Symptom 1 - Dextromethorphan

Serotonin syndrome (sibutramine) The rare, but serious, constellation of symptoms also has been reported with the concomitant use of selective serotonin reuptake inhibitors and agents for migraine therapy (eg, sumatriptan, dihydroergotamine), certain opioids (eg, dextromethorphan, meperidine, pentazocine, fentanyl), lithium, or tryptophan. Because sibutramine inhibits serotonin reuptake, it should not be administered with other serotonergic agents. 

It is beheved that phenomena such as sensitization, tolerance and drug-dependence might also involve synaptic plasticity. In fact, numerous studies indicate that NMDA receptor antagonists block sensitization to amphetamine and cocaine as well as tolerance and dependence to ethanol and opioids in animal models (Trujillo and Akil 1991 Pasternak and Inturrisi 1995 Trujillo and Akil 1995 Mao 1999). Recent studies indicate that the uncompetitive NMDA receptor antagonists dextromethorphan, memantine and neramexane not only prevent the development of morphine tolerance, but also reverse estabhshed tolerance in the continuing presence of this opioid, prevent the expression of withdrawal symptoms in rats (Popik and Skolnick 1996 Popik and Danysz 1997 Popik and Kozela 1999 Houghton et al. 2001) and attenuate the expres-... 

Medications with serotonergic activity may also have other monaminergic or sympathomimetic activity. Combining MAOIs with these medications may result in a complex side effect profile. For example, combining meperidine or dextromethorphan with MAOIs may result in respiratory depression, in addition to symptoms of serotonin excess. Furthermore, interactions between MAOIs and tricyclic antidepressants (TCAs) more commonly result in potentiating shared adverse events such as othostatic hypotension, as opposed to hyperadrenergic crises or the serotonin syndrome. 

Mercadante, S., Casuccio, A., Genovese, G. Ineffectiveness of dextromethorphan in cancer pain, J. Pain Symptom Manage. 1998, 16, 317-322. 

Dextromethorphan should be used with caution in individuals who are debilitated or under sedation. Individuals who are prescribed bed rest should also use the drug with great caution. If the symptoms of the condi-... 

Dextromethorphan-induced psychotic and/or manic-like symptoms have been reported. 

A 2-year-old child developed hyperirritability, incoherent babbling, and ataxia after being over-medicated with a pseudoephedrine/dextromethorphan over-the-counter combination cough formulation for upper respiratory symptoms (224). The symptoms abated after withdrawal of the product. 

In another three cases (girls aged 10, 13, and 15 years) severe acute psychosis was associated with the use of an over-the-counter formulation containing ephedrine or pseudoephedrine and dextromethorphan combined with other compounds (225). The psychopathology included agitation, depressed mood, flat affect, pressure of speech, visual and auditory hallucinations, and paranoia. All three improved dramatically, with residual symptoms of irritability, 2-4 days after withdrawal of the mixture and treatment with risperidone 0.5-2.0 mg/day. 

An 18-year-old student had dissociative phenomenon, nihilistic and paranoid delusions, vivid visual hallucinations, thought insertion, and broadcasting after having consumed 1-2 bottles of cough syrup (dextromethorphan 711 mg per bottle) every day for several days (226). The psychotic symptoms remitted completely without any treatment 4 days after withdrawal of dextromethorphan. He was hospitalized twice more over the next 2 months with similar symptoms each time he had consumed large doses of dextromethorphan. 

Tylenol Multi-Symptom APAP 650 mg Pseudoephedrine hydrochloride 60 mg Dextromethorphan hydrobromide 30 mg Chlorpheniramine maleate 4 mg... 

An 8-year-old boy complained of abnormal facial movements and hallucinations. One day before these symptoms, he had been given his sister s Cordec DM droplets (carbinoxamine maleate 2 mg, pseudoephe-drine hydrochloride 25 mg, and dextromethorphan 4 mg) for a cold. He had facial dyskinesia, dilated pupils, pyrexia, tachycardia, and reduced bowel sounds and responded to a benzodiazepine. 

Chevlen E. Morphine with dextromethorphan conversion from other opioid analgesics. J Pain Symptom Manage 2000 19(Suppl l) S42-9. 

No effective treatment is known. Drugs that counteract the effect of glycine on neuronal cells, such as strychnine, diazepam, and dextromethorphan, could bring mild benefits in milder forms of the condition. Ketamine, an anesthetic blocker of the N-methyl-n-aspartate (NMDA) receptor channel, brought a partial improvement of neurological symptoms and EEG findings m some patients, but their developmental milestones were delayed. 

Symptoms sweating, rigidity, myoclonus, hyperthermia, ANS instability, seizures ° Drugs SSRIs, TCAs, meperidine, dextromethorphan... 

Aylward M, Maddock J, Davies DE, Protheroe DA, Leideman T (1984) Dextromethorphan and codeine comparison of plasma kinetics and antitussive effects. Eur J Respir Dis 65 283-291 Barbee RA, Halonen M, Kaltenbom WT, Burrows B (1991) A longitudinal study of respiratory symptoms in a community population sample. Correlations with smoking, allergen skin-test reactivity, and serum IgE. Chest 99 20-26... 

Cough suppressants containing dextromethorphan or codeine should be employed initially for symptomatic therapy of respiratory symptoms. Prolonged coughing unrelieved by codeine might benefit from a semisynthetic, centrally acting narcotic... 

II. Toxic dose. The toxic dose is highly variable and depends largely on other ingredients in the ingested product. Symptoms usually occur when the amount of dextromethorphan ingested exceeds 10 mg/kg. The usual recommended adult daily dose of dextromethorphan is 60-120 mg/day in children age 2-5 years, up to 30 mg/day. 

In a study in 14 healthy subjects, two 20-mg doses of dextromethorphan given 4 hours apart, before and during the use of linezolid 600 mg every 12 hours, had no effect on linezolid pharmacokinetics. The AUC and maximum level of the dextromethorphan metabolite, dextrorphan was decreased by 30%, but this was not considered sufficient to warrant any dosing alterations. There was no evidence of the serotonin syndrome, as measured by changes in body temperature, alertness and mental performance. However, the manufacturers describe one case where the concurrent use of linezolid and dextromethorphan resulted in the serotonin syndrome. Linezolid has mild reversible MAOI activity, and the serotonin syndrome has been described when dextromethorphan was taken by patients also taking antidepressant MAOIs, see MAOIs or RIMAs + Dextromethorphan , p.l 134. If the concurrent use of linezolid and dextromethorphan is considered necessary, it would seem prudent to monitor for symptoms of the serotonin syndrome , (p.9). 

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. 

The authors of this report very briefly deseribe another patient taking paroxetine who developed symptoms consistent with the serotonin syndrome within a few hours of taking a non-preseription eough remedy containing dextromethorphan and guaifenesin. She needed intensive care treatment. ... 

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