According to the Centers for Disease Control and Prevention (CDC), about nine percent of Americans experience constant feelings of regret, anxiety, and despair at some point during their adult life. Depression has often been associated with such feelings and continues to be targeted by the mainstream medical community. The most common anti-depressive drug, selective serotonin reuptake inhibitors (SSRIs) is used to tackle such lapses in mental clarity by increasing the amount of serotonin in the brain. By blocking the reuptake of serotonin by neurons, SSRI medications like Prozac, Celexa, and Zoloft have been able to increase serotonin availability and temporarily alleviate depression in some patients. Despite the progressive development in these drugs, more than half of the patients on them may likely report no improvement of their current mental state.
Adjunctive therapies or therapies used in conjunction with the primary treatment have been effective in improving the treatment of depression. The aim of such therapies is to create a synergistic effect, while maintaining the tolerability to the drug. Recently, researchers have examined the effects of L-Methylfolate as an adjunctive therapy with SSRIs in treating those battling the unpredictable woes of depression.
Unlike previous robins to SSRIs’ batman, L-Methylfolate is a nutraceutical or food product that may be used as a supplement to the diet and even provide medical benefits. This isolated food product is the most common bioactive form of folate. In its most natural state, folate can be found in grains, fruits, vegetables, beans, and other food products. Belonging to the family of essential B-vitamins, folate is necessary for the formation of red blood cells, cell growth and division, protein metabolism, and preventing neural tube defects. During the 1990s, the high prevalence of neural tube defects in newborns pushed food companies (predominantly cereal products) to fortify their products with folate, while also encouraging medical professionals to closely monitor folate levels in pregnant women. With the subsequent fortification, the medical community has seen a dramatic reduction in neural tube defect cases over the more recent years. However, foods such as breads, cereals, and energy bars fortified with folate may still not provide a daily adequate amount of 400 micrograms (mcg) after further absorption and metabolism by the gastrointestinal (GI) tract. Scientists have made a valiant effort though to try to further understand absorption of this essential B-vitamin beyond the GI tract.
Converted to its most active or bioactive form, L-Methylfolate passes through the GI tract and transported to the circulatory system to perform its active duty. Once it makes its way throughout the bloodstream, this powerful nutraceutical passes through the blood-brain barrier, a filtering mechanism by the capillaries that blocks the passage of certain substances from entering the brain and spinal cord. As the only form of folate to accomplish this feat, L-methylfolate usually will then play an indirect role in the synthesis of the three tenors primarily responsible for mood regulation, serotonin, dopamine, and norepinephrine. The increased synthesis of these three hormones provided by the addition of L-Methylfolate has been shown to enhance the efficacy of selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs), which are the two most commonly prescribed antidepressants.
Associate Professor of Psychiatry at Harvard Medical School, George I. Papakostas has been involved in a plethora of studies dedicated to the diagnosis, treatment, and management of severe depression including complimentary alternative therapies like the use of L-methylfolate with SSRIs. In two randomized, placebo-controlled studies, Papakostas and colleagues have examined the effects of L-methylfolate supplementation in the treatment of major depressive disorders for patients who had a partial or no response to SSRIs. For the first trial, 148 outpatients with SSRI-resistant major depressive disorder were randomly assigned to three groups. The first group was to receive L-methylfolate for 60 days (7.5 mg/day for 30 days followed by 15 mg/day for the last 30 days). The second group was given a placebo for the first 30 days followed by L-methylfolate (7.5 mg/day) supplementation for the final 30 days. Finally, the last group received only a placebo for the standard 60 days. The SSRI dosages were kept constant throughout the study. In the second trial, the design was almost identical to the first, but instead, the L-methylfolate dosage remained at 15 mg/day during both 30-day periods.
Despite the investigators’ expectations, no significant difference was observed between the placebo and group receiving L-methylfolate. However, in the second trial, adjunctive L-methylfolate treatment at 15 mg/day showed a faster response rate to the SSRIs compared to those who received the continued just SSRI therapy plus the placebo. In addition, treatment with L-Methylfolate for both trials did not compromise the health and safety of all subjects participating in the study. Further research needs to be done looking at the effectiveness this type of adjunctive therapy, in order to reach a more concrete conclusion.
Optimism continues to be pushing the interest of health professionals in exploring the mysterious natural benefits of L-Methylfolate. Besides being both safe and effective, this nutraceutical is also more affordable than other previous adjunctive therapies. With the global nutraceutical product market reaching $142.1 billion in 2011, it is expected to nearly double that amount by 2017. As this business continues to expand, more research will be encouraged to further understand and improve the therapeutic management of L-Methylfolate.
The link of folate deficiency or malabsorption to major depressive disorder has been understood by the medical community for over 50 years. Now, with the advent of biotechnology and growing attention of nutraceuticals, scientists have been able to convert the basic and essential B-vitamin, folate into its more bioactive companion, L-Methylfolate. Rightfully so, critics will continue to scrutinize the rationality of substituting established anti-depressant adjunctive drugs like SSRIs with high doses of L-Methylfolate. It is without question and hard to ignore the debilitating effects and dependency that ultimately follows down the path of long-term use with SSRIs. The same has yet to be found with the supplementation of L-Methylfolate. If the consistent adjunctive therapy of L-Methylfolate could improve the condition of patients with depression, the rate at which SSRIs are delivered and increased in dosage may not have to be as frequent. The road to recovery from depression may be long and unpredictable, but providing the safest and most effective treatment should be the end-goal. Allowing L-Methylfolate to take the wheel could be best solution.