A search of online computerized medical data-bases (Medline, Peruse) at McGill University, Montreal, Canada, revealed four reported cases of fatal fulminant hepatic failure (FHF) associated with pemoline (Cylert) use as a treatment for attention deficit hyperactivity disorder. Transient increases in hepatic enzymes, with or without symptoms of hepatitis, have been reported in several articles. Of the four reported cases of FHF, one was a deliberate pemoline overdose, one had preexisting cirrhosis, a third developed FHF after addition of methylphenidate (MPH), and one had taken pemoline alternating with MPH for 5 years and pemoline alone for one year. Of these cases, only one appeared justified. The risk of hepatic failure with pemoline may have been overemphasized, but precautions with its use are advised. [1]

COMMENT. Since the presentation of this article for publication, Abbott Laboratories has notified practitioners of the concern regarding further cases of pemoline associated hepatic failure, and the FDA has advised that pemoline should not be prescribed as a first line treatment for ADHD. Preexisting liver disease is a contraindication, and polytherapy with methylphenidate should be avoided. Baseline and monthly routine liver function monitoring are probably advisable, although the value of this screening in prediction and prevention of hepatic failure is unproven. Significant increases in liver enzymes or symptoms of hepatic dysfunction, such as nausea, anorexia, vomiting, and jaundice, are indications for immediate withdrawal of pemoline treatment. The authors propose a central registry for cases of pemoline-associated hepatic failure.

Amantadine hydrochloride, a dopamine agonist, adjunct treatment for ADHD, is reported of value in 30 children who failed to respond to stimulant therapy. The doses employed were 75 mg bid in liquid form (50 mg/5 ml), for children 8 years of age and younger, and 100 mg bid as 100 mg capsules, for children 9 years of age and older. Advantages of amantadine over tricyclic antidepressants and antihypertensive agents used as adjunct therapies for ADHD include freedom from cardiovascular effects and effects on appetite, and lack of daytime sedation. Vivid dreams were the only side effect witnessed by the author. Further controlled trials are indicated. [2]