Phenelzine Dextromethorphan

Wiley JL, LaVecchia KL, Martin BR, Damaj MI (2002) Nicotine-like discriminative stimulus effects of bupropion in rats. Exp Clin Psychopharmacol 10 129-135 Williams M, Robinson JL (1984) Binding of the nicotinic cholinergic antagonist, dihydro-beta-erythroidine, to rat brain tissue. J Neurosci 4 2906-2911 Witkin JM, Dykstra LA, Carter RB (1982) Acute tolerance to the discriminative stimulus properties of morphine. Pharmacol Biochem Behav 17 223-228 Wooters TE, Bardo MT (2007) The monoamine oxidase inhibitor phenelzine enhances the discriminative stimulus effect of nicotine in rats. Behav Pharmacol 18 601-608 Wright JM Jr, Vann RE, Gamage TE, Damaj MI, WUey JL (2006) Comparative effects of dextromethorphan and dextrorphan on nicotine discrimination in rats. Pharmacol Biochem Behav 85 507-513... 

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. 

Patients should not use dextromethorphan if they are taking any drug in the class known as monoamine oxidase inhibitors (MAOI), including phenelzine (Nardil), isocarboxazid (Marplan), and tranylcypromine (Parnate), which are used in the treatment of depression. The combination of MAOIs with dextromethorphan can lead to toxic levels of dextromethorphan in the blood. 

Clinically important, potentially hazardous interactions with desvenlafaxine, dextromethorphan, dihydroergotamine, ephedra, ergot, fluoxetine, fluvoxamine, isocarboxazid, linezolid, lithium, MAO inhibitors, meperidine, methysergide, naratriptan, nefazodone, paroxetine, phenelzine, rizatriptan, sertraline, sumatriptan, tranylcypromine, tryptophan, venlafaxine, verapamil, zolmitriptan, zuclopenthixol... 

A few fatal cases and a couple of severe adverse effects have been reported with the combination of phenelzine and dextromethorphan. 

Two fatal cases of hyperpyrexia and coma (symptoms similar to the serotonin syndrome) have occurred in patients taking phenelzine with dextromethorphan (in overdosage in one case). Three other serious but non-fatal reactions occurred in patients taking dextromethorphan with isocarboxazid or phenelzine. MAOIs should not be used with dextromethorphan. Mo-clobemide inhibits the metabolism of dextromethorphan, and isolated cases of severe CNS reactions have occurred with the combination, which is also contraindicated. 

A 15-year-old girl taking phenelzine 15 mg three times daily (as well as thioridazine, procyclidine and metronidazole) took 13 capsules of Romilar CF (containing dextromethorphan hydrobromide 15 mg, phenindamine tartrate 6.25 mg, phenylephrine hydrochloride 5 mg and paracetamol (acetaminophen) 120 mg in each capsule). She became comatose, hyper-pyrexic (lOS F), had a blood pressure of 100/60 mmHg, a pulse of 160 bpm and later died ofa cardiac arrest. This case is complicated by the overdosage and multiplicity of drugs present, particularly the phenylephrine. See MAOIs or RIMAs + Sympathomimetics Phenylephrine , p.1148. 

The US manufacturer of tranylcypromine notes that the concurrent use of MAOIs and dextromethorphan has resulted in brief episodes of psychosis or bizarre behaviour. Similarly, the US manufacturer of phenelzine mentions one case of drowsiness and bizarre behaviour when dextromethorphan lozenges were used by a patient taking phenelzine. They also note that concurrent use of dextromethorphan may cause a reaction similar to... 

Sauter D, Macneil P, Weinstein E, Azar A. Phenelzine sulfate-dextromethorphan interaction a case report. Vet Hum Toxicol (1991) 33, 365,... 

---