depression

Two studies examining whether interventions centered on diet and lifestyle can improve depression had mixed results.

Neither an intervention geared at improving dietary behaviors and promoting a Mediterranean diet (“food-related behavioral activation therapy”) nor one involving a multinutrient supplement reduced the onset of major depressive disorders, data from the MooDFOOD trial found.

However, patients undergoing a behavioral weight loss intervention involving calorie reduction, physical exercise, and lifestyle videos combined with a problem-solving therapy and as-needed antidepressants did significantly reduce depression in the Research Aimed at Improving Both Mood and Weight (RAINBOW) trial — and much of the benefit appeared to stem from drug treatment.

The pair of studies, both published in JAMA, contribute to a growing body of nutritional psychiatry research that has generally shown positive results; however, most prior studies have involved non-clinically depressed patients, or those with subsyndromal depressive symptoms or other somatic conditions, wrote Michael Berk, MD, PhD, and Felice Jacka, PhD, both of Deakin University, in Victoria, Australia in an accompanying editorial.

Preventing major depressive disorder is difficult, they noted, partially because obesity and depression interact bidirectionally and can be influenced by a host of other factors such as poor diet. Additionally, studies examining the effect of dietary depression therapies often lack statistical power because only a small number of participants with subsyndromal depressive symptoms will actually develop depression in the follow-up period, they added.

“Dietary change is not likely to be a sole treatment for depression,” Berk and Jacka wrote. Instead, “integrated care packages” that incorporate psychological, pharmacological, and lifestyle treatments may have more positive effects, they added.

MooDFOOD

In this trial involving over 1,000 overweight or obese adults with depressive symptoms, neither a supplement containing folic acid, vitamin D, zinc, and selenium (odds ratio 1.06, 95% CI 0.87-1.29, P=0.57) or the food-related behavioral activation therapy (OR 0.93, 95% CI 0.76-1.13, P=0.47) significantly reduced the onset of major depressive disorder at 1 year, reported Mariska Bot, PhD, of Vrije Universiteit Amsterdam, and colleagues.

When combined, the two interventions did not reduce depression either (OR 0.93, 95% CI 0.76-1.14, P=0.48).

“Multinutrient supplements appeared to result in slightly poorer depressive and anxiety symptoms scores compared to placebo,” Bot told MedPage Today in an email. “It is therefore unlikely that including more participants — and having a higher number of persons that developed depression — would have favored supplements over placebo for the prevention of depression.”

However, anxiety severity (GAD-7 scores) was significantly lower for participants receiving the food-related behavioral activation therapy (adjusted mean difference −0.48, 95% CI −0.84 to −0.12, P=0.01) and supplements (adjusted mean difference 0.50, 95% CI 0.16-0.84, P=0.004) compared to those who did not, they noted.

This signal suggests “more symptomatic individuals derived greater benefit from the therapy intervention, a finding concordant with most of the depression literature showing greater efficacy in more unwell individuals,” Berk and Jacka noted. They added that the supplementation group did worse on certain measures such as self-rated depression, though.

Still, supplements significantly improved depression severity as observed through both PHQ-9 (adjusted mean difference 0.65, 95% CI 0.25-1.06, P=0.002) and IDS 30-SR scores (adjusted mean difference 1.20, 95% CI 0.29-2.10, P=0.01), researchers reported.

But no significant difference was observed in any secondary outcomes when combined supplement and food-related behavioral activation therapy were used, according to the study.

This 2×2 factorial randomized clinical trial recruited 1,025 adults from a dietary study conducted across four European countries. In total, 105 participants developed a major depressive disorder across the study period, including 25 of those receiving placebo alone, 26 getting placebo with therapy, 32 on supplements alone, and 22 with combined supplements and therapy.

RAINBOW

This study enrolled patients with both obesity and depressive symptoms with the aim of determining whether a multimodal intervention could alleviate both conditions.

Compared to participants assigned to receive usual care, those in the intervention arm had clinically slight but statistically significant reductions in both depression (between-group mean difference −0.2, 95% CI −0.4 to 0, P=0.01) and weight (between-group mean difference −0.7, 95% CI −1.1 to −0.2, P=0.01) at 1 year, reported Jun Ma, MD, PhD, of the University of Illinois, and colleagues.

At 6 months, a higher percentage of patients in the intervention group had a 50% reduction in depressive symptoms than in the control arm (31% vs 16%), and more attained full depression remission as well (18% vs 6%), they noted. However, neither of these outcomes persisted at 12 months.

Berk and Jacka noted in their editorial that although this result is “clinically meaningful,” it might in part be explained by the rate of antidepressant prescriptions administered, as this increased in the intervention group across this time period, while decreasing in the control arm. The biggest advantages over usual care were seen among patients who started antidepressant treatment during the trial.

Certain characteristics appeared to influence the intervention effect. For example, non-Hispanic whites had greater reductions in both weight and depression than other races or ethnicities, and responses varied by age and sex as well.

“For different patient subgroups, there might be a need for tailored strategies,” Ma told MedPage Today. “Our results show that men and women seem to respond differently to this same intervention in the sense that men responded more favorably to weight loss whereas women responded more favorably to depression treatment.”

This study recruited 409 adult patients from four of Sutter Health’s Palo Alto Medical Foundation centers who were then randomly assigned to either control or intervention, which merged two programs: the Group Lifestyle Balance program and the Program to Encourage Active, Rewarding Lives for Seniors.

In total, 344 patients completed the follow-up, of whom 70% were women, 71% were non-Hispanic white, and 69% had completed college education. Participants had a mean BMI of 36.7 and were classified as having moderate depression. Nearly 60% reported they had not taken antidepressants.

In the MooDFOOD trial, 98 patients were hospitalized and one died, although the death was “judged as unrelated to interventions.” In RAINBOW, 31 serious adverse events were reported, of which 13 resulted in hospitalization and two were designated as “possibly related to the study,” although the events were evenly distributed across both intervention and usual care groups. There were no deaths in this study.