Advances in Pediatric Psychopharmacology

Neal Ryan, MD
Joaquim Puig-Antioch Professor Child & Adolescent Psychiatry, University of Pittsburgh

Q: Could you tell us a little about depression in childhood and adolescence?

A:Among children there has been an increase.  In clinical samples, there is a 70% recurrence in 5 years.  We have also found that 20%-40% of clinical samples become bipolar in time and the average duration of a depressive episode is 3 to 9 months.  Children with depression have earlier onset of smoking and substance use along with  increased rates of substance dependence, educational underachievement, depression, anxiety and suicide attempts. Regarding adolescent depression, the point prevalence is 15% to 25%.  Females are over represented two to one.  Studies have also shown that depressed teens have an increased rate of pregnancy as compared to non-depressed teens.

Q: What is the relationship between genes and depression?

A:Well first of all, gene frequencies change slowly, so genes are not responsible for the increased prevalence we have seen.  We do know that it is not a single point mutation, and that there could be different genes involved for men and women.  We also know environment has a huge impact on risk of depression.

Q: What do you think about the FDA public hearings?

A:The FDA has a hard task and is, in my opinion, doing it very well.  They need to see if these medications that are routinely used in children and adolescents are safe or not and how to use them. They are approaching this problem in a superb fashion.

Q:  Do the old school TCAs do the same thing as the SSRIs…increase suicide attempts?

A:There is no specific data to suggest that.  But the data do suggest that TCAs are not very effective in children.  The TCAs are lethal if there is an overdose so there is little or no role for them in treating depressed youth.

Q: In the United States, how many completed suicides have occurred in all of the clinical trials of all of the antidepressants that have been studied in children and adolescents?

A:None

Q:  So why has there been such a focus on increased suicide risk among teens taking antidepressants?

A:The question of increased suicide risk is an important and difficult question that needs to be answered.  It is also important to keep in mind that by regulatory precedent, side-effects are lumped into groups such as “emotional lability” but these may not be related to the medication.  We know that teens are already at increased risk for suicide.  In 2001, it was the third leading cause of death for this age group.  In some studies there is actually a correlation between the use of SSRIs and decreased suicide risk. 

Q: Do you think the prescription of antidepressants by family MDs and pediatricians are part of the problem?

A:No. I think it is critical that we find treatments that primary doctors can use.  They are the 1st line of therapy for uncomplicated depression.

Q: Are mood stabilizers effective in children and adolescents?  What does the literature support?

A:Clinically my colleagues and I suspect they work as well in adolescents as they do for adults with Bipolar Disorder.  There have only been a few studies thus far but several are ongoing.  They are not well studied in kids yet.

Q:  Is a 50% placebo response rate among depressed kids your experience?

A:No, that is not my experience.  Clinically there are a couple of issues.  With placebo, it is not that they get all better.  Subjects are not symptom or impairment free, just improved.  In my clinical experience the response rate to placebo is much smaller than 50% but it certainly does occur.  We also shouldn’t expect placebo to be inactive because there is such a powerful effect of talking to a caring person as occurs with all good treatment of depression in children, including administration of placebo.

Q: Should placebo be declared an antidepressant for kids?  

A: I think that studies of the biological effect of placebo show they have profound effects on the brain. Should be no surprise that they help in treating pain and depression.  The ethics of using placebo is a different question, not just in children.  Again, when we give placebo to a child in a study, the effect we get is probably as much or more from the treatment relationship as from the expectancy effects of taking a pill..

Q: Are there special issues that must be considered when these disorders occur in children and adolescents? 

A:First, if the parent who is the child’s primary caretaker is also depressed this increases the environmental strain on the child and greatly increases the chance that the family will drop out of treatment.  So if the mom or dad is depressed, make sure you help them get treatment.  Also depression in children and adolescents can lead to increased risk of substance abuse, alcohol use and higher risk of suicide attempts.  Finally, treating with medication alone does not necessarily address psychosocial impairment. 

Q: What types of research are needed in pediatric psychopharmacology?

A:A couple of things are needed.  We need to have more centers adequately trained to recruit large numbers so that our studies have greater statistical power.  More pharmacodynamic studies are needed.  We also need to better survey for rare serious side effects.

Q: Where can we find out more information about the FDA public hearings?

A:The slide presentations are available at http://www.fda.gov/ohrms/dockets/ac/04/slides/4006s1.htm. A transcript of the meeting is available at  http://www.fda.gov/ohrms/dockets/ac/04/transcripts/4006T1.pdf

Dr. Ryan is a professor of psychiatry at the University of Pittsburgh, School of Medicine and a Joaquim Puig-Antioch Professor of Child and Adolescent Psychiatry. He is the director of education and director of psychiatric informatics at the Western Psychiatric Institute and Clinic, Department of Psychiatry, University of Pittsburgh Medical Center. Dr. Ryan’s main research work is in the nosology, psychobiology and treatment of children and adolescents with mood and anxiety disorders. He has authored or co-authored over 100 articles and chapters on these subjects. He is currently principal investigator on a large, NIMH-funded Program Project grant entitled, “Psychobiology of Childhood Anxiety and Depression”. He also has ongoing studies of the pharmacological treatment of unipolar and bipolar depression in adolescents.