Fluoxetine with MAOI

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). 

Few data are available about fluvoxamine interactions with MAOIs, even though they might be comparable to those of fluoxetine. It must be remembered that the concurrent use of fluoxetine and MAOIs (phenelzine and tranylcypromine) can induce a high incidence (up to 50%) of toxic reactions, including fatal serotonin syndrome. 

Few data are available about paroxetine interactions with MAOIs, even though they might be similar to those of other selective serotonin reuptake inhibitors (SSRIs). Clinically significant or severe interactions have not been found to date. Administered together in patients with depression, moclobemide and paroxetine or fluoxetine appeared to produce adverse effects indicative of potentiated serotonergic activity. 

The effects of buspirone are decreased when the drug is administered with fluoxetine Increased serum levels of buspirone occur if the drug is taken with erythromycin or itraconazole Should any of these combinations be required, the dosage of buspirone is decreased to 2.5 mg BID, and the patient is monitored closely. Venlafaxine blood levels increase with a risk of toxicity when administered witii MAOIs or cimetidine There is an increased risk of toxicity when trazodone is administered with the phenothiazines and decreased effectiveness of trazodone when it is administered with carbamazepine Increased serum digoxin levels have occurred when digoxin is administered with trazodone There is a risk for increased phenytoin levels when phenytoin is administered witii trazodone... 

Monoamine Oxidase Inhibitors (MAOIs). Controlled trials comparing the M AOl phenelzine to clomipramine or fluoxetine have produced mixed results. Given the limited data regarding any efficacy of MAOIs in the treatment of OCD coupled with their potentially dangerous interactions, we cannot recommend MAOIs in the treatment of OCD until other approaches have been tried. 

Changing a patient from one MAOI to another, or to a TCA, requires a "wash-out" period of at least 2 weeks to avoid the possibility of a drug interaction. There is evidence to suggest that a combination of an MAOI with clomipramine is more likely to produce serious adverse effects than occurs with other TCAs. Regarding the newer non-tricyclic antidepressants, it is recommended that a "wash-out" period of at least 5 weeks be given before a patient on fluoxetine is given an MAOI this is due to the very long half-life of the main fluoxetine metabolite norfluoxetine. 

The field of antidepressant research was revolutionized in the late 1980s by the introduction of selective serotonin reuptake inhibitors (SSRIs), exemplified by fluoxetine (9). In addition to their antidepressant action, SSRIs have also proven effective for a broad range of psychiatric illnesses, and, more importantly, they demonstrated an improved tolerability profile as compared to TCAs and MAOIs due to their increased selectivity. On the other hand, SSRIs proved inferior to TCAs and MAOIs in their reduced antidepressant effects, slower onset of action, lower remission rates, and decreased ability to control the physical symptoms associated with depression. 

There is a great disparity of current knowledge regarding the effects of antidepressants on GYP enzymes. There have been almost no studies to test the potential effects of TCAs, MAOIs, and trazodone on GYP enzymes. There has only been one study with bupropion but it demonstrated that bupropion produces substantial inhibition of GYP 2D6 comparable with the effect of fluoxetine and paroxetine. In contrast to studies in these antidepressants, there have been extensive in vitro and in vivo studies of SSRIs, nefazodone, and venlafaxine. 

MAOIs, TCAs, lithium, clomipramine (alone or with topical steroids), fluoxetine, and fluvoxamine may reduce the frequency and intensity of this disorder ( 210, 226, 255, 256, 257, 258, 259, 260 and 261) however, controlled trials are needed to conclusively establish efficacy. Relapse after initial improvement has also been reported, however. Data also indicate that both trichotillomania and OCD may respond to venlafaxine ( 262, 263). For children, such treatments should be reserved for only those with the more severe, refractory forms. 

SSRIs PROCARBAZINE T risk of serotonin syndrome and CNS toxicity Additive toxicity Monitor BP closely and also CNS side-effects. Because of the long half-life of fluoxetine and its active metabolites, at least 5 weeks should elapse between discontinuation of fluoxetine and initiation of therapy with an MAOI... 

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 long half-lives of fluoxetine (2 to 5 days in young healthy subjects) and of its active metabolite, norfluoxetine (7 to 9 days), ensure that following discontinuation of the drug, active compounds persist in the body for weeks. The very slow elimination of fluoxetine makes it critical to ensure a 5-week washout after fluoxetine discontinuation before starting an MAOI. For all other SSRIs, a 2-week washout is recommended. Serious and potentially fatal reactions may occur when any SSRI is coadministered with an MAOI, and coadministration is contraindicated. ... 

Antidepressant drugs A major class of psychotropic drugs with diverse chemical configurations including the monoamine oxidase inhibitors (MAOIs), the heterocyclic drugs (composed of mono-, di-, tri-, and hetero-cyclics), the serotonin reuptake inhibitors (fluoxetine, paroxetine, sertraline, trazodone, and venlafaxine), and bupropion are more recent innovations. Antidepressants usually must be taken for several weeks to have the desired effect and they often have a low therapeutic index, so they must be closely monitored. 

In general, a two-week waiting period is required between therapy with a MAOI and subsequent therapy with a SSRI. The exception is with fluoxetine, as it has a delayed onset of action. A change in therapy from fluoxetine to a MOAI requires a five-week interval, due to fluoxetine s long duration of action. 

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