Today’s post on the safety of antipsychotic medication in kids is the sixth in a series on Hot Topics in Children’s Mental Health offered in recognition of Mental Health Month, National Children’s Mental Health Awareness Week (May 6-12), and National Children’s Mental Health Awareness Day (May 9).

Back in the days when I was on the medical lecture circuit, I observed that physicians (and by extension, their patients) often worry about the wrong things.

Broadcast, traditional and online media have used a broad brush in painting a picture of indiscriminate use of dangerous medication in kids. In the case of kids being treated for ADHD with stimulants, a complete Medline search would identify somewhere in excess of 2,000 published studies over a 75 year period of time evaluating the safety and effectiveness of that class of medication. In our recent look at antidepressant medication, we saw more unanswered questions about the effectiveness of medicine used to treat depression in kids than exist around the safety of such medicine. Among the classes of medication commonly used for kids and teens with mental health disorders, I’m most concerned about the potential long-term safety risks associated with the use of antipsychotics.

Antipsychotics (the vast preponderance of which are second-generation antipsychotics…risperidone, quetiapine, aripiprazole, olanzapine) are clearly the most effective medications for kids with a valid diagnosis of bipolar disorder. Risperidone and aripiprazole have been shown to be effective in reducing the frequency and severity of aggressive behavior associated with autism spectrum disorders. The medications are also helpful for early-onset schizophrenia.

There’s a fundamental flaw in the way in which studies have been conducted for the FDA with antipsychotics in children and teens that has obscured the true impact of the side effects associated with the medications. Most kids who were in the FDA studies that led to pediatric approval of the second-generation antipsychotics had been treated with other antipsychotics in the past. It appears that prior exposure to antipsychotics significantly attenuates the side effects kids experience when treated with a new antipsychotic. But what happens when kids are started on antipsychotics for the first time?

The best study (funded exclusively from non-commercial sources) examining the safety of antipsychotics among kids who hadn’t previously been treated was published by Dr. Christoph Correll in the Journal of the American Medical Association. This study examined metabolic issues in 338 kids treated for an average of 10.8 weeks with either olanzapine, quetiapine, risperidone or aripiprazole. Below is a graph looking at the mean weight gain per child over the course of an eleven week study. To put this data in perspective, the mean increase in waist circumference ranged from 2.0 inches on risperidone to 3.4 inches on olanzapine. Kids gained from 8-15% (on average) of their baseline body weight over the course of the study. Weight gain levels off in some patients over time, but in my experience, other patients continue to gain weight with long term use.

In addition to weight gain, other metabolic concerns emerged in the course of Dr. Correll’s study. Antipsychotics were also associated with increases in fasting glucose levels, insulin levels and insulin resistance (a pre-diabetic state) in the case of olanzapine, increased total cholesterol, decreased HDL cholesterol and an increased triglyceride to HDL cholesterol ratio with quetiapine and significantly increased triglycerides with olanzapine, quetiapine and risperidone.

It’s important to acknowledge that the data presented here is derived from a short-term  study, and it’s difficult to interpolate long-term risks from a short term study. But data from another short-term study, the Treatment of Early-Onset Schizophrenia (TEOSS) study produced similar results. The NIMH-funded controlled study compared tolerability and efficacy of olanzapine, risperidone and molindone in patients ages 8-19. The study monitors suspended the olanzapine portion of the study because of changes in liver function and the severity of cholesterol elevation noted in kids randomized to that medication.

Another known long-term risk associated with the use of antipsychotic medication is tardive dyskinesia, a chronic movement disorder associated with long-term use of medications that decease the activity of dopamine in the central nervous system.

Personally, if a kid clearly has bipolar disorder or a psychotic illness or an autism spectrum disorder with aggressive behavior of a severity that they may no longer be able to live at home or a severe tic disorder I have no problem prescribing these medications when the benefits outweigh the risks. But the majority of kids coming into my office after having been prescribed antipsychotics don’t fall under any of those categories.

A 2006 study by Dr. Mark Olfson in the Archives of General Psychiatry reported that the most common indication for use of antipsychotics in kids was disruptive behavior, and that nearly 20% of psychiatric visits for patients age 20 and younger resulted in a prescription for an antipsychotic. Since Dr. Olfson’s study, the absolute number of prescriptions written for antipsychotics in kids has increased every year, to 4.8 million per year for children in the U.S.

My frustration is that I see kids all the time who’ve been referred to our practice with a history of having been treated with antipsychotics coming in with parents who have little idea as to why their child is/was taking the medication prescribed, little understanding of the possible side effects associated with the medication and lacking the required monitoring for side effects while taking the medication. (from Correll, CU, J. Am. Acad. Child Adolesc. Psychiatry 2008; 47(1) 9-20.)

Here are some reasonable questions to ask your child’s health care professional prior to agreeing to treatment with an antipsychotic…

• What condition are we hoping to treat effectively with this medication?
• What evidence supports the use of this medication for the condition we’re attempting to treat?
• What are the alternative treatments to antipsychotic medication for this condition?
• What will be the plan to monitor for side effects my child might experience while taking this medication?
• How long will my child likely need to continue this medication?
• What will the alternative plan be if the weight gain or metabolic effects of the medication become problematic?
• Here’s a question the parent(s) need to ask themselves…Has the treating physician taken the time to fully understand the nature of my child’s problems prior to prescribing an antipsychotic medication?