According to our research, taking certain nutritional supplements with antidepressants can enhance the effects of the drug.
Published this week in the American Journal of Psychiatryour review of the evidence found that supplements of omega-3 fish oil, methylfolate, vitamin D and the amino acid compound S-adenosine methionine (known as SAMe) increased the effects of antidepressants in people with clinical depression.
We reviewed 40 clinical trials that explored the effects of using nutritional supplements with antidepressants as a treatment for clinical depression.
The strongest finding from our meta-analysis—combining outcome data from multiple studies into a single analysis—was that taking EPA-rich omega-3 fish oil supplements, in combination with antidepressants, was significantly more effective than a dummy pill.
Numerous studies have shown that omega-3 supplements are good for general brain health and improve mood. But this is the first analysis of studies looking at the use of the supplements in combination with antidepressants for clinical depression.
Our results mean we have a safe, evidence-based approach that could be considered 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 essential for brain health. We also know that when taken as supplements they can be beneficial for 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 the use of supplements as part of mental health therapy. This is partly because it is unclear whether prescribing nutrients with antidepressants is more effective for depression and whether there are safety concerns with this approach.
To answer these questions, our research team from the University of Melbourne and Harvard Medical School looked at global trials from the 1960s to the present. The studies aimed to find out if certain nutrients were effective in improving a person’s depression when combined with different types of antidepressants, such as selective serotonin reuptake inhibitors (SSRIs).
Overall, we found that more patients in the studies showed improved mood when prescribed omega-3 fish oil, methylfolate, vitamin D and SAMe supplements in combination with antidepressants, compared to those taking only medication.
The evidence showed mixed results for zinc, vitamin C and tryptophan (an amino acid molecule that is a precursor to certain 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 certain nutrients can improve depression.
Omega-3s and SAMe, for example, can alter levels of mood-regulating neurotransmitters in the brain in the same way as some antidepressant drugs.
Other nutrients, when taken with antidepressants, could potentially give people with depression the extra boost they need because they can act on an additional range of brain chemical pathways. Omega-3s and zinc, for example, can work by reducing inflammationwho has been implicated in depression.
Almost 2 million Australians take antidepressants. But research shows that many people with depression still experience some symptoms despite several months of treatment with antidepressant drugs.
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 may consider therapeutic doses of particular nutrients as a potential low-cost approach to reducing depression in these cases.
Our review of the evidence revealed no major safety issues with combining many studied nutritional supplements with medications, but it is important to note that supplements can differ in quality. We advise people to always speak with their healthcare professional before changing or starting treatment.
It’s also important for people with depression to see medications and supplements as a potentially important part of an integrative approach. This should include psychological care and consideration of lifestyle factors, such as a good whole-food diet, exercise and adequate sleep.
We are recruiting for an NHMRC funded program clinical trial in Melbourne and Brisbane to see if using these nutrients in combination will further enhance the effects of antidepressants.
