Citalopram cytochrome P450 inhibition

Selective serotonin reuptake inhibitors. Currently available selective serotonin reuptake inhibitors (SSRIs) include fluoxetine, paroxetine, sertraline, fluvoxamine, and citalopram. At present, expert opinion does not support the usefulness of these serotonergic compounds in the treatment of core ADHD symptoms (National Institute of Mental Health, 1996). Nevertheless, because of the high rates of comorbidity in ADHD, these compounds are frequently combined with effective anti-ADHD agents (see Combined Pharmacotherapy, below). Since many psychotropics are metabolized by the cytochrome P450 system (Nemeroff et ah, 1996), which in turn can be inhibited by the SSRIs, caution should be exercised when combining agents, such as the TCAs, with SSRIs. 

SSRI drug interactions The SSRls are inhibitors of hepatic cytochrome P450 isozymes, an action that has led to increased activity of other drugs including tricyclic antidepressants and warfarin. Huvoxamine inhibits the metabolism of cisapride, astemizole, and terfena-dine, and the resultant cardiotoxicity has led to the withdrawal of the latter two thugs (see Table 30-3). Citalopram causes fewer drug interactions than other SSRls. 

Fluoxetine and paroxetine inhibit the cytochrome P450 isoenzyme CYP2D6 thus inhibiting the metabolism of some beta blockers (e.g. propranolol, metoprolol, carvedilol) so that they accumulate, the result being that their effects, such as bradycardia, may be increased. Citalopram and escitalopram may also inhibit CYP2D6. In vitro studies with human liver microsomes found that fluoxetine and paroxetine are potent inhibitors of metoprolol metabolism and fluvoxamine, sertraline and citalopram less potent. However, fluvoxamine also potently inhibits the metabolism of propranolol by CYP1A2. Beta blockers that are not extensively me-... 

Fluvoxamine and nefazodone are inhibitors of the cytochrome P450 isoenzyme CYP3A4, the main isoenzyme by which ciclosporin is metabolised. Concurrent use can therefore lead to increased ciclosporin levels. Fluoxetine may interact similarly. Citalopram and sertraline do not usually signifrcantly inhibit CYP3A4 and would therefore not be expected to interact. 

It appears that the plasma levels of trazodone may be increased by fluoxetine due to inhibition of cytochrome P450 isoenzymes by fluoxetine and/or norfluoxetine. Trazodone is a substrate for CYP3A4 and, although fluoxetine is a weak inhibitor, its metabolite norfluoxetine is a moderate inhibitor of this enzyme. vitro data suggest citalopram has little inhib-... 

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