At a Glance

Features of amphetamine/methamphetamine overdose include restlessness,irritability,hyperactivity,hypertension,insomnia, diaphoresis,mydriasis,and tachypnea. Life threatening overdose may cause delirium, arrhythmia,convulsion,and coma.Overdose with 3,4-methylene dioxy methamphetamine (MDMA, ecstasy) and 3,4-methylene dioxyamphetamine (MDA) produce similar symptoms.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

A urine drug screen should be ordered in any patient presenting with a clinical history or symptoms suggestive of amphetamine overdose. Urine drug screens provide rapid turnaround times and are available in most laboratories. Common urine drug screens available to detect amphetamine overdose include amphetamine, methamphetamine, amphetamine/methamphetamine, and MDMA immunoassays, each with varying specificities to the drugs within the amphetamine class. The assay(s) utilized depend on the laboratory. A positive result on the screening assay can be consistent with amphetamine overdose with some common exceptions noted below.

If available, confirmatory techniques, such as gas chromatography-mass spectrometry (GC/MS), can confirm amphetamine/methamphetamine overdose, including those due MDMA and MDA.

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Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications – OTC drugs or Herbals – that might affect the lab results?

Urine drug screens have limitations, including the generation of false-positive and false-negative results. False-negative results can occur if the amphetamine screening assay has low cross-reactivity for the ingested amphetamine. For example, some amphetamine immunoassays will not detect MDMA use. For this reason, specific MDMA immunoassays are now available.

False-positive results are common in amphetamine immunoassays. Many over-the-counter (OTC) cold and cough medications interfere with amphetamine/methamphetamine screening immunoassays in urine and can trigger positive results.

Active ingredients known to interfere include ephedrine, pseudoephedrine, phentermine, and phenylephrine. In addition, the OTC drug ranitidine and the diet pill tyramine interfere with amphetamine/methamphetamine immunoassay and may trigger positive results. Finally, certain prescription drugs interfere with amphetamine/methamphetamine screening assays. These drugs include buflomedil, chloroquine, chlorpromazine, isometheptene, isoxsuprine, mexiletine, mebeverine, perazine, promethazine, propylhexedrine, quinacrine, tolemetin, trimethobenzamide, and N-acetyl procainamide. Results in patients taking any of the OTC or prescription drugs should be interpreted with caution.

Positive screening results due to therapeutic use can be obtained in patients taking amphetamine/methamphetamine for attention deficit disorders and narcolepsy or patients taking certain drugs metabolized to amphetamine/methamphetamine. For example, amphetamine is an active ingredient of Adderall and related brands, whereas methamphetamine is the active ingredient of Desoxyn. Compounds that metabolize to amphetamine or methamphetamine include amphetaminil, ethylamphetamine, fenproporex, selegiline, benzphetamine, famprofazone, furfenorex, clobenzorex, fencamine, mefenorex, fenethylline, and prenylamine. All of these drugs trigger clinical positive results.

Vick’s inhaler contains primarily l-methamphetamine, as opposed to d-methamphetamine, which is abused. Although l-methamphetamine has low cross-reactivity with amphetamine immunoassays and should not cause false-positive results, positive results can be seen in patients using excessive amounts of Vick’s inhaler. In these cases, chiral derivatization and GC/MS confirmation can be utilized to determine if l- (due to Vick’s inhaler) or d- (due to amphetamine abuse) methamphetamine is present.

Ephedra-containing herbal weight loss products (ma huang) interfere with amphetamine/methamphetamine screening test but do not interfere with GC/MS confirmation.

What Lab Results Are Absolutely Confirmatory?

Confirmatory techniques, such as GC/MS, can confirm amphetamine/methamphetamine overdose, including those due MDMA and MDA. However, if methamphetamine is confirmed by GC/MS, amphetamine, the metabolite of methamphetamine should also be present in the specimen.

Although thin layer chromatography test (Toxi Lab) has better specificity than urine drugs of abuse screening test for confirming amphetamine/methamphetamine overdose, GC/MS is the most specific test to confirm this diagnosis.