New antidepressants and the cytochrome P450 system: Focus on venlafaxine, nefazodone, and mirtazapine

Owen, John; Nemeroff, Charles B.

doi:10.1002/(sici)1520-6394(1998)7:1+<24::aid-da7>3.0.co;2-f

Cited by 72 publications

(28 citation statements)

References 23 publications

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“…An additional variable that may have contributed to ADRs is the number of co‐administered drugs including those that are CYP2D6 inhibitors . We found only a non‐significant trend on regression analysis ( P = 0·17) of the carvedilol dose being less in patients treated with antidepressants and amiodarone.…”

Section: Discussionmentioning

confidence: 70%

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Variation in the CYP2D6 genotype is not associated with carvedilol dose changes in patients with heart failure

et al. 2014

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Section: Discussionmentioning

confidence: 70%

“…Concomitant medications that might affect CYP2D6 enzymatic activity were recorded. This included strong CYP2D6 inhibitors such as fluoxetine, paroxetine, bupropion and quinidine and weak CYP2D6 inhibitors such amiodarone, sertraline, terbinafine, mirtazapine, citalopram, duolexetine …”

Section: Methodsmentioning

confidence: 99%

Variation in the CYP2D6 genotype is not associated with carvedilol dose changes in patients with heart failure

et al. 2014

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“…Mirtazapine is extensively metabolized in the liver and the major metabolic routes are N‐demethylation, N‐oxidation and 8‐hydroxylation. CYP2D6 and, to a lesser extent, CYP3A4, are involved in the formation of hydroxymetabolites, CYP3A4 and CYP1A2 catalyse the N‐demethylation, while CYP3A4 is the major isoform involved in the N‐oxidation [140,141]. Based on preclinical studies in human liver microsomes, mirtazapine has minimal inhibitory effects on CYP1A2, CYP2D6 and CYP3A4 and, therefore, it is not expected to cause clinically significant interactions interact with substrates for these isoforms [140].…”

Section: Mirtazapinementioning

confidence: 99%

Metabolic drug interactions with new psychotropic agents

Spina

Scordo

D'Arrigo

2003

Fundamemntal Clinical Pharma

118

104

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New psychotropic drugs introduced in clinical practice in recent years include new antidepressants, such as selective serotonin reuptake inhibitors (SSRI) and 'third generation' antidepressants, and atypical antipsychotics, i.e. clozapine, risperidone, olanzapine, quetiapine, ziprasidone and amisulpride. These agents are extensively metabolized in the liver by cytochrome P450 (CYP) enzymes and are therefore susceptible to metabolically based drug interactions with other psychotropic medications or with compounds used for the treatment of concomitant somatic illnesses. New antidepressants differ in their potential for metabolic drug interactions. Fluoxetine and paroxetine are potent inhibitors of CYP2D6, fluvoxamine markedly inhibits CYP1A2 and CYP2C19, while nefazodone is a potent inhibitor of CYP3A4. These antidepressants may be involved in clinically significant interactions when coadministered with substrates of these isoforms, especially those with a narrow therapeutic index. Other new antidepressants including sertraline, citalopram, venlafaxine, mirtazapine and reboxetine are weak in vitro inhibitors of the different CYP isoforms and appear to have less propensity for important metabolic interactions. The new atypical antipsychotics do not affect significantly the activity of CYP isoenzymes and are not expected to impair the elimination of other medications. Conversely, coadministration of inhibitors or inducers of the CYP isoenzymes involved in metabolism of the various antipsychotic compounds may alter their plasma concentrations, possibly leading to clinically significant effects. The potential for metabolically based drug interactions of any new psychotropic agent may be anticipated on the basis of knowledge about the CYP enzymes responsible for its metabolism and about its effect on the activity of these enzymes. This information is essential for rational prescribing and may guide selection of an appropriate compound which is less likely to interact with already taken medication(s).

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“…Cisapride (Propulsid) should not be concurrently prescribed with nefazodone. 18 Also, because nefazodone increases blood levels of digoxin 8 (which has a narrow therapeutic index and is highly toxic to the heart and gastrointestinal tract at inappropriately elevated plasma concentrations), concurrent use of these agents should be carefully monitored.…”

Section: Nefazodonementioning

confidence: 99%

“…Data on the interaction of mirtazapine with the P-450 system are incomplete; thus far the drug has been shown to weakly or minimally inhibit the 1A2, 206, and 3A4 isoenzymes. 18 Given its affinity for multiple receptors, however, mirtazapine might be expected to interact with other drugs pharmacodynamically (table 6). The only interaction that has been identified thus far is additive impairment of motor skills that occurs when mirtazapine is given concurrently with diazepam.…”

Section: Mirtazapinementioning

confidence: 99%

Antidepressant drug interactions in the elderly

Cadieux

1999

Postgraduate Medicine

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Antidepressant treatment in patients 65 years of age or older carries increased risks of adverse drug events because of age-related physiologic changes, polypharmacy, and individual variability in drug metabolism (due to genetic factors, concurrent disease, diet, and consumption habits). Reduction of total drug burden, adjustment of dose levels, and careful selection of an appropriate agent are important steps toward avoiding adverse drug interactions, In addition, the documented and potential drug interactions of the various classes of antidepressants, and specific agents within each class, should be considered. Each elderly patient should be treated individually and monitored carefully during the initiation and maintenance of antidepressant therapy.

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New antidepressants and the cytochrome P450 system: Focus on venlafaxine, nefazodone, and mirtazapine

Cited by 72 publications

References 23 publications

Variation in the CYP2D6 genotype is not associated with carvedilol dose changes in patients with heart failure

Variation in the CYP2D6 genotype is not associated with carvedilol dose changes in patients with heart failure

Metabolic drug interactions with new psychotropic agents

Antidepressant drug interactions in the elderly

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