Trends in the News

June 1, 2002

Antidepressant use among children and adolescents is on the rise. What prescribing patterns are being formed? Researchers are suggesting that more research into psychiatric pharmacogenetics may produce better treatment outcomes. Will it one day be possible to predict treatment response?

Antidepressant Use Rising in Children

Since their introduction 15 years ago, antidepressants have been widely used to treat psychiatric disorders in adults. In recent years, antidepressants have been increasingly prescribed for children and adolescents as well, despite very little data to support such use. In a study published in the May issue of Pediatrics, Julie Magno Zito, Ph.D., and colleagues explored some of the reasons for this trend and highlighted the associated dangers. Zito may be familiar to readers for her research that brought the increasing use of psychotropics in children to national attention when it was published in JAMA in 2000.

For the current study, researchers retrospectively evaluated prescription and clinical service records for nearly 1 million youths ages 2 to 19 years, using data sets for each year from 1988 to 1994. Subjects were enrolled in either a state Medicaid program or a group HMO.

Prevalence of antidepressant use was found to have increased three- to five-fold in the study period for all three major subclasses defined in the study (tricyclic antidepressants, selective serotonin reuptake inhibitors and other antidepressants). While TCAs were the most prescribed psychotropic in 1988, by 1994, SSRI prescriptions nearly reached their numbers. Attention-deficit/hyperactivity disorder (ADHD) and depression were the leading diagnoses associated with an antidepressant prescription, followed by anxiety disorder, conduct disorder and adjustment disorder. Use of SSRIs increased with patient age, whereas TCA use decreased with age.

The prescribing patterns found in this study raise several important concerns. For example, the authors noted, 40% to 45% of TCA use was associated with a diagnosis of depression, although clinical trial data do not support such use in this population. Adolescents ages 15 to 19 years made up the majority of antidepressant users, but a trend was noted for younger youths being viewed as candidates -- a practice with questionable appropriateness.

For youths with service claims in 1994, 72.1% received prescriptions from primary care providers, while 27.9% received psychiatric services. Prescriptions for youths being treated in primary care were more likely to be associated with an ADHD diagnosis, whereas youths who received psychiatric services were more likely to have been diagnosed with depression. This suggests, according to the authors, that future outcome studies must include both primary care and psychiatric service providers -- JH

Psychiatric Pharmacogenetics

Patients A, B and C come into your office and present with the same symptoms for a disorder easily diagnosed using DSM-IV criteria. You are thankful for today's "simple" patients, write them all a prescription for the same medication and go home satisfied that your patients are on the road to recovery. However, Patient A eventually calls back with complaints of substantial weight gain, gastrointestinal upset and persistent headaches; Patient B's initial symptoms are worsening; while Patient C is feeling great.

This scenario is an oversimplified example of the well-known fact that not all patients suffering from the same symptoms of a disorder will respond equally to the same treatment. Psychiatric pharmacogenetics attempts to define genetic variations in patients that will predetermine their responses to a specific medication. Not only will this allow for the more effective treatment of patients, but it will also give researchers specific genes and receptors to target when developing new pharmacological treatments.

The basis of pharmacogenetics is single nucleotide polymorphism (SNP). Researchers are pinpointing variations in an enzyme's response to a certain drug -- such as rapid versus slow metabolism of a drug -- comparisons between individuals with known responses to certain medications and those who have yet to undergo the same treatment, thus predicting the untreated patient's response.

These mapping technologies have already advanced significantly: Over 1 million SNPs in the human genome have been identified by the SNP Consortium. Some are responsible for a patient's susceptibility to a disease and others for the individual's susceptibility to positive/negative treatment response and side effects. Researchers are currently studying the genetic basis for differences in patient response to pharmacologic treatments for schizophrenia, bipolar disorder, attention-deficit/hyperactivity disorder and others.

Knowledge that an individual possesses certain polymorphisms will allow the treating physician to tailor their course of treatment, thus enhancing the likelihood for effective treatment of a disorder. Comparing SNPs before actually beginning treatment can also spare the wasted time and unwanted side effects that often accompany trials of different pharmacologic treatments. The ability to individualize therapy based on SNPs will allow for more timely and effective treatment of your patients A, B and C.

(This news brief is based on a symposium that was presented at the 6th Internet World Congress for Biomedical Sciences -- Ed.) -- RR