Modern antipsychotic drugs are increasingly prescribed to children and adolescents diagnosed with a broad variety of ailments. The drugs help to alleviate symptoms in some disorders, such as schizophrenia and bipolar disorder, but in others their effectiveness is questionable. Yet off-label prescribing is on the rise, especially in children receiving public assistance and Medicaid. Psychotic disorders typically arise in adulthood and affect only a small proportion of children and adolescents. Off-label prescriptions, however, most often target aggressive and disruptive behaviors associated with attention-deficit hyperactivity disorder (ADHD). “What's really concerning now is that a lot of this prescription is occurring in the face of emerging evidence that there are significant adverse effects that may be worse in youth than in adults,” says David Rubin, a general pediatrician and co-director of PolicyLab at Children's Hospital of Philadelphia. Here we review the evidence for the effectiveness of antipsychotic medications commonly prescribed for five childhood conditions. But do the benefits outweigh the risks?
Evidence from several randomized controlled trials conducted in the past 10 years strongly suggests that antipsychotics are an effective treatment for youths with schizophrenia. Indeed, the FDA has approved five medications—risperidone, aripiprazole, olanzapine, quetiapine and paliperidone—for use in adolescents aged 13 to 17.
Recent research indicates that antipsychotics may hasten the resolution of manic and mixed episodes in children with bipolar disorder and increase the likelihood that the illness will go into remission. The FDA has approved the same set of drugs for 10- to 17-year-olds with bipolar disorder as it has for youths with schizophrenia, with the exception of paliperidone.
The FDA has approved risperidone and aripiprazole for the treatment of behavioral problems associated with autism spectrum disorder in children as young as five or six. Both medications have been found to reduce irritability, aggression, self-injury, tantrums and mood swings in children with autism. In one of the largest studies to date, risperidone reduced behavioral symptoms and lessened the rigid interests and repetitive behaviors typical of autism, but it had no effect on social and communication deficits.
ADHD and Disruptive Behavior Disorders
Doctors frequently prescribe antipsychotics to young people with conduct disorder, oppositional defiant disorder or ADHD, even though the drugs are not approved for these conditions. In a 2012 review of eight randomized controlled trials that took place between 2000 and 2008, researchers concluded that modern antipsychotics diminished aggressive tendencies in children with disruptive behavior disorders, but the effects were only marginally significant. A 2011 survey of off-label uses of these antipsychotics found that evidence supporting their effectiveness in children diagnosed with ADHD alone was “low or very low.”
OCD and Tourette's Syndrome
Studies have indicated that risperidone and quetiapine can improve symptoms of obsessive-compulsive disorder (OCD) in adults when used in combination with an antidepressant, but several case reports suggest that such antipsychotics may worsen or induce new OCD symptoms and anxiety in children. Several open-label trials, in which both the researchers and participants are aware of what treatment the participants are receiving, have found that antipsychotics can reduce compulsions and tics in children, but more rigorous study is needed.
Prescriptions on the Rise
Between 2002 and 2009 pediatric prescriptions for atypical antipsychotics increased by 65 percent, from 2.9 million to about 4.8 million. A staggering 90 percent of those prescriptions are off-label, according to a 2012 study published in JAMA Psychiatry, with ADHD and disruptive behavior disorders accounting for about 38 percent of all antipsychotic use in children and teens. The increase may be partly caused by a “lack of alternative resources,” Rubin says, because many doctors consider antipsychotic medication a stopgap or Band-Aid when therapy and other interventions are unavailable.
Are the Side Effects Worth It?
Modern antipsychotics, called “atypical” to distinguish them from the first generation of antipsychotic drugs, were initially promoted as a safer alternative to their forerunners. Yet it has become clear that atypical antipsychotics are associated with a host of serious side effects, such as weight gain, diabetes, high cholesterol and cardiovascular disease. In a study of 116 youths with early-onset schizophrenia, children taking risperidone gained eight pounds on average after taking the medication for eight weeks, whereas children taking olanzapine gained 13 pounds on average—prompting a safety review board to terminate the olanzapine arm of the trial early. Children taking antipsychotics are also three times more likely to develop type 2 diabetes than children not taking the medication, according to a 2013 study by researchers at Vanderbilt University.
In addition, risk of tardive dyskinesia—a neurological disorder resulting in compulsive movement—accompanies both classes of antipsychotics. A 2008 study found that it occurs in about 4 percent of patients taking atypical antipsychotics, compared with 5.5 percent for typical antipsychotics. Although the risk is higher with the older medications, an important caveat is that tardive dyskinesia usually occurs only after someone has taken the medication for years—longer than most clinical trials on atypical antipsychotics to date.