Antipsycholitc Drugs for Children and Teenagers

Antipsychotic prescriptions for children and teenagers have increased dramatically since the late 1990s, although the FDA has approved only three such drugs for use in young people: haloperidol (Haldol), thioridazine (Mellaril), and risperidone (Risperdal). An analysis of data from the Medical Expenditure Panel Survey, an annual compilation of information about health care services used by 23,000 to 35,000 Americans, found that the number of children and teenagers taking antipsychotics more than tripled between 1997 and 2005, increasing from 0.2% to 0.7% of all youths. Other studies have reported similar increases.

A variety of factors have contributed to this trend, including aggressive marketing by pharmaceutical companies and lack of reimbursement for psychotherapy and other nondrug treatments by insurance companies. Pressed for time, clinicians may be tempted to prescribe antipsychotics based on a one-session evaluation of a patient's symptoms, but a more thorough diagnostic evaluation might suggest other treatments more in tune with the child's needs.

It's important to understand the risks of antipsychotic treatment in children and teenagers, and how to monitor and manage side effects. Several reviews have provided specific advice that may be helpful (see table for a summary).

Weight gain and metabolic problems

U.S. children and teenagers are about three to four times as likely to receive second-generation antipsychotics such as risperidone or olanzapine (Zyprexa) rather than first-generation drugs such as haloperidol or molindone (Moban). Although second-generation antipsychotics are less likely to cause neurological problems than the older drugs, they are more likely to cause weight gain, resulting in metabolic problems that can cause serious long-term health problems. Weight gain is even more pronounced in young patients taking more than one antipsychotic and in those taking another psychiatric drug in addition to an antipsychotic.

A review of 19 double-blind and 22 open-label studies of second-generation antipsychotics in youngsters found weight gain ranging from 1 kg (2.2 pounds) after 16 weeks of risperidone treatment to 13 kg (almost 29 pounds) after a year of treatment with olanzapine. The researchers concluded that every second-generation antipsychotic is associated with some weight gain in children.

Another review suggests that the problem appears to be most pronounced with clozapine (Clozaril) and olanzapine, moderate with risperidone or quetiapine (Seroquel), and lower with ziprasidone (Geodon). But still other research indicates that both aripiprazole (Abilify) and ziprasidone, which have a minimal impact on weight in adults, may cause significant weight gain in children, particularly in those who have never before taken antipsychotics. So it's probably wise to assume that children taking antipsychotics will gain weight.

It's not clear how second-generation antipsychotics cause weight gain. Some increase appetite, so that patients eat more. Others cause sedation, thus reducing a patient's resting metabolic rate, which accounts for roughly 70% of calories burned every day. Some psychiatric disorders may also independently cause biological abnormalities that lead to weight gain. And of course any underlying susceptibility may be further aggravated by the psychosocial effects of mental illness, such as poor diet, increased isolation, and lack of physical activity.

Being overweight can harm a child's self-esteem and may lead to anxiety or depression. Antipsychotic-induced weight gain also increases the likelihood that patients will stop taking their medication.

Metabolic problems. The metabolic effects of antipsychotic-induced weight gain — such as increased cholesterol and insulin levels — are causing particular concern. For example, the eight-week Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS) study found that youths treated with the second-generation drugs olanzapine or risperidone both gained significant weight, while those treated with a first-generation drug, molindone, did not. Total cholesterol, LDL (unhealthy) cholesterol, and insulin levels increased significantly in youths receiving olanzapine. Although the TEOSS study was not designed to assess long-term outcomes, the authors point out that such cholesterol and insulin abnormalities pose considerable health risks in the long-term — raising the risk that children treated with antipsychotics might develop cardiovascular disease or type 2 diabetes as adults.

Another study supports this conclusion. Researchers who analyzed claims data collected by the South Carolina Medicaid program found that youngsters treated with antipsychotics were twice as likely as age-matched controls to become obese, three times as likely to develop type 2 diabetes, and almost three times as likely to develop cardiovascular problems.

Interventions. Clinicians may want to consider prescribing an antipsychotic that is least likely to cause weight gain or metabolic problems, and advise patients about the importance of exercise and calorie control. Regular blood tests can help to detect metabolic effects of antipsychotic treatment, such as blood sugar and cholesterol abnormalities, early on. If exercise and an improved diet aren't enough to alleviate these abnormalities, consider medications to reduce blood sugar or cholesterol.

Sedation and sleepiness

Both first- and second-generation antipsychotics can cause sedation or sleepiness in young patients. According to South Carolina Medicaid data, for example, 18% of young patients feel sedated or sleepy after receiving antipsychotics. Usually these effects are mild, so they don't interfere with daily activities or medication adherence.

If sedation becomes a problem, studies suggest that it may help to lower the drug dosage, prescribe smaller doses taken more often, or have the patient take the drug at bedtime rather than in the morning. The wakefulness-promoting drug modafinil (Provigil) is an option for adults, but the FDA has not approved it for use in children.

Neurological side effects

Neurological problems may occur in youngsters taking any antipsychotic, but are more common with the first-generation drugs or with second-generation drugs prescribed at high doses.

Extrapyramidal side effects. Tremors, muscle spasms, and stiffness are the most common neurological side effects of antipsychotic treatment. One double-blind, randomized study in youngsters found that 67% of those taking haloperidol developed some type of extrapyramidal side effect, compared with 56% of those taking olanzapine and 53% of those taking risperidone. The symptoms caused by haloperidol were more severe than those produced by the second-generation drugs.

The best approach to extrapyramidal side effects is to avoid them by starting with very low doses and raising them slowly. If a child does develop an intolerable symptom, the dose can be lowered or the drug can be switched to one like quetiapine, which — according to studies in adults — may be less likely to cause extrapyramidal effects. A further option is to prescribe a medication to counter the extrapyramidal side effects, such as an anticholinergic drug or a beta blocker.

Tardive dyskinesia. First-generation antipsychotics such as haloperidol are more likely than second-generation drugs to cause tardive dyskinesia. These irregular, repetitive, purposeless and involuntary movements develop with prolonged antipsychotic treatment and may persist even when the drugs are stopped. Thus, at the first signs that this problem may be developing, clinicians may need to reduce the dose or completely stop prescribing an antipsychotic.

Physical and sexual development

Both first- and second-generation antipsychotics may temporarily increase levels of the hormone prolactin. People usually have only low levels of this hormone circulating in the bloodstream. In women, levels rise during pregnancy because the hormone helps lactation. But the elevation of prolactin levels during antipsychotic treatment has raised concerns about possible influence on physical and sexual development in children taking these drugs.

Although data are sparse, the available research suggests that elevated prolactin levels are more likely at higher doses of antipsychotics and that levels normalize as drug treatment continues. Most children who experience elevated prolactin levels develop normally.

Correll CU. "Antipsychotic Use in Children and Adolescents: Minimizing Adverse Effects to Maximize Outcomes," Journal of the American Academy of Child and Adolescent Psychiatry (Jan. 2008): Vol. 47, No. 1, pp. 9–20.

McIntyre RS, et al. "Metabolic and Cardiovascular Adverse Events Associated with Antipsychotic Treatment in Children and Adolescents," Archives of Pediatric and Adolescent Medicine (Oct. 2008): Vol. 162, No. 10, pp. 929–35.

Shin L, et al. "An Overview of Obesity in Children with Psychiatric Disorders Taking Atypical Antipsychotics," Harvard Review of Psychiatry (March–April 2008): Vol. 16, No. 2, pp. 69–79.

Sikich L, et al. "Double-Blind Comparison of First- and Second-Generation Antipsychotics in Early-Onset Schizophrenia and Schizoaffective Disorder: Findings from the Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS) Study," American Journal of Psychiatry (Nov. 2008): Vol. 165, No. 11, pp. 1420–31.

For more references, please see www.health.harvard.edu/mentalextra.