About bipolar disorder

ladyIndividuals with bipolar disorder experience episodes of an elevated or agitated mood known as mania (or hypomania, which simply means a little mania) alternating with episodes of depression. Bipolar disorder used to be called manic-depressive illness; the two disorders are one in the same.

Mania can occur with different levels of severity. At milder levels of mania, called “hypomania”, individuals are energetic, excitable, goal directed, require less sleep, but may be highly productive. As mania becomes more severe, individuals begin to behave erratically and impulsively, often making poor decisions due to unrealistic ideas about the future, and often need very little sleep. They report as if they are driven with extra energy. At the most severe level, individuals can lose touch with reality, called psychosis. Mixed episodes include mania or hypomania mixed with depression or anxiety.

Bipolar disorder is incredibly common with 4% of the population suffering from it at some point in their life. Late adolescence and early adulthood are peak years for the onset of bipolar disorder. However, one study also found that in 10% of bipolar cases, the onset of mania had happened after the patient had turned 50.

Two major categories of bipolar disorder exist. Bipolar I disorder exists when patients have one or more manic episodes. A depressive episode is not required for diagnosis, but it frequently occurs after the mania.

Bipolar II disorder is diagnosed when no manic episodes occur, but one or more hypomanic episodes and one or more major depressive episodes occur. Bipolar II disorder is more difficult to diagnose than Bipolar I disorder, as hypomanic episodes may simply appear as a period of successful high productivity and patients report it less frequently than they do a depression.

How we treat bipolar disorder

The primary treatment for bipolar disorder consists of medications (mood stabilizers and atypical antipsychotics), which are used to prevent or control episodes of mania or depression. Mood stabilizers include lithium, Depakote, Lamictal, Trileptal and others. Many mood stabilizers are also used to control epilepsy. Atypical antipsychotics include Zyprexa, Abilify, Seroquel, Geodon, Risperdal and others.

Many patients also require an antidepressant after their mania or hypomania is stabilized. However, antidepressants should be avoided if possible as they often trigger mania and its subsequent depression. Usually antidepressants are not used until the mood is stabilized. Wellbutrin is commonly prescribed for bipolar depression as some studies show it is less likely to induce mania.

Many if not most individuals with bipolar disorder require a combination of medication to achieve full remission of symptoms. Also, many individuals with bipolar disorder also have anxiety disorders such as panic disorder and thus may need multiple medications. As it is impossible to predict which medications will work best for a particular individual, it may take some trial and error to find the best medication or combination for a specific patient. In bipolar disorder, depression is the main complaint as mania and hypomania may be enjoyable to the patient until the episodes end and depression follows.

Except in mild cases, the mainstay of treatment of bipolar disorder is prescription medication. In mild depression with mild hypomania some of the supplements listed below may be tried alone. However, for most patients with bipolar disorder, supplements are adjunctive treatments and never take the place of prescription medication.

However, for mild to moderate bipolar depression, proper supplements may help a lot. Perhaps the single 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.,sup>1  However, like most effective antidepressants, SAMe can trigger mania.

patient doctorSome 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.

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 Like most effective antidepressants, it can also 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 meta-analysis 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 degrees in life-threatening cases. Antidepressants combined with the pain killer Tramadol frequently causes the serotonergic syndrome.

Several studies have shown fish oil is effective in bipolar depression. A recent systematic review of clinical trials using nutrient-based nutraceuticals in combination with standard pharmacotherapies to treat bipolar disorder showed that omega-3 fatty acid as adjunctive treatment results significant improvement in bipolar depression.4

The body’s master antioxidant, glutathione, is reduced in depressed brains. The rate-limiting (controlling) step for the production of glutathione in the brain is the amount of the amino acid cysteine in the diet. As part of your treatment for bipolar depression, you will be put on a special multivitamin/mineral/supplement product that contains cysteine. In addition, you will be encouraged to use a protein powder that is rich in cysteine. In some patients extra cysteine will be required as a study has shown such supplementation is beneficial in depression.5  A recent systematic review of clinical trials indicated that adjunct treatment of a common formulation of cysteine, N-acetyl cysteine, together with standard pharmacotherapies for bipolar disorder show positive evidence with large improvements noted in the N-acetyl cysteine groups.6

Perhaps the single 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.7 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.8

Vitamin D controls several very important genes in the brain; one of them is the gene that makes the enzyme, tyrosine hydroxylase.9 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.10 So, given adequate amino acid building blocks such as tryptophan, vitamin D will certainly affect the functioning of the brain.

We will also put you on a multivitamin preparation that contains many vitamins, antioxidants, vegetable extracts and minerals that some studies show will help depression. For example, selenium has been shown to help mood in randomized placebo controlled trials and you will be getting plenty of selenium.11 That same special multivitamin formula we will put you on has enough zinc in it to have an independent antidepressant effect,12 as well as enough magnesium, another mineral often deficient in depression.13


  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. Sarris J, Mischoulon D, Schweitzer I. Omega-3 for bipolar disorder: meta-analyses of use in mania and bipolar depression. J Clin Psychiatry Jan 2012;73(1):81–6.
  5. Berk M, Dean O, Cotton SM, Gama CS, Kapczinski F, Fernandes BS, et al. The efficacy of N-acetylcysteine as an adjunctive treatment in bipolar depression: an open label trial. J Affect Disord 2011;135:389–94.
  6. Sarris J, Mischoulon D, Schweitzer I. Adjunctive nutraceuticals with standard pharmacotherapies in bipolar disorder: a systematic review of clinical trials. Bipolar Disord 2011;13:454–65.
  7. 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.
  8. 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.
  9. 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.
  10. 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).
  11. Benton D. Selenium intake, mood and other aspects of psychological functioning. Nutr Neurosci. 2002 Dec;5(6):363-74. Review.
  12. Maes M, Galecki P, Chang YS, Berk M. A review on the oxidative and nitrosative stress (O&NS) pathways in major depression and their possible contribution to the (neuro)degenerative processes in that illness. Prog Neuropsychopharmacol Biol Psychiatry 2011;35:676–92.
  13. Derom ML, et al. Magnesium and depression: a systematic review. Nutr Neurosci. 2013 Sep;16(5):191-206.