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The American Journal of Psychiatry has just published a meta-analyses of supplements, or nutraceuticals, that, used in adjunction to antidepressants, have evidence of reducing depressive symptoms. The primary positive results were found with SAMe (adenosylmethionine) methylfolate, omega 3 (primarily EPA or ethyl-EPA), and vitamin D. Positive isolated studies were found for creatine, folinic acid, and an amino acid combination. Mixed results were found for zinc, folic acid, vitamin C, and tryptophan. With all the supplements available on the market today for depression, it is important to know which ones are supported by evidence. I would start with these four:

1. SAMe

SAMe has been available in in Europe by prescription since the 1970s for the treatment of various conditions, including depression. It became available in the United States in 1999. In a 2010 double-blind randomized clinical study, participants with major depressive disorder who had not responded to a serotonin reuptake inhibitor (SRI) continued to take their SRI treatment for six weeks. Some of the patients were treated with adjunctive SAMe and some placebo. At the end of the study, the remission rates were higher for patients treated with SAMe than placebo.

In a 2013 open-label, fixed dose, single-blind study published in The Scientific World Journal, researchers evaluated 33 outpatients with major depressive episode who failed to respond to at least eight weeks of treatment with two antidepressants. They were given 800 mg of SAMe for 8 weeks, in addition to their existing medication. At eight weeks, 60 percent of the patients had a significant decrease in Hamilton Rating Scale for Depression (HAM-D) scores, and remission was achieved by 36 percent.

“SAMe may improve depressed mood through enhanced methylation of catecholamines and increased serotonin turnover, reuptake inhibition of norepinephrine, enhanced dopaminergic activity, decreased prolactin secretion, and increased phosphatidycholine conversion,” says the article.

2. Methylfolate

As I explained in another blog, research has linked folate deficiencies to depression. The B vitamin is important for stabilizing our mood. Many of us are folate deficient because up to 40 percent of the general population can’t convert folate to its active form, methylfolate. Lots of folks have a gene mutation in their methylenetetrahydrofolate reductase (MTHFR) enzyme that prevents the conversion.

Supplementing with L-methyfolate, a bioavailable form of folate that plays a role in neurotransmitter synthesis, can improve a person’s response to antidepressant medications. In fact, several studies have documented the enhanced efficacy of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) when taken with L-methyfolate.

In a 2012 study published in the American Journal of Psychiatry, researchers conducted two randomized, double-blind, parallel sequential trials to evaluate the effect of L-methylfolate augmentation in the treatment of major depressive disorder in patients who had a partial response or no response to selective serotonin reuptake inhibitors (SSRIs). Adjunctive L-methylfolate at 15 mg/day showed significant improvement in response rate and degree of change in depression scores as compared to continued SSRI therapy plus placebo.

3. Omega 3

The American Journal of Psychiatry meta-analyses evaluated eight studies of Omega 3 that were double-blind randomized controlled trials. The trials involved both eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) combinations; however analysis showed that the data was stronger when studying EPA-inclusive studies (removing the DHA-only trials). Per the meta-analyses:

The findings from the omega-3 meta-analysis demonstrates this augmentation approach significantly reduces depressive symptoms beyond placebo and thus has potential clinical and public health significance. As detailed in a recent general meta-analysis, it is advised that EPA or ethyl-EPA dominant formulas be used, as DHA may not be effective.

In a 2013 study published in European Neuropsychopharmacology, researchers conducted a randomized, double-blind trial comparing the efficacy of EPA versus DHA as adjuncts to maintenance medication treatments for mild-to-moderate depression. Patients receiving the EPA showed significantly lower scores on the Hamilton Depression Rating Scale (HDRS) than did those receiving DHA or placebo.

I order my Omega 3 from OmegaBrite because their capsules contain 70 percent EPA in a 7:1 ratio of EPA to DHA. I noticed a difference in switching from a brand of mostly DHA to mostly EPA.

4. Vitamin D

As I said in my post, “6 Conditions That Feel Like Depression But Aren’t,” a deficiency in vitamin D will feel very much like depression. Lots of studies have found a close association between depression (or increased odds for depression) and vitamin D deficiencies. And as many as three-quarters of U.S. teens and adults are deficient, according to a 2009 study published in the Archives of Internal Medicine.

In a 2013 study published in the Australian and New Zealand Journal of Psychiatry, researchers compared the therapeutic effects of vitamin D3 plus fluoxetine and fluoxetine alone in patients with major depressive disorder. Patients received either 1500 IU vitamin D3 plus 20 mg fluoxetine or fluoxetine alone for eight weeks. Depression was assessed at two week intervals using the Hamilton Depression Rating Scale (HDRS) and the Beck Depression Inventory (BDI). Depression scores of the group who took the vitamin D in addition to their antidepressant were significantly better than those just taking fluoxetine from the fourth week of treatment.

Per the meta-analyses:

Vitamin D can be considered a neurosteroid, with vitamin D receptors being identified in areas involved with depression, such as the prefrontal cortex, hypothalamus, and substantia nigra. Vitamin D has been revealed to increase the expression of genes, encoding for tyrosine hydroxylase (precursor of dopamine and norepinephrine). Further, a major dopamine metabolite in the striatum and accumbens has been found in methamphetamine-treated animals administered vitamin D.

“To be nobody-but-yourself—in a world which is doing its best, night and day to make you everybody else,” wrote American poet E. E. Cummings, “means to fight the hardest battle which any human being can fight; and never stop fighting.”

According to a recent survey by the charityAction for Happiness, in collaboration with online behavior change program Do Something Different, self-acceptance, or “being comfortable with who you are,” was the factor that best predicted life satisfaction (out of 10 “happy habits”). However, for the 5,000 respondents, it was also the most difficult to do.

Living authentically is not for the weak. The average person does not like to stand out in the crowd, risking rejection and mockery. Perhaps that’s why public speaking is our number one fear, followed by death. As Jerry Seinfeld pointed out, “That means to the average person if you have to be at a funeral, you would rather be in the casket than doing the eulogy.”

Being comfortable with yourself—liking yourself enough not to want to change in order to better blend with the crowd—takes guts, integrity, stamina, and the inner calm of a Tibetan monk.

In her book “Being Perfect,” Anna Quindlen writes:

Nothing important, or meaningful, or beautiful, or interesting, or great, ever came out of imitations. What is really hard, and really amazing, is giving up on being perfect and beginning the work of becoming yourself.

More difficult because there is no zeitgeist to read, no template to follow, no mask to wear. Terrifying, actually, because it requires you to set aside what your friends expect, what your family and your co-workers demand, what your acquaintances require, to set aside the messages this culture sends, through its advertising, its entertainment, its disdain, and its disapproval, about how you should behave.

This is especially true when you have “the little man”—the voice of disapproval or the echo of negative intrusive thoughts, hanging over your every sentence and action during a depressive episode.

Being okay with yourself when you’re depressed is well near impossible because your self-esteem is so far below sea level. It’s all we can really do to force ourselves out of bed in the morning and get three meals a day, right? Forget about aiming for a confident stride.

I haven’t done a good job of writing authentically on this blog, “Sanity Break.” I have wanted to fit in with the site, which is very different from the spirituality site I came from (Beliefnet.com). Because Everyday Health does a great job of covering all kinds of health conditions, offering current research on various illnesses, I thought I should concentrate on all the new studies on different mood disorders and new trends in psychology and neuroscience. I left out much of my story, my frustrations, my insights, and my breakthroughs. Impressed by the other health bloggers on the site, I swapped my voice for one of theirs.

Writing from the heart is terribly difficult when you are not feeling well, and, as I’ve mentioned in places, I have really wrestled with the “black dog” (as Winston Churchill referred to his depression) this last past year. I am gradually getting better, but the journey has been exhausting, and I can see now that I have been without a sense ofhumor—something that I know readers appreciate!—and other trademarks of my writing style for too long.

Next week will mark the one-year anniversary of this blog. I am excited to share with you all what I have learned during this arduous year—my journey to functional (integrative or holistic) medicine, to an eight-week intensive mindfulness-based stress reduction program, to a new nutritional plan that has me drinking kale for breakfast, and to many unusual places that are leading to healing and health.

When I was six months pregnant, I attended a birthing preparation class with my husband and about 12 other expectant parents. During the fifth session, the instructor asked the mothers whether or not they were going to use medication to get through the pain of childbirth labor.

“Everyone who wants to try for a natural birth, stand over here,” she said. “And everyone who plans on having an epidural or taking other pain medication, stand over here.”

I looked at the two groups, which held about the same number of people. My head went from one to the other, much like a puppet with a tic. Like most decisions in my life (including which dressing I want on my salad), I had analyzed the hell out of this one — done all the research on both sides — and still couldn’t commit.

“What a feeling of triumph to be able to do it without drugs,” I thought to myself. “I could wear a T-shirt for the rest of my life that says, WOMAN WARRIOR: I GAVE BIRTH NATURALLY.” But I also knew that acute pain — just like severe depression — has devastating effects on the body, and that white-knuckling it isn’t always the heroic thing to do. Plus, I’m not a huge fan of pain. I try not to bring it on when I don’t have to. I could see myself wearing another T-shirt, too: PAIN IS NOT MY FRIEND: I CAVED TO THE EPIDURAL.

I walked up to the two groups and stood in the middle of them.

Alone.

“I’m undecided,” I explained to both camps, who glared at each other with disdain.

I’ve tried my best to stay in that spot — in the middle, gazing at the opposing sides from my peripheral vision — for most of my time as a mental-health blogger. I believe that the center is by far the most interesting place to be, because you get to read the memos from each group and decide whether or not you agree.

But it also gets lonely.

And that’s because the world of medication is so divisive, especially when it comes to using antidepressants or any kind of psychotropic medication to treat depression and anxiety. There is the camp that believes anyone who uses them is avoiding the hard work that has to be done to move beyond sadness — that the meds are agents of evil, poisoning our systems with harmful toxins. And then there is the camp that believes that medication is the one-and-only way of treating depression, that mood disorders are strictly biological and can’t benefit from any introspective work, and that the disorders are in no way influenced by one’s diet or lifestyle habits.

For the first 10 years of my blogging life, I was publicly pummeled for “copping out” and popping pills. People called me irresponsible for disseminating harmful information to the public, accused me of sleeping with Big Pharma (even though I never saw any cash), and also of being weak, small-minded, and caving to a popular culture that says good health is only one prescription away. I’ve never believed that medication alone will heal you from depression — that a script is all you need to get to sanity. But that’s what some people heard.

Now I’m getting lambasted from the other side. I’m getting the “Shame on you” a lot for pursuing natural therapies to treat depression, and thereby supposedly influencing people to go off of their meds, which could “kill 20 people.” The tragedies that are so often attached to mental illness in the news are the fault of people like me who encourage folks to mistrust psychiatry.

Let me say this about medication:

I would not be alive today without it.

I credit my psychiatrist for saving my life in March of 2006.

I believe that antidepressants and mood stabilizers are agents of healing.

There is absolutely a place for medication, and I would never say otherwise.

When I was holed up in my bedroom closet, sobbing in fetal position with a bag of prescriptions that I intended to use to flatten my pulse, I was incapable of pursuing the steps I am now — Bikram yoga, helping others, working with an integrative doctor — to deliver me from that hell. Rarely did I have the stamina to make it to the grocery store, let alone to blend green smoothies and learn how to cook nutritious meals. It was through the intervention of a skillful doctor, and the right combination of meds, that I stabilized.

Being on meds was absolutely the right thing to do.

But over the last seven years, I have not responded to the medications as I did earlier in my life. They have failed to bring relief from my death thoughts. Plus, their side effects compromised my health in ways that were keeping me depressed.

For example, I believe (after reviewing some research) that my experimentation with antipsychotics, or possibly my long-term use of Zoloft (sertraline), is what caused my pituitary tumor, which completely throws off the hypothalamic-pituitary-adrenal axis that is critical to mood. If the tumor gets big enough, it can affect your vision and even render you blind (the pituitary gland pushes up next to the optical nerve). To manage the growing tumor, I went on a medication called Cabergoline, which, according to research, is linked to aortic valve regurgitation, which I now have — andthe connection between cardiovascular disease and depression has long been established. At the same time, I developed hypothyroidism and some expanding nodules in my thyroid gland that can happen with Lithium use. As I’ve written in the past, the thyroid is a delicate and powerful gland that governs so many essential activities in our body related to hormones and mood. Finally, many of my medications have gastrointestinal side effects, which I suspect have something to do with my current inflammatory bowel disease. Our gut is our second brain, so problems there leak into anxiety and depression.

Therefore, I was forced to look into other kinds of therapies to treat my symptoms.

If I’ve been inching closer to the tree-hugger camp in my writing as of late, it’s only to make these two points:

1. Diet and lifestyle are more effective than I previously thought to managesymptoms of depression, if you know what you’re doing: some adjustments COULD help reduce the amount of medication you need to take.
2. Medications aren’t risk-free. Their side effects can inadvertently contribute to your depression and negatively impact your health for years to come, so do your homework.

Ultimately, though, it’s about doing a cost-benefit analysis.

I would live with blindness and a goiter the size of a football if that’s what I had to do to stay alive. Chronic illness isn’t fun, but it’s better than being dead. And if I felt some relief from the medications, I would tolerate a host of side effects. I believe a person should take the course he or she needs in order to relieve the most suffering. So in my case, when the negatives began to outweigh the positives, I knew it was time to take my health in a different direction.

That’s not to say I don’t support the use of medication for people who struggle with depression.

My son’s birth ended up being a traumatic one. I held off on the epidural until the very last moment, but was glad I had taken it, because when his heart rate began to plummet, the doctors performed an emergency C-section. Had I opted to do it naturally, they would have completely knocked me out for the surgery, and I would have missed the entire birth.

Modern science saved little David’s life, much like my own.

Fifteen years later, if I were in that birthing class, I’d stand in the same place.

Consider these statistics:

• Nearly 50 percent of asthma patients have symptoms of depression.
• At least 40 percent of people with Parkinson’s disease experience depression, and anxiety is often reported.
• 45 percent to 65 percent of people who have had a heart attack live with depression.
• The lifetime risk for depression in people with multiple sclerosis (MS) is 40 percent to 60 percent.
• Nearly 30 percent of stroke patients develop depression.

A 2009 study published in Archives of Gerontology and Geriatrics confirms that “when pain is severe, impairs function, and/or is refractory to treatment, it is associated with more depressive symptoms and worse depression outcomes. Similarly, depression in patients with pain is associated with more complaints and greater functional impairment.” The study goes on to explain that there is growing evidence that “depression and pain share genetic factors, biological pathways, and neurotransmitters. Thus, the most promising area of future research is elucidating the neurobiological alterations in pain pathways that intersect with those involved in depression.”

This is important to know since, according to research published by the Robert Wood Johnson Foundation, the number of people with chronic illnesses will increase 37 percent, or 46 million people, between 2000 and 2030. That means those of us who are predisposed to depressive episodes to begin with would be wise to familiarize ourselves with those illnesses that are most often associated with depression and can exacerbate our symptoms. The following 10 are a good start.

1. Parkinson’s Disease

The National Parkinson Foundation’s Parkinson’s Outcomes Project, the largest clinical study of Parkinson’s disease ever conducted, shows that depression is the most important factor influencing the health status of people with Parkinson’s. According to the study: “A clear finding from our study is that, taken together, mood, depression, and anxiety, have the greatest effect on quality of life, even more than the motor impairments commonly associated with the disease. Further, our analysis found that QII [quality improvement initiative] participants who receive care from clinics with the most active approach to psychological counseling report the lowest rates of depression.”

2. Heart Disease

Depression is three times more common in people after a heart attack than in the general public, with 15 to 20 percent of heart attack victims qualifying for a diagnosis of major depression disorder and many others experiencing depression symptoms. “Depression after a heart attack is bad not only because of the accompanying emotional distress and suffering,” says Redford B. Williams, MD, professor of psychiatry at Duke University Medical Center in Durham, North Carolina, “it also increases one’s risk of having another heart attack or dying over the ensuing months and years.” People with heart disease who are depressed tend to have more cardiac symptoms than those who are not depressed. Depression and anxiety affect heart rhythms, increase blood pressure, elevate insulin and cholesterol levels, and raise levels of stress hormones.

3. Stroke

Nearly 30 percent of stroke patients develop depression, either in the early or in the late stages after a stroke, according to a study published in the medical journalNeuropsychiatric Disease and Treatment. It is so common that the Diagnostic and Statistical Manual (DSM)-5 categorizes “post-stroke depression” as a mood disorder (due to a general medical condition, i.e., stroke). Stroke causes physical damage to the brain, affecting brain cells that monitor mood and mental function. It’s also a frightening experience that can cause trauma. Although depression may affect functional recovery and quality of life after stroke, it is often ignored. In fact, only a minority of patients are diagnosed and even fewer are treated in the common clinical practice.

4. Dementia

Up to 40 percent of people with Alzheimer’s disease may also experience severe depression according to the Alzheimer’s Association. In fact, a new study published in the journal Neurology found that for people who develop Alzheimer’s disease, depression and other “noncognitive” changes can happen before any of the hallmark symptoms like memory and thinking problems associated with the disease. Another report in the British Journal of Psychiatry found that depressed older adults (over the age of 50) were more than twice as likely to develop vascular dementia and 65 percent more likely to develop Alzheimer’s disease than people who weren’t depressed. It can be difficult to distinguish depression in persons with dementia because the symptoms are similar: a lack of interest in hobbies and activities, difficulty communicating, weight loss, and difficulty sleeping.

5. Hypertension

High blood pressure can impact depression; however, it is more likely that depression affects high blood pressure. Stress hormone levels are raised during depressive episodes, which, in turn, elevates blood pressure. Acute stress and severe depression will elevate blood pressure to the point where damage to blood vessels is caused.

6. Diabetes

I was shocked to find out how many people in my depression communities, Project Beyond Blue and Group Beyond Blue, have diabetes. In a 2010 study published in the Archives of Internal Medicine, it was determined that the diabetes-depression relation is, in fact, “bidirectional,” meaning that just as people with diabetes have a higher risk for developing depression than those without the condition, people who have depression are more likely to develop diabetes, at least type 2 diabetes. “We can say that the two conditions are linked to each other and are both the causes and the consequences of each other,” says the study’s senior author, Frank Hu, MD, PhD, professor of nutrition and epidemiology at Harvard School of Public Health.

7. Cancer

The prevalence of mood disorders among persons with cancer can vary depending on the type of cancer and its clinical stage. In an older 1983 study published in theJournal of the American Medical Association, 47 percent of the patients were diagnosed with a kind of psychiatric disorder — most of them adjustment disorders. However, a more recent study published in the journal Cancer shows that 53.7 of people with terminal cancer were diagnosed with a psychiatric disorder: delirium, dementia, adjustment disorders, major depression, or generalized anxiety disorder.

8. Multiple Sclerosis

Depression is the most frequent psychiatric diagnosis in people with MS, according to a study published in the Journal of Rehabilitation Research & Development. The lifetime risk for depression in people with MS ranges from 40 to 60 percent. Depression could be a result of the disease process, since MS damages the myelin and nerve fibers deep within the brain — areas involved in emotional expression and control. Depression may also be associated with changes that occur in the immune and neuroendocrine systems. According to the study, “the etiology of depression is multifactorial and likely associated with psychosocial stress, focal demyelinating lesions, and immune dysfunction.”

9. Asthma

I was surprised to learn that nearly 50 percent of people with asthma may experience clinically significant depressive symptoms. The stress involved in having this particular illness and the disruptive symptoms seem to be what contribute most to psychiatric diagnoses. For example, those who experience dyspnea and nighttime awakening are at increased risk for major depression according to a study published in the Medical Journal of Australia. Asthma has also been associated with anxiety in a study of children and adolescents. In general, the depression and anxiety is worse among persons whose asthma is difficult to control: 87.5 percent of people with frequent asthma attacks experienced mood disruptions, compared to 25 percent of people with less frequent attacks, according to other research.

10. Arthritis

A study from the Centers for Disease Control and Prevention published in the journal Arthritis Care & Research indicates that one third of Americans aged 45 years and older with arthritis have either anxiety or depression. Interestingly enough, anxiety was almost twice as common as depression. Most people who had depression (85 percent) also had anxiety. But only half (50 percent) of the people who had anxiety also had depression. The study suggests that everyone with arthritis may be at risk for mood disruptions, and that screening all adults with arthritis for anxiety and depression is more important than ever, especially since the results found that only 50 percent of those with anxiety and depression sought help in the past year.