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      Ritalin (Methylphenidate) Use in Childhood Linked to Depression in Adult Rats: Presented at ACNP

      By Bonnie Darves

      SAN JUAN, PUERTO RICO -- December 21, 2004 -- Ritalin (methylphenidate), the drug used to treat attention-deficit hyperactivity disorder (ADHD) in children, may lead to development of depression in adulthood, according to a new study by Harvard Medical School researchers.

      The findings were presented here on December 13th at the Annual Meeting of the American College of Neuropsychopharmacology.

      Although the study was conducted in rats, its findings may have broad implications for both patients and treating clinicians, as diagnosis and treatment of the disorder with Ritalin and other psychotropic drugs continues to increase dramatically, noted the study's lead author William Carlezon, PhD, associate professor of psychiatry, Harvard Medical School, and director, McLean Hospital Behavioral Genetics Laboratory, Boston, Massachusetts.

      ADHD affects an estimated 3% to 12% of school-age children, and is twice as common among boys. While newer drugs have been developed and are being used more widely in recent years, approximately 90% of children receiving treatment for the disorder in 1999 were taking Ritalin. In addition, there has been a trend toward earlier treatment of ADHD, in some cases during the preschool years. If the disorder is inappropriately diagnosed or medication is prescribed unnecessarily, children who take Ritalin could develop impaired brain performance when they reach adulthood, Dr. Carlezon said.

      "Ritalin is effective … and improves quality of life for children with ADHD, but it is essential to ensure accurate diagnosis and the correct treatment, considering that those [treatment-associated] health effects could last through adulthood," he said. He added that the study's findings are important not only because they suggest that Ritalin could have long-term effects on normal-functioning brains but also because of the well recognized difficulty of diagnosing ADHD correctly.

      In earlier animal studies, altered CREB (cAMP response element binding protein) was linked to development of depressive-like symptoms.

      To determine some of the consequences of exposure to stimulant drugs during early development, Dr. Carlezon and colleagues exposing rats to 2 mg/kg twice daily of Ritalin during a period of their development equivalent to the 4- to 12-year age period in humans. The researchers then performed a series of tests to detect possible molecular or behavioral alterations and compared the results against those of control rats. In 1 test, the rats were given cocaine (15 mg/kg) to test brain reward systems; in another they were exposed to electrical stimulation.

      Results show that the rats that were exposed to the Ritalin exhibited measurable evidence of depression-like behaviors and dysfunctional reward systems compared to controls when they reached adult age. Intermediate doses of cocaine that had no effects in control rats caused conditioned place aversions, whereas higher doses of cocaine that caused conditioned place preferences in control rats had no effect on the rats treated with Ritalin.

      The researchers also studied behavioral patterns in the forced swim test (FST), and found that rats exposed to Ritalin became immobile faster and spent more time in immobility postures during this test. These findings, Dr. Carlezon said, suggest that exposure to Ritalin in childhood might cause a tendency toward despair-like behavior.

      He concluded that exposure to Ritalin during this developmental period may promote dysphoria-like or anhedonia-like signs in rats, and added that his study and others like it "highlight the need for a more thorough understanding of the long-term consequences of early developmental exposure" to psychotropic drugs.

      The study was funded by the US National Institutes of Health.


      [Presentation title: Neurobiological Consequences of Early Developmental Exposure to Methylphenidate in Rats.]



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