LIFE-AND-DEATH PARADOX
In the need to protect our children with depression from the risk of increased suicidal behavior associated with antidepressant use, are we creating a paradox?
By Michelle B. Ciriacruz
Medical Writer
Teenage suicide is a major problem worldwide. The World Health Organization (WHO) reveals that it is now one of the leading causes of death among people aged 15 to 34 years.
Studies show that problems from growing up, in the family, in relationships, at work and community, and substance abuse could all cause intense mental and emotional turmoil, which many youths find unbearable.
Unfortunately, the escape or solution that these depressed kids find most attractive is to die.
The United States in particular must be a teenage wasteland that so many adolescents wish to escape it.
The suicide rate there for people between ages 15 and 24 is 9.9 per 100,000, according to the US National Institute of Mental Health (NIMH). Suicide trails only homicide and accidents in the list of the leading causes of teenage death in the US.
Primarily, mental illness is to blame, health officials say, but the prevalence of drug use and firearms in the home becoming more available also contribute to this high rate of suicide.
Antidepressants help, of course, along with psychotherapy. They somehow restore the brain's chemical balance and control the symptoms of depression.
The American Psychiatric Association (APA) says that 80 to 90 percent of all cases of depression can be treated effectively. However, research into the treatment of depression with antidepressants had always been focused on their efficacy and how adults respond to them.
In 2003, antidepressant use in kids with depression came under fire. There were reports of antidepressants, particularly the selective serotonin-reuptake inhibitors (SSRIs), worsening the depression in some teenagers and making them more suicidal, instead of helping them with their mood disorder.
Andrew Mosholder, a US Food and Drug Administration (FDA) drug-safety analyst, found a link between antidepressant use and suicide in teenagers and children in a number of clinical trials. He brought these concerns to the attention of his superiors at the FDA.
But skeptical of Mosholder's findings, the FDA commissioned a team of independent experts from Columbia University in New York City to reanalyze the same data.
The findings of the team simply validated Mosholder's findings.
The Columbia reviewers found a cause-and-effect relationship between antidepressants and suicidal thoughts and actions (suicidality). In 100 depressed children and teenagers taking antidepressants, two or three will become suicidal, which would not have happened had they been on placebo, the reviewers found.
Other studies have already established that the majority of those with major depression do not commit suicide though the disorder does increase suicide risk compared with those without depression. These new data, however, though not yet conclusive--no suicides actually took place in any of the studies--must have touched too closely to the sense of overprotectiveness most adults have for children.
In October 2003, the FDA called the attention of health-care professionals to reports of suicidality in pediatric patients being treated with antidepressants for major depressive disorders.
In August 2004, the FDA announced that the analysis of these clinical trials on over 4,000 kids with depression by its team of independent experts backed the idea that some antidepressants increased the risk of suicide in teenagers. It ordered stronger black-box warnings on all antidepressant drugs and the creation of a patient medication guide. The guide will advise parents to monitor their kids for worsening depression, agitation, irritability, and unusual changes in behavior-which could come within the first months of starting antidepressants or when drug doses change.
The antidepressant drugs the FDA focused on included fluoxetine, sertraline, paroxetine, fluvoxamine, citalopram, escitalopram, bupropion, venlafaxine, nefazodone, and mirtazapine. The only FDA-approved drug for children with major depressive disorder is fluoxetine.
Both the warning and guide should include details of pediatric studies on antidepressants.
The British government acted more quickly, actually. In 2003, it already banned the use of antidepressants except fluoxetine for youths under 18 upon the urgings of its British Medicines and Healthcare Products Agency.
Reactions to the FDA public-health advisories were mixed. They were hailed as appropriate precautionary measures. On the other hand, health officials were also worried that the strong warnings would deter physicians from prescribing antidepressants to depressed kids-which would also increase their suicide risk.
A recent NIMH-sponsored study, Treatment for Adolescents with Depression Study (TADS), found that treatment with fluoxetine was actually more effective in treating depression in kids than counseling alone. A combination of drug treatment and counseling is the most effective treatment, the NIMH found.
Banning or severely curtailing the use of antidepressants "would turn the clock back 25 years, to a time when the only thing that we could offer the families of suicide victims was the hope that someday we would have effective treatments," pointed out David Brent, a member of the FDA's psychopharmacologic drugs and pediatric advisory committees (Suicide and Pediatric Depression: The Risk of Doing Nothing, New England Journal of Medicine, October 2004).
Nevertheless, Brent also pointed out that though the suicide risk is small in kids taking antidepressants, it is statistically significant and its effect is real.
Also, "treatment with antidepressants is much more likely to unmask an underlying bipolar disorder in children or adolescents than it is in adults," he said. A mixed manic and depressive state carries a very high risk of suicidal behavior, he explained.
Another member of the FDA's advisory committees, Dr. Thomas Newman, said that besides TADS, other randomized trials "had less favorable results." According to the FDA, "only three of 15 trials on antidepressant use in children with depression had found a statistically significant benefit," he related ("A Black-Box Warning for Antidepressants in Children?" New England Journal of Medicine, October 2004).
His questions--Does the suicide risk increase if the antidepressant drugs are taken for a year? Does increased suicidality mean more suicides? Will there be more adverse effects if treatment with the antidepressant drugs were stopped? What are the important differences between the antidepressant drugs? At what age would these drugs be safe to use?--represent wide gaps in what we know about antidepressants.
(The FDA-commissioned metaanalysis was of trials that lasted only two to three months.)
Just this month, the FDA issued another advisory on antidepressant use. The agency announced that adults who take antidepressants should be closely watched for increasing suicidal behavior. The current labeling of antidepressant drugs already includes this particular warning.
Depression is...
General emotional dejection, withdrawal, and restlessness that usually interferes with daily functioning, together with at least five of the following:
-
Depressed mood
-
Loss of interest in usual activities
-
Significant change in weight and/or appetite
-
Insomnia or hypersomnia (abnormally excessive sleep)
-
Psychomotor agitation or retardation
-
Increased fatigue
-
Feelings of guilt or worthlessness
-
Slowed thinking or impaired concentration
-
Suicide attempt or suicidal ideation
Forever young, forever blue
In a third of all countries, the predominance of suicide has now shifted from the elderly to young people, the WHO points out.
In the United States, the suicide rates for people between ages 15 and 24 tripled between 1950 and 1993 (Microsoft Encarta Encyclopedia, 2000). Though, suicide rates have started to decline since 1992, the NIMH says that depression still affects up to 2.5 percent of children and about eight percent of adolescents in the US. About 20 to 40 percent of adolescents with depression will go on to reveal bipolar disorder within five years after onset of depression.
Studies do show that being depressed increases one's risk of dying from suicide compared with those without depression. As high as seven percent of those with depression commit suicide, according to the NIMH. It also says that about 60 percent of people who commit suicide has had a mood disorder (e.g., major depression, bipolar disorder, and dysthymia).
A big problem, however, the NIMH points out, is that about two-thirds of those who suffer from depression don't get the help they need. This is because their condition remains unidentified or they think they just lack sleep, have poor diet, are fatigued, or they are simply ashamed to discuss their depression with anyone, the APA notes.
Some health officials fear these issues about antidepressant use could further hamper access of those with mood disorders to mental health care, as they could make physicians reluctant to prescribe antidepressants to those who should benefit from them.
M. Ciriacruz
|
