Fluvoxamine antidepressant

It may be fair to ask, Is this much ado about nothing Although test tube studies have shown that particular drugs interact, it is seldom that this causes problems for patients taking the medications. For example, the antidepressant fluvoxamine inhibits the enzyme that deactivates the antipsychotic haloperidol (Haldol). Does this mean that fluvoxamine and haloperidol cannot be taken together By no means. Although this would probably raise the blood level of haloperidol somewhat, the main effect if any would be that a smaller dose of haloperidol would be more effective. 

SSRI activity is interestingly maintained even in the absence of one of the aromatic rings. Attaching the oxygen atom to an oxime leads to the antidepressant fluvoxamine. The requisite oxime (25-2) is obtained by reaction of the starting ketone (25-1) with hydroxylamine. Treatment of that intermediate with ethylene oxide adds the ether-linked side chain that will carry the amine. The hydroxyethyl product (25-3) is thus converted to its mesylate by means of methanesulfonyl chloride. This leaving group is then displaced by any one of several methods to afford the primary amine and thus fluvoxamine (25-4) [25]. 

FIGURE 11-44. Clozapine and olanzapine are substrates for cytochrome P450 1A2 (CYP450 1A2). When these drugs are given with an inhibitor of this enzyme, such as the antidepressant fluvoxamine, plasma levels of olanzapine and clozapine can rise. 

Duphar Laboratories, Study of the effects of the antidepressant fluvoxamine on driving skills and its interaction with alcohol. Data on file, 1981. 

SSRIs are widely used for treatment of depression, as well as, for example, panic disorders and obsessive—compulsive disorder. These dmgs are well recognized as clinically effective antidepressants having an improved side-effect profile as compared to the TCAs and irreversible MAO inhibitors. Indeed, these dmgs lack the anticholinergic, cardiovascular, and sedative effects characteristic of TCAs. Their main adverse effects include nervousness /anxiety, nausea, diarrhea or constipation, insomnia, tremor, dizziness, headache, and sexual dysfunction. The most commonly prescribed SSRIs for depression are fluoxetine (31), fluvoxamine (32), sertraline (52), citalopram (53), and paroxetine (54). SSRIs together represent about one-fifth of total worldwide antidepressant unit sales. 

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. 

Zanardi, R., Serretti, A. etal. (2001). Factors affecting fluvoxamine antidepressant activity influence of pindolol and 5-HTTLPR in delusional and nondelusional depression. Biol. Psychiatry, 50(5), 323-30. 

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. 

Drug therapies include tricyclic antidepressants and SSRIs. Treatment should be continued for at least 29 weeks. Nortriptyline, amitriptyline, clomipramine, desipramine, fluvoxamine, and bupropion have been used successfully. 

Alternatively, the current antidepressant may be augmented (potentiated) by the addition of another agent (e.g., lithium, T3), or an atypical antipsychotic (e.g., risperidone). Risperidone has been shown to be effective in combination with fluvoxamine, paroxetine, or citalopram in treatment-resistant depression. Olanzapine and fluoxetine have been found to be safe and effective in treatment-resistant depression. 

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. 

Duverneuil and coworkers (2003) have developed a method for the determination of 11 of the most commonly prescribed non-tricyclic antidepressants and some of their metabolites these include paroxetine, fluoxetine, norfluoxetine, sertraline, citalopram, fluvoxamine mirtazapine, venlafaxine, and 0-des-methylvenlafaxine. The method involves an LLE procedure followed by an HPLC separation with photodiode-array UV detection at three different wavelengths (220, 240, and 290 nm). The total run time was 18 min. The extraction recoveries were calculated to be in the range of 74-109% and the lower limit of detection (LLOD) reported was 2.5-5 ng/ml. A method published by Tournel and associates (2001) also reported the simultaneous determination of several newer antidepressants by RP-HPLC with UV detection. The compounds were isolated from human serum using an LLE process. The LLOQ ranged from 15-50 ng/ml depending on the analyte of interest. The total run time for all compounds eluted was approximately 20 min. 

In 1983, the first SSRI, fluvoxamine (Luvox), debuted in Switzerland. Five years later, fluoxetine (Prozac) was introduced in the United States. The SSRIs revolutionized the treatment of depression. They improved safety and tolerability, removing much of the stigma of taking an antidepressant. In fact, some think that it has become too easy to take antidepressants and that psychotherapy is being neglected or discouraged. 

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). 

SSRls. SSRI antidepressants have also received considerable scrutiny in the treatment of OCD. Fluoxetine, fluvoxamine, paroxetine, and sertraline are all approved by the FDA for the treatment of OCD. Current studies suggest that each of these medications is more effective for OCD when administered at the higher end of the therapeutic dose range, that is, fluoxetine 60-80 mg/day, fluvoxamine 200-300 mg/ day, paroxetine 40-60 mg/day, and sertraline 150-200 mg/day. No controlled studies are yet available regarding the use of citalopram or escitalopram for OCD. Refer to Chapter 3 for more information regarding SSRl antidepressants. 

Beta agonists (terbutaline, albuterol) Theophylline Antidepressants Bupropion Citalopram Escitalopram Duloxetine Fluoxetine Fluvoxamine... 

Fluvastatin (Lescol) Antihyperlipidemic Cap 20, 40 mg Fluvoxamine (LuVox) Antidepressant Tab 50,100 rrg... 

SSRI antidepressants (paroxetine = fluoxetine > sertraline > fluvoxamine)... 

CypP450 3A3 /4 Antidepressants tricyclics, nefazodone, fluoxetine, fluvoxamine, citalopram, mirtazepine, venlafaxine Antipsychotics chlorpromazine, clozapine, pimozide, quetiapine, risperidone... 

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