Tryptophan Fluvoxamine

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., Rossini, D. etal. (2001b). Influence of tryptophan hydroxylase and serotonin transporter genes on fluvoxamine antidepressants activity. Mol. Psychiatry, 6, 586-92. 

Figure 7. A serotonergic synapse including a depiction of the acute tryptophan depletion method discussed in the text. All large neutral amino acids (SLNAAs) share a common blood-brain barrier transporter. The serotonergic precursor, tryptophan, essentially competes with the other LNAAs for transport. Thus tryptophan is uniquely susceptible to acute dietary manipulation. Numerous serotonergic receptor types exist, including presynaptic S-HTm and (somatodendritic) 5-HTia autoreceptors and postsynaptic 5-HTia, 5-HTid, 5-HT2a 5-HT2c 5-HT3 and 5-HT4 receptors. Additional modulation of serotonin activity can occur via the action of selective serotonin re-uptake inhibitors (SSRls) including fluoxetine, fluvoxamine, and citalopram.

The effects of a short-term tryptophan depletion were examined in 15 patients with OCD who had responded to treatment with various SRIs such as CMI, fluvoxamine, and fluoxetine. These patients underwent tryptophan depletion under double-blind, placebo-controlled conditions. Reduction of tryptophan had no significant effects on either obsessions or compulsions, but mean depression ratings were significantly increased during tryptophan depletion [Barr et al. 1994]. 

We recently investigated whether the administration of a selective serotonin reuptake inhibitor, fluvoxamine, could interfere with the sleep patterns induced after TED. In this double-blind placebo-controlled cross-over study, 12 healthy male volunteers aged 18-40 years were assigned to two treatment conditions tryptophan or sham depletion and fluvoxamine or placebo. During each session, separated by a 2-day wash-out period, subjects took either fluvoxamine or placebo and either tryptophan... 

Fig. 2. Effects of a tryptophan versus a sham depletion on the REM sleep alterations induced by 150 mg fluvoxamine in 12 healthy subjects a double blind placebo-controlled 4-way cross over study...

Clinically important, potentially hazardous interactions with amitriptyline, amoxapine, bupropion, citalopram, clomipramine, desipramine, doxepin, fluoxetine, fluvoxamine, imipramine, meperidine, nefazodone, nortriptyline, paroxetine, pizotifen, protriptyline, rizatriptan, sertraline, sibutramine, sumatriptan, trimipramine, tryptophan, venlafaxine, zolmitriptan... 

Clinically important, potentially hazardous interactions with desvenlafaxine, dextromethorphan, dihydroergotamine, ephedra, ergot, fluoxetine, fluvoxamine, isocarboxazid, linezolid, lithium, MAO inhibitors, meperidine, methysergide, naratriptan, nefazodone, paroxetine, phenelzine, rizatriptan, sertraline, sumatriptan, tranylcypromine, tryptophan, venlafaxine, verapamil, zolmitriptan, zuclopenthixol... 

The manufacturers of duloxetine contraindicate the concurrent use of MAOIs because of the theoretical risk of the serotonin syndrome. Similarly they recommend caution with other serotonergic drugs, including the SSRIs, venlafaxine, and tryptophan. Fluvoxamine should not be used with duloxetine, because it markedly increases duloxetine levels. Low-dose paroxetine caused a modest increase in the duloxetine ATJC, and fluoxetine is predicted to interact similarly. 

A warning by the CSM in the UK about the risks of giving fluvoxamine with tryptophan appears to be an extrapolation from the serious reaction (the serotonin syndrome) which has been seen with fluoxetine (see above). 

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