The Ortho Molecular Answer

Depression - Phenylalanine for Endogenous Depression

Phenylalanine for Endogenous Depression
I. A. Yaryura-Tobias, B. Heller, H. Spatz, and E. Fischer
Orthomolecular Psychiatry
Vol. 3, Number 2, 1973

Phenylalanine for Endogenous Depression

I. A. Yaryura-Tobias, B. Heller, H. Spatz, and E. Fischer

It has been shown that the urinary elimination of phenylethylamine (PEA) is usually decreased in endogenous depression (Fischer et al., 1968; Fischer et al., 1972) and the 2-PEA is also present in the human brain (Mosnaim et al., 1973). PEA is also to antagonize almost completely the reserpine effect in pretreated rats (Fischer et al., 1972,Mosnaim and Sabelli, 1971). Replacing PEA by its precursor, phenylalanine, it was observed that the levorotatory form had little effect in antagonizing rats pretreated with reserpine; a better effect was observed with the racemic form (d-1) while greatest efficacy was obtained with d-phenylalanine. These results are in agreement with the increase of PEA in the rat brain, after the administration of the racemic form, l-form and d-form, the latter being the best (Mosnaim et al., 1973; Fischer et al., 1973).
Based upon that information, PEA was administered to patients suffering from endogenous depression, but severe cephaleas forced us to discontinue the study (Mosnaim et al., 1973). This preliminary report consisted of 15 patients, eight females and seven males, with ages ranging from 36 to 72 (x= 50.66), onset of illness ranging from 2 to 45 years (x= 16.73), and the duration of the last period of depression ranging from six days to 520 days (x= 130.40). Target symptoms were early morning depression, with later evening improvement, anorexia, irregular sleep, suicidal ideation or attempt, lack of drive, feeling of hopelessness and helplessness. The intensity was rather severe in most cases. Patients were divided in two groups - Group A (Dr. Yaryura-Tobias' patients) (N = 6) received d-I phenylalanine in 100 mg capsules b.i.d., and Group B (Dr. Heller's patients) (N = 9) received d-phenylalanine in 100 mg capsules b.i.d. Before treatment, PEA levels in urine were measured in six patients of Group A and found to be low in five cases (x= 34_/24 hours) and normal in a psychotic patient with depression (209 _/24 hours). Duration of treatment was two weeks. Improvement, if any, was usually reported and observed within the first five days of treatment. In Group A, three cases improved out of six, and in Group B, seven cases improved out of nine.

In the positive cases, no further medication was needed. In those who required additional therapy, it seemed that phenylalanine (d or d-l form) enhanced the clinical action of tricyclic antidepressants. Although the experimental trial was very short in duration and the amount of drug given was small, it seems that some form of endogenous depression responded well to phenylalanine therapy, mainly with the dextrorotatory form. The psychotic patient with depression worsened his psychosis. In three cases, mild cephalea was reported. No toxic effects were observed.

It is postulated that the better response obtained by the use of d-phenylalanine over d-l phenylalanine is due to higher specificity of the hydroxylase that converts the I form into dihydroxyphenylalanine where d-phenylalanine would follow only the phenylethylamine pathway.