Antidepressants and Adolescents: The Controversy and Its Ramifications
The U.S. Food and Drug Administration (FDA) has advised that selective serotonin reuptake inhibitors (SSRIs), sold under trade names such as Prozac, Paxil, Zoloft, and Celexa, must carry a warning that their use in adolescents may pose a risk by leading to an increase in suicidal thoughts. Although many young people have benefited from the use of SSRIs, there also are indications that these drugs can lead to self-destructive behavior in young adults. It is important to know how and why the FDA reached the decision to add an advisory warning to prescription antidepressant drugs; but first the causes of depression and how SSRIs work to alleviate it must be examined.
One could say that it all begins with serotonin, a mood-regulating neurotransmitter. Defined as substances that carry neural impulses across a synapse (a space between two neurons), neurotransmitters are essential to the electrochemical transmission of messages through the nervous system and within the brain. Insufficient amounts of serotonin produce dysphoric, or unfavorable, emotions such as depression and certain types of anxiety. SSRIs work to prolong surges of serotonin into the neural synapses. Theoretically, taking SSRIs should provide relief to individuals suffering from depression as well as from obsessive compulsive disorder.
Fact seemed to follow theory when SSRIs were first introduced en masse to the population. During the mid-1980s they were determined to be more effective than existing antidepressants and to cause fewer debilitating side effects, such as addiction. At that time, however, the medical community's attention was focused on substantiating these early findings, and little thought was being given to the possibility that various subgroups, such as children and adolescents, might be affected differently by the drugs. It was only around 1991 that a series of unnerving stories began to emerge regarding suicides and suicide attempts among adolescents who had been prescribed SSRIs. These cautionary tales clearly indicated that more research, coupled with a systematic review by the pharmaceutical companies, the National Institute of Mental Health, and the FDA, was needed to establish the effectiveness and safety of SSRIs for use by children and adolescents.
Unfortunately, the maze of research that resulted did not offer definitive conclusions. One reason was that the methods used in conducting the research were not consistent from project to project. It is only when methodologies across projects are consistent that useful comparisons can be drawn. The lack of credible conclusions, however, did not prevent debate before congressional panels, which in turn demanded that some form of action be taken by the FDA. In the meantime more refined hypotheses and designs relating to the efficacy and safety of SSRI use among adolescents emerged.
Tests were conducted in which subjects who met the experimental criteria were divided into two groups, one receiving a placebo (often nothing more than a sugar pill) and the other the active ingredient. Both groups improved significantly, with only a very modest difference between the gains made by individuals who were administered the actual drug and those receiving the placebo. This finding indicates that SSRIs alone are not a "magic bullet" and that the placebo effect in relation to the treatment of depression should be examined further. The most important finding, however, was that when use of these drugs was combined with talk therapy, such as cognitive behavioral treatment, the medications' benefits soared. Since it is now clear that SSRIs are one thing that works for adolescents, a final question remains: Why is this population at greater risk when it uses them?
One answer may be that teenagers are less compliant about medical directives. They may purposely skip or inadvertently forget doses, or they may self-medicate by increasing or decreasing their dosage. For an SSRI to work effectively, the dosage should remain constant in the system. Abrupt changes in the consumption of the drug can lead to agitated or even violent behavior. (One exception, however, is Prozac, which tends to remain stable in the system over a longer period of time than do other SSRIs. This makes a missed dose less of a problem.)
Another reason that adolescents are in particular danger may be found in studies indicating that most suicide attempts and other self-destructive behaviors tend to occur in the third and fourth week after the initiation of a drug regimen. This is because SSRIs take approximately four weeks to reach a concentration in the brain sufficient to begin counteracting depression. During this interim period the patient still experiences emotional pain, which is compounded by the discomfort of feeling edgy or "wired" as the body becomes more activated through the use of the drug. This can lead to impulsive, self-destructive behavior. While an adult may be conscious of what is happening to him- or herself, a young person is more likely to act upon impulse, and the resultant action can, unfortunately, be lethal.
Although it acknowledged the danger of SSRI use among adolescents, the FDA chose not to prevent them from using this class of drugs. The agency has, however, added a warning to prescription labels and offered a list of suggestions. First, only child psychologists and psychiatrists should prescribe SSRIs; pediatricians and general practitioners should not be dispensing the drugs. Second, young patients should be monitored closely, especially during the critical first four weeks of SSRI use, and every attempt must be made to determine the correct dosage. Third, talk therapy should be a mandatory adjunct to the use of the drug. Finally, standardized methodologies must be utilized in all future research so that comparisons among results will be valid and large-scale meta-analyses can be undertaken.
Quite clearly SSRIs have improved the quality of life for many young people, but to safeguard this benefit into the future, precautions must be exercised. The FDA has taken the first steps in this direction, and it is hoped that the medical profession and the nation's major drug and medical insurance companies will follow the FDA's suggestions; only then can the safe use of these valuable drugs be assured and potential tragedy averted.
One could say that it all begins with serotonin, a mood-regulating neurotransmitter. Defined as substances that carry neural impulses across a synapse (a space between two neurons), neurotransmitters are essential to the electrochemical transmission of messages through the nervous system and within the brain. Insufficient amounts of serotonin produce dysphoric, or unfavorable, emotions such as depression and certain types of anxiety. SSRIs work to prolong surges of serotonin into the neural synapses. Theoretically, taking SSRIs should provide relief to individuals suffering from depression as well as from obsessive compulsive disorder.
Fact seemed to follow theory when SSRIs were first introduced en masse to the population. During the mid-1980s they were determined to be more effective than existing antidepressants and to cause fewer debilitating side effects, such as addiction. At that time, however, the medical community's attention was focused on substantiating these early findings, and little thought was being given to the possibility that various subgroups, such as children and adolescents, might be affected differently by the drugs. It was only around 1991 that a series of unnerving stories began to emerge regarding suicides and suicide attempts among adolescents who had been prescribed SSRIs. These cautionary tales clearly indicated that more research, coupled with a systematic review by the pharmaceutical companies, the National Institute of Mental Health, and the FDA, was needed to establish the effectiveness and safety of SSRIs for use by children and adolescents.
Unfortunately, the maze of research that resulted did not offer definitive conclusions. One reason was that the methods used in conducting the research were not consistent from project to project. It is only when methodologies across projects are consistent that useful comparisons can be drawn. The lack of credible conclusions, however, did not prevent debate before congressional panels, which in turn demanded that some form of action be taken by the FDA. In the meantime more refined hypotheses and designs relating to the efficacy and safety of SSRI use among adolescents emerged.
Tests were conducted in which subjects who met the experimental criteria were divided into two groups, one receiving a placebo (often nothing more than a sugar pill) and the other the active ingredient. Both groups improved significantly, with only a very modest difference between the gains made by individuals who were administered the actual drug and those receiving the placebo. This finding indicates that SSRIs alone are not a "magic bullet" and that the placebo effect in relation to the treatment of depression should be examined further. The most important finding, however, was that when use of these drugs was combined with talk therapy, such as cognitive behavioral treatment, the medications' benefits soared. Since it is now clear that SSRIs are one thing that works for adolescents, a final question remains: Why is this population at greater risk when it uses them?
One answer may be that teenagers are less compliant about medical directives. They may purposely skip or inadvertently forget doses, or they may self-medicate by increasing or decreasing their dosage. For an SSRI to work effectively, the dosage should remain constant in the system. Abrupt changes in the consumption of the drug can lead to agitated or even violent behavior. (One exception, however, is Prozac, which tends to remain stable in the system over a longer period of time than do other SSRIs. This makes a missed dose less of a problem.)
Another reason that adolescents are in particular danger may be found in studies indicating that most suicide attempts and other self-destructive behaviors tend to occur in the third and fourth week after the initiation of a drug regimen. This is because SSRIs take approximately four weeks to reach a concentration in the brain sufficient to begin counteracting depression. During this interim period the patient still experiences emotional pain, which is compounded by the discomfort of feeling edgy or "wired" as the body becomes more activated through the use of the drug. This can lead to impulsive, self-destructive behavior. While an adult may be conscious of what is happening to him- or herself, a young person is more likely to act upon impulse, and the resultant action can, unfortunately, be lethal.
Although it acknowledged the danger of SSRI use among adolescents, the FDA chose not to prevent them from using this class of drugs. The agency has, however, added a warning to prescription labels and offered a list of suggestions. First, only child psychologists and psychiatrists should prescribe SSRIs; pediatricians and general practitioners should not be dispensing the drugs. Second, young patients should be monitored closely, especially during the critical first four weeks of SSRI use, and every attempt must be made to determine the correct dosage. Third, talk therapy should be a mandatory adjunct to the use of the drug. Finally, standardized methodologies must be utilized in all future research so that comparisons among results will be valid and large-scale meta-analyses can be undertaken.
Quite clearly SSRIs have improved the quality of life for many young people, but to safeguard this benefit into the future, precautions must be exercised. The FDA has taken the first steps in this direction, and it is hoped that the medical profession and the nation's major drug and medical insurance companies will follow the FDA's suggestions; only then can the safe use of these valuable drugs be assured and potential tragedy averted.
Comments
Post a Comment