Nefazodone inhibitors

Specific concomitant medications or consumptions (check specific statin package insert for warnings) fibrates (especially gemfibrozil, but other fibrates too), nicotinic acid (rarely), cyclosporine, azole antifungals such as itraconazole and ketoconazole, macrolide antibiotics such as erythromycin and clarithromycin, protease inhibitors used to treat Acquired Immune Deficiency Syndrome, nefazodone (antidepressant), verapamil, amiodarone, large quantities of grapefruit juice (usually more than 1 quart per day), and alcohol abuse (independently predisposes to myopathy)... 

A controlled trial of duloxetine (Cymbalta)—like venlafaxine a dual serotonin-norepinephrine reuptake inhibitor—in the treatment of GAD is currently underway. Anecdotal data suggests that nefazodone (Serzone) and mirtazapine (Remeron) may be effective in the treatment of GAD, though no controlled data is available. In addition, recent concerns regarding nefazodone and liver toxicity have limited this medication s utility. Please refer to Chapter 3 for more information regarding these antidepressants. 

All patients with the following conditions Serum potassium greater than 5.5 mEq/L at initiation Ccr 30 mL/min or less concomitant use with the following potent CYP3A4 inhibitors Ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, and nelfinavir. 

Drugs that may affect HMG-CoA reductase inhibitors include alcohol, amiodarone, antacids, azole antifungals, bile acid sequestrants, cimetidine, cyclosporine, diltiazem, erythromycin, gemfibrozil, isradipine, nefazodone, niacin, nicotinic acid, omeprazole, phenytoin, propranolol, protease inhibitors, ranitidine, rifampin, St. John s wort, and verapamil. 

Coadministration with CYP450 inhibitors- Nhen coadministered with potent CYP3A4 inhibitors (eg, ketoconazole, itraconazole, ritonavir, nelfinavir, clarithromycin, nefazodone), do not exceed a daily dose of darifenacin 7.5 mg. 

Drugs that may affect antihistamines include aluminum/magnesium-containing acids, cimetidine, erythromycin, ketoconazole, MAO inhibitors, and rifamycins (eg, rifampin). Drugs that may be affected by antihistamines include alcohol and CNS depressants, beta-blockers, MAO inhibitors, metyrapone, nefazodone, selective serotonin reuptake inhibitors (SSRIs), and venlafaxine. 

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. 

Maintenance/Continuation/Extended treatment There is no evidence to indicate how long the depressed patient should be treated with nefazodone. However, it is generally agreed that pharmacologic treatment for acute episodes of depression should continue for at least 6 months. Whether the dose of antidepressant needed to induce remission is identical to the dose needed to maintain euthymia is unknown. In clinical trials, more than 250 patients were treated for at least 1 year. Switching to or from a monoamine oxidase inhibitor (MAOi) At least 14 days should elapse between discontinuation of an MAOI and initiation of therapy with nefazodone. In addition, wait at least 7 days after stopping nefazodone before starting an MAOI. 

MAOis- Because nefazodone is an inhibitor of both serotonin and norepinephrine reuptake, it is recommended that nefazodone not be used in combination with an MAOl, or within 14 days of discontinuing treatment with an MAOI. Allow at least 1 week after stopping nefazodone before starting an MAOl. 

Antihistamines, nonsedating/Cisapride/Pimozide- Cisapride and pimozide are metabolized by the cytochrome P-450 3A4 isozyme inhibitors of 3A4 can block the metabolism of these drugs, resulting in increased plasma concentrations of parent drug, which is associated with QT prolongation and with rare cases of serious cardiovascular adverse events, including death, because of ventricular tachycardia of the torsades de pointes type. In vitro, nefazodone inhibits 3A4. It is recommended that nefazodone not be used in combination with cisapride or pimozide. 

Drugs that affect nefazodone include general anesthetics, sibutramine, sumatriptan, buspirone, carbamazepine, and propranolol. Drugs that may be affected by nefazodone include alcohol, benzodiazepines, buspirone, carbamazepine, cisapride, digoxin, haloperidol, HMG-CoA reductase inhibitors, MAOIs, propranolol, St. John s wort, cyclosporine, and tacrolimus. 

Pimozide Drugs that prolong the QT interval - CYP3A inhibitors (eg, clarithromycin, dirithromycin, erythromycin, itraconazole, ketoconazole, nefazodone, protease inhibitors, sertraline, telithromycin, troleandomycin, voriconazole)... 

Drugs that can increase carbamazepine serum levels include cimetidine, danazol, diltiazem, erythromycin, felbamate, clarithromycin, fluoxetine, isoniazid, niacinamide, propoxyphene, ketaconazole, itraconazole, verapamil, valproate, troleandomycin, loratadine, nicotinamide, tricyclic antidepressants, SSRIs, nefazodone, protease inhibitors. 

Drugs that may affect tacrolimus include nephrotoxic agents (aminoglycosides, amphotericin B, cisplatin, cyclosporine), antifungals, bromocriptine, calcium channel blockers, cimetidine, clarithromycin, danazol, diltiazem, erythromycin, methylprednisolone, metoclopramide, carbamazepine, phenobarbital, phenytoin, rifamycins, cisapride, chloramphenicol, metronidazole, nefazodone, omeprazole, protease inhibitors, macrolide antibiotics, fosphenytoin, and St. John s wort. 

Drugs that may affect cyclosporine include allopurinol, amiodarone, androgens (eg, danazol, methyltestosterone), anticonvulsants (eg, carbamazepine, phenobarbital, phenytoin), azole antifungals (eg, fluconazole, ketoconazole), beta-blockers, bosentan, bromocriptine, calcium channel blockers, colchicine, oral contraceptives, corticosteroids, fluoroquinolones (eg, ciprofloxacin), foscarnet, HMG-CoA reductase inhibitors, imipenem-cilastatin, macrolide antibiotics, methotrexate, metoclopramide, nafcillin, nefazodone, orlistat, potassium-sparing diuretics, probucol, rifamycins (rifampin, rifabutin), serotonin reuptake inhibitors (SSRIs eg, fluoxetine, sertraline),... 

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. 

Use with caution in oider patients with Concurrent treatment with potent CYP 3A4 inhibitors (e.g., nefazodone) leads to increased plasma concentrations of diazepam COPD untreated sleep apnea... 

Most child and adolescent studies published thus far have focused on the effects of the tricyclic antidepressants (TCAs) and, more recently, the SSRIs. A few open studies have also shown that monoamine oxidase inhibitors (MAOIs) can be used safely with children and adolescents (Ryan et ah, 1988b), but noncompliance with dietary requirements may present a significant problem for minors. Other antidepressants, including the heterocyclics (HTC) (e.g., amoxapine, maprotiline), buproprion, venlafaxine, and nefazodone, have been found to be efficacious for the treatment of depressed adults (APA, 2000), but they have not been well studied for the treatment of MDD in children and adolescents. Therefore, this chapter mainly describes the use of SSRIs and TCAs for youth with MDD. 

Montgomery SA, Brown RE, Clark M Economic analysis of treating depression with nefazodone v. imipramine. Br J Psychiatry 168 768-771, 1996 Monti JM Effect of a reversible monoamine oxidase-A inhibitor (moclobemide) on sleep of depressed patients. Br J Psychiatry Suppl 155 61-65, 1989 Monti JM, Alterwain P, Monti D The effects of moclobemide on nocturnal sleep of depressed patients. J Affect Disord 20 201-208, 1990 Montkowski A, Holsboer F Absence of cognitive and memory deficits in transgenic mice with heterozygous disrupt of the brain-derived neurotrophic factor gene. J Psychiatr Res [in press)... 

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