Normal Folate Levels Associated With Depression in Diabetes

HONOLULU – Low-normal serum folate, at a level between 2 and 7ng/mL, is associated with an increased risk of depression in diabetes patients, a finding that suggests that, as with other depressed patients, folate supplementation might boost responses to antidepressants.

Among 58 patients with diabetes and low-normal serum folate levels, the age-adjusted prevalence of depression in the study was 6.3%; it was 4.9% in 488 patients with serum folate at or above 7ng/mL. Low-normal folate was associated with a twofold increase in the odds of depression in patients with diabetes (odds ratio, 2.29; confidence interval, 1.01-5.18).

Although folate levels have been previously correlated with depression, the study seems to be the first to find the connection in people with diabetes. Supplementation "has the potential to reduce the dosage of antidepressants necessary for these patients and potentially minimize metabolic side effects," something to which people with diabetes are particularly prone. However, those with diabetes might need more than the typical daily dose of about 400 mcg to overcome the disease’s metabolic derangements, Dr. Kurt Peters reported at the annual meeting of the American Psychiatric Association.

Also, "this study indicates the need to include diabetic patients in future research regarding folic acid supplementation in depression," he and his colleagues concluded.

Dr. Peters, a psychiatrist in private practice in Colorado Springs, said that he routinely supplements his depressed patients with folic acid. "It’s fairly innocuous, and so I think many of us go ahead and treat people with folate. It’s hard to identify who’s going to respond," perhaps 20% in a month or two."

In addition, he said, he has found women to be more responsive to this approach than men, a finding that is consistent with the literature.

The study was based on National Health and Nutrition Examination Survey data collected in 1999-2006. Depression was assessed by either the World Health Organization Composite International Diagnostic Interview or the Patient Health Questionnaire, both of which match the DSM-IV criteria for major depression.

The researchers excluded diabetes patients who had frank folate deficiency (levels below 2 ng/mL). They also adjusted for depression risk factors, including age, sex, race, marital status, and smoking.

In a separate talk, Dr. Srijan Sen, a psychiatrist at the depression center of the University of Michigan, Ann Arbor, agreed that there’s a role for folic acid supplementation in treatment-resistant depression.

"Omega-3 fatty acids and SAM-e [S-adenosyl methionine] have also been shown [to help] in randomized trials. The number needed to treat and the absolute increase in remission rates [are] relatively small, but they seem to have very mild to no side effects, so they are worth considering and using," he said.

Psychiatrist John Greden, the depression center’s executive director, noted, however, that "methyl folate seems to be an inducer of hepatic enzymes that lower the level of mood stabilizers. If people are adding methyl folate, and these people are on mood stabilizers, you may need to adjust doses of mood stabilizers."

Dr. Peters said he has no relevant disclosures. The study was funded by the Philadelphia College of Osteopathic Medicine’s D’Alonzo Memorial Scholarship.

HONOLULU – Low-normal serum folate, at a level between 2 and 7ng/mL, is associated with an increased risk of depression in diabetes patients, a finding that suggests that, as with other depressed patients, folate supplementation might boost responses to antidepressants.

Among 58 patients with diabetes and low-normal serum folate levels, the age-adjusted prevalence of depression in the study was 6.3%; it was 4.9% in 488 patients with serum folate at or above 7ng/mL. Low-normal folate was associated with a twofold increase in the odds of depression in patients with diabetes (odds ratio, 2.29; confidence interval, 1.01-5.18).

Although folate levels have been previously correlated with depression, the study seems to be the first to find the connection in people with diabetes. Supplementation "has the potential to reduce the dosage of antidepressants necessary for these patients and potentially minimize metabolic side effects," something to which people with diabetes are particularly prone. However, those with diabetes might need more than the typical daily dose of about 400 mcg to overcome the disease’s metabolic derangements, Dr. Kurt Peters reported at the annual meeting of the American Psychiatric Association.

Also, "this study indicates the need to include diabetic patients in future research regarding folic acid supplementation in depression," he and his colleagues concluded.

Dr. Peters, a psychiatrist in private practice in Colorado Springs, said that he routinely supplements his depressed patients with folic acid. "It’s fairly innocuous, and so I think many of us go ahead and treat people with folate. It’s hard to identify who’s going to respond," perhaps 20% in a month or two."

In addition, he said, he has found women to be more responsive to this approach than men, a finding that is consistent with the literature.

The study was based on National Health and Nutrition Examination Survey data collected in 1999-2006. Depression was assessed by either the World Health Organization Composite International Diagnostic Interview or the Patient Health Questionnaire, both of which match the DSM-IV criteria for major depression.

The researchers excluded diabetes patients who had frank folate deficiency (levels below 2 ng/mL). They also adjusted for depression risk factors, including age, sex, race, marital status, and smoking.

In a separate talk, Dr. Srijan Sen, a psychiatrist at the depression center of the University of Michigan, Ann Arbor, agreed that there’s a role for folic acid supplementation in treatment-resistant depression.

"Omega-3 fatty acids and SAM-e [S-adenosyl methionine] have also been shown [to help] in randomized trials. The number needed to treat and the absolute increase in remission rates [are] relatively small, but they seem to have very mild to no side effects, so they are worth considering and using," he said.

Psychiatrist John Greden, the depression center’s executive director, noted, however, that "methyl folate seems to be an inducer of hepatic enzymes that lower the level of mood stabilizers. If people are adding methyl folate, and these people are on mood stabilizers, you may need to adjust doses of mood stabilizers."

Dr. Peters said he has no relevant disclosures. The study was funded by the Philadelphia College of Osteopathic Medicine’s D’Alonzo Memorial Scholarship.

HONOLULU – Low-normal serum folate, at a level between 2 and 7ng/mL, is associated with an increased risk of depression in diabetes patients, a finding that suggests that, as with other depressed patients, folate supplementation might boost responses to antidepressants.

Among 58 patients with diabetes and low-normal serum folate levels, the age-adjusted prevalence of depression in the study was 6.3%; it was 4.9% in 488 patients with serum folate at or above 7ng/mL. Low-normal folate was associated with a twofold increase in the odds of depression in patients with diabetes (odds ratio, 2.29; confidence interval, 1.01-5.18).

Although folate levels have been previously correlated with depression, the study seems to be the first to find the connection in people with diabetes. Supplementation "has the potential to reduce the dosage of antidepressants necessary for these patients and potentially minimize metabolic side effects," something to which people with diabetes are particularly prone. However, those with diabetes might need more than the typical daily dose of about 400 mcg to overcome the disease’s metabolic derangements, Dr. Kurt Peters reported at the annual meeting of the American Psychiatric Association.

Also, "this study indicates the need to include diabetic patients in future research regarding folic acid supplementation in depression," he and his colleagues concluded.

Dr. Peters, a psychiatrist in private practice in Colorado Springs, said that he routinely supplements his depressed patients with folic acid. "It’s fairly innocuous, and so I think many of us go ahead and treat people with folate. It’s hard to identify who’s going to respond," perhaps 20% in a month or two."

In addition, he said, he has found women to be more responsive to this approach than men, a finding that is consistent with the literature.

The study was based on National Health and Nutrition Examination Survey data collected in 1999-2006. Depression was assessed by either the World Health Organization Composite International Diagnostic Interview or the Patient Health Questionnaire, both of which match the DSM-IV criteria for major depression.

The researchers excluded diabetes patients who had frank folate deficiency (levels below 2 ng/mL). They also adjusted for depression risk factors, including age, sex, race, marital status, and smoking.

In a separate talk, Dr. Srijan Sen, a psychiatrist at the depression center of the University of Michigan, Ann Arbor, agreed that there’s a role for folic acid supplementation in treatment-resistant depression.

"Omega-3 fatty acids and SAM-e [S-adenosyl methionine] have also been shown [to help] in randomized trials. The number needed to treat and the absolute increase in remission rates [are] relatively small, but they seem to have very mild to no side effects, so they are worth considering and using," he said.

Psychiatrist John Greden, the depression center’s executive director, noted, however, that "methyl folate seems to be an inducer of hepatic enzymes that lower the level of mood stabilizers. If people are adding methyl folate, and these people are on mood stabilizers, you may need to adjust doses of mood stabilizers."

Dr. Peters said he has no relevant disclosures. The study was funded by the Philadelphia College of Osteopathic Medicine’s D’Alonzo Memorial Scholarship.