Moclobemide dextromethorphan

Dmg-induced serotonin syndrome is generally mild and resolves when the offending drugs are stopped. However, it can be severe and deaths have occurred. A large number of drugs have been implicated including tricyclic antidepressants, monoamine oxidase inhibitors (MAOIs), selective serotonin re-uptake inhibitors (SSRIs), pethidine, lithium, and dextromethorphan. The most severe type of reaction has occurred with the combination of selective serotonin re-uptake inhibitors and monoamine oxidase inhibitors. Both non-selective MAOIs such as phenelzine and selective MAOIs such as moclobemide and selegiline have been implicated. 

Tyramine-rich foods, sympathomimetics, dextromethorphan, anorectics, and other antidepressants should be avoided when treating with moclobemide. It also interacts with opioid analgesics, serotonin agonists, NSAIDs, levodopa, and cimetidine.140,141... 

Four subjects had markedly reduced O-demethylation of dextromethorphan after they had taken moclobemide 300 mg bd for 9 days (60). A-demethylation was not affected. This result supports the hypothesis that moclobemide or a metabolite reduces the activity of the cytochrome enzyme CYP2D6. The clinical implications of this particular interaction remain to be clarified. 

Hartter S, Dingemanse J, Baier D, Ziegler G, Hiemke C. Inhibition of dextromethorphan metabolism by moclobemide. Psychopharmacology (Berl) 1998 135(l) 22-6. 

A 23-year-old man was found dead in his apartment, having previously been confused. At autopsy there was no clear cause of death. His urine was positive for amphetamines, opiates, moclobemide, dextromethorphan, cyclizine, oxazepam, diazepam, and temazepam. The coroner concluded that the death was from a combination of ecstasy and moclobemide, with a possible contribution from dextromethorphan. 

Extracted amoxapine, brompheniramine, chlorpheniramine, chlorpromazine, clomipramine, c5q)roheptadine, dsipramine, diphenhydramine, dothiepin, doxepin, fluoxetine, hal-operidol, imipramine, loxapine, maprotihne, meperidine, mesoridazine, methadone, metoclopramide, mianserin, moclobemide, nomifensine, nordoxepin, norfluoxetine, norpropoxyphene, northiaden, nortriptyline, pentobarbital, pheniramine, propojgrphene, propranolol, protriptyline, quinidine, quinine, sulforidazine, thioridazine, thiothixene, tranylcypromine, trazodone, trihe q)henidyl, triprolidine Nonintetfering dextromethorphan, norphetidine, pheno benzamine, prochlorperazine, trifluoperazine... 

Moclobemide 300 mg twice daily for 9 days markedly reduced the O-demethylation of dextromethorphan (seven 20-mg doses given every 4 hours over 2 days), in 4 healthy subjects. The manufacturer notes that isolated cases of severe CNS adverse reactions have been seen with the combination. Concurrent use of dextromethorphan may have contributed to a fatality involving the illicit use of moclobemide and ecstasy , (p.1144). 

Moclobemide appears to inhibit the metabolism of dextromethorphan by the cytochrome P450 isoenzyme CYP2D6, and the combination may also cause adverse CNS effects. 

Despite the very limited information available, the severity of the reactions indicates that patients taking MAOIs should avoid taking dextromethorphan. The manufacturer of moclobemide also contraindicates the concurrent use of dextromethorphan. Patients should be warned that many cough preparations contain dextromethorphan. 

Four patients died after taking moclobemide and ecstasy (MDMA, methylenedioxymethamfetamine). The clinical evidence is limited, but in each case the forensic pathologist concluded that the cause of death was the combined use of these drugs. It was suggested that what happened is consistent with the serotonin syndrome, although the evidence is fairly slim. Two patients had taken maximum therapeutic doses and two moderate overdoses of moclobemide. Note that moclobemide had not been prescribed to any of them. Post-mortem analysis also found the presence of dextromethorphan in one patient, which was thought to have contributed, see also MAOIs or RIMAs -i- Dextromethorphan , p.ll34. 

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