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Are Antidepressants Enough?

Are Antidepressants Enough?Zinc, exercise, Vitamin D and potential stress busters top the list of new possibilities to supplement the widespread use of antidepressant medicines. The latest research is welcome because antidepressants only work about half the time, and they often come with unwanted side effects, such as low libido, weight gain, and in some cases (believe it or not) depression.

One approach to new treatments views depression through a different lens. Research published in Current Psychiatry in 2014 has done a review of a variety of new treatments. Researchers Murali Rao, M.D., and Julie M. Alderson, D.O., have reported on such wide-ranging management protocols from stimulation of the brain via electrical and magnetic prompts, stress management techniques from cognitive-behavioral therapy (CBT) and new medications.

CBT has been shown particularly effective in reducing the symptoms of stress and some new medicines are interesting as they seek to influence not only the typical neurotransmitters like dopamine, norepinephrine, and serotonin, but also affect other areas of the brain. Rao and Alderson have sought “to look beyond neurotransmitters for an understanding of depressive disorders” and point toward chronic stress as “the leading cause of depression.”

Stress impacts the brain in a variety of ways, such as changing the communication pathways in the brain, causing brain cells to die off (particularly in the hippocampus region where our ability to feel and recall information is formed), increasing inflammation, and altering neural density. The new treatments are not meant to usurp the existing ones, but rather to be integrated into the treatment arsenal.

At the core of the research is identifying new biomarkers, which are indicators of depression that will look to restore the appropriate balance between excitatory and inhibitory neurotransmitters and hippocampal neurogenesis and regulation of the hypothalamic-pituitary-adrenal axis (HPA), part of the neuroendocrine system that controls our reaction to stress.

The researchers note some promising biomarkers that are being targeted: Monoamine regulators (such as enzymes); proinflammatory cytokines and other inflammatory mediators (such as C-reative protein); mediators of glutaminergic activity (such as kynurenic and quinolinic acid); and GABAergic activity.

Exercise boosts a protein known as BDNF (brain-developed neurotropic factor), which is the protein that helps neurotransmitters perform function more efficiently. To understand the essence of how this happens, researcher Dr. John Ratey, associate clinical professor of psychiatry at Harvard Medical School, describes BDNF as “Miracle-Gro for the brain.”

While exercise isn’t the only thing that can increase the expression of BDNF, it may be one of the more natural and easiest ways. Antidepressants and electroconvulsive therapy also increase BDNF but often come with side effects mentioned above for antidepressants, and memory loss with ECT.

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How effective is exercise? It is now considered an evidence-based treatment both as a stand-alone and an augmentation therapy for depression. Even moderate levels of exercise can be helpful because it enhances the effectiveness of neurotransmitters in your brain and should be considered as an aid in coping with the symptoms of depression. To learn how much exercise you need click here.

Zinc is an “essential trace element” and has long been known as an immune system enhancer for helping to treat colds and ear infections. It has additional antioxidant properties. But it has other healing benefits as well.

Wounds, night blindness, high blood pressure, and thwarting respiratory infections are all positively affected by zinc. It can be found in nuts, dairy, and whole grains as well as in some meats and seafood. But new research shows it may also play an important role in understanding depression.

In 2013 the journal, Biological Psychiatry reviewed 17 studies on depression. The finding? Blood circulating in depressed individuals has lower zinc concentrations than those without depression. What’s more, lower zinc levels means more severe depression when compared to controls.

But the researchers are careful to note that linking lower levels of zinc to depression doesn’t necessarily mean causation. It may be that depression causes the lower levels. The authors concluded that “a causal association between zinc status and depression is biologically plausible.” They also pointed out that lower zinc levels have been associated with cardiovascular disease, which often co-occurs with major depressive disorder (MDD).

Vitamin D, the vitamin we can get from sunshine, is a prohormone, which means it is a substance that can be converted into a hormone. It is unique in that it does not have to be attained through food — it can be synthesized when the skin is exposed to an adequate amount ultraviolet radiation found in natural sunlight.

Vitamin D is helpful in the absorption of calcium and phosphorous through the intestines (which is one reason it is used as an additional supplement with calcium.) It can be ingested through supplements, foods such as salmon, cod liver oil, milk or tuna, or synthesized via sunlight through the skin. It then goes to the liver and kidneys where it is converted into a hormone.

Research shows there is a link between low levels of vitamin D and the symptoms of depression. But just as with zinc, we don’t know if low levels of vitamin D causes depression — or the other way around. Either way the chances are good you may not be getting enough of it.

More than a billion people are vitamin D deficient. Some studies have found that increasing vitamin D can improve well being, but others have questioned its effectiveness.

For now exercise and CBT are the best evidence-based approaches. They appear to be among the best to use in conjunction with antidepressants, or as stand-alone interventions. To check if your levels of zinc and vitamin D are deficient, have your physician do the blood work and ask if supplementation can be of help.

Are Antidepressants Enough?

Daniel Tomasulo, Ph.D.

Dan Tomasulo Ph.D., TEP, MFA, MAPP teaches Positive Psychology in the graduate program of Counseling and Clinical Psychology at Columbia University, Teachers College and works with Martin Seligman, the Father of Positive Psychology in the Masters of Applied Positive Psychology (MAPP) program at the University of Pennsylvania. He is Director of the New York Certification in Positive Psychology for the Open Center in New York City and on faculty at New Jersey City University. Sharecare has honored him as one of the top 10 online influencers on the topic of depression. For more information go to: He also writes for Psych Central's Ask the Therapist column and the Proof Positive blog.

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APA Reference
Tomasulo, D. (2018). Are Antidepressants Enough?. Psych Central. Retrieved on January 28, 2020, from
Scientifically Reviewed
Last updated: 8 Jul 2018 (Originally: 22 Jun 2014)
Last reviewed: By a member of our scientific advisory board on 8 Jul 2018
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