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A randomised controlled trial of dietary improvement for adults with major depression (the ‘SMILES’

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Abstract Background:

The possible therapeutic impact of dietary changes on existing mental illness is largely unknown. Using a randomised controlled trial design, we aimed to investigate the efficacy of a dietary improvement program for the treatment of major depressive episodes.


‘SMILES’ was a 12-week, parallel-group, single blind, randomised controlled trial of an adjunctive dietary intervention in the treatment of moderate to severe depression. The intervention consisted of seven individual nutritional consulting sessions delivered by a clinical dietician. The control condition comprised a social support protocol to the same visit schedule and length. Depression symptomatology was the primary endpoint, assessed using the Montgomery–Åsberg Depression Rating Scale (MADRS) at 12 weeks. Secondary outcomes included remission and change of symptoms, mood and anxiety. Analyses utilised a likelihood-based mixed-effects model repeated measures (MMRM) approach. The robustness of estimates was investigated through sensitivity analyses.


We assessed 166 individuals for eligibility, of whom 67 were enrolled (diet intervention, n = 33; control, n = 34). Of these, 55 were utilising some form of therapy: 21 were using psychotherapy and pharmacotherapy combined; 9 were using exclusively psychotherapy; and 25 were using only pharmacotherapy. There were 31 in the diet support group and 25 in the social support control group who had complete data at 12 weeks. The dietary support group demonstrated significantly greater improvement between baseline and 12 weeks on the MADRS than the social support control group, t(60.7) = 4.38, p < 0.001, Cohen’s d = –1.16. Remission, defined as a MADRS score <10, was achieved for 32.3% (n = 10) and 8.0% (n = 2) of the intervention and control groups, respectively (χ 2 (1) = 4.84, p = 0.028); number needed to treat (NNT) based on remission scores was 4.1 (95% CI of NNT 2.3–27.8). A sensitivity analysis, testing departures from the missing at random (MAR) assumption for dropouts, indicated that the impact of the intervention was robust to violations of MAR assumptions.


These results indicate that dietary improvement may provide an efficacious and accessible treatment strategy for the management of this highly prevalent mental disorder, the benefits of which could extend to the management of common co-morbidities.

Trial registration:

Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12612000251820. Registered on 29 February 2012.

Keywords: Depression, Major depressive disorder, Diet, Nutrition, Randomised controlled trial, Dietetics



There is now extensive observational evidence across countries and age groups supporting the contention that diet quality is a possible risk or protective factor for depression [1–5]. Although there are many versions of a ‘healthful diet’ in different countries and cultures, the available evidence from observational studies suggests that diets higher in plant foods, such as vegetables, fruits, legumes and whole grains, and lean proteins, including fish, are associated with a reduced risk for depression, whilst dietary patterns that include more processed food and sugary products are associated with an increased risk of depression [1, 6, 7]. Whilst cognisant of the limitations of observational data, these associations are usually observed to be independent of socioeconomic status, education and other potentially confounding variables and not necessarily explained by reverse causality (see, e.g. [7–10]). Recently, a meta-analysis confirmed that adherence to a ‘healthful’ dietary pattern, comprising higher intakes of fruit and vegetables, fish and whole grains, was associated with a reduced likelihood of depression in adults [1]. Similarly, another meta-analysis reported that higher adherence to a Mediterranean diet was associated with a 30% reduced risk for depression, with no evidence for publication bias [11]. The Mediterranean diet is recognised as a healthful dietary pattern and has been extensively associated with chronic disease risk reduction [12]. More recently, a systematic review confirmed relationships between unhealthful dietary patterns, characterised by higher intakes of foods with saturated fat and refined carbohydrates, and processed food products, and poorer mental health in children and adolescents [2]. Several cohort studies also reported associations between the quality of women’s diets during pregnancy and the risk for emotional dysregulation in children [13–15], with new insights into potential mechanisms of action that include brain plasticity [16], the gut microbiota [17] and inflammatory [18] and oxidative stress [19] pathways. Although there are data suggesting that some nutritional supplements may be of utility as adjunctive therapies in psychiatric disorders [20], the field of research focusing on the relationships between overall dietary quality and mental disorders is new and has thus far been largely limited to animal studies and observational studies in humans. Thus, whilst the existing observational data support a causal relationship between diet quality and depression on the basis of the Bradford Hill criteria [3] and are supported by extensive experimental data in animals (see, e.g. [21]), randomised controlled trials are required to test causal relationships and identify whether or not dietary change can improve mental health in people with such conditions. We conducted a systematic review and identified a number of interventions with a dietary change component that had examined mental health-related outcomes [22]. Whilst approximately half of these studies reported improvements in measures of depression or anxiety following the intervention, at the time of the review no studies fulfilling quality criteria had been conducted in mental health populations or had been designed to test the hypothesis that dietary improvement might result in improvements in mental health. Since then, one study has been published evaluating the possible impact of a lifestyle program, comprising both diet and exercise, on mental health symptoms in patients with depression and/or anxiety; this study failed to show any differences in symptom levels between those in the intervention and those in the attention control group [23]. On the other hand, post hoc analysis of a large-scale intervention trial provides preliminary support for dietary improvement as a strategy for the primary prevention of depression. Individuals at increased risk for cardiovascular events were randomised to a Mediterranean diet supplemented with either extravirgin olive oil or mixed nuts, or a low-fat control diet [12]. Whilst not statistically powered to assess the effectiveness of the intervention for preventing depression, there was evidence (albeit non-significant) of a reduced risk for incident depression for those randomised to a Mediterranean diet with nuts. This protective effect was statistically significant in those with type 2 diabetes, who comprised approximately half the sample [24]. Using a randomised controlled trial (RCT) design, we thus aimed to investigate the efficacy of a dietary program for the treatment of major depressive episodes. In this trial, Supporting the Modification of lifestyle In Lowered Emotional States (SMILES), we hypothesised that structured dietary support, focusing on improving diet quality using a modified Mediterranean diet model, would be superior to a social support control condition (befriending) in reducing the severity of depressive symptomatology.


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