December 23, 2011

Nutrition and Antidepressants

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M. Elizabeth Sublette, MD, PhD

Columbia University and New York State Psychiatric Institute, New York, New York


A colleague recently e-mailed me and asked, “If omega-3 fatty acids are effective in depression, should we ask research subjects to discontinue them before entering our antidepressant study?” My response: “I believe they are effective, but are you going to assess how much fish all of your participants are eating and ask frequent fish eaters to stop?” This virtual conversation crystallized some thoughts I have been having about the interface between nutrition and psychopharmacology.

Psychiatrists are puzzled by the inability of evidence-based medicine to convincingly show that antidepressants work better than placebo. Personally, although I have seen patients who don’t respond to treatment, I find that many do respond or remit in a manner that is not consistent with placebo effect or spontaneous recovery. That is, improvement occurs after the dose has been titrated and the correct time frame has been achieved; patients stay well for months or years; and they decompensate if they discontinue and respond again when rechallenged. From conversations with colleagues, I find that my experience is not unusual.

A number of suggestions have been put forward to explain different sources of variance that might create confusion in clinical trials. Prominent theories are that (1) there is more to placebo response than we understand, and (2) our definition of depression includes a heterogeneous array of etiologies—analogous to the situation with cancer research, which started out with the naïve belief that we could find a single approach that would be “the cure for cancer.”

Here’s another idea: perhaps nutritional factors have a significant influence on response to antidepressants. Nutritional assessments are not a standard feature of clinical trials, beyond some cursory information such as BMI, and are rarely if ever used as analysis covariates. And yet, we know that patients with a history of depression will relapse on a tryptophan-free diet. We know that, in depression that is comorbid with the nutritional deficiencies of anorexia nervosa, antidepressants have not been shown to be effective; food is effective. We know that folic acid deficiency and low vitamin B12 levels may contribute to psychiatric symptoms, including depression. And colleagues and I demonstrated that omega-3 fatty acid supplements containing 60% or more EPA are effective in major depressive episodes.

This idea has face validity. The body must have access to a variety of nutrients to perform its complex array of functions, and we often assume that everyone gets these nutrients in the diet. However, I take a brief diet history with every private patient, and I am often shocked by what many people eat. No fish. No milk. No vegetables. Some people live on burgers, fried chicken, and french fries.

Thus, maybe some patients don’t respond to antidepressants simply because they don’t have an adequate framework of nutritional support. Let’s hope that someone decides to test this idea in a clinical trial—and NOT by excluding patients with poor nutrition, but by assessing and/or repleting a panel of essential nutrients.

Financial disclosure:Dr Sublette has received grant/research support from NIMH and Unicity.​

Category: Depression , Eating Disorders
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18 thoughts on “Nutrition and Antidepressants

  1. Some patients are resistant and even some colleagues are skeptical of the above referenced findings.Any suggestions on patient education materials?
  2. Diet and nutrition modulate the pathophysiological factors underpinning depressive illness.Observational studies on dietary patterns suggest that both low intakes of nutrient-dense foods, high intakes of high-energy and/or nutrient-poor foods are related to an increase in either nutritional deficiencies or impact on biological systems. The hypothesis of depression pathophysiology can be linked to diets high in saturated fats, high in sugar, (western type dietary patterns) environmental causes and genetic polymorphisms. Malnutrition promotes systemic inflammation, in turn pro inflammatory cytokines, affecting neural plasticity, and neurotropic factors, increase mitochondrial dysfunction which in turn will affect neuronal pathways. Evidence shows increased efficacy of combination nutritional medicine/pharmaceuticals, compared to monotherapy in MDD treatment. It seems to me that even with the poor evidence based response with antidepressants they are still used like “lollies” even after a recent review by the food and drug admin. which suggests unless alternative treatments have failed to show or provide any benefit that there is little support for prescription anti depressants. This does not include the severe depressive population type.
  3. Think about this for a minute. For many patients suffering from depression we find they do not meet proper acceptable weight ranges in standard weight tables. Is it the depression that causes these people to eat improperly or is it learned behaviors that have complicated their lives to the point where the individual now finds himself with a depressed mood? Can an overall change in lifestyle (including diet and exercise) have a dramatic impact on these individual’s diagnosed mental illnesses?
  4. I wish that we could also look into the effects of magnesium and anxiety. We know that is has CNS stabilizing effects – alcoholics and seizures, for example. Perhaps dietary magnesium is a good adjunct for anxiety disorders as well.
  5. any disease either physical or mental should be appoached holistically. medicaltion only one side of treatement.
    what is etiology of depresseion- genetical, enviromental, lifestyle factors etc ?. we dont know yet? How much of each of these factors has role needs to be studied. is it similar to diabetes and heart disease? stress phenomenon? i expect further comments on this by experts in this field
  6. Very insightful. We in Pakistan are routinely screening patients for vitamin b12 , folic acid and vitamin D and we are regularly having our workload of correcting these deficiencies on a regular basis.
  7. i saw your recent article on this and immediately looked at my personal omega-3 supplement for the percentage of EPA versus total EPA + DHA; it wasn’t there. haven’t had a chance yet to check other manufacturers at the store. Do you know if the OTC omega-3’s specify this on the label? thanks–susan o’connor, md
  8. Interesting and thought provoking article. Nutritional considerations in current medical practice should be much more prominent. I assume my patients are nutritionally depleted until proven otherwise because, as Dr. Sublette has found, American dietary habits are abysmal. This can be traced directly to our agricultural policies which emphasize high production/high caloric foods/low cost, with nutritional content being ignored.
  9. The ratio of EPA/DHA is on the label of most Omega-3 supplements. Sam’s Club, for example, has one by Member’s Mark which is 647mg EPA/253mg DHA.
  10. very good and interesting article,in my country Uruguay. South America,we are changing the diatery habits to treat multiples diseases and depression.
  11. It is very interesting and thought provoking as we forget to ask elderly with depression of their nutritional intake. Also in countries where there is poor nutrition due to various reasons how effective are antidepressants?
  12. I believe anorexia nervosa is the ultimate form of ADHD. The patients attempts to develop structure by controlling this aspect of their lives. I have successfully treated several anorexic patients with psych stimulants & they GAINED weight. I met an elderly psychiatrist from Hungary & he stated in the old days amphetamines were given to these patients to stimulate the appetite. We must think outside the box and re evaluate these disorders.
  13. Bringing a nutritionist into the pts care team is a plus in treating the whole person. That person takes on the role of listener, educator, point of accountability. Weekly sessions for up to 1 year have been helpful for many pts. However, no research into outcomes, pt feedback to their pcp is or psychiatrist is good information for us to continue or modify the pts treeatment plan.
  14. There are a number of neurological diseases that have a link with deficits in nutrients. It’s understandable that deficit in a healthy diet could a risk factor for depression.
    The folic acid is essential for the development of the neural tubule . That could be a common pathway with mood disorders.

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