Paroxetine interaction with other drugs

All SSRIs have common 5-HT agonistic effects and because of this, SSRIs have common interactions and side effects. SSRIs are potent inhibitors of serotonin reuptake by CNS neurons and may interact with other drugs such as monoamine oxidase inhibitors (MAOIs) or circumstances which cause serotonin release. A minimum 2 weeks wash-out period should be observed between stopping a MAOI and starting an SSRI. Conversely, a MAOI should not be started for at least 1 week after an SSRI has been stopped, 5 weeks after fluoxetine, and 2 weeks for paroxetine and sertraline. Escitalopram and citalopram are hypersensitive to each other. 

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. 

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). 

The most common interactions with SSRIs are pharmacokinetic interactions. For example, paroxetine and fluoxetine are potent CYP2D6 inhibitors (Table 30-4). Thus, administration with 2D6 substrates such as TCAs can lead to dramatic and sometimes unpredictable elevations in the tricyclic drug concentration. The result may be toxicity from the TCA. Similarly, fluvoxamine, a CYP3A4 inhibitor, may elevate the levels of concurrently administered substrates for this enzyme such as diltiazem and induce bradycardia or hypotension. Other SSRIs, such as citalopram and escitalopram, are relatively free of pharmacokinetic interactions. The most serious interaction with the SSRIs are pharmacodynamic interactions with MAOIs that produce a serotonin syndrome (see below). 

There appears to be little or no information about adverse interactions between zotepine and other drugs, but the manufacturers warn about the concurrent use of antihypertensives, anaesthetics, antipsycho tics, and drugs that prolong the QTc interval. Two cases of deep vein thrombosis have been reported in patients taking zotepine with paroxetine. 

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. 

The study of ecstasy with citalopram was primarily undertaken to find out how eestasy works, but on the basis of these results and animal studies it seems likely that patients already taking citalopram may not be able to get as high on usual doses of ecstasy, and some adverse effects may also be redueed. Furthermore, if the proposed mechanism of interaction is correct, the same is also likely to be true if they are taking any other SSRI and some cases have been reported. However, be aware of possible pharmaeokinetie interaetions with some SSRIs that are potent CYP2D6 inhibitors (e.g. fluoxetine, paroxetine), which may increase ecstasy levels. There is also a risk of increased serotonergic activity and there have been a few reports of interaetions involving other sympathomimetics and SSRIs or related drugs, see Phentermine + Fluoxetine , p.205. 

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