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Selegiline for the Delivery of Small Doses of Amphetamine in Autism, ADHD and Mental Retardation

From the Journal of Neuropsychiatry - Reprinted with permission.

We found a practical and unique use for selegiline in a young adult with pervasive developmental disorder (PDD), mental retardation (MR), and attention-deficit/hyperactivity disorder (ADHD).

It can deliver tiny doses of its metabolites, desmethyldeprenyl (half-life of 2 hours), methamphetamine (half-life of 17.7 hours), and amphetamine (half-life of 20.5), in patients suffering overdose side effects from the smallest marketed doses of other stimulants. Selegiline is an irreversible monoamine oxidase (MAO) inhibitor that selectively inhibits MAO type B if the dose is 10 mg or less. Its peak blood level occurs around one hour after ingestion. It was originally marketed for Parkinson's disease. The combined blood level of amphetamines from 10 mg selegiline is about half that from 10 mg dextroamphetamine.

In the 1980's selegiline improved six of 11 ADHD cases. The dosing (average 30 mg, maximum 50 mg) caused side effects that patients rejected. Jankovic used this medication to treat ADHD and Tourette's syndrome in 29 children (age 6 to 18 years). Approximately 90% reported experiencing moderate or greater improvement on doses of 5 to 15 mg a day.

A dosage of 2.5 mg of selegiline worked successfully in our patient, most likely because of its capacity to deliver a very low dose of methamphetamine and amphetamine.

CASE REPORT

Our 19-year old patient took methylphenidate (Ritalin) 5 mg for a month. He became "a zombie" after two days and was nonfunctional lying on his couch for over a month.

The chief referral complain was that he has been "jumping up and down daily, racing all around the house and breaking holes in the ceiling by throwing furniture up at the ceiling." He hit his mother and grandmother" every couple months. I.Q. scores were in the 40s. On examination, he exhibited abnormal posture, inappropriate grimacing, excitability, rocking, labile mood, hyperacusis, and fear of cars and of the air conditioner.

His present school complained he "did not listen, was easily distracted, had difficulty concentrating, and had profound impulsivity" (Conners Scale score 14/30).

The patient was started on selegiline 2.5 mg in the morning for approximately one month and improved. His mother was "delighted." Calls from the school immediately stopped (Conners score of 8/30). A second 2.5 mg. dose at noon gave the patient "droopy, glazed eyes," with an appearance and behavior identical to that on methylphenidate 5 mg.

In the evening he did have some return of his pre-medicated behaviors, yet was better than at baseline. He remained on the medication for approximately eight months, until his mother lost a prescription. She and the school reported a prompt resumption of the patient's troubling behaviors, and repeated Conners Scales yielded high scores.

The patient's selegiline was restarted at 2.5 mg with the same immediate benefit. The patient continued on the medication for 14 months and then stopped. He maintained the benefits he had gained on the medication.

In summary, the mother observed that medication lasted from 7:15 a.m. until 5:00 p.m., with"some residual benefit in the late evening." She noted that he was not agitated or punching holes in ceilings and walls.

This naturalistic "on-off-on" clinical experiment supports the use of selegiline in patients needing a dose too low to be available on the stimulant market.

James L. Schaller, M.D., M.A.R., P.C.

David Behar, M.D.
Eastern Pennsylvania Psychiatric Institute
Division of Child and Adolescent Psychiatry
Philadelphia, PA


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