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Antipsychotic Use in Children
The types and numbers of medications available to treat mental health disorders have increased dramatically in the last decade. Drugs that were initially targeted at one group of disorders now are prescribed for other conditions as well.
Each class of drugs carries specific risks and side effects and holds different benefits for the patient. Treatment decisions must be carefully considered by physician and patient to find the best match.
Antipsychotic drugs have a potentially important role in the treatment of children and teens, but concern has been raised that certain newer antipsychotics have not been extensively studied in the pediatric population, and their use in younger age groups has been increasing.
The short- and long-term side effects of these medications are particularly an issue in young patients. The risks may, in some cases, outweigh the benefits.
One of the biggest concerns about these drugs is their effect on metabolism. Adults on antipsychotics often become obese, and there is no reason why children, whose metabolisms are still developing, shouldn't be similarly affected. A recent study of children and teens taking antipsychotic agents looked at their risk of developing type 2 diabetes, comparing that risk in relation to two different classes of antipsychotic drugs.
Classes of Antipsychotic Drugs
Originally, antipsychotic medications, both conventional or first generation (FGA), and atypical or second generation (SGA), were used primarily for the treatment of psychosis, schizophrenia and bipolar disorder.
As the uses for antipsychotic drugs have expanded in adults, their use in children has grown as well.
Conventional AntipsychoticsFirst-generation antipsychotics, also known as neuroleptics or conventional antipsychotics, include thorazine, prolixine, haldol, and others. Though they can be effective medications, they can create new problems for the patient, for example movement abnormalities like rigidity, bradykinesia (slow Parkinsonian movements), tremor, and akathisia (restlessness). They also frequently lead to a condition called tardive dyskinesia that causes involuntary, hyperactive spasmodic movements most readily observed in the face and extremities.
Atypical AntipsychoticsThe second generation of antipsychotics was introduced in 1998. They currently include quetiapine (Seroquel), risperidone (Risperdal), ziprasidone (Geodon) aripiprazole (Abilify), olanzapine (Zyprexa), clozapine (Clozaril), and others.
These drugs are called “atypical” because they have a different set of side effects from conventional antipsychotics. Specifically, they cause fewer uncontrollable movements and tardive dyskinesias than classical antipsychotics.
Over the past several years, additional uses for SGAs have been approved by the Food and Drug Administration (FDA). These include augmentation treatment (use with another class of agent) for major depressive disorder, and treatment of the irritability associated with autism spectrum disorder.
There are still other types of significant side effects from these second generation drugs. In adults, their use has been linked to weight gain, increased blood sugar, insulin resistance, metabolic syndrome and type 2 diabetes. It is this set of side effects targeted in a study published online recently in JAMA Psychiatry.
A Long List of Off-Label Uses
While atypical antipsychotics have a limited number of FDA-approved uses, they are used for numerous “off-label” indications with increasing frequency.
Using a drug “off-label” means that the indication, age group, dose or route of administration has not been approved. It is a very common practice, as each drug, dose, and indication cannot be subjected to the rigorous testing required for full FDA approval.
A 2006 study estimated that one-fifth of all drugs prescribed were prescribed off-label. Antipsychotics are often prescribed off-label for all sorts of mental and behavioral problems:
Several of these are conditions are found in children and teens as well as adults, and so their use in ounger age groups has been increasing. As mentioned earlier, research on their side effects has not kept pace.
Over a 17-year period there was an eight-fold increase in prescriptions of antipsychotics to children. Researchers tracked the prescription rates for children 0-13 years, and teens 14-20 years over two time periods, from 1993-1998 and 2005-2009, and compared the number of prescriptions written during those intervals.
ADHD and behavioral disorders were the two main diagnoses for which the medications were prescribed to children. Both are considered to be off-label uses of SGAs.
The upswing may be due to the increased diagnoses of mental health conditions in children and teens, or it may be related to the increase in the number of new antipsychotics on the market, according to the researchers.
At the same time fewer children — and adults — receive "talk therapies" (psychotherapy and psychosocial interventions) and, instead, are being treated for behavioral and mental health disorders primarily with drug therapy.
The Study: Type 2 Diabetes Risk in Children Taking Antipsychotics
The study of the risk type 2 diabetes in children and teens taking antipsychotic agents compared the risk in children and youth aged 6-24 years who had recently started antipsychotic medication to a control group who had recently started another type of psychiatric medication.
There were 28,858 children and teens in the study group and 14,429 controls. Among the test group, 87% were prescribed an atypical antipsychotic agent such as risperidone quetiapine and olanzapine. Most of the participants were being treated for mood disorders, ADHD, and conduct disorder.
Those in the control groups were most often prescribed lithium or anticonvulsants for mood stabilization, antidepressants, psychostimulants such as methylphenidate or dextroamphetamine, alpha agonists for ADHD or behavior disorders, and benzodiazepines for sleep and anxiety.
Patients on antipsychotic medications were three times more likely to develop diabetes than their control group peers. This risk became apparent within the first year of treatment. Equally concerning is the finding that the risk increased as the cumulative dose increased and it remained elevated for up to one year following discontinuation of the medication.
Within the study group, the younger patients, the 6-17-year-olds, showed a higher risk for developing diabetes than the 17-24-year-olds and the patients who took atypical antipsychotics rather than FGAs also showed higher risk.
The JAMA Psychiatry study is consistent with data from adult studies, which show similar profiles of risk for metabolic abnormalities in patients treated with antipsychotics, especially the second generation, or atypical, drugs. The study did not specifically compare one atypical antipsychotic agent against another for relative risk.
This study raises important questions about the upside and downside of using atypical antipsychotics in the pediatric population. It highlights the fact that while the SGAs cause fewer movement disorders than the first generation drugs, they are not benign medications.
Parents of children being treated with antipsychotics — as well as adults taking these medications — should be aware of the need for close monitoring of metabolic side effects. If the drug cannot be safely discontinued, then children should be treated for metabolic problems, including diabetes. Consideration of alternative medications when medically advisable is also recommended.
Even in the face of these results, however, patients should never stop taking medications without consulting their doctors about the risk of discontinuation nor without discussing proper tapering schedules. It is important to first develop a plan to monitor withdrawal or recurrence of symptoms, and obtain a recommendation for a medication substitute to continue treating the underlying condition effectively.
September 17, 2013