Article

Serum folate, vitamin B12, and homocysteine in major depressive disorder, Part 1: predictors of clinical response in fluoxetine-resistant depression.

Depression Clinical and Research Program, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
The Journal of Clinical Psychiatry (Impact Factor: 5.14). 08/2004; 65(8):1090-5. DOI: 10.4088/JCP.v65n0810
Source: PubMed

ABSTRACT In the present study, we assessed the relationship between serum folate, vitamin B12, and homocysteine levels and clinical response in patients with major depressive disorder (MDD) who had previously failed to respond to open treatment with fluoxetine 20 mg/day and were enrolled in a 4-week, double-blind trial of either (1) fluoxetine dose increase, (2) lithium augmentation of fluoxetine, or (3) desipramine augmentation of fluoxetine.
Fifty-five outpatients (mean +/- SD age = 41.7 +/- 10.6 years; 50.9% women) with MDD as assessed with the Structured Clinical Interview for DSM-III-R who were enrolled in the double-blind trial had serum folate, vitamin B12, and homocysteine measurements completed at baseline (prior to fluoxetine treatment initiation). Folate levels were classified as either low (< or = 2.5 ng/mL) or normal. Vitamin B12 levels were classified as either low (< or = 200 pg/mL) or normal. Homocysteine levels were classified as either elevated (> or = 13.2 micromol/L) or normal. With the use of a logistic regression, we then assessed the relationship between (1) low or normal folate levels, (2) normal or low B12 levels, and (3) elevated or normal homocysteine levels and clinical response to double-blind treatment. The study was conducted from November 1992 to January 1999.
Low serum folate levels (chi2=3.626, p =.04), but not elevated homocysteine (p >.05) or low vitamin B12 levels (p >.05), were associated with poorer response to treatment. The response rates for patients with (N = 14) and without (N = 38) low folate levels were 7.1% versus 44.7%, respectively.
Low serum folate levels were found to be associated with further treatment resistance among patients with fluoxetine-resistant MDD.

0 Bookmarks
 · 
109 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Recent literature has identified links between vitamin B12 deficiency and depression.We compared the clinical response of SSRI-monotherapy with that of B12-augmentation in a sample of depressed patients with low normal B12 levels who responded inadequately to the first trial with the SSRIs. Patients with depression and low normal B12 levels were randomized to a control arm (antidepressant only) or treatment arm (antidepressants and injectable vitamin B12 supplementation). A total of 199 depressed patients were screened. Out of 73 patients with low normal B12 levels 34 (47%) were randomized to the treatment group while 39 (53%) were randomized to the control arm. At three months follow up 100% of the treatment group showed at least a 20% reduction in HAM-D score, while only 69% in the control arm showed at least a 20% reduction in HAM-D score (p<0.001). The findings remained significant after adjusting for baseline HAM-D score (p=0.001). Vitamin B12 supplementation with antidepressants significantly improved depressive symptoms in our cohort.
    The Open Neurology Journal 01/2013; 7:44-8.
  • Article: Depression
    [Show abstract] [Hide abstract]
    ABSTRACT: Omega-3 fatty acids, folate and vitamin B12 are essential nutrients that show promise in mitigating the rising tide of depression. Sixteen percent of the adult US population experience major depression but only one in five is adequately treated. Depression is the leading cause of death and disability in people aged 18–44 years in the US, and affects the lives of the elderly more than physical illness. While patients can be easily screened for depression, currently more than one-third of patients treated with antidepressants do not improve. Converging lines of evidence for a role for omega-3 fatty acids in treating or preventing depression are epidemiological and biochemical, perhaps due to their significant anti-inflammatory role in the arachidonic acid cytokine cascades. High-quality fish oil supplements do not pose the same risk of heavy metal exposure as eating mercury-concentrating fish such as tuna, shark, swordfish, tilefish and king mackerel. The growing awareness of morbidity and mortality associated with properly prescribed pharmaceuticals, the importance of genomic polymorphisms, a renewed appreciation for nutrition in healthy functioning and the burgeoning supplement industry suggest the time is ripe for large clinical trials to build on preliminary studies into the effect of omega-3 fatty acids on depression. Four recent small clinical trials showed improved depression scores when omega-3 fatty acids were added to conventional pharmaceutical treatment. Folate and vitamin B12 are crucial for methylation in the biosynthetic pathways of brain myelin and biogenic amines. Borderline or low red blood cell folate is present in one-third of depressed patients, and three well designed trials showed that depressed patients had better responses to conventional antidepressants when they were supplemented with folate. Patients with the single nucleotide polymorphism methylene tetahydrofolate reductase (MTHFR) C677T are at greater risk for depression and are likely to benefit from supplemental folate. The potential unmasking of pernicious anaemia, in the setting of vitamin B12 deficiency or insufficiency, can be mitigated by supplementing with oral vitamin B12. There has been a meteoric rise in the use of nutritional supplements in the US, including omega-3 fatty acids and B vitamins; however, level 1 a evidence (systemic reviews free of worrisome heterogeneities) is lacking. The time is ripe for large, definitive randomised controlled trials of these promising interventions both as mono- and add-on therapy.
    Evidence-Based Integrative Medicine 01/2005; 2(4).
  • [Show abstract] [Hide abstract]
    ABSTRACT: Introduction: This study was conducted to assess the nutritional status in Iranian major depres¬sive disorder patients. We also determined the relationship between nutrients intake with depres¬sion severity. Methods: Seventy major depressive patients were selected randomly from outpatient depressive subjects, referred to Razi Psychiatry Hospital in Tabriz, Iran in 2007. Dietary intakes were rec¬orded and compared with dietary reference intakes (DRIs). Definition of the disease and its se¬verity were according to DSM-IV-TR and Hamilton Depression Rating Scale, respectively. Nu¬tritionist III program, Chi-square, correlation and t-test were used for data analyses. Demo¬graphic, clinical and laboratory data were analyzed using SPSS software for windows (ver¬sion13.0). Results: According to dietary analysis, 11.4% and 55% of patients had dietary protein and energy deficiency, respectively. 97.1% and 95.7% of patients had less folate and B12 intakes than recom¬mended dietary allowances. The mean (Mean ± SD) for plasma folate and B12 was 5.18±6.11 ng/ml and 389.05±346.9 pg/ml, respectively. Low plasma folate and B12 was observed in 51.4% and 50.0 % of patients, respectively. There was no significant relationship between blood folate and B12 levels with depression severity. Similarly, nutrients intake had no effect on depression se¬verity. Conclusion: Low plasma concentrations and low dietary intakes of folate and B12 are common among Tabrizian depressive patients. It seems that nutritional intervention for increasing folate and vitamin B12 intake must be considered as health promotive and preventative program for patients suffering from depression disorders.
    Health promotion perspectives. 01/2012; 2(2):145-52.