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Oral 5′-methyltetrahydrofolic acid in senile organic mental disorders with depression: Results of a double-blind multicenter study

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Abstract

5′-Methyltetrahydrofolic acid (5′- MTHF) in addition to standard psychotropic medication significantly improved clinical recovery in depressed patients with borderline or definite folate deficiency, and significantly reduced depressive symptoms in elderly normofolatemic patients after 3 weeks of treatment. In this equivalence study the effect of 5′- MTHF on depressive symptoms and cognitive status was compared to Trazodone (TRZ) in normofolatemic elderly patients with mild to moderate dementia and depression. Ninety-six patients with dementia, scoring 12–23 at the Mini Mental State Examination (MMSE) and ≥18 at the Hamilton Depression Rating Scale (HDRS) after a 2-week placebo run-in, were randomized to receive either 5′-MTHF (50 mg/day p.o.) (47 patients) or TRZ (100 mg/day p.o.) (49 patients) in a double-blind design for 8 weeks. HDRS was assessed before, after 4 weeks and at the end of treatment; Rey’s Verbal Memory (RVM) test for immediate and delayed recall was evaluated before and after treatment. After 4 weeks of treatment HDRS score was reduced from 23±5 to 20±6 in the 5′-MTHF (p<0.05 vs baseline), and from 23±3 to 21±4 in the TRZ group (p<0.05 vs baseline). p]A further significant decrease to 18±6 and 19±5 respectively was obtained at the end of the treatment period (p<0.05 vs week 4) with 5′-MTHF and TRZ. HDRS was administered again after a 4-week, drug-free, follow-up period: no change vs the post treatment scores was observed either in the 5′-MTHF or in the TRZ group (18±7 and 19±5 respectively). RVM test for immediate recall was significantly improved (p<0.05) at week 8 vs baseline in the 5′-MTHF group whereas no significant change occurred in the TRZ group. No change in delayed recall was observed after treatment in either group. Tolerability was good for both treatments. This study shows that 5′-MTHF and TRZ are equally effective in improving depressive symptoms in patients with mild to moderate dementia and suggests that pharmacological doses of 5′-MTHF may exert psychotropic effects irrespective of folate status. (Aging Clin. Exp. Res. 1: 63–71, 1993)

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Passen, M., Cucinotta, D., Abate, G. et al. Oral 5′-methyltetrahydrofolic acid in senile organic mental disorders with depression: Results of a double-blind multicenter study. Aging Clin Exp Res 5, 63–71 (1993). https://doi.org/10.1007/BF03324128

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