Folic Acid
Here are some fascinating current references...
Torrey, E. F. and J. M. Davis (2012). "Adjunct treatments for schizophrenia and bipolar disorder: what to try when you are out of ideas." Clin Schizophr Relat Psychoses 5(4): 208-216.
The pharmacologic treatment of schizophrenia and bipolar disorder leaves much to be desired. Repurposed drugs, which are approved for other medical conditions, represent an underutilized therapeutic resource for patients who have not responded to other drugs. Using experience gained from a decade of repurposed drug studies by the Stanley Medical Research Institute and search of the literature, we have identified nine such drugs for which there is some evidence of efficacy for schizophrenia and/or bipolar disorder. These include: aspirin; celecoxib; estrogen/raloxifene; folate; minocycline; mirtazapine; omega-3 fatty acids; pramipexole; and, pregnenolone. The evidence of efficacy is reviewed for each drug. Because there is little or no financial incentive for pharmaceutical companies to promote such drugs, there is a paucity of definitive trials, and these drugs are less widely known than they deserve to be. Biomarker studies should also be carried out to identify subgroups of patients who do respond to these drugs.
Budni, J., A. E. Freitas, et al. (2012). "Role of potassium channels in the antidepressant-like effect of folic acid in the forced swimming test in mice." Pharmacol Biochem Behav 101(1): 148-154.
Potassium (K(+)) channels have been implicated in depressive disorders and in the mechanism of action of antidepressants. Considering that several studies have indicated that folic acid plays an important role in the pathophysiology of depression, the present study investigated the involvement of potassium channels in the antidepressant-like effect of this vitamin. For this aim, the effect of the combined administration of different types of K(+) channel blockers and folic acid in the forced swimming test (FST) was investigated. Treatment of mice by intracerebroventricular (i.c.v.) route with subactive doses of glibenclamide (an ATP-sensitive K(+) channels blocker, 0.5pg/site), charybdotoxin (a large- and intermediate-conductance calcium-activated K(+) channel blocker, 25pg/site) or apamin (a small-conductance calcium-activated K(+) channel blocker, 10pg/site), augmented the effect of folic acid (10mg/kg, p.o., subeffective dose) in the FST. Additionally, the administration of folic acid and the K(+) channel blockers, alone or in combination, did not affect locomotion in the open-field test. Moreover, the reduction in the immobility time in the FST elicited by folic acid administered at a higher dose (50mg/kg, p.o.) was prevented by the pretreatment of mice with the K(+) channel opener cromakalim (10mug/site, i.c.v.), without affecting locomotor activity. The results of this study indicate that the antidepressant-like effect of folic acid in the FST may be at least partly due to its modulatory effects on neuronal excitability, via inhibition of K(+) channels.
Budni, J., K. R. Lobato, et al. (2011). "Involvement of PI3K, GSK-3beta and PPARgamma in the antidepressant-like effect of folic acid in the forced swimming test in mice." J Psychopharmacol.
Preclinical and clinical studies indicate that deficiency in folic acid plays a role in the pathophysiology of depression. Considering that alterations in the signaling pathways that regulate neuroplasticity and cellular survival are implicated in depressive disorders, the present study investigated the involvement of the phosphoinositide 3-kinase (PI3K), glycogen synthase kinase-3 (GSK-3beta), and peroxisome proliferator-activated receptor-gamma (PPARgamma) in the antidepressant-like effect of folic acid in the forced swimming test (FST). The intracerebroventricular (i.c.v.) pre-treatment of mice with LY294002 (10 nmol/site, a PI3K inhibitor) or GW-9662 (1 microg/site, a PPARgamma antagonist) prevented the antidepressant-like effect of folic acid (50 mg/kg, p.o.) in the FST. In addition, the administration of subeffective doses of the selective GSK-3beta inhibitor, AR-A014418 (3 mg/kg, i.p.), a non-selective GSK-3beta inhibitor, lithium chloride (10 mg/kg, p.o) or a PPARgamma agonist, rosiglitazone (1 microg/site, i.c.v.) in combination with a subeffective dose of folic acid (10 mg/kg, p.o.) significantly reduced the immobility time in the FST as compared with either drug alone, without altering the locomotor activity. These results indicate that the antidepressant-like effect of folic acid in the FST might be dependent on inhibition of GSK-3beta and activation of PPARgamma, reinforcing the notion that these are important targets for antidepressant activity.
Nahas, R. and O. Sheikh (2011). "Complementary and alternative medicine for the treatment of major depressive disorder." Can Fam Physician 57(6): 659-663.
OBJECTIVE: To review the clinical evidence supporting complementary and alternative medicine interventions for treating major depressive disorder. QUALITY OF EVIDENCE: PubMed was searched from January 1966 to February 2010 using the term depressive disorder in combination with St John's wort, S-adenosylmethionine (SAM-e), exercise, acupuncture, omega-3 fatty acids, and folate. Only relevant human trials were selected. MAIN MESSAGE: In a large meta-analysis, St John's wort was found to be equivalent to antidepressant drugs with fewer side effects. Exercise reduced depressive scores in 3 meta-analyses. Omega-3 fatty acids reduced depressive scores in a meta-analysis of 16 trials, but publication bias was identified. Oral SAM-e monotherapy reduced depressive scores in 4 of 5 small randomized controlled trials. Folate deficiency is associated with more severe and refractory depression, and supplementation reduced depressive scores in 2 of 3 randomized controlled trials. Acupuncture demonstrated limited efficacy in 1 meta-analysis and 5 other trials. CONCLUSION: St John's wort and regular exercise appear effective in the treatment of depression. Acupuncture appears ineffective for depression, but it might offer other health benefits. Other promising therapies include SAM-e, omega-3 fatty acid, and folic acid supplementation in selected patients; further study is warranted.
Fava, M. and D. Mischoulon (2010). "Evidence for folate in combination with antidepressants at initiation of therapy." J Clin Psychiatry 71(11): e31.
Although the goal of treatment for major depressive disorder is full remission, for most patients, remission is the exception rather than the rule. Carefully choosing medications with synergistic mechanisms of action at treatment initiation may increase rates of response and remission and decrease the risk for relapse. An agent such as folate, which is a naturally occurring B vitamin and is necessary for the synthesis of the trimonoamine neurotransmitters implicated in depression, may enhance the effects of a traditional antidepressant.
Almeida, O. P., K. Marsh, et al. (2010). "B-vitamins reduce the long-term risk of depression after stroke: The VITATOPS-DEP trial." Ann Neurol 68(4): 503-510.
OBJECTIVE: The consumption of certain B-vitamins through diet or supplementation decreases the total plasma concentration of homocysteine (tHcy) and may enhance response to standard antidepressant treatment. It is unclear if treatment with B-vitamins can reduce the long-term prevalence of depression in people at risk, such as stroke survivors. The purpose of this research was to determine if treatment with B-vitamins reduces the hazard of poststroke depression compared with placebo. METHODS: Randomized, double-blind, placebo-controlled trial of tHcy-lowering treatment with daily folic acid (2 mg), vitamin B6 (25 mg), and vitamin B12 (0.5 mg) for 1 to 10.5 years in survivors of stroke. The primary endpoint was the onset of Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) major depression after randomization. Secondary outcomes were the prevalence of DSM-IV major or minor depression at the end of treatment. Other measured factors included age, gender, poststroke handicap associated with stroke, recurrence of strokes, cognitive impairment, and use of antidepressants. RESULTS: Among 273 people who completed the final assessment after 7.1 +/- 2.1 years (mean +/- standard deviation) of follow up, random assignment to B-vitamins was associated with a lower hazard of major depression compared with placebo (18.4% vs 23.3%, adjusted hazard ratio [HR] = 0.48; 95% confidence interval [CI] = 0.31-0.76) and a trend toward a lower odds of major or minor depression at the end of the trial compared with placebo (19.1% vs 27.7%; adjusted odds ratio [OR] = 0.58; 95%CI = 0.31-1.09). INTERPRETATION: Long-term treatment of poststroke survivors with folic acid, B6, and B12 was associated with a reduction in the hazard of major depression in our patient population. If these findings can be validated externally, B-vitamin supplementation offers hope as an effective, safe, and affordable intervention to reduce the burden of poststroke depression.
Fava, M. (2010). "Using complementary and alternative medicines for depression." J Clin Psychiatry 71(9): e24.
The use of complementary and alternative medicines (CAM) has increased among patients with psychiatric disorders over recent decades. Therefore, clinicians must inquire and be knowledgeable about the use of CAM therapies, not only to give their patients accurate and up-to-date information but also to know when to appropriately prescribe CAM therapies to patients. Of the available CAMs, omega-3 fatty acids, folate, SAM-e, and St John's wort are reviewed.
Gaweesh, S. and A. A. Ewies (2010). "Folic acid supplementation cures hot flushes in postmenopausal women." Med Hypotheses 74(2): 286-288.
Over the past four decades, it was found that folic acid supplementation produced an antidepressant-like effect mediated by interaction with the brain noradrenergic receptors (inhibitory effect) and serotonergic receptors (stimulatory effect). Hot flushes occur in postmenopausal women because of disturbances in the thermoregulatory centre, most likely as a result of estrogen deficiency-related increase in central noradrenergic activity and reduced serotonergic activity. Therefore, we hypothesize that folic acid supplementation may ameliorate hot flushes by the same mechanism as estrogen replacement, i.e., by interacting with monoamine neurotransmitters in the brain; namely norepinephrine and serotonin. This article discusses the hypothesis and presents supportive preliminary data.
