Bipolar Disorder

Also indexed as: Cyclothymia, Manic Depression

Bipolar disorder is a mood disorder characterized by alternating states of depression and mania that follow each other in a repeating cycle. People with bipolar disorder may cycle through these states quickly or may experience long periods of depression or mania. Often one mood state predominates, while the other occurs only infrequently or briefly. The cause of bipolar disorder is unknown.

Checklist for Bipolar Disorder

Rating Nutritional Supplements Herbs
2Stars Vitamin-mineral-amino acid formula (currently proprietary)
Fish oil		  
1Star 5-HTP
Choline
Folic acid
Inositol
SAMe
Vitamin B12
Vitamin C		  
3Stars Reliable and relatively consistent scientific data showing a substantial health benefit.
2Stars Contradictory, insufficient, or preliminary studies suggesting a health benefit or minimal health benefit.
1Star An herb is primarily supported by traditional use, or the herb or supplement has little scientific support and/or minimal health benefit.

What are the symptoms of bipolar disorder? Symptoms of the elevated mood stage of bipolar disorder include an exaggerated sense of confidence and well-being, racing thoughts, excessive talking, distractibility, increased desire for pleasurable activity, decreased need for sleep, impulsivity, irritability, and impairment in judgment. The depressed phase includes symptoms of sadness, fatigue, pessimism, feelings of helplessness, low self-esteem, and loss of interest in life, possibly with thoughts of suicide.

How is it treated? Conventional treatment includes medications such as lithium carbonate, valproate, carbamazepine, and lamotrigine to stabilize the mood and offset depression. In addition, psychological therapies and sleep management are sometimes recommended. Other medications, such as antidepressants, antipsychotics, and antianxiety drugs, are also common components of conventional treatment. In severe cases requiring hospitalization due to rapid or pronounced mood swings, electroconvulsive therapy (electrical impulses applied to the brain) may be administered.

Lifestyle changes that may be helpful: Exercise influences the production and use of neurotransmitters and hormones in the body, and its antidepressant effect is well known.1 A preliminary study of the effects of vigorous exercise on the body chemistry of patients with bipolar disorder found that exercise increased a specific chemical associated with better mood.2 However, exercise may adversely influence the effectiveness of some medications used for bipolar disorder. Many people with bipolar disorder take lithium, and because lithium is lost in sweat, exercise that involves significant sweating may change blood levels of lithium. Such a change has been reported in one person;3 therefore, people taking lithium who intend to start a vigorous exercise program should be monitored by their doctor.

Nutritional supplements that may be helpful: People diagnosed with depression may have lower blood levels of omega-3 fatty acids.4 5 A double-blind trial found that bipolar patients taking 9.6 grams of omega-3 fatty acids from fish oil per day in addition to their conventional medications had significant improvements compared with those taking placebo.6

L-tryptophan is the amino acid used by the body to produce serotonin, a chemical messenger important for proper brain function. Supplementation with L-tryptophan has led to improvement in depression in many studies,7 8 but information is limited about its effect on bipolar disorder. Case reports on two bipolar patients treated with lithium or an antidepressant drug described marked improvements when they were given 12 grams daily of L-tryptophan.9 10 Two trials using 6 grams of L-tryptophan daily for acute mania in patients with bipolar disorder found little or no improvement,11 12 but another double-blind, controlled study using 9.6 grams daily reported better results.13

L-tryptophan is converted to 5-hydroxytryptophan (5-HTP) before it becomes serotonin in the body. In a controlled trial, 200 mg daily of supplemental 5-HTP had antidepressant effects in bipolar patients, though it was not as effective as lithium.14 In a double-blind trial, patients with bipolar disorder had greater improvement with a combination of 5-HTP at 300 mg daily plus an antidepressant drug than with 5-HTP alone.15

S-adenosylmethionine (SAMe) is another amino acid that has an impact on serotonin levels, and it has demonstrated significant antidepressant effects in clinical trials.16 17 18 In both controlled and preliminary studies, SAMe has been shown to be helpful for the depressive symptoms of bipolar disorder. However, some patients have switched from depression to mania while using SAMe at 500 to 1,600 mg daily.19 20 This is a known side effect of other antidepressant medications.21 The mania induced by SAMe resolved when the supplement was discontinued, and in one case resolved spontaneously while the patient continued taking SAMe.22 Therefore, people with bipolar disorder should supplement with SAMe only under the supervision of a qualified healthcare practitioner.

Both folic acid and vitamin B12 are used in the body to manufacture serotonin and other neurotransmitters. It is well known that deficiency of either nutrient is associated with depression.23 24 There is some evidence that patients diagnosed with mania are also more likely to have folate deficiencies than healthy controls.25 Other studies, however, have found that folic acid deficiency was not more common in bipolar patients taking lithium than in healthy people.26 27 28 Some studies have found that people who take lithium long term, and who also have high blood levels of folic acid, respond better to lithium.29 30 Not all studies have confirmed these findings, however.31 A double-blind study of patients receiving lithium therapy showed that the addition of 200 mcg of folic acid per day resulted in clinical improvement, whereas placebo did not.32

There have been case reports of both mania and depression associated with vitamin B12 deficiency, and these symptoms cleared after treatment with injections of B12.33 34 However, B12 deficiency has not been reported in bipolar disorder patients, and no studies have been published investigating the effects of vitamin B12 supplementation in people with bipolar disorder.

Vitamin C helps the body to reduce its load of vanadium and this has been studied for its possible role in treatment of bipolar disorder.35 A double-blind trial found that both manic and depressed bipolar patients were significantly improved after one-time administration of 3 grams of vitamin C, compared with a placebo.36 The same study found that both manic and depressed patients did better on a reduced-vanadium diet compared to a normal diet. Another double-blind study reported that 4 grams per day of vitamin C in combination with a drug known as EDTA (which also helps remove elements such as vanadium from the body) was helpful to depressed bipolar patients but not to those experiencing mania.37 Until more is known, people with bipolar illness should avoid supplements containing vanadium and consider supplementing with vitamin C.

Inositol is a nutrient found in large amounts in the brain, but its possible role in mood disorders is unclear. Inositol levels may be reduced in certain parts of the brains of depressed and bipolar patients.38 However, lithium reduces normal brain levels of inositol, and this may be one of the ways lithium helps people with bipolar disorder.39 40 41 Although inositol is known to have significant antidepressant properties when administered in large amounts of 12 grams per day,42 43 case reports involving bipolar patients have reported either no benefit,44 some benefit,45 or worsening of symptoms from inositol supplementation.46 Until controlled research clarifies the effects of inositol in people with bipolar illness, it should only be used under the supervision of a qualified healthcare practitioner.

Acetylcholine levels in the brain may affect mood disorders, and supplemental choline can increase acetylcholine levels. In a preliminary trial, six people with bipolar disorder were given 1 to 2 grams of choline twice per day (2 to 4 grams per day). Five of the six had a significant reduction in manic symptoms, and four of the six had a reduction in all mood symptoms.47 No properly controlled trials have yet investigated the effects of choline in treating people with bipolar disorder.

Restriction of dietary calcium was reported to alleviate manic episodes in one bipolar patient, and calcium supplementation (approximately 800 mg per day) increased mania symptoms slightly in six manic-depressive patients, according to another uncontrolled report.48 Therefore, if calcium supplementation is desired by people with bipolar disorder, it should be taken with caution.

Lithium is a mineral contained in certain drugs used in the medical treatment of bipolar disorder. Lithium may be present in some trace mineral supplements, but amounts are too small to have any effect on bipolar disorder.

Vanadium is a trace mineral nutrient that may adversely influence bipolar disorder. Elevated blood and hair levels of vanadium have been reported in people with mania and depression, and one effect of the bipolar medication lithium is to interrupt a biochemical action of vanadium in the body.49 Vanadium is therefore one suspect in the search for a cause of bipolar disorder. People with bipolar disorder should avoid supplements containing vanadium until more is known.

In a preliminary trial, 11 patients with bipolar disorder were treated for six months with a moderate-potency vitamin-mineral formula (E.M. Power+ manufactured by Evince International, of Farmington, Utah) that also contained a proprietary blend of amino acids and other nutrients. The severity of depression decreased on average by 71% and the severity of mania decreased by 60% during the study.50 A double-blind study is needed to confirm these promising results.

Are there any side effects or interactions? Refer to the individual herb for information about any side effects or interactions.

References:

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24. Fine EJ, Soria ED. Myths about vitamin B12 deficiency. Southern Med J 1991;84:1475–81.

25. Hasanah CI, Khan UA, Musalmah M, Razali SM. Reduced red-cell folate in mania. J Affect Disord 1997;46:95–9.

26. McKeon P, Shelley R, O’Regan S, O’Broin J. Serum and red cell folate and affective morbidity in lithium prophylaxis. Acta Psychiatr Scand 1991;83:199–201.

27. Lee S, Chow CC, Shek CC, et al. Folate concentration in Chinese psychiatric outpatients on long-term lithium treatment. J Affect Disord 1992;24:265–70.

28. Stern SL, Brandt JT, Hurley RS, et al. Serum and red cell folate concentrations in outpatients receiving lithium carbonate. Int Clin Psychopharmacol 1988;3:49–52.

29. Coppen A, Abou-Saleh MT. Plasma folate and affective morbidity during long-term lithium therapy. Br J Psychiatry 1982;141:87–9.

30. Lee S, Chow CC, Shek CC, et al. Folate concentration in Chinese psychiatric outpatients on long-term lithium treatment. J Affect Disord 1992;24:265–70.

31. Stern SL, Brandt JT, Hurley RS, et al. Serum and red cell folate concentrations in outpatients receiving lithium carbonate. Int Clin Psychopharmacol 1988;3:49–52.

32. Coppen A, Chaudhry S, Swade C. Folic acid enhances lithium prophylaxis. J Affect Disord 1986;10:9–13.

33. Goggans FC. A case of mania secondary to vitamin B12 deficiency. Am J Psychiatry 1984;141:300–1.

34. Verbanck PM, LeBon O. Changing psychiatric symptoms in a patient with vitamin B12 deficiency. J Clin Psychiatry 1991;52:182–3 [letter].

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36. Naylor GJ, Smith AH. Vanadium: a possible aetiological factor in manic depressive illness. Psychol Med 1981;11:249–56.

37. Kay DS, Naylor GJ, Smith AH, Greenwood C. The therapeutic effect of ascorbic acid and EDTA in manic-depressive psychosis: double-blind comparisons with standard treatments. Psychol Med 1984;14:533–9.

38. Shimon H, Agam G, Belmaker RH, et al. Reduced frontal cortex inositol levels in postmortem brain of suicide victims and patients with bipolar disorder. Am J Psychiatry 1997;154:1148–50.

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40. Belmaker RH, Agam G, van Calker D, et al. Behavioral reversal of lithium effects by four inositol isomers correlates perfectly with biochemical effects on the PI cycle: depletion by chronic lithium of brain inositol is specific to hypothalamus, and inositol levels may be abnormal in postmortem brain from bipolar patients. Neuropsychopharmacology 1998;19:220–32 [review].

41. Belmaker RH, Bersudsky Y, Agam G, et al. How does lithium work on manic depression? Clinical and psychological correlates of the inositol theory. Annu Rev Med 1996;47:47–56 [review].

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43. Levine J, Barak Y, Kofman O, Belmaker RH. Follow-up and relapse analysis of an inositol study of depression. Isr J Psychiatry Relat Sci 1995;32:14–21.

44. Souza FG, Mander AJ, Foggo M, et al. The effects of lithium discontinuation and the non-effect of oral inositol upon thyroid hormones and cortisol in patients with bipolar affective disorder. J Affect Disord 1991;22:165–70.

45. Grisaru N, Belmaker RH. Lithium dosage and inositol levels. Br J Psychiatry 1994;164:133–4 [letter].

46. Levine J, Witztum E, Greenberg BD, Barak Y. Inositol-induced mania? Am J Psychiatry 1996;153:839 [letter].

47. Stoll AL, Sachs GS, Cohen MB, et al. Choline in the treatment of rapid-cycling bipolar disorder: clinical and neurochemical findings in lithium-treated patients. Biol Psychiatry 1996;40:382–8.

48. Carman JS, Wyatt RJ. Calcium: bivalent cation in the bivalent psychoses. Biol Psychiatry 1979;14:295–336 [review].

49. Naylor GJ. Vanadium and manic depressive psychosis. Nutr Health 1984;3:79–85 [review].

50. BJ, Simpson JSA, Ferre RC, et al. Effective mood stabilization with a chelated mineral supplement: an open-label trial in bipolar disorder. J Clin Psychiatry 2001;62:936–44.