MAOIs Fluvoxamine

Buspirone generally is well tolerated and does not cause sedation. Most common side effects include dizziness, nausea, and headaches. Drugs that inhibit CYP3A4 (e.g., verapamil, diltiazem, itraconazole, fluvoxamine, nefa-zodone, and erythromycin) can increase buspirone levels. Likewise, enzyme inducers such as rifampin can reduce buspirone levels significantly. Bupirone may increase blood pressure when coadministered with an monoamine oxidase inhibitor (MAOI). 

Mirtazapine does not significantly inhibit hepatic cytochrome P450 enzymes. Additive effects may occur when mirtazapine is combined with other drugs with sedative or vascular effects. Mirtazapine should not be used in combination with an MAOI or within 14 days of discontinuing treatment with an MAOI. When it is combined with fluvoxamine, a potent inhibitor of P450 enzymes— including 1A2, 2D6, and 3A4, which metabolizes mirtazapine—the plasma concentration of mirtazapine may be increased by up to fourfold (AnttUa et al. 2001 Demers et al. 2001). 

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. 

There were two cases of hypertension from the United States, or possible serotonin syndrome reported with fluvoxamine while on St. John s wort concomitantly. A 44-year-old male with obsessive-compulsive disorder received fluvoxamine and experienced severe hypertensive crisis (160-170/ 120mmHg) after two tablets of St. John s wort. The physician stated that the reaction was probably due to the combination of fluvoxamine and St. John s wort, which has MAOI activity. A 38-year-old male was on fluvoxamine for approximately two months and hypericum 600 mg daily for approximately two weeks before reporting possible serotonin syndrome with severe bitemporal headache. He was hospitalized to rule out myocardial infarction. There were no electrocardiogram (EKG) changes or apparent causative pathology. Symptoms resolved on discontinuation of both drugs. 

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). 

Reboxetine Reboxetine should not be given, even after termination of MAOI therapy. Care must be exercised when treating with antihypertensive drugs, antiar-rhythmics, cyclosporin, antipsychotics, tricyclics, fluvoxamine, antidepressants, azole antifungals, and macrolide antibacterials. 

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. 

SSRI [most studied are fluoxetine (in USA), fluvoxamine, paroxetine, sertaline] or MAOI... 

Selective serotonin reuptake inhibitors (SSRIs) are regarded as first-line treatment in social phobia. Fluvoxamine, paroxetine, and sertraline have been shown to be effective in double-blind placebo-controlled studies. - The irreversible monoamine oxidase inhibitor (MAOI) phenelzine shows robust results in terms of efficacy and has demonstrated (at least anecdotally), its efficacy in improving some of the cognitive aspects associated with SAD. However, phenelzine is usually less well tolerated than alternative treatments due to its associated dietary restrictions and adverse side-effect profile, including sedation and postural hypotension. Results with the reversible inhibitor of monoamine oxidase type A (RiMA) mociobemide are inconsistent. 

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. 

---