Tryptophan antidepressive

Cooper AJ. Tryptophan antidepressant physiological sedative fact or fancy Psychopharmacology (Berl) 1979 61(1) 97-102. 

TRYPTOPHAN ANTIDEPRESSANTS -MAOIs Risk of confusion and agitation Tryptophan is a precursor of a number of neurotransmitters, including serotonin. MAOIs inhibit the breakdown of neurotransmitters 1 dose of tiyptophan... 

Cooper, A. J., Tryptophan antidepressant physiological sedative Fact or fancy Psychopharmacology, 61(1), 97, 1979. 

Yoshida, K. et al. (2002). Monoamine oxidase a gene polymorphism, tryptophan hydroxylase gene polymorphism and antidepressant response to fluvoxamine in Japanese patients with major depressive disorder. Prog. Neuropsychopharmacol. Biol. Psychiatry, 26, 1279-83. 

Serretti, A., Zanardi, R., Cusin, C. etal. (2001a). Tryptophan hydroxylase gene associated with paroxetine antidepressants activity. Eur. Neuropsychopharmacol., 11, 375-80. 

In animal studies, high levels of cortisol have been shown to induce (increase) the activity of the enzyme tryptophan 2,3-dioxygenase in the liver, thereby decreasing the bioavailability of tryptophan to the brain. It is interesting to note that low acute doses of a number of different antidepressants inhibit the activity of this enzyme and, as a result, increase brain tryptophan concentrations, thus stimulating 5-HT synthesis (Badawy and Evans, 1982). In this way a link between the two key monoamine neurotransmitters and the hormone may be seen namely, reduced brain NA activity leads to decreased inhibition of the HPA axis, while increased levels of cortisol reduce 5-HT activity in the brain. Activation of the HPA axis has also been shown to result in tissue atrophy, in particular of the limbic system s hippocampus, and a reduction in the levels of neurotrophic factors responsible for the maintenance and optimal function of brain neurons (Manji et al., 2001). In conclusion, manipulation of the HPA axis (Nemeroff, 2002) and stimulation of neurotrophic factor activity (Manji et al., 2001) might open up new avenues for the treatment of affective disorders. 

The amino acid precursor for 5-HT, L-tryptophan, increases the biosynthesis 5-HT and, therefore, has been investigated for potential antidepressant properties, but with mixed results (Green and Costain, 1979). It was withdrawn in 1990, following a number of fatal cases of eosinophilia myalgia (a disorder characterised by severe muscle pain and abnormally high levels of one type of white blood cell, the eosinophil) in individuals principally using it as a natural hypnotic. 

L-tryptophan An amino acid precursor of serotonin, once used as an antidepressant. 

Badawy AA-B and Evans M (1982). Inhibition of rat liver tryptophan pyrrolase and elevation of brain tryptophan concentrations by acute administration of small doses of antidepressants. British Journal of Pharmacology, 77, 59-67. 

Add tryptophan to a standard antidepressant (usually an SSRI). There is a danger that the serotonin syndrome may occur however and occasionally the eosinophilia myalgia syndrome. The symptoms that occur with increasing severity are restlessness, diaphoresis, tremor, shivering, myoclonus, confusion, convulsions, death. 

Serretti A, Zanardi R, Cusin C, Rossini D, Lorenzi C, Smeraldi E (200 lb) Tryptophan hydroxylase gene associated with paroxetine antidepressant activity. Em Nemopsychopharma-col 11 375-380... 

Serretti A, Zanardi R, Rossini D, Cusin C, LUli R, Smeraldi E (2001c) Influence of tryptophan hydroxylase and serotonin transporter genes on fluvoxamine antidepressant activity. Mol Psychiatry 6 586-592... 

Sovner et al. (1998) have done an excellent job summarizing the data on antidepressants in patients with developmental disabilities. There have been nine reports of antidepressant use in adults with depression and MR and three reports of antidepressant use in children and adolescents. Eight of nine reports in adults were positive. The drugs studied included nialimide (n = 27), fluoxetine (9), imipramine (6), amoxapine (2), and nortriptyline (1) (total n = 45). In addition, Sovner et al. identified four reports of antidepressant use in children. One involved successful treatment with fluoxetine in an adolescent, another indicated efficacy with imipramine and amitriptyline in 9 of 12 children (Do-sen, 1982), and a third showed successful management in 3 of 4 children treated with imipramine or tryptophan plus nicotinamide (Dosen, 1990). One study of fluoxetine in depressed children with autism and MR witnessed improvement in depression but not in compulsive symptoms (Ghaziuddin and Tsai, 1991). 

Charney DS, Nelson JC Delusional and nondelusional unipolar depression further evidence for distinct subtypes. Am J Psychiatry 138 328-333, 1981 Charney DS, Menekes DB, Heninger GR Receptor sensitivity and the mechanism of action of antidepressant treatment. Arch Gen Psychiatry 38 1160-1180, 1981 Charney DS, Price LH, Heninger GR Desipramine-yohimbine combination treatment for refractory depression. Arch Gen Psychiatry 43 1155-1161, 1986 Charney DS, Goodman WK, Price LH, et al Serotonin function in OGD a comparison of the effects of tryptophan and mGPP in patients and healthy subjects. Arch Gen Psychiatry 45 177-185, 1988... 

Delgado PL, Charney DS, Price LH, et al Serotonin function and the mechanism of antidepressant action reversal of antidepressant-induced remission by rapid depletion of plasma tryptophan. Arch Gen Psychiatry 47 411-418, 1990b Delgado PL, Price LH, Miller HL, et al Rapid serotonin depletion as a provocative challenge test for patients with major depression relevance to antidepressant action and the neurobiology of depression. Psychopharmacol Bull 27 321-330, 1991... 

Various antidepressants bupropion hydrochloride nefazodone hydrochloride trazodone hydrochloride L-tryptophan... 

Serotonin precursors (L-tryptophan. 5-hydroxytryptophan) have some antidepressant action, whereas a reduction in the blood levels of tryptophan in remitted depressed patients can provoke clinical relapse. 

Depietion of piasma tryptophan precursors may reverse antidepressant-induced remissions (49). 

Tryptophan and 5-hydroxytryptophan, the precursors of 5-HT, may have antidepressant effects, alone or in combination with other drugs ( 50). 

MAOIs have the most serious pharmacodynamic interactions of any antidepressant class. As discussed earlier, they can cause a hypertensive crisis and the serotonin syndrome. They potentiate the hypertensive effects of most sympathomimetic amines, as well as tyramine, which is the reason for the avoidance of over-the-counter preparations containing such agents, in addition to the tyramine-free diet ( 508, 509). The serotonin syndrome occurs most often when MAOIs are used in combination with SSRIs and venlafaxine but it can also occur when MAOIs are used with tryptophan, 5-hydroxytryptophan, and some narcotic analgesics. In addition, MAOIs can also significantly potentiate the sedative and respiratory depressant effects of narcotic analgesics. 

---