Depression, Adolescents, and Antidepressants
Earlier this month, the Food and Drug Administration (FDA) approved Lexapro (escitalopram oxalate) for the acute and maintenance treatment of major depressive disorder (MDD) in adolescents 12- to 17-years-old.
Here's some basic information about the approval from a Forest Laboratories press release (I have put some parts in bold for added attention):
"The approval of Lexapro for the treatment of adolescent depression was supported by two placebo-controlled studies, one conducted in adolescent patients taking Lexapro and one conducted in children and adolescents taking citalopram (Celexa). In an 8-week flexible- dose, placebo-controlled study that compared Lexapro 10-20 mg/day to placebo in 12 to 17 year old patients reported in 2008, Lexapro showed statistically significant greater mean improvement from baseline, compared to placebo, on the Children's Depression Rating Scale-Revised (CDRS-R).
In another 8-week, flexible-dose, placebo-controlled study, children and adolescents 7 to 17 years of age treated with racemic citalopram (Celexa) 20-40 mg/day showed statistically significant greater mean improvement from baseline on the CDRS-R compared to patients treated with placebo. The positive results for this trial largely came from the adolescent subgroup. The FDA's determination of the efficacy of Lexapro in the acute treatment of MDD in adolescents was established, in part, on the basis of extrapolation from this study.
Two additional flexible-dose, placebo-controlled MDD studies were conducted: one Lexapro study in patients ages 7 to 17 and one citalopram (Celexa) study in adolescents. Neither study demonstrated efficacy on the primary efficacy parameter.
Although maintenance efficacy in adolescent patients has not been systematically evaluated, the FDA in its review concluded that maintenance efficacy can be extrapolated from adult data along with comparisons of escitalopram pharmacokinetic parameters in adults and adolescent patients..."
This approval has sparked a wave of controversy, especially in light of a five-year probe by the Justice Department that, last month, culminated in accusations of Forest attempting to sway pediatricians to prescribe Celexa and Lexapro. The prosecutors allege that Forest offered doctors inducements including spa visits, fishing trips, and tickets to Broadway shows and sports events (before this Lexapro approval). Prosecutors have also accused Forest of ignoring a study that showed Celexa to be ineffective for pediatric use, encouraging sales staff to promote another, more positive study.
For purposes of discussion, it should be noted that Lexapro and many other antidepressants already carries this black box warning:
WARNINGS: SUICIDALITY AND ANTIDEPRESSANT DRUGS
Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of Lexapro or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Lexapro is not approved for use in pediatric patients less than 12 years of age. [See Warnings and Precautions: Clinical Worsening and Suicide Risk (5.1), Patient Counseling Information: Information for Patients (17.1), and Used in Specific Populations: Pediatric Use (8.4)].
The use of antidepressants in adolescents is a difficult issue. Research has shown that, as in adults, depression in children and adolescents is treatable. Certain antidepressant medications, called selective serotonin reuptake inhibitors (SSRIs), can be beneficial to children and adolescents with MDD. Certain types of psychological therapies also have been shown to be effective. However, our knowledge of antidepressant treatments in youth, though growing substantially, is limited compared to what we know about treating depression in adults.
Due to concerns that the use of antidepressants themselves may induce suicidal thoughts in behaviors, a review was conducted of both published and unpublished clinical trial data, and the black box warning above was added to labels.
A child or adolescent with MDD should be carefully and thoroughly evaluated by a doctor to determine if medication is appropriate. Psychotherapy often is tried as an initial treatment for mild depression. Psychotherapy may help to determine the severity and persistence of the depression and whether antidepressant medications may be warranted. Types of psychotherapies include "cognitive behavioral therapy," which helps people learn new ways of thinking and behaving, and "interpersonal therapy," which helps people understand and work through troubled personal relationships.
Those who are prescribed an SSRI medication should receive ongoing medical monitoring. Children already taking an SSRI medication should remain on the medication if it has been helpful, but should be carefully monitored by a doctor for side effects. Parents should promptly seek medical advice and evaluation if their child or adolescent experiences suicidal thinking or behavior, nervousness, agitation, irritability, mood instability, or sleeplessness that either emerges or worsens during treatment with SSRI medications.
Once started, treatment with these medications should not be abruptly stopped. Although they are not habit-forming or addictive, abruptly ending an antidepressant can cause withdrawal symptoms or lead to a relapse. Families should not discontinue treatment without consulting their doctor.
All treatments can be associated with side effects. Families and doctors should carefully weigh the risks and benefits, and maintain appropriate follow-up and monitoring to help control for the risks. It's important to note that "all treatments" includes "natural" products and supplements. Remember that these substances were mankind's first drugs, and they still act as drugs in our bodies. They can have interactions and side effects potentially as serious as those of prescription medications, and a doctor should be consulted before taking them.
So, what about antidepressants for adolescents?
Here's my take on it... Adolescents can have major depressive disorder just as adults can. Depression in adolescents should not be ignored. Parents, teachers, and others responsible for adolescents should not hesitate to help these young people seek help for depression.
In an ideal world, nobody would need medications, especially not children and adolescents. But, we don't live in a perfect world, and sometimes medications are necessary.
I'm a bit uncertain about the FDA's approval of Lexapro for adolescents. There was one positive clinical trial with Lexapro for adolescents, and one that did not demonstrated the hoped for efficacy. Effectiveness in maintenance treatment for adolescents has not been evaluated, so the FDA approval took into account extrapolation from clinical trials of adults. When it comes to our children, I'm especially reluctant to agree with extrapolating data rather than conducting studies to obtain specific data.
Some adolescents with major depressive disorder need medications to balance their levels of neurotransmitters such as serotonin. I don't see a way around that. For some, medication will be effective enough treatment alone, but for others, the best treatment will be medication combined with psychotherapy. One question I have is whether pediatricians and family doctors should be prescribing antidepressants for adolescents. If it were my child, I'd want a psychiatric consult to confirm the need for the medication and tell me if my child needed therapy as well.
What do you think? Please click on the "Add Comment" link below and share your thoughts with us.
Press Release, "Forest Laboratories, Inc. Announces FDA Approval of Lexapro(R) for the Treatment of Major Depressive Disorder in Adolescents." Forest Laboratories, Inc. March 20, 2009.
Reuters. "FDA approves antidepressant Lexapro for adolescents." Los Angeles Times (online). March 20, 2009.
Child and Adolescent Mental Health. "Antidepressant Medications for Children and Adolescents: Information for Parents and Caregivers." National Institute of Mental Health. February 19, 2009.