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      Is Depression Related to Low Folate Levels in People with Epilepsy? An Observational Study and Meta-analysis

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          Abstract

          Background:

          Both depression and low serum levels of folate are common in people with epilepsy (PWE), the latter especially in patients on hepatic enzyme-inducing antiepileptic drugs (AEDs). We did a cross-sectional study and a meta-analysis to assess if lower folate levels have any relation with depression in PWE.

          Materials and Methods:

          Two hundred and one PWE were recruited and assessed for depression using the Inventory of Depressive Symptomatology-Self-Rated (IDS-SR) and Inventory of Depressive Symptomatology-Clinician Rated; serum folate levels were measured in them at the same time. Literature search was carried out and studies with data on depression as well as folate levels in PWE were included. Statistical analysis to determine frequency of depression, low folate levels, and relation between them among our cases and the pooled data from the included studies was done.

          Results:

          Depression was observed in 65.68% and low serum folate (<4 ng/ml) in 48.75% of PWE (over 80% on older AEDs); there was no statistically significant correlation between them. However, on analyzing the pooled data of six studies including the present, the Fisher's z-transformed correlation coefficient was −0.1690 (95% confidence interval [−0.3175, −0.0124], P = 0.0464).

          Conclusions:

          Depression and low folate levels are common in PWE. Low folate levels have a mild but significant negative correlation with depression in this population, and folate supplementation would be advisable for those on the older AEDs.

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          Most cited references37

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          Prevention of neural-tube defects with folic acid in China. China-U.S. Collaborative Project for Neural Tube Defect Prevention.

          Robert J. Berry, Zhu Hua Li, J Erickson … (1999)
          Periconceptional administration of folic acid can reduce a woman's risk of having a fetus or infant with a neural-tube defect. As part of a public health campaign conducted from 1993 to 1995 in an area of China with high rates of neural-tube defects (the northern region) and one with low rates (the southern region), we evaluated the outcomes of pregnancy in women who were asked to take a pill containing 400 microg of folic acid alone daily from the time of their premarital examination until the end of their first trimester of pregnancy. Among the fetuses or infants of 130,142 women who took folic acid at any time before or during pregnancy and 117,689 women who had not taken folic acid, we identified 102 and 173, respectively, with neural-tube defects. Among the fetuses or infants of women who registered before their last menstrual period and who did not take any folic acid, the rates of neural-tube defects were 4.8 per 1000 pregnancies of at least 20 weeks' gestation in the northern region and 1.0 per 1000 in the southern region. Among the fetuses or infants of the women with periconceptional use of folic acid, the rates were 1.0 per 1000 in the northern region and 0.6 per 1000 in the southern region. The greatest reduction in risk occurred among the fetuses or infants of a subgroup of women in the northern region with periconceptional use who took folic acid pills more than 80 percent of the time (reduction in risk, 85 percent as compared with the fetuses or infants of women who registered before their last menstrual period and who took no folic acid; 95 percent confidence interval, 62 to 94 percent) [corrected]. In the southern region the reduction in risk among the fetuses or infants of women with periconceptional use of folic acid was also significant (reduction in risk, 41 percent; 95 percent confidence interval, 3 to 64 percent). Periconceptional intake of 400 microg of folic acid daily can reduce the risk of neural-tube defects in areas with high rates of these defects and in areas with low rates.
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            Is low folate a risk factor for depression? A meta-analysis and exploration of heterogeneity.

            Trevor Sheldon, Tracy Lightfoot, Simon Gilbody (2007)
            Low folate has been causatively linked to depression, but research is contradictory. An association may arise due to chance, bias, confounding or reverse causality. A systematic review of observational studies which examined the association between depression and folate was conducted. 11 relevant studies (15 315 participants; three case-control studies, seven population surveys and one cohort study) examining the risk of depression in the presence of low folate were found. Pooling showed a significant relationship between folate status and depression (odds ratio (OR)(pooled unadjusted) = 1.55; 95% CI 1.26 to 1.91). This relationship remained after adjustment for potential confounding (OR)(pooled adjusted) = 1.42; 95% CI 1.10 to 1.83). Folate levels were also lower in depression. There is accumulating evidence that low folate status is associated with depression. Much of this evidence comes from case-control and cross-sectional studies. Cohort studies and definitive randomised-controlled trials to test the therapeutic benefit of folate are required to confirm or refute a causal relationship.
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              Enhancement of the antidepressant action of fluoxetine by folic acid: a randomised, placebo controlled trial.

              Alec Coppen, John Bailey (2000)
              A consistent finding in major depression has been a low plasma and red cell folate which has also been linked to poor response to antidepressants. The present investigation was designed to investigate whether the co-administration of folic acid would enhance the antidepressant action of fluoxetine. 127 patients were randomly assigned to receive either 500 microg folic acid or an identical looking placebo in addition to 20 mg fluoxetine daily. All patients met the DSM-III-R criteria for major depression and had a baseline Hamilton Rating Scale (17 item version) score for depression of 20 or more. Baseline and 10-week estimations of plasma folate and homocysteine were carried out. Patients receiving folate showed a significant increase in plasma folate. This was less in men than in women. Plasma homocysteine was significantly decreased in women by 20.6%, but there was no significant change in men. Overall there was a significantly greater improvement in the fluoxetine plus folic acid group. This was confined to women where the mean Hamilton Rating Scale score on completion was 6.8 (S.D. 4. 1) in the fluoxetine plus folate group, as compared to 11.7 (S.D. 6. 7) in the fluoxetine plus placebo group (P 50% reduction in score) as compared to 61.1% of women who received placebo supplement (P<0.005). Eight (12.9%) patients in the fluoxetine plus folic acid group reported symptoms possibly or probably related to medication, whereas in the fluoxetine plus placebo group 19 (29.7%) patients reported such symptoms (P<0.05). Folic acid is a simple method of greatly improving the antidepressant action of fluoxetine and probably other antidepressants. Folic acid should be given in doses sufficient to decrease plasma homocysteine. Men require a higher dose of folic acid to achieve this than women, but more work is required to ascertain the optimum dose of folic acid.
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Neurosci Rural Pract
                Journal ID (iso-abbrev): J Neurosci Rural Pract
                Journal ID (publisher-id): JNRP
                Title: Journal of Neurosciences in Rural Practice
                Publisher: Medknow Publications & Media Pvt Ltd (India )
                ISSN (Print): 0976-3147
                ISSN (Electronic): 0976-3155
                Publication date (Print): Jul-Sep 2017
                Volume: 8
                Issue: 3
                Pages: 381-388
                Affiliations
                [1 ]Department of Neurology, Postgraduate Institute of Medical Education and Research, Dr. Ram Manohar Lohia Hospital, New Delhi, India
                [2 ]Department of Neurology, All India Institute of Medical Sciences, New Delhi, India
                [3 ]Department of Pathology, Postgraduate Institute of Medical Education and Research, Dr. Ram Manohar Lohia Hospital, New Delhi, India
                Author notes
                Address for correspondence: Dr. Bhupender Kumar Bajaj, Department of Neurology, Postgraduate Institute of Medical Education and Research, Dr. Ram Manohar Lohia Hospital, New Delhi - 110 001, India. E-mail: docbajaj@ 123456yahoo.co.in
                Article
                Publisher ID: JNRP-8-381
                DOI: 10.4103/jnrp.jnrp_468_16
                PMC ID: 5488558
                SO-VID: 9a7ffe7b-0cd8-4f14-b25e-f358b09c1394
                Copyright © Copyright: © 2017 Journal of Neurosciences in Rural Practice
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

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                Subject: Original Article

                ScienceOpen disciplines: Neurosciences
                Keywords: depression,folate levels,people with epilepsy
                Data availability:
                ScienceOpen disciplines: Neurosciences
                Keywords: depression, folate levels, people with epilepsy

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