Nefazodone Reboxetine

Atypical antidepressants Bupropion Duloxetine Mianserin Mirtazapine Nefazodone Reboxetine Trazodone Venlafaxine... 

An antidepressant should be selected to match individual patients requirements, such as the need or otherwise for a sedative effect or the avoidance of antimuscarinic effects (especially in the elderly). In the absence of special factors the choice rests on tolerability, safety in overdose and likelihood of an effective dose being reached. SSRIs, lofepramine, mirtazapine, nefazodone, reboxetine and venlafaxine are highlighted as best fulfilling these needs. 

Bupropion, MAOl, nefazodone, reboxetine, TeCA, trazodone... 

Benzodiazepines (low-potency), carbamazepine, inositol, mirtazapine, nefazodone, reboxetine, reversible inhibitors of MAO type A (RiMA), valproate, venlafaxine... 

Other antidepressants Duloxetine, Iprindole, Mirtazapine, Milnacipran, Nefazodone, Reboxetine, Trazodone, Venlafaxine, Viloxazine... 

Taken together, the efficacy of antidepressants covers the spectrum of anxiety disorders, although there are important differences between drugs in the group (Table 3). Several new antidepressants have been marketed since the SS-RIs venlafaxine and mirtazapine are discussed later (Sects. 3.2.1.2 and 3.2.1.4) nefazodone, a serotonin reuptake inhibitor and postsynaptic 5-HT2 blocker showed promise in early studies but was recently withdrawn by its manufacturers reboxetine, a noradrenaline reuptake inhibitor (NARI) showed benefits in panic disorder in one published study (Versiani et al. 2002) and further evidence of its anxiolytic efficacy is awaited. 

A critical review by Olver et al. (2001) on so-called third-generation antidepressants (venlafaxine, reboxetine, nefazodone, mirtazapine) covered 30 controlled therapeutic trials and a number of relapse prevention studies. Questions addressed were overall efficacy, speed of onset and safety but, according to this review, none of the third-generation antidepressants was specifically tested with respect to its potential effects on cognitive function in depressed patients. 

Newer antidepressants. Although the SSRIs are the only antidepressants formally approved for the treatment of panic disorder, recent evidence suggests that several other antidepressants are promising treatments for panic disorder as well. These include nefazodone, venlafaxine XR, mirtazapine, and reboxetine. Bupropion, however, does not seem to have apparent antipanic actions. Since the documentation of efficacy of these newer antidepressants in panic disorder is still emerging, they tend to be used as second-line therapy after SSRIs foil to improve panic or in patients who cannot tolerate them. 

Novel antidepressants Given the importance of SSRIs in the treatment of panic disorder, other, newer antidepressants are developing an efficacy portfolio for panic disorder (and other anxiety disorders) as well. Thus, venlafaxine XR, nefazodone, and mirtazapine hold promise for the treatment of panic disorder. One early study also suggests that the new antidepressant reboxetine may be effective in panic disorder. 

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. 

The novel compounds nefazodone and trazodone usually require titration to a minimum therapeutic dose of at least 200 mg/day. Response to reboxetine, venlafaxine and mirtazapine may occur at the starting dose but some dose titration is commonly required. Venlafaxine is licensed for treatment-resistant depression by gradual titration from 75 to 375 mg/day. There is some need for dose titration when using MAOIs although recommended starting doses (e.g. phenelzine 15 mg t.d.s.) may be effective. Unlike other drug classes, reduction to a lower maintenance dose is recommended after a response is achieved. 

Reboxetine is metabolized by CYP3A4. In 11 healthy volunteers ketoconazole, an inhibitor of CYP3A4, increased the plasma AUC of reboxetine by about 50% and prolonged the half-life (5). The adverse effects profile of reboxetine was not altered by ketoconazole, but the finding suggests that reboxetine should be used with caution in combination with drugs that inhibit CYP3A4, for example nefazodone and fluvoxamine. 

Compared to other forms of antidepressant medication treatment, the SSRI s and other newer compounds identified to treat depression such as venlafaxine, miitazapine, nefazodone and reboxetine are newcomers in... 

For treatment-resistant patients who do not respond to SSRIs or TCAs, or to the combination of TCAs/SSRIs with benzodiazepines, other antidepressants have shown at least some beneficial effects in alleviating PD symptoms (e.g. mirtazapine, moclobemide, nefazodone, phenelzine, reboxetine, and venlafaxine). Other agents have also been reported to exert beneficial effects in PD, especially when combined with SSRIs/TCAs (lithium, pindolol, and propranolol). In cases where all treatments have failed, valproate or olanzapine should be considered.2 - ° In order to optimize treatment, patients should avoid or reduce the consumption of compounds that could potentially induce/exacerbate panic attacks (e.g. caffeine, alcohol, and nicotine) and should exercise regularly. i... 

There are isolated cases of apparent interactions between clozapine, and ampicillin, buspirone, caffeine, haloperidol, loperamide, modafinil, nefazodone, nicotinic acid, tryptophan, or vitamin C. Grapefruit juice, influenza vaccine mirtazapine, reboxetine, or venlafaxine do not appear to interact Cocaine levels may increase when taken with clozapine. 

Nefazodone may increase the plasma concentrations of reboxetine, see Reboxetine + Antidepressants , p.l210. 

Ketoconazole may inhibit the metabolism of reboxetine. The manufacturer therefore advises avoiding the concurrent use of azoles, macrolides and nefazodone. 

A study in 11 healthy subjects found that ketoconazole 200 mg daily for 5 days increased the plasma coneentrations of a single 4-mg dose of reboxetine, taken on the second day, by about 50%. Although the adverse effeet profile of reboxetine was not altered, beeause reboxetine has a narrow therapeutic index it was coneluded that eaution should be used and a reduetion in reboxetine dosage eonsidered if it is given with ketoconazole. The manufacturer recommends that potent inhibitors of CYP3A4, ineluding azoles, macrolides (erythromycin) and nefazodone should not... 

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