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Higher Folate Levels Correlate with Improved Outcome for SSRI-Treated Geriatric Patients

Geriatric patients who are treated with the selective serotonin reuptake inhibitor (SSRI) sertraline appear to experience greater improvement in depression if they have higher than normal folate levels at the start of therapy, according to the findings of a small observational study.

Previous studies suggested that lower folate levels are associated with reduced responsiveness to SSRI treatment. Furthermore, depressed geriatric patients have lower levels of folate than controls, and folate supplements have been found to reduce depressive morbidity.

In their study, Murray Alpert, PhD, with the Department of Psychiatry, New York University Medical Center, New York, United States and colleagues randomized 12 geriatric patients to receive sertraline and 10 to receive nortriptyline for 12 weeks after a 1-week single-blind placebo lead-in period. They measured folate levels at baseline and after treatment.

At baseline, all patients had folate levels within the normal range, and the treatment groups did not differ either at baseline or outcome. However, patients who had higher folate levels at baseline achieved greater improvement. Hamilton Depression Scalefor Depression (HAM-D) score and folate level correlation for the sertraline-treated group, was r(2) = 0.29 (P<0.10) and r(2) = 0.18, (P = NS) for the nortriptyline-treated group. Likewise, for the Profile of Mood States (POMS) depression scores, values were r(2) = 0.39, (P<0.05) for the sertraline-treated group and r(2) = 0.00, (p = NS) for the nortriptyline group.

According to the researchers, folate deficiency causes a reduction of brain serotonin and a reduction of 5-hydroxyindoleacetic acid, which may contribute to depression in individuals with a predisposition to depression, they note.

They also point out that a metabolic step removed from the action of folate on serotonin is a reduction in S-adenosylmethionine, which may also contribute to brain serotonin levels. "It has been argued that folate is not a methyl donor for dopaminergic metabolism, but a possible role for serotonin metabolism via transmethylation has not been examined," they add.

"Further research to assess folate levels of patients entering treatment and to evaluate adjunctive folate supplements in patients with folate levels in the low normal range would be worthwhile," they conclude.
J Clin Psychopharmacol 2003;23:3:309-313. "Prediction of Treatment Response in Geriatric Depression From Baseline Folate Level: Interaction With an SSRI or a Tricyclic Antidepressant"

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