Venlafaxine interaction with other drugs

Highly suicidal patients should be given agents posing less risk of lethality with overdose and less risk of interacting with other drugs taken in an overdose attempt (i.e., sertraline, citalopram, or venlafaxine). 

This antidepressant can interact with other drugs via its two mechanisms of action serotonin and NE uptake inhibition. The former action means that the same pharmacodynamic interactions will occur with venlafaxine as with SSRIs, including the serotonin syndrome. At higher doses, venlafaxine is also prone to the same pharmacodynamic interactions as NSRIs such as secondary amine TCAs like desipramine and with newer NSRIs such reboxetine. Thus, the combination of high-dose venlafaxine plus an MAOl could produce a hypertensive crisis as well as the serotonin syndrome. 

The selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment of depression in the elderly. Compared with tricyciic antidepressants (TCAs), they are much safer in overdose and, for the most part, their side-effects are better tolerated. The antidepressants that have been shown, in controlled studies, to be effective in geriatric major depression are the SSRIs fluoxetine, paroxetine, and sertraline, the TCAs clomipramine and nortriptyline, and the serotonin and norepinephrine reuptake inhibitor (SNRi) venlafaxine. Given that most antidepressants are effective in the elderly, the choice of drug is based on its side-effect profile and its potential to interact with other medications. 

Although venlafaxine is a weak inhibitor of CYP2D6, variability has been observed in the pharmacokinetic parameters of venlafaxine in patients with hepatic or renal function impairment. As a precaution, elderly patients taking venlafaxine concurrently with a drug that has a narrow therapeutic index and also is metabolized by CYP2D6 should be carefully monitored. Concurrent use of CYP3A4 inhibitors with venlafaxine has been shown to interfere with its metabolism and clearance. Similar to the other antidepressants that block 5-HT reuptake, venlafaxine may interact pharmacodynamically to cause toxic levels of 5-HT to accumulate, leading to the 5-HT syndrome. 

Also note that the development of the serotonin syndrome has been attributed to the sequential use of an SSRI (fluoxetine, paroxetine, or sertraline) and venlafaxine. It has also occurred with concurrent use of venlafaxine and mirtazapine or trazodone. The manufacturers of venlafaxine caution its use with other drugs that affect serotonergic transmission, such as the SSRIs because of the potential risks of the serotonin syndrome. For more about the serotonin syndrome see Additive or synergistic interactions , (p.9). 

Although many patients believe that dietary supplements will not interact with medications, recent literature suggests otherwise. Recently, many St. John s wort-drug interactions have been reported in the literature. Cases of patients developing symptoms of serotonin syndrome have been reported with St. John s wort alone and in concomitant therapy with other antidepressants such as monoamine oxidase inhibitors, serotonin reuptake inhibitors, and venlafaxine. St. John s wort may exacerbate the sedative effects of benzodiazepines, alcohol, narcotics, and other sedatives. St. John s wort may decrease the levels of protease inhibitors, cyclosporine, digoxin, and theophylline. 

Entacapone and imipramine did not interact adversely in a single-dose study. Similarly, tolcapone and desipramine did not interact adversely. Nevertheless, the manufacturers of entacapone and tolcapone recommend caution if they are used with tricyclic antidepressants or other drugs that inhibit noradrenaline (norepinephrine) uptake, such as maprotiline or venlafaxine. 

The manufacturers of duloxetine contraindicate the concurrent use of MAOIs because of the theoretical risk of the serotonin syndrome. Similarly they recommend caution with other serotonergic drugs, including the SSRIs, venlafaxine, and tryptophan. Fluvoxamine should not be used with duloxetine, because it markedly increases duloxetine levels. Low-dose paroxetine caused a modest increase in the duloxetine ATJC, and fluoxetine is predicted to interact similarly. 

Although venlafaxine can have more interactions than SSRIs pharmacodynamically, it is comparable with citalopram and sertraline in terms of not causing CYP enzyme mediated pharmacokinetic drug-drug interactions (Table 7-29). Thus, these three antidepressants have a distinct advantage over drugs such as fluoxetine, particularly in patients who are likely to be on other medications in aaaition to their antidepressant. 

LITHIUM OTHER-VENLAFAXINE Possible risk of serotonin syndrome Additive effect Be aware of the possibility of serotonin syndrome. Also need to monitor lithium levels with appropriate dose adjustments during co-administration >- For signs and symptoms of serotonin toxicity, see Clinical Features of Some Adverse Drug Interactions, Serotonin toxicity and serotonin syndrome... 

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