Correspondence

“Invisible” Synthetic Opiates and Acute Psychosis

N Engl J Med 2001; 345:469August 9, 2001

Article

To the Editor:

Many acute psychotic episodes encountered in emergency situations are related to addictive substances. Nalbuphine is a synthetic opiate agonist–antagonist, chemically related to both the opioid antagonist naloxone and the analgesic oxymorphone.1 It has been widely prescribed in Mexico for palliative care and in the United States for obstetrical analgesia.1-3 Nalbuphine is a low-priced analgesic and is not a tightly controlled substance.

We wish to report the case of a 53-year-old man with no known psychiatric or substance-abuse history. Police found him walking public streets unclothed and apparently responding to internal stimuli. He was taken to the emergency room, where he was found to have slurred speech, generalized tremors, and an altered level of consciousness. In the initial medical workup, the results of a lumbar puncture and a computed tomographic scan of the head were normal; the creatine kinase level was 2008 U per liter. The urine toxicology screen was negative on two occasions over a 48-hour period. The creatine kinase level normalized, but the patient continued to be delirious and psychotic. He received risperidone, 1 mg twice daily for two days, and showed dramatic improvement. After his mental status returned to normal, he reported that he had been crossing the border between the United States and Mexico to obtain nalbuphine, which he had been taking for many months for chronic back pain.

Nalbuphine has been reported to have an analgesic potency equivalent to that of morphine. The most commonly reported side effects are sedation and euphoria. Delusions and hallucinations have also been reported.1,3

It has been reported that nalbuphine has less addictive potential than codeine or propoxyphene and therefore in many countries it is not a tightly controlled substance.1-3 This assumption needs revisiting. Another striking fact is that nalbuphine may interfere with enzymatic methods for the detection of specific opiates, and it is virtually invisible to routine toxicologic tests,1,4 as in the case we report. When there is suspicion of nalbuphine intoxication, routine screening for opiates should be supplemented with a more specific assay such as gas chromatography–mass spectrometry.

Given the widespread use of nalbuphine in Mexico and the increasing number of prescriptions for it in the United States, it is important for emergency room physicians to be alert for this “invisible opiate” as a possible cause of acute psychosis. The problem may not be confined to regions near the Mexican border but may be more widespread. A recent report, for instance, noted abuse of nalbuphine among bodybuilders who treat themselves for chronic pain.5

Alvaro Camacho, M.D.
Scott C. Matthews, M.D.
Joel E. Dimsdale, M.D.
University of California, San Diego, La Jolla, CA 92093
acamacho@ucsd.edu

5 References

1. 1

   Nubain product information. Chadds Ford, Pa.: Endo Pharmaceuticals, September 1999.
   

2. 2

   Montejo Rosas G, Bruera E. Palliative care in Mexico. J Palliat Care 1993;9:35-36
   Medline

3. 3

   Hoover RC, Williams RB. Survey of butorphanol and nalbuphine diversion in US hospitals. Am J Hosp Pharm 1985;42:1111-1113
   Medline

4. 4

   Kintz P, Tracqui A, Mangin P. Determination of nalbuphine using high-performance liquid chromatography coupled to photodiode-array detection and gas chromatography coupled to mass spectrometry. J Chromatogr 1992;579:172-176
   CrossRef | Web of Science | Medline

5. 5

   Wines JD Jr, Gruber AJ, Pope HG Jr, Lukas SE. Nalbuphine hydrochloride dependence in anabolic steroid users. Am J Addict 1999;8:161-164
   CrossRef | Web of Science | Medline

Citing Articles (3)

Citing Articles

1. 1

   2006. Nalbuphine. , 2416-2417.
   CrossRef

2. 2

   Ewan McNicol, Nathalie Horowicz-Mehler, Ruth A Fisk, Kyle Bennett, Maria Gialeli-Goudas, Priscilla W Chew, Joseph Lau, Daniel Carr. (2003) Management of opioid side effects in cancer-related and chronic noncancer pain: a systematic review. The Journal of Pain 4:5, 231-256
   CrossRef

3. 3

   &NA;. (2001) Nalbuphine. Reactions Weekly &NA;:865, 9
   CrossRef