Serotonin fluvoxamine

Indeed, 5-HT is also a substrate for the 5-HT transporter, itself an important player in the treatment of depression, and more recently for the whole range of anxiety disorders spectrum (GAD, OCD, social and other phobias, panic and post-traumatic stress disorders). It is the target for SSRIs (selective serotonin reuptake inhibitors) such as fluoxetine, paroxetine, fluvoxamine, and citalopram or the more recent dual reuptake inhibitors (for 5-HT and noradrenaline, also known as SNRIs) such as venlafaxine. Currently, there are efforts to develop triple uptake inhibitors (5-HT, NE, and DA). Further combinations are possible, e.g. SB-649915, a combined 5-HTia, 5-HT1b, 5-HT1d inhibitor/selective serotonin reuptake inhibitor (SSRI), is investigated for the treatment of major depressive disorder. 

The first-line therapeutic options for PMDD include the selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine, fluvoxamine, sertraline, paroxetine, and citalopram. These agents can be given either continuously or only during the luteal phase of the menstrual cycle, i.e., initiated at the time of ovulation and discontinued on the first day of menses. 

Smeraldi, E., Zanardi, R. et al. (1998). Polymorphism within the promoter of the serotonin transporter gene and antidepressant efficacy of fluvoxamine. Mol. Psychiatry, 3(6), 508-11. Wang, S. L., Huang, J. D. et al. (1993). Molecular basis of genetic variation in debrisoquin hydroxylation in Chinese subjects polymorphism in RFLP and DNA sequence of CYP2D6. Clin. Pharmacol. Ther., 53(4), 410-18. 

Yoshida, K., Ito, K. etal. (2002). Influence of the serotonin transporter gene-linked polymorphic region on the antidepressant response to fluvoxamine in Japanese depressed patients. Prog. Neuropsychopharmacol. Biol. Psychiatry, 26(2), 383-6. 

Ito, K. et al. (2002). A variable number of tandem repeats in the serotonin transporter gene does not affect the antidepressant response to fluvoxamine. Psychiatry Res, 111, 235-9. 

Smeraldi, E. et al. (1998). Polymorphism within the promoter of the serotonin transporter gene and antidepressant efficacy of fluvoxamine. Mol. Psychiatry, 3, 508-11. 

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. 

Since the introduction of fluoxetine (3) in 1987, a series of selective serotonin reuptake inhibitors (SSRIs) have been discovered that have seen broad application in many facets of mood disorders. These compounds include fluvoxamine (4) which contains a trifluoromethyl group and paroxetine (5) and citalopram (6) which contain 4-fluorophenyl groups [5,6]. 

Tricyclic drugs have, as the name implies, a three-ring structure, and interfere with reuptake of norepinephrine and/or serotonin into axon terminals. Tricyclic drugs include imipramine (Tofranil), amitriptyline (Elavil), clomipramine (Anafranil), and nortriptyline (Pamelor, Aventil). Tricyclics have the occasional but unfortunate cardiovascular side effects of arrhythmia and postural hypotension. Newer, nontricyclic antidepressants have been developed that are collectively referred to as SSRIs. These have a potent and selective action on serotonin, and lack the cardiovascular side effects of the tricyclics. These include fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), and fluvoxamine (Luvox). A fifth SSRI, citalopram (Celexa) has been used in Europe and has recently been approved in the United States. Venlafaxine (Effexor) blocks reuptake of norepinephrine and serotonin, while bupropion (Wellbutrin) acts on both dopamine and norepinephrine. 

Other Antidepressants. Antidepressant refinements for the next 30 years primarily consisted of the development of new TCAs. However, in 1988, a novel antidepressant class, the selective serotonin reuptake inhibitors (SSRIs), was introduced in the United States. The chief innovation of the SSRIs was that they afforded the comparable effectiveness of the TCAs with fewer side effects and minimal toxicity. The debut of the SSRIs coincided with the reworking of the nosology of the anxiety disorders in DSM-III and DSM-IV. As a result, the SSRIs have been studied extensively in each of the respective anxiety disorders and in many cases have obtained FDA approval for the treatment of one or more of these anxiety syndromes. The SSRIs currently available in the United States include citalopram (Celexa), escitalo-pram (Lexapro), fluoxetine (Prozac), fluvoxamine (Luvox), paroxetine (Paxil), and sertraline (Zoloft). 

The TCAs were once widely used to treat depression in brain-injured patients, but they have been replaced as first-line treatments by the so-called selective serotonin reuptake inhibitors (SSRIs) including citalopram (Celexa), fluoxetine (Prozac), fluvoxamine (Luvox), paroxetine (Paxil), sertraline (Zoloft), and, most recently. 

Selective serotonin re-uptake inhibitors, such as fluvoxamine, are used with caution in patients with epilepsy and should be discontinued if convulsions occur. 

Obsessive compulsive disorder in an 8-year-old can be treated using fluvoxamine (selective serotonin reuptake inhibitor, SSRI). It is usually administered initially os 25 mg daily, and increased if necessary in steps of 25 mg every 4-7 days to a maximum of 200 mg daily. If there is no improvement within 10 weeks, treatment should be reconsidered. A selective serotonin reuptake inhibitor should not be started until 2 weeks after stopping a monoamine oxidase inhibitor (MAOl), and conversely a MAOl should not be started until at least a week after an SSRI has been stopped. 

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.

Yu YW, Tsai SJ, Chen TJ, Lin CH, Hong CJ (2002) Association study of the serotonin transporter promoter polymorphism and symptomatology and antidepressant response in major depressive disorders. Mol Psychiatry 7 1115-1119 Zanardi R, Benedetti F, Di Bella D, Catalano M, Smeraldi E (2000) Efficacy of paroxetine in depression is influenced by a functional polymorphism within the promoter of the serotonin transporter gene. J Clin Psychopharmacol 20 105-107 Zanardi R, Serretti A, Rossini D, et al (2001) Factors affecting fluvoxamine antidepressant activity influence of pindolol and 5-HTTLPR in delusional and nondelusional depression. Biol Psychiatry 50 323-330... 

Gill, M., LoVecchio, E, and Selden, B. (1999) Serotonin syndrome in a child after a single dose of fluvoxamine. Ann Emerg Med 33 457-459. 

Initial pharmacogenetic studies of serotonin transporter gene (HTT) variants used case-control methods and have generated disparate results in different populations. Positive association of the promoter VNTR polymorphism (5-HTTLPR) with clinical response to fluvoxamine was seen in Italian patients with bipolar or unipolar delusional depression subjects with one or... 

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