Children and Adolescents

Abstract

Special considerations arise in treating children and adolescents with antidepressants. Empirical data on antidepressants (and other pharmacological agents) in young patients are quite limited. Psychiatrists, faced with depriving children of potentially effective medication or prescribing medications “off label,” need information on which to base treatment decisions, and efforts are underway (e.g., by the National Institutes of Health, the American Academy of Pediatrics, and the Food and Drug Administration) to promote research in this area. Clinically significant differences in pharmacokinetics and possibly pharmacodynamics between adults and younger patients can also complicate treatment (e.g., younger patients may need higher doses on a milligram-per-kilogram basis to achieve the same drug concentration as an adult on a usually effective adult dose). Younger patients may also be more sensitive to adverse effects of medications.

The selective serotonin reuptake inhibitors (SSRIs) have superceded tricyclic antidepressants (TCAs) as first-choice pharmacotherapy based on studies demonstrating their superior safety and efficacy in children with major depressive disorder (MDD). TCAs are now usually reserved for children or adolescents with at least moderate depression who have not responded to at least one newer antidepressant; it is recommended that therapeutic drug monitoring (TDM) of the TCA be done at least once to ensure that the patient does not develop toxic plasma levels. The safety, pharmacokinetics, and tolerability of venlafaxine and nefazodone have been tested in children, but data on efficacy are not yet available. The adverse effect profiles of the SSRIs, the TCAs, venlafaxine, and nefazodone are similar to those in adults.

The TCA clomipramine and the SSRIs fluvoxamine and sertraline have indications for obsessive-compulsive disorder in pediatric patients. A number of TCAs and SSRIs have been studied in the treatment of other anxiety disorders (e.g., separation anxiety disorder, school phobia, elective mutism, generalized anxiety disorder) but none has received labeling for those indications. Antidepressants have been studied in the treatment of attention-deficit/hyperactivity disorder (ADHD). The TCA desipramine and bupropion have been found efficacious in ADHD, although desipramine causes higher rates of adverse effects than stimulant medications. Current treatment algorithms generally recommend trying an antidepressant after failed trials of several different stimulant medications. Atomoxetine, a nonstimulant medication, was recently approved for the treatment of ADHD in children, adolescents, and adults. Although behavioral management is preferred for treatment of enuresis, the TCA imipramine has also been found effective, although the relapse rate is as high as 50% upon discontinuation.

Given the paucity of data on antidepressants in pediatric patients and the clinically significant pharmacokinetic differences between younger patients and adults, clinicians should carefully consider and cautiously monitor any treatment plan involving antidepressant medications in order to maintain the risk to benefit ratio in favor of the child or adolescent patient.