SSRI's are known to reduce essential amino acid uptake (1) and deplete systemic levels of monoamines (2), including plasma and brain concentrations of serotonin. The reduced level of aromatic amino acids has been reported in depressed patients. However, I cant find an explicit reference regarding effects of antidepressants on the plasma concentration of aromatic amino acids. I would appreciate any published or unpublished records.
1. Urdaneta E, Idoate I, Larralde J. Drug-nutrient interactions: inhibition of amino acid intestinal absorption by fluoxetine. The British journal of nutrition 1998;79(5):439-46.
2. Hinz M, Stein A, Uncini T. Monoamine depletion by reuptake inhibitors. Drug, healthcare and patient safety 2011;3:69-77.
Many studies have shown that plasma tryptophan (Trp) concentration and the Trp/competing amino acid (CAA) ratio are decreased in depression. The latter is due to the low [Trp] and not a high [CAA] [for references, see Badawy et al (2010) Int J Tryptophan Res 3: 23-34]. Various antidepressants, including SSRIs, normalise this ratio by increasing [Trp], almost certainly by inhibition of liver Trp 2,3-dioxygenase (TDO) activity and/or its induction by cortisol [see, e.g., Moller et al (1986) Psychopharmacol 88: 96-100].
In rats, SSRIs increase liver, serum and brain [Trp] and brain [5-HT] and [5-HIAA] by inhibition of liver TDO activity [Badawy & Morgan: Br J Pharmacol 103: 429-433, 1991). In this latter study, the increases caused by paroxteine in liver, serum and brain [Trp] occurred dose-dependently for the entire 0.5-25 mg/kg range. The increase in brain [5-HT] was observed only after doses of 0.5-1.0 mg/kg, with larger doses causing decrease. By contrast and as expected from an SSRI, brain [5-HIAA] was decreased by paroxetine doses of 1-25mg/kg.
I appreciate your response.
In your reports assay have been completed shortly after administration of inhibitors. I can identify several other reports that confirm your result on 5-HT and 5-HIAA. However, I can also see a number of good works reporting significant or dramatic reduction in the plasma and tissue references of Trp metabolism, including 5-HT and 5HTP. In particular all assay that that have been performed after extended or repeated administration of inhibitor report such a reduction. So, I am interested if you have any data or comments regarding Trp or Phe level after long term treatment of subject with SSRI. In other words, how long you can maintain Trp high with SSRI?
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