Diet Alone Not Enough to Prevent Depression in Obese, Overweight Patients

Batya Swift Yasgur, MA, LSW

March 12, 2019

Dietary and nutritional interventions alone are unlikely to prevent or treat depression in overweight individuals but may be a helpful part of a broader strategy that includes other approaches, new research suggests.

Two randomized trials published March 5 in JAMA focus on comorbid depression and obesity.

The MooDFOOD study, which was conducted in four countries, randomly assigned more than 1000 overweight or obese adults with subsyndromal depressive symptoms to receive one of four interventions: placebo without food-related behavioral activation therapy; placebo with therapy; supplements without therapy; and supplements with therapy.

Neither multlinutrient supplementation (compared with placebo) nor therapy (compared with no therapy) reduced episodes of major depressive disorder (MDD) at 1 year.

"We found no benefits in preventing new-onset depression from either of these interventions — nutrient pills and therapy — either separately or in combination," senior author Marjolein Visser, PhD, professor of healthy aging in the Section of Nutrition and Health, Department of Health Sciences, Faculty of Science, Vrije Universiteit Amsterdam and the Amsterdam Public Health Research Institute, the Netherlands, told Medscape Medical News.

"Of course, something we didn't study is that patients with deficiencies in nutrients might still benefit [from supplementation], so if there is a nutritional deficiency, one should always try to treat it, because nutrient deficiencies harm the body, but not specifically to deal with depression," she said.

In the second study, investigators in the RAINBOW trial randomly allocated 400 overweight adults with depressive symptoms into two groups. The study was conducted in the primary care setting.

The usual-care group received general medical care, information about services for obesity and depression, and wireless activity trackers. The intervention group received usual care plus a 12-month intervention that integrated a behavioral weight loss treatment with problem-solving therapy for depression and, if indicated, antidepressants.

The integrative intervention significantly improved weight loss and depressive symptoms at 12 months compared with usual care.

"The RAINBOW trial provides first-ever evidence to show that obesity and depression can be effectively treated together through integrated behavior therapy with as-needed antidepressant medications," Jun Ma, PM, PhD, professor of academic internal medicine and geriatrics, associate head of research, and director of the Department of Medicine, Center for Health Behavior Research, Institute for Health Research and Policy, University of Illinois, in Chicago, told Medscape Medical News.

"It is also the first to demonstrate that the integrated intervention is suited to being delivered as part of primary care, without requiring specialist referrals," she said.

High-Risk Population

The MoodFOOD study was conducted because previous studies of nutrition and depression focused on patients who already had clinical depression, and "we did not know whether nutrition could also play a role in the prevention of depression," said Visser.

The researchers chose to study the impact of nutritional intervention on depression in overweight and obese individuals because they are "at high risk for developing depression over time and many have elevated symptoms, but not high enough to be diagnosed with depression," she explained.

The nutrients chosen for study were eicosapentaenoic and docosahexaenoic omega-3 polyunsaturated fatty acids (1412 mg, 3:1 ratio); selenium (30 μg); folic acid (400 μg); and vitamin D3 (20 μg) with calcium (100 mg).

The other arm of the study focused on behavioral activation, because "we knew it might be a good way of treating people who already have depression, so we thought it might also help to reduce the risk of new-onset depression."

The behavioral activation therapy consisted of an intervention that utilized standard behavioral activation approaches and activity application to improve mood by changing dietary habits and food-related behaviors, increasing positive behaviors, and emphasizing a Mediterranean-style diet.

Because the researchers were particularly interested in nutrition, they developed behavioral activation sessions that targeted dietary behavior.

The primary outcome was the 12-month cumulative onset of an episode of MDD, as assessed with the Mini International Neuropsychiatric Interview 5.0, which was administered at 3, 6, and 12 months.

Secondary outcomes included depression severity, anxiety severity, health-related quality of life, eating behavior, physical activity, sedentary behavior, and body weight perception.

The study, which spanned sites in four European countries, utilized a 2×2 factorial model in which participants (n = 1025; mean age, 46.5 years; 75% women; mean body mass index [BMI], 31.4) were randomly assigned to one of four groups: placebo without therapy (n = 257), placebo with therapy (n = 256), supplements without therapy (n = 256), and supplements with therapy (n = 256).

Adherence rates were high for those taking supplements or placebo, with 77% of participants showing an adherence of >70% to their regimens.

Of those assigned to therapy, 71% attended ≥8 of 21 sessions. Adherence was higher for individual sessions than for group sessions.

Of the total number of participants, 10% experienced an MDD episode during the 12-month follow-up period (9.7% in the placebo-alone group, 10.2% in the placebo-plus-therapy group, 12.5% in the supplements-alone group, and 8.6% in the supplements-with-therapy group).

Less Anxiety

With regard to the main effect of each intervention, the investigators found that for patients who received placebo alone, 9.9% developed MDD (1.1 per 100 person-months); for those who received supplements, 10.5% developed MDD (1.2 per 100 person-months); for those who did not received therapy, 11.1% developed MDD (1.3 per 100 person-months); and for those who received therapy, 9.4% developed MDD (1.0 per 100 person-months).

Logistic regression showed no significant effect of supplements or food-related behavioral activation therapy or significant supplements × therapy interaction on the onset of MDD or time to first onset of MDD.

There were no significant supplement × food-related behavioral activation therapy interactions for any of the secondary outcome scores (P values for interaction ranged from .41 to .98).

However, food-related behavioral activation therapy was significantly related to lower anxiety scores, as measured by the Generalized Anxiety Disorder 7-Item Scale (GAD-7), at 12 months.

Moreover, a post hoc analysis found a more beneficial effect of behavioral activation therapy on depressive symptoms for those with higher baseline depression scores, suggesting that with "sufficient dose and a higher-risk sample, food-related behavioral activation therapy might prevent depression," the researchers write.

"We can only draw conclusions for the types of participants we recruited — overweight people with elevated depressive symptoms — and our conclusions are relevant for this group," said Visser.

"These data might be valuable for other groups as well, including people in the general population, but it would take a huge trial to get enough new-onset depression to draw conclusions from a study like this," she added.

Critical Unmet Need

The RAINBOW study was "motivated by a critically unmet need for effective treatments for patients with obesity and depression, which are major public health problems," said Ma.

"Obesity and depression share common risk factors, such as poor diet and lack of exercise, and they cause other health problems, such as diabetes and cardiovascular disease," she noted.

She pointed out that "people with obesity are at increased risk of being depressed, and, likewise, people with depression are at increased risk of being obese. Consequently, obesity and depression often co-occur."

To date, "there has been no integrated therapy to effectively treat patients affected by both conditions at the same time," Ma said.

To investigate the potential role of an integrated collaborative care intervention in improving obesity and depression, the researchers randomly assigned 409 adults (mean age, 51.0 years [SD, 12.1 years]; 70% women; mean BMI, 36.7 [6.4]; 71% white, non-Hispanic) to receive either an integrative collaborative care intervention (n = 204) or usual care (n = 205).

The collaborative care model integrated two independent programs into a synergistic, two-phase curriculum that included goal-based approaches to promote weight loss through healthy dietary changes; problem-solving approaches; behavioral activation strategies; and supplementation with as-needed antidepressant medications.

Participants in the both groups continued to receive medical care from their personal physicians as well as information on mental health services, weight management, and other wellness programs routinely available at their clinic.

Usual-care participants also received a wireless activity tracker but not the other self-care materials used in the integrative group.

Depression was measured by the PHQ-9 score and the 20-item Depression Symptom Checklist (SCL-20).

Depression scores and BMI were collected at baseline and at 6, 12, 18, and 24 months, although the current study only reports on 12-month results.

The co–primary outcome measures were BMI and SCL-20 score at 12 months.

Secondary outcome measures included weight, depression treatment response, depression remission, and total score on the GAD-7 scale.

Routine Screening a Must

The intervention group showed significantly greater improvements in BMI and SCL-20 score compared to the usual-care participants, with a reduction in mean BMI from 36.7 (SD, 6.9) to 35.9 (7.1) vs a change from 36.6 (5.8) to 36.6 (6.0; between-group mean difference, −0.7; 95% CI, −1.1 to −0.2; P = .01).

The mean SCl-20 score declined from 1.5 (0.5) to 1.1 (1.0) among participants in the intervention group, vs 1.5 (0.6) to 1.4 (1.3) in the usual-care group (between-group mean difference, −0.2; 95% CI, −0.4 to 0; P = .01).

The between-group mean differences for BMI (−0.6; 95% CI, −0.9 to −0.3) and SCL-20 score (−0.3; 95% CI, −0.4 to −0.1) were statistically significant at 6 months.

Mean weight among intervention participants declined from 103.4 kg (22.3 kg) at baseline to 100.8 kg (22.8 kg) at 12 months. By contrast, the change in mean weight among usual-care participants was from 103.2 kg (19.6 kg) to 103.4 kg (20.9 kg).

The post hoc outcome of weight loss of ≥5% differed significantly by group (28% for the intervention group vs 15% for the usual-care group).

The proportion of participants who were prescribed antidepressant medications increased from 48.5% during the 12 months before randomization to 62.7% during the 12 months after randomization among intervention participants but decreased from 47.3% to 42.0% among usual-care participants.

The most commonly prescribed antidepressants were bupropion (multiple brands), sertraline (Zoloft, Pfizer), and citalopram/escitalopram (multiple brands).

"The main finding from this trial is that, among adult patients with obesity and depression, a collaborative care intervention integrating behavioral weight loss treatment, problem-solving therapy, and as-needed antidepressant medications significantly improved weight loss and depressive symptoms over 1 year, compared with usual care that patients receive through their primary care physicians. Per obesity and depression guidelines, practicing clinicians should routinely screen patients for these conditions," said Ma.

Paving the Way

Commenting on the studies for Medscape Medical News, Felice N. Jacka, PhD, director, Food and Mood Center, IMPACT SRC, Deakin University, Australia, and author of Brain Changer (Macmillan Australia, 2019), who was not involved in either study, observed that there are "many, many studies linking diet to mental health."

She cited a new meta-analysis, for which she is a coauthor, that confirmed that dietary interventions "significantly reduce depression symptoms."

In an accompanying editorial that she coauthored, Jacka, who is also the president of the International Society for Nutritional Psychiatry Research, noted that "prevention of MDD is difficult to study."

The two studies in JAMA "pave the way to new therapeutic interventions that address common mental health disorders and noncommunicable physical disorders simultaneously, recognizing common risk determinants and shared endpoints," the editorialists write.

Ma added that her team is conducting further research "to study behavioral and biological mechanisms underlying the intervention effect and patient factors that may affect engagement with, and response to, the intervention, as well as system and provider factors that may enable or hinder implementation of the intervention."

The MooDFOOD study was funded by the European Union. In the United Kingdom, it is supported by the National Institute for Health Research (NIHR) through the Primary Care Research Network and the NIHR Exeter Clinical Research Facility. Visser reports no relevant financial relationships. The other authors' disclosures are listed on the original article. The RAINBOW study was supported by the National Heart, Lung, and Blood Institute and received internal funding from the Palo Alto Medical Foundation Research Institute and the University of Illinois, Chicago. Ma reports no relevant financial relationships. The other authors' disclosures are listed on the original article. Jacka reported receiving grants from the A2 Milk Company and BeFit Foods; support from the Wilson Foundation and the Fernwood Foundation; grant and research support from the Brain and Behaviour Research Institute, the Australian National Health and Medical Research Council, Australian Rotary Health, the Geelong Medical Research Foundation, the Ian Potter Foundation, Eli Lilly, Meat and Livestock Australia, Woolworths, and the University of Melbourne; and speakers honoraria from Sanofi-Synthelabo, Janssen Cilag, Servier, Pfizer, Health Ed, Network Nutrition, Angelini Farmaceutica, Eli Lilly, and Metagenics. Her coauthor's disclosures are listed in the original article.

JAMA. Published online March 5, 2019. Visser et al, Abstract; Ma et al, Abstract; Editorial

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