Supplements including fish oil and vitamin D can boost effects of antidepressant medications

Taking some nutrient supplements together with antidepressants can enhance the medication’s effects, our research has found.

Published this week in the American Journal of Psychiatry, our review of the evidence found that omega-3 fish oil, methylfolate, vitamin D and amino acid compound S-adenosine methionine (known as SAMe) supplements increased the effects of antidepressant medication for those with clinical depression.

We reviewed 40 clinical trials that explored the effects of using nutrient supplements together with antidepressants as therapy for clinical depression.

The strongest finding in our meta-analysis – a combination of outcome data from several studies into one analysis – was that taking omega 3 fish oil supplements high in the fatty acid EPA, in combination with antidepressants, was significantly more effective than a dummy pill.

Many studies have shown omega-3 supplements are good for general brain health and improving mood. But this is the first analysis of studies that looks at using the supplements in combination with antidepressant medication for clinical depression.

Our findings mean we have an evidence-based, safe approach that could be considered a mainstream treatment for depression. But we advise anyone considering changing or initiating treatment to consult their doctor.

Nutrients and mental health

Dietary nutrients, such as vitamins B, C and D, omega-3 fatty acids and minerals such as zinc and magnesium, are critical for brain health. We also know that when given as supplements, they may be beneficial to mental health.

Doctors recommend some of these supplements in cases where a blood test has confirmed nutrient deficiencies. But doctors are often hesitant to advise using supplements as part of mental health therapy. This is partly because it’s unknown whether prescribing nutrients with antidepressants is more effective for depression, and whether there are safety concerns about this approach.

To answer these questions, our research team from the University of Melbourne and Harvard Medical School examined worldwide trials from the 1960s to today. The studies had aimed to see if certain nutrients were effective in improving a person’s depression when taken together with different types of antidepressants, such as the popular selective serotonin re-uptake inhibitors (SSRIs).

Overall, we found more patients in the studies showed an improvement in mood when prescribed omega-3 fish oil, methylfolate, vitamin D and SAMe supplements in combination with antidepressant medication, compared to those who took medication only.

The evidence revealed mixed results for zinc, vitamin C and tryptophan (an amino acid molecule that is a precursor to some neurotransmitters such as serotonin). Folic acid didn’t work particularly well, nor did the compound inositol (a small molecule structurally similar to glucose).

How nutrients could complement medications

We are increasingly understanding how some nutrients may improve depression.

Omega-3 and SAMe, for instance, can alter mood-regulating neurotransmitter levels in the brain in a similar way to certain antidepressant medications.

Other nutrients, when taken together with antidepressants, could potentially give depression sufferers the extra boost they need as they may work on an additional range of brain chemical pathways. Omega-3 and zinc, for instance, may act by reducing inflammation, which has been implicated in depression.

Nearly 2 million Australians take antidepressants. But research shows many with depression still experience some symptoms despite several months of treatment with antidepressant medication.

The mental health of people who have an inadequate response to antidepressants can potentially be improved by supplementing their use with nutrients. Clinicians and the public can consider therapeutic doses of particular nutrients as a potential low-cost approach to reducing depression in these instances.

Our evidence review found no major safety concerns in combining many of the nutrient supplements studied with medications, but it is important to stress that supplements can differ in quality. We advise people to always speak with their medical professional before changing or initiating any treatment.

It is also important for those suffering from depression to see medications and supplements as one potentially important element in an integrative approach. This should include psychological care and consideration of lifestyle factors, such as a good wholefood diet, exercise and sufficient sleep.

We are recruiting for an NHMRC-funded clinical trial in Melbourne and Brisbane to see if using these nutrients in combination will enhance the effects of antidepressant medication even more.

Dr Jerome Sarris has received either presentation honoraria, travel support, clinical trial grants, book royalties from Integria Healthcare & MediHerb, Pfizer, Taki Mai, Bioceuticals & Blackmores, Soho-Flordis, Elsevier, the National Health and Medical Research Council. He is affiliated with The International Society for Nutritional Psychiatric Research, and The International Network of Integrative Mental Health