Neurochemistry of withdrawal emergent symptoms in children

The probenecid procedure was used to study the metabolite accumulations of dopamine (DA) and serotonin (5-HT) in the cerebrospinal fluid (CSF) of 11 children receiving chronic neuroleptic therapy. Specimens were obtained while the children were being given chronically prescribed medication (Condition 1) and again 3–4 weeks later, following the discontinuation of drugs (Condition 2). At that time, five children showed typical dyskinetic withdrawal emergent symptoms (WES) and six were free of symptoms. CSF specimens were also obtained from eight drug-free children, diagnosed as having chronic organic brain disease, who served as a contrast population against which the findings were evaluated. CSF accumulations of 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) did not differentiate the drug-treated children who showed WES from those who did not manifest these symptoms. A significant decrease in 5-HIAA was found in Condition 2, suggesting that chronic treatment with neuroleptics may effect 5-HT metabolism in children. The contrast population was found to have lower CSF concentrations of probenecid and were consequently of little help in clarifying the nature of the 5-HIAA decrement. A number of serious deficiences were noted regarding the use of the probenecid procedure, and it is felt that the use of spinal taps for studying neuroleptic effects on brain metabolism in children is unlikely to provide important information with regard to either CNS drug actions or toxicity.