Paroxetine Nefazodone

A number of SSRIs and SNRIs were tested for their effects on cognitive function in repeated-dose studies in healthy, non-depressed volunteers. Studies with SSRIs before 1999 have been reviewed by Lane and O Hanlon (1999) and some more recent reports deal with nefazodone. paroxetine and sertraline (Furlan et al., 2001 Schmitt et al., 2001 van Laar et al.. 2002). However, considering the populations studied in these trials (non-depressed subjects), the duration of drug administration (1 2 weeks) and the mostly low drug doses used, the relevance of these studies for a clinical situation may be questioned. 

The other tertiary TCA that has dual serotonergic-noradrenergic effects, amitriptyline, like imipramine, appears to be consistently effective in anxiety disorders. Newer antidepressants such as mirtazapine, nefazodone, paroxetine, and venlafaxine may also benefit patients with anxiety disorder ( 60, 61, 62 and 63). 

Inhibitors obtained from in vitro data include a number of compounds with different selectivities and specificity toward this enzyme. Most of them have not been tested for their in vivo effects and some may also inhibit other enzymes (ticlopidine, fluvoxamine, miconazole, nefazodone, paroxetine, etc.). This query did not yield any additional inhibitors. A summary of substrates (including partial ones) and inhibitors is shown in Table 1 and indicates that clopidogrel and ticlopidine, whose effects have been well documented in vivo and in vitro, are effective inhibitors of CYP2B6 and can be used in an in vivo DI program. 

Fluoxetine Fluvoxamine Nefazodone Paroxetine Sertraline - Trazodone Venlafaxine... 

However, the agency s conclusions were based on a limited number of new antidepressants, including bupropion, citalopram, fluoxetine, flu-voxamine, mirtazapine, nefazodone, paroxetine, sertraline, escitalopram, and venlafaxine, according to an FDA Talk Paper (2004a). These were the drugs most often cited by the public at the two FDA hearings. 

Campo JV, Smith C, Perel JM. Tacrolimus toxic reaction associated with the use of nefazodone paroxetine as an alternative agent. Arch Gen Psychiatry 1998 55(ll) 1050-2. 

Anxious or agitated Trazodone, nefazodone, paroxetine, consider tertiary amine TCA or MAOl... 

The older tricyclic agents show less than a ten-fold selectivity in inhibiting noradrenaline over that for 5-HT (e.g. desipramine, imipramine, nortriptyline) through amitryptyline. which shows virtually no selectivity, to trazodone, zimelidine and clomipramine, which are somewhat 5-HT selective. The newer Serotonin-Selective Reuptake Inhibitors (SSRIs) show a higher selectivity for inhibition of 5-HT reuptake in the brain, and have a different pharmacology. Examples clinically used include citalopram, fluoxetine, fluvoxamine, nefazodone, paroxetine, sertraline, trazodone and venlafaxine. Experimental agents include 6-nitroquipazine, alaproclate, litoxetine, indatraline and p-CIT. 

Preskorn SH Comparison of the tolerability of bupropion, fluoxetine, imipramine, nefazodone, paroxetine, sertraline, and venlafaxine. J Clin Psychiatry 56(suppl 6) 12-21,1995... 

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... 

Clinically important, potentially hazardous interactions with citalopram, fluoxetine, fluvoxamine, ginkgo biloba, linezolid, lopinavir, nefazodone, paroxetine, sertraline, venlafaxine... 

Selective serotonin reuptake inhibitors (SSRIs) are frequently prescribed medications. Their therapeutic actions are diverse, ranging from efficacy in depression to obsessive-compulsive disorder, panic disorder, bulimia, and other conditions. They include bupropion, fluoxetine, nefazodone, paroxetine, and miscellaneous other drugs. 

Ajmaline, ajamlicine, flecainide, fluoxetine, isoniazid, ketoconazole, lobeline, nefazodone, paroxetine, (7 )-propaphenooe, quinidine, ritonavir, "statins," yohimbine, venlafaxine... 

Antidepressants Desipramine, imipramine, sertraline, fluoxetine, paroxetine, venlafaxine, bupropion, nefazodone, mirtazapine, gepirone, amineptine Mixed findings suggest that better designed studies may find a niche for some of these drugs. Amineptine was effective for withdrawal symptoms. 

TCAs, noradrenaline and specific SSRIs SNRIs, ECT, TMS combination SSRIs, SNRIs, mirtazapine nefazodone, TCAs Paroxetine... 

Serotonin-Boosting Antidepressants. The SSRIs have also been studied in the treatment of generalized social anxiety disorder, and paroxetine, sertraline, and venlafaxine are effective. Preliminary data suggests that the serotonin-boosting atypical antidepressants (mirtazapine and nefazodone) may also be helpful. Like the MAOIs, they appear to be effective at doses comparable to those used to treat depression. They may help avoidant patients to gradually increase their social interaction and become more assertive. 

Drugs that may affect aprepitant include CYP 3A4 inhibitors (eg, clarithromycin, diltiazem, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, troleandomycin), CYP3A4 inducers (eg, carbamazepine, phenytoin, rifampin), and paroxetine. 

Aprepitant (Emend) [Centrally Acting Antiemetic] Uses Pre-vents N/V assoc w/ emetogenic CA chemo (eg, cisplatin) (use in combo w/ other antiemetics) Action Substance P/neurokinin l(NKi) receptor antagonist Dose 125 mg PO day 1, 1 h before chemo, then 80 mg PO qAM days 2 3 Caution [B, /-] Contra Use w/ pimozide, Disp Caps SE Fatigue, asthenia, hiccups Interactions T Effects W/ clarithromycin, diltiazem, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, troleandomycin T effects OF alprazolam, astem-izole, cisapride, dexamethasone, methylprednisolone, midazolam, pimozide, terfe-nadine, triazolam, chemo agents, eg, docetaxel, etoposide, ifosfamide, imatinib, irinotecan, paclitaxel, vinblastine, vincristine, vinorelbine i effects W/ paroxetine,... 

The initial reports from open studies (Artigas et al. 1994 Blier and Bergeron 1995) suggest that the combination is associated with improved efficacy with probable faster onset of action. This rapid response was reported with augmentation of fluoxetine and paroxetine, and more recently with nefazodone (Bakish et al. 1997), but interestingly not with sertraline or low doses of fluvoxamine. These results needed to be confirmed in placebo-controlled studies, and the reports from large studies do indeed find an acceleration of response measured as time to response and possible superiority of action with some antidepressants at the end of treatment (Perez et al. 1997 Tome de la Granja et al. 1997). 

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. 

Van Laar, M.W., Volkerts, E.R., Verbaten, M.N., et al. Differential effects of amitriptyline, nefazodone and paroxetine on performance and brain indices of visual selective attention and working memoiy. Psychophannacology 162, 351-363, 2002. 

In contrast to anticonvulsants and alcohol, drugs such as bupropion, fluoxetine, fluvoxamine, nefazodone, quinidine, paroxetine, and some antipsychotics can inhibit specific CYP enzymes (7, 11, 36, 37, 41, 42, 43 and 44). Thus, TCAs, certain BZDs, bupropion, some steroids, and antipsychotics can all have their metabolism inhibited by drugs such as fluoxetine. For example, fluoxetine at 20 mg/day produces on average a 500% increase in the levels of coprescribed drugs which are principally dependent on CYP 2D6 for their clearance. That can lead to serious or even life-threatening toxicity if the drug has a narrow therapeutic index and the dose is not adjusted for the change in clearance caused by the coadministration of fluoxetine. 

TABLE 7-25. Comparison of the placebo-adjusted incidence rate (%) of frequent adverse effects for fluoxetine, sertraline, paroxetine, venlafaxine, and nefazodone... 

TABLE 7-26. Placebo-adjusted, dose-dependent adverse effects of paroxetine, venlafaxine, and nefazodone (mg/d)... 

There is a great disparity of current knowledge regarding the effects of antidepressants on GYP enzymes. There have been almost no studies to test the potential effects of TCAs, MAOIs, and trazodone on GYP enzymes. There has only been one study with bupropion but it demonstrated that bupropion produces substantial inhibition of GYP 2D6 comparable with the effect of fluoxetine and paroxetine. In contrast to studies in these antidepressants, there have been extensive in vitro and in vivo studies of SSRIs, nefazodone, and venlafaxine. 

Drugs that may inhibit cytochrome P450 metabolism of other drugs include amiodarone, androgens, atazanavir, chloramphenicol, cimetidine, ciprofloxacin, clarithromycin, cyclosporine, delavirdine, diltiazem, diphenhydramine, disulfiram, enoxacin, erythromycin, fluconazole, fluoxetine, fluvoxamine, furanocoumarins (substances in grapefruit juice), indinavir, isoniazid, itraconazole, ketoconazole, metronidazole, mexile-tine, miconazole, nefazodone, omeprazole, paroxetine, propoxyphene, quinidine, ritonavir, sulfamethizole, verapamil, voriconazole, zafirlukast, and zileuton. 

High fluvoxamine fluvoxamine fluoxetine paroxetine fluoxetine fluvoxamine nefazodone fluoxetine... 

---