Mirtazapine Fluvoxamine

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. 

SSRb are the most recent class, named after the drugs mechanisms of action (Selective Serotonin Reuptake Inhibitors), of which fluoxetine is the archytype. Other examples include danopramine, dtalopram, fluvoxamine, mirtazapine and paroxetine. Later members, such as venlafaxine, differ in being serotonin (re) UPTAKE INHIBITORS that also inhibit noradrenaline reuptake (but are weaker against dopamine uptake). The SSRIs show less side-effects, particularly less sedative actions, than the other classes. 

Fluvoxamine SSRIs, SNRIs, mirtazapine, nefazodone, TCAs Milnacipran... 

Maprotiline, Moclobemide, Mianserin, Fluoxetine (Prozac), Paroxetine, Sertraline, Fluvoxamine, Citalopram, Venlafaxin (generic IR formulation and the brand Venlafaxine XR), Mirtazapine, Flupentixol-melitracen (Deanxit), Tianeptine, Extract of St. John s Wort, Buspirone Depression and anxiety... 

Mirtazapine does not significantly inhibit hepatic cytochrome P450 enzymes. Additive effects may occur when mirtazapine is combined with other drugs with sedative or vascular effects. Mirtazapine should not be used in combination with an MAOI or within 14 days of discontinuing treatment with an MAOI. When it is combined with fluvoxamine, a potent inhibitor of P450 enzymes— including 1A2, 2D6, and 3A4, which metabolizes mirtazapine—the plasma concentration of mirtazapine may be increased by up to fourfold (AnttUa et al. 2001 Demers et al. 2001). 

Anttila AK, Rasanen L, Leinonen EV Fluvoxamine augmentation increases serum mirtazapine concentrations three- to fourfold. Ann Pharmacother 35 1221-1223, 2001... 

Although the efficacy of tricyclic antidepressants in the treatment of unipolar depression is beyond reproach, the side-effect profile of these agents makes them less desirable as first-line therapeutic agents. Introduction of selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine, paroxetine, sertraline, citalopram and fluvoxamine in the past decade has revolutionized the treatment of depression universally. The side-effect profile of SSRIs, such as nausea, diarrhea and sexual dysfunction, is considerably more benign than that of tricyclic drugs. Multiple controlled trials have proven the efficacy of SSRIs vs. placebo (Nemeroff, 1994). Recently, a number of SNRIs (serotonin and noradrenaline reuptake inhibitors) and so-called atypical antidepressants have been marketed that may have additional advantages over SSRIs, such as more rapid onset of action (venlafaxine. mirtazapine) and low sexual side-effect potential ( bupropion, nefazodone). Additionally, it appears that venlafaxine may be more efficacious in cases of treatment-refractory depression (Clerc et al., 1994 Fatemi et al., 1999). Finally, in a recent report (Thase et al., 2001),... 

Treatment of GAD can be undertaken using a number of pharmacological agents. Benzodiazepines have been found to be superior to placebo in several studies and all benzodiazepines appear to be equally effective. However, side effects include sedation, psvchomotor impairment, amnesia and tolerance (Chapter 1). Recent clinical data indicate that SSRIs and SNRIs are effective in the treatment of acute GAD symptoms. Venlafaxine, paroxetine and imipramine have been shown to be effective antianxiety medications in placebo-controlled studies. Case studies also indicate the usefulness of clomipramine, nefazodone, mirtazapine, fluoxetine and fluvoxamine in GAD. Buspirone, a 5-HTla receptor partial agonist, has been shown to be effective in several placebo-controlled, double-blind trials (Roy-Byme and Cowley, 2002). Buspirone has a later onset of action than both benzodiazepines and SSRIs but with the advantage of being non-addictive and non-sedating. 

Fluvoxamine (Luvox) Imipramine (Tofranil) Mirtazapine (Remeron, Remeron SolTab) Nefazodone (Serzone) Nortriptyline (Aventyl, Pamelor)... 

Three antidepressants—nefazodone, venlafaxine, and mirtazapine—are all related to earlier agents in either structure or mechanism of action. Nefazodone is closely related to trazodone but is less sedating. It produces fewer adverse sexual effects than the SSRIs but is a potent inhibitor of CYP3 A4. (Fluvoxamine causes the same inhibition of CYP3 A4.)... 

Imipramine, desipramine, amitriptyline, nortriptyline, trimipramine, clomipramine, lofepramine, amoxapine, dosulepin, maprotiline, mianserin, setiptiline, trazodone, fluvoxamine, paroxetine, milnacipram, sulpiride, tandspirone, methylpheni-date, melitracen Amitriptyline, imipramine, trimipramine, clomipramine, citalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, venlafaxine, reboxetine, viloxazine, doxepin, maprotiline, mianserine, mirtazapine, moclobemide, trazodone, opipramol (and some metabolites)... 

Castaing et al., 2007 [109] Fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, milnacipram, venlafaxine, mirtazapine (and some metabolites) M ethy lr isp eri do ne... 

In the 1980s an entirely new class of antidepressant arrived with the SSRIs, firstly fluvoxamine immediately followed by fluoxetine (Prozac). Within 10 years, the SSRI class accounted for half of antidepressant prescriptions in the United Kingdom. Further developments in the evolution of the antidepressants have been novel compounds such as venlafaxine, reboxetine, nefazodone and mirtazapine, and a reversible monoamine oxidase inhibitor, moclobemide. 

Fluvoxamine inhibits the cytochrome P450 liver catabolic enzymes (predominantly this is inhibition of N-demethylation), leading to an increase in tricyclic antidepressant (TCA) serum levels. Plasma levels of several antidepressant drugs (e.g. amitriptyline, clomipramine, desipramine, imipramine, maprotiline, and nortriptyline) have been reported to increase by up to 4-fold during co-administration with fluvoxamine. Fluvoxamine at a daily dose of 50-100 mg causes a 3-4-fold increase in the plasma concentration of mirtazapine. 

The cytochrome P450 isoenzyme CYP2D6 is inhibited by fluoxetine and paroxetine and CYP1A2 is inhibited by fluvoxamine. Both of these isoenzymes are involved in the metabolism of mirtazapine, which may explain the raised mirtazapine levels reported. 

Demers JC, Malone M. Serotonin syndrome induced by fluvoxamine and mirtazapine. Arm Pharmaco er (200 ) 35,1217-20. 

Duvemeuil, C. de la Grandmaison, G.L. De Mazancourt, P. Alvarez, J.-C. A hi -performance liquid chromatography method with photodiode-array UV detection for therapeutic drug monitoring of the nontricyclic antidepressant drugs, Ther.Drug Monit.,2003,25,565-573. [LOD 2.5-10 ng/mL plasma fluoxetine norfluoxetine sertraline paroxetine citalopram fluvoxamine moclobemide mirtazapine milnacipran toloxatone venlafaxine viloxazine]... 

Dallet, P. Labat, L. Richard, M. Langlois, M.H. Dubost, J.P. A reversed-phase HPLC method development for the separation of new antidepressants, J.Liq.Chromatogr.Rel.Technol., 2002, 25, 101-111. [fluvoxamine fluoxetine sertraline paroxetine citalopram venlafaxine milnacipran mirtazapine]... 

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