Healthy diet/antiinflammatories dec depression

Healthy diet/antiinflammatories dec depression

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Geoff A. Modest, M.D.

Wed 10/30/2019 8:18 AM

• Geoff A. Modest, M.D.

A recent Australian study found that depressed young adults stratified to a healthy diet had significantly fewer depressive symptoms 3 weeks later (see depression improved with diet PLoS2019 in dropbox, or doi.org/10.1371/journal.pone.0222768).

Details:

--76 individuals participated in the study, all either for course credit in an undergraduate psychology course or for cash reimbursement via advertisement on the University campus area

-- age 20, 63% female, BMI 22, current smokers 13%, comorbid disorders 25%, physical activity 5900 Mets, psychopharmacology 12%

    -- there was no significant difference in baseline characteristics; though, in terms of their numbers, those in the Diet Change group had some more physical activity (6490 vs 5381 Mets), fewer comorbidities (21% vs 28%) and a slightly worse diet

-- participants had at least moderate symptoms of depression and habitually consumed a poor diet; they were randomized in a single-blind RCT to a three-week dietary intervention (Diet Group) vs their usual (bad) diet

    -- the Diet Group received dietary advice via a 13-minute video, emphasizing Mediterranean-style diets known to be associated with reduced risk of depression (5 servings/d of vegetables, 2-3/d of fruits, 3/d whole grain cereals, 3/d protein from lean meat/poultry/eggs/tofu/legumes, 3/d unsweetened dairy, 3/wk fish, 3 T/d nuts and seeds, 2 T/d olive oil, 1 t/d of both turmeric and cinnamon), as well as instructions to decrease refined carbohydrates, sugar, fatty or processed meats, and soft drinks. They also were given sample meal plans and recipes, were given several of these food items and a $60 gift card for their shopping. They also had phone calls weekly to troubleshoot problems with their diet. The Control Group just continued their usual diet without intervention

    -- diet was assessed based on a self-reported 10-item questionnaire regarding the recommended food groups, and spectrophotometry assessing skin carotinoid levels, as a quantitative measure reflecting fruit and vegetable intake

-- primary measurements:

    -- Center for Epidemiological Studies Depression Scale (CESD-R), 20 items scoring from 0 to 3, total score range 0 to 60; a score >16 suggests clinical depression

    -- Depression and Anxiety and Stress Scale - 21 depression subscale (DASS-21-D), an assessment of depressive symptoms over the prior week with readings on a 4-point scale, total score 0 to 21. A score of at least 7 suggested moderate or higher depressive symptoms; they also evaluated the anxiety and stress scales

    -- current mood assessment via Profile of Mood States

    -- self-efficacy, via New General Self-Efficacy Scale

    -- memory via Hopkins Verbal Learning Test

-- baseline CESD-R: 20; baseline DASS-21-D: 7 [both suggesting at least moderate depression]

-- primary outcome: change in CESD-R

-- secondary outcomes: DASS-21-D; current mood; and self-efficacy (scales as noted above)

Results:

-- depression symptoms:

    -- CESD-R at Day 21: the average in the Diet Group improved from the elevated range (>16)  to the not clinically depressed range; there was no significant change in the usual diet  group, all controlling for baseline depression measurements, p=0.007

        -- this difference remained significant controlling for age, gender, physical activity, and baseline BMI

    -- DASS-21-D at Day 21: the average in the Diet Group improved from moderate severity (7-10) to the normal range (0-4), with no significant difference in the usual diet group, p=0.002

        -- this change  remained significant controlling for age, gender, physical activity, and baseline BMI

    -- their bar graphs are impressive: a major decrease in depression scores by both scales at 3 weeks, and for DASS-21-D at both 3 weeks and 3 months (after the study had stopped)

        -- adherence to diet: significant increase in participants' self-recorded consumption in those in the Diet Group, as confirmed by the spectrophotometer scales; and a decrease in foods high in saturated fats and refined sugar.

        -- 33 people were contacted briefly by telephone at 3 months, though minimal specific data were collected, finding: 7 continued the diet, 19 maintained some aspects of the diet and 7 reverted to their old diet. 

-- secondary outcomes: the Diet Group had lower DASS-21-Anxiety and Stress scores, but no difference in mood or memory tests

Commentary:

--there are many observational studies finding a relationship between poor diet and depression, though causality is unclear in observational studies (did poor diet lead to depression or vice versa??).  Hence the utility of an intervention study

--there have been some RCTs on dietary interventions for depression, though they typically did not assess depression as a primary outcome

--the presumptive mechanism is that these healthy diets decrease inflammation, and there are many studies finding that depression is associated with a systemic inflammatory state: eg, patients with major depressive disorders have increased inflammatory markers (IL-6, soluble interleukin-2 receptor, CRP, TNF-a) as well as increased levels of cell-mediated immune response (associated cytokines, such as soluble IL-2 receptor, soluble CD8 molecules)

--the three-week time course for the intervention was chosen because it takes 2 to 4 weeks for inflammation reduction following antidepressant treatment; and the fear that a longer study might lead to decreased adherence

--another article just came out, a systematic review and meta-analysis of RCTs, finding that anti-inflammatory medications were associated with decreased depression, both as monotherapy and as adjunctive therapy (see depression anti-inflam helps neurolneurosurg2019 in dropbox, or doi.org/10. 1136jnnp-2019-320912). Brief details of this analysis:

    --30 RCTs were found with 1610 particpants, using NSAIDs (4 studies, with celecoxib added to antidepressant meds), omega-3 fatty acids (17 studies, some as monotherapy and some as added therapy), statins (3 studies with statins added to antidepressants, 1 each with lovastatin, simvastatin, and atorvastatin), minocycline (3 studies, all as adjunctive therapy), pioglitazone (1 study), modafinil (2 studies) and N-acetylcysteine (1 study)

    --several depression scores were used in these studies, including the Hamilton Rating Scale for Depression, the Montgomery-Asberg Depression Rating Scale, the Beck's Depression Inventory, etc

    --there was a highly significant standard mean difference (SMD) of antidepressant effect, SMD -0.55 (-0.5 to -0/35), p<0.00001; a highly significant 52% increased depression response rate of anti-inflammatory agents over placebo, RR 1.52 (1.30-1.79), p<0.00001; and a 79% increased depression remission rate, RR 1.79 (1.29-2.49), p=0.00005

    --the depression improvement was both when anti-inflammatories were used as monotherapy and in conjuction with antidepressant meds, though more so in the latter case (??because of the common cytochrome P450 metabolism, which might have augmented their effects)

    --and adverse effects were minimal

--see https://gmodestmedblogs.blogspot.com/2018/02/diet-and-depression-in-teens.html , another Australian study finding that in adolescents followed longitudinally from birth, a Western diet was associated with increased risk of a high BMI, as well as the development of depressive and mental health disorders at age 17, in contradistinction to those on a healthy diet

--as a related issue, exercise (which also decreases inflammation) also improves mental health, including decreasing number of depressive days, and was particularly helpful in those with a history of prior depression: see http://gmodestmedblogs.blogspot.com/2018/09/exercise-helps-mental-health.html

--there are evident limitaitons to this trial: it was not a full RCT and those on diet did receive additional supports, those in the dietary intervention group received much more attention than those in the control diet group, these were University students and not representative of the general population, it was a small study with limited followup

--but, in conjuction with the many other studies on diet and depression, and the other recent study of anti-inflammatory drugs, it does reinforce some conclusions:

    --healthy diets seem to be associated with decreased depression (as well as the plethora of other clinical benefits, eg cancer, heart disease, all-cause mortality....)

    --inflammation seems to be an important factor in depression (and, by the way, if inflammation is actually a primary factor for many patients, the approach of decreasing inflammation by diet, exercise, anti-inflammatory meds makes more sense than trying to rewire neurotransmitters in the brain which may have gone awry because of the effect of inflammation: see https://www.ncbi.nlm.nih.gov/pubmed/24189118 

    --and minimizing inflammation at a young age might even decrease the likelihood of developing depression (and the other bad sequelae associated with chronic inflammation)

so, given how incredibly common depression is (6% of adults worldwide every year; in the US prevalence is close to 20% and likely higher in those seeking health care), and given the broad health benefits from diet and exercise, it certainly makes sense to reinforce these lifestyle issues in depressed patients (and probably everyone), instead of just jumping to antidepressants with or without counseling...

there are lots of prior blogs on diet/exercise, inflammation, and health outcomes: eg see http://gmodestmedblogs.blogspot.com/search?q=Mediterranean+diet for the benefits of the Mediterranean diet

geoff​

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