Enhancing Treatment for Depression with Supplements

Not everyone has depression for the same reasons. Some may have an inherited tendency, others may have experienced trauma, and many suffer from situational anxiety or abusive relationships.

Because not everyone experiences depression for the same reasons, therapy for every patient is different. Here at The Hayakawa Mental Health Clinic Issha, we take a whole-body approach to mental health, including continually evaluating the effectiveness of medications and how to improve your overall health.

For many patients diagnosed with depression, treatment begins with a class of drugs called SSRIs (Serotonin Selective Uptake Reinhibitors.) SSRIs limit the amount of serotonin being absorbed back from the brain and into the bloodstream. The premise is that higher serotonin levels in your brain help manage your depressive thoughts.

Additionally, there is evidence that some supplements called Nutraceuticals (a word that combines “nutrient” and “pharmaceutical”) improve the efficacy of SSRIs. 1 A study published in the American Journal of Psychiatry reviewed the results of 40 clinical trials that evaluated the effects of taking Nutraceuticals in conjunction with antidepressants. It revealed that four supplements, in particular, upped the potency of the medications. 2

Among the Nutraceuticals judged to be the most promising are the following:

Vitamin D:
While there is still more clinical study to be done, results so far indicate a connection between low vitamin D levels and depression. Vitamin D seems to play a role in the regulation of our mood. In fact, low Vitamin D levels alone are a cause for concern. If you are low on Vitamin D, you may experience aching muscles, bones and joints, and fatigue. Those with obesity need a higher dose to increase the circulating levels of the vitamin.

S-adenosylmethionine (SAMe)
Some studies suggest that SAMe improves the efficacy of antidepressants. It is believed to target brain neurotransmitters like many antidepressants and is said to have the effect of lifting your mood. Additionally, it targets inflammation which is linked to depressive symptoms.

Methylfolate and Folinic Acid
Methyfolate and folinic acid are naturally occurring B vitamins needed in the brain for the synthesis of norepinephrine, serotonin, and dopamine, which may help reduce depressive symptoms. 3

Far and away, clinical evidence broadly concurs that Omega-3 fatty acids are beneficial for several reasons. One to consider is that inflammation is closely connected to depression and that Omega 3 acts as an anti-inflammatory agent. 4

Supplementing antidepressants with Nutraceuticals can begin when treatment starts or during re-evaluation if medication alone does not significantly improve symptoms. The prescription of pharmaceutical-grade nutrients can provide an effective and safe approach to enhancing the effects of antidepressants. 5

The bottom line? When beginning treatment for depression, consider what supplements and diet changes you can use to improve your chances of success.


1:V. Prakash, Martinus A.J.S. van Boekel, in Ensuring Global Food Safety, 2010

2: Sarris J, Murphy J, Mischoulon D, Papakostas GI, Fava M, Berk M, Ng CH. Adjunctive Nutraceuticals for Depression: A Systematic Review and Meta-Analyses. Am J Psychiatry. 2016 Jun 1;173(6):575-87. doi: 10.1176/appi.ajp.2016.15091228. Epub 2016 Apr 26. PMID: 27113121.

3:Simopoulos AP. Omega-3 fatty acids in inflammation and autoimmune diseases. J Am Coll Nutr. 2002 Dec;21(6):495-505. doi: 10.1080/07315724.2002.10719248. PMID: 12480795.

4:Fava M, Mischoulon D. Folate in depression: efficacy, safety, differences in formulations, and clinical issues. J Clin Psychiatry. 2009;70 Suppl 5:12-7. doi: 10.4088/JCP.8157su1c.03. PMID: 19909688.

5:Sarris J, Stough C, Bousman C, et al.: An adjunctive antidepressant nutraceutical combination in treating major depression: study protocol, and clinical considerations. Adv Integr Med 2015; 2:49–55 Crossref, Google Scholar