About depression

Depression, also known as major depressive disorder, clinical depression, major depression and unipolar depression, is a physical illness characterized by a pervasive and persistent low mood, accompanied by low self-esteem, loss of interest in life and loss of pleasure in normally enjoyed activities. There may be a sleep disturbance, an appetite change, anxiety, feelings of fear, loss of energy, worry, feelings of guilt, and difficulty with memory and concentration.

It is important to stress that depression is a physical illness not a psychological disorder. If moderate or severe, depression has adverse medical consequences and – in more severe cases – carries a risk of suicide. About a million people kill themselves every year in the world and about 36,000 people in the USA kill themselves every year.


Moderate to severe depression requires prescription antidepressant medication, which San Luis Integrative Medicine will provide. In 35 years of practicing medicine, Dr. Cannell has seldom seen a patient with depression that failed to get better with aggressive treatment. The mainstay of treatment is prescription antidepressant medications, of which there are many different ones.

At San Luis Obispo Integrative Medicine, we prescribe proper antidepressants as well as anti-anxiety and sleep medications to immediately help with depressive symptoms. We also think that certain supplements and dietary changes are important in treating and preventing depression.

Complimentary and holistic treatments for depression

With mild to moderate depression, proper supplements may help a lot. Based on your condition, we will implement some of these into your treatment.

Vitamin D

Vying for the title of most important supplement in depression is vitamin D at proper doses, but this assertion remains to be proven. Lower blood vitamin D levels were found in people with depression compared with non-depressed controls and there is a significantly increased risk of depression in those with the lowest vitamin D levels compared to the highest.[5] The same review found that prospective studies show a doubled risk of depression for those who started the study with the lowest vitamin D levels. In an 8-week randomized controlled trial, vitamin D plus Prozac was more effective than Prozac alone.[6]

Vitamin D controls several very important genes in the brain; one of them is the gene that makes the enzyme, tyrosine hydroxylase.[7] Tyrosine hydroxylase is the rate-limiting step for the production of the neurotransmitters epinephrine, norepinephrine and dopamine. Vitamin D also regulates tryptophan hydroxylase, which is the enzyme that makes serotonin from tryptophan.[8] So, given adequate amino acid building blocks such as tryptophan, vitamin D will certainly affect the functioning of the brain.

No one knows if high doses of vitamin D alone would serve as an effective anti-depressant but Dr. Cannell’s experience at San Luis Obispo Integrative Medicine indicates the right dose of vitamin D serves as an effective antidepressant in many people, especially when taken with tryptophan.


Perhaps the most important supplements in mild depression is S-adenosyl-methionine or SAMe. More than 40 metabolic reactions involve the transfer of a methyl group from SAMe to various important building blocks in the body. However, SAMe is expensive, especially if one takes the right dose, which is 800 to 1600 mg/day in a divided dose, preferably on an empty stomach. SAMe is as effective as imipramine (an old but effective antidepressant) in treating depression.[1] Some other research suggests that SAMe is more effective than placebo in treating mild-to-moderate depression and is just as effective as antidepressant medications without the side effects (headaches, sleeplessness, and sexual dysfunction). In addition, antidepressants tend to take 6-8 weeks to begin working, while SAMe seems to begin more quickly. Researchers speculate SAMe might increase the amount of serotonin in the brain (just as some antidepressants do). However, SAMe can cause mania so should be taken with caution by anyone with bipolar disorder.shutterstock_111315713

Saint John’s Wort

The other supplement (actually a herb) that is effective treatment in depression is Saint John’s Wort (SJW). However, it has as many interactions with other medications as do conventional antidepressants. The standard dose for adults is 300 milligrams of SJW (0.3% hypericin extract) taken three times a day but higher doses have been used in clinical trials. A Cochrane Review (one of the most respected reviews in medicine) found SJW to be superior to placebo in patients with major depression and as effective as standard antidepressants but with better tolerability and concluded that it was effective treatment for mild to moderate depression.[2] It can trigger mania in those with bipolar disorder.


Another supplement that has been shown to be effective in mild to moderate depression is folate especially L-methylfolate. The association of depressive symptoms and folate deficiency has been known for five decades. Numerous studies have found low serum folate levels or low RBC folate concentrations in depressed patients. Other studies suggested that low folate levels are associated with reduced response to antidepressants, which in turn suggested that folic acid might be used to augment antidepressants. The antidepressant dose of L-methylfolate is 15 mg/day. Two large chain pharmacies report that a 30-day supply of L-methylfolate at 15 mg/day costs about $90, and it is not likely to be covered by insurance. The efficacy of L-methylfolate in treatment resistant depression has not been compared with that of other treatment agents, nor has long-term use of the agent been studied.


Yet another supplement that may be useful in depression is tryptophan. It is the precursor to serotonin and melatonin in the brain. A 2002 Cochrane review concluded, “Available evidence does suggest these substances (tryptophan) are better than placebo at alleviating depression.”[3] However, adequately conducted studies were rare. The dose of tryptophan is 500 to 2,000 mg before sleep on an empty stomach. However, tryptophan can cause severe side effects when taken along with some antidepressant medications. Taken with many prescription antidepressants, it can produce the central serotonergic syndrome.

The serotonergic syndrome can be fatal. When mild, it causes increased agitation, increased heart rate, shivering, sweating, dilated pupils, muscle twitching and hyperactive reflexes. Moderate serotonergic intoxication includes additional signs such as increased bowel sounds, high blood pressure and elevated body temperature. Severe symptoms include severe increases in heart rate and blood pressure that may lead to shock. Temperature may rise to above 106 in life-threatening cases.


Omega-3 fatty acids such as fish oil have been shown, in some studies, to help depression. However, the fish oil used may need to be more than 60% EPA as opposed to DHA.[4] That is, some studies show that more than 60% of the total omega-3 fats in the fish oil formulation must be EPA. The total dose of fish oil should be approximately 3 grams per day.shutterstock_132113294


  1. Delle Chiaie R, Pancheri P, Scapicchio P.  Efficacy and tolerability of oral and intramuscular S-adenosyl-L-methionine 1,4-butanedisulfonate (SAMe) in the treatment of major depression: comparison with imipramine in 2 multicenter studies. Am J Clin Nutr. 2002 Nov;76(5):1172S-6S.
  2. Linde K, Berner MM, Kriston L; St John’s wort for major depression. Cochrane Database Syst Rev. 2008 Oct 8;(4):CD000448.
  3.  Shaw K, Turner J, Del Mar C. Tryptophan and 5-hydroxytryptophan for depression. Cochrane Database Syst Rev. 2002;(1):CD003198. Review.
  4. Sublette ME, Ellis SP, Geant AL, Mann JJ. Meta-analysis of the effects of eicosapentaenoic acid (EPA) in clinical trials in depression.  J Clin Psychiatry. 2011 Dec;72(12):1577-84.
  5. Anglin RE, Samaan Z, Walter SD, McDonald SD.  Vitamin D deficiency and depression in adults: systematic review and meta-analysis. Br J Psychiatry. 2013 Feb;202:100-7.
  6. Khoraminya N, Tehrani-Doost M, Jazayeri S, Hosseini A, Djazayery A. Therapeutic effects of vitamin D as adjunctive therapy to fluoxetine in patients with major depressive disorder. Aust N Z J Psychiatry. 2013 Mar;47(3):271-5.
  7.  Cui X, Pelekanos M, Liu PY, Burne TH, McGrath JJ, Eyles DW. The vitamin D receptor in dopamine neurons; its presence in human substantia nigra and its ontogenesis in rat midbrain. Neuroscience. 2013 Apr 16;236:77-87.
  8. Wang, T. T. et al. Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol 19, 2685-2695, doi:10.1210/me.2005-0106 (2005).