Antidepressants and Suicide in Children
A warning has been issued that common antidepressants prescribed to children are not only largely ineffective, but they also may increase the risk of suicidal behavior and self-harm among children. Despite this warning, physicians are often told that depression is often missed in patients, and a lack of diagnosis and treatment can lead to serious harm. The recommended “treatment of choice” is antidepressant drugs.
The inconsistency displayed by this contradiction is the subject of two commentaries in the Canadian Medical Association Journal as they seek to explain why the lack of benefit and potential for harm from antidepressant use among children took so long to be exposed. They bring up important points including:
The prescribing rate for antidepressants in young people has increased steadily in the past decade
Many studies show that antidepressants have little to no effectiveness compared to placebos
There is a large gap between the quality of evidence needed to get a drug to market and the actual treatment needs of patients
In addition to their weak or nonexistent evidence of efficacy, antidepressants may have serious side effects in children beyond suicidal behavior, including agitation, irritability and behavioral disinhibition
Patient reports of adverse drug reactions are commonly dismissed as anecdotal or unscientific
There has been no formal response to this crisis from leaders in child psychiatry, many of whom were investigators in both published and unpublished trials
All trial participants and--the broader public--should have access to the results of clinical trials
Study data must be subject to analysis by independent experts who are alert to conflicts of interest that may distort the interpretation of data
Guidelines for physicians need to be rewritten so they reflect the full body of evidence, both published and unpublished
Canadian Medical Association Journal (Full-Text Article) February 17, 2004; 170(4):487
Canadian Medical Association Journal (Full-Text Article) February 17, 2004; 170(4):489
New Warnings on Antidepressants’ Link to Suicide Drug regulators have reported that Paxil, which is closely related to the other SSRIs, may increase the risk of suicide among teenagers and children, especially during the first few weeks of treatment. Regulators have recommended that no new Paxil prescriptions be written for patients under the age of 18 years. Some say the suicide risk may extend to adults as well. Recent studies have focused on the antidepressants’ effectiveness, as studies have found that the drugs are no more effective than a placebo, rather than their safety. SSRIs bring in billions of dollars in sales each year. New York Times August 7, 2003
Sugar Pills Work as Well As Antidepressants
Sugar pills cure depression just as well as antidepressants. What’s more is that sometimes they work better.
According to a new analysis, the majority of antidepressant trials conducted by drug companies have found that sugar pills, or placebos, produce results similar to or better than antidepressant drugs. In one study of 96 antidepressant trials conducted between 1979 and 1996, no difference could be determined between the effects of antidepressants and sugar pills in some 52 percent of trials.
Drug companies are required to conduct two trials that yield positive results before the product will be approved by the Food and Drug Administration (FDA), and reportedly numerous trials had to be conducted before positive results could be shown. The makers of Prozac ran five trials before obtaining two that were positive, while the makers of Paxil and Zoloft had to conduct even more, according to researchers.
In one recent trial, which compared the effectiveness of the herb St. John’s wort to that of antidepressant drug Zoloft, St. John’s wort alleviated depression in 24 percent of study participants compared with 25 percent for Zoloft. However, the placebo cured depression in 32 percent of participants.
The findings do not mean that antidepressants such as Prozac, Paxil and Zoloft do not work, however researchers say that Americans may be overestimating the drugs’ effectiveness. Much of the improvement shown during clinical trials may be due to the close attention and evaluation the patients receive during the study -- a phenomenon that does not occur for most patients who use the drugs in everyday life.
Moreover, the sugar pills actually cause changes to occur in the same areas of the brain affected by the antidepressant drugs, according to recent research. It was also found that more patients’ depression is being alleviated due to placebos now than 20 years ago.
Placebos, or pills that have no effect, have long been used by scientists to distinguish the real effects of medicine from the illusive feelings of patients. Often in the field of medicine patients experience what is known as the placebo effect -- the feeling of getting better after being treated with placebos.
However, it seems that placebos may actually make a difference in the treatment of depression, as the disease is characterized by how people feel.
Many psychiatrists say that drugs alone will not cure depression. Instead, a combination of medication and psychotherapy appears to yield the best results. Despite this, antidepressants have become the automatic treatment for most cases of depression.
In 2002, there were close to 25 million doctor visits for depression, up from 14 million in 1987. Of these visits, medications were prescribed for nine out of 10 patients, according to recent research.
It is not known how many of these patients received therapy in addition to the medication, however, in 2001 less than one-third of doctor visits for depression were to psychiatrists and two-thirds of them were to primary care physicians. According to researchers, psychiatrists are more likely to administer medicines along with therapy, while physicians, who are less knowledgeable about therapy, are less likely to offer therapy to their patients.
Other studies have shown that in an average eight-week trial, each study participant, whether taking drugs or placebos, is questioned and examined by experts and caregivers for about 20 hours. Comparatively, the average depressed patient likely sees a doctor for only 20 minutes a month.
To add a piece to the puzzle, researchers say that often patients with similar symptoms have different problems with their brain chemistry. The neural mechanisms behind this, and the reasons why antidepressant medications work, are not fully understood.
In one study that followed changes in the brain associated with antidepressant drugs, results showed that many of same changes occurred in patients who took placebos. The parts of the brain that were primarily affected are thought to play a role in mood.
In this particular study, 38 percent of depressed patients got better from taking the placebo, compared with 52 percent from the medicines.
However, once the trial ended and the patients were told what they had been taking, the patients who had been on placebos fell back into their depression. It appears that one’s belief in the effect of antidepressant may account for the improved feeling in patients.
While some say that antidepressants drugs work primarily because of the placebo effect, others believe that the drugs produce an effect of their own. A related study found, through the use of a brain imaging technique, that these medications do in fact produce changes in the brain stem that did not occur in patients taking placebos. However, the effects of these changes are not yet understood.
The analysis led many to say that an integrated treatment that takes into account both biological and mental aspects may prove beneficial in the treatment of depression.
International Journal Neuropsychopharmacology September 2002;5(3):193-7
Antidepressant Paxil May Increase Suicide Risk
While drug manufacturers and regulators claim that antidepressants reduce the risk of suicide, a leading expert in psychopharmacology has uncovered evidence that shows otherwise. The expert gained access to confidential company documents of GlaxoSmithKline and found that results of the company’s own clinical trials of Paxil, a selective serotonin reuptake inhibitor (SSRI) antidepressant, show that the drug increases the risk of suicide. The results show that about one out of every 60 people on Paxil attempt to commit suicide, compared with one out of every 550 people taking a placebo. This means that the risk of committing suicide while on Paxil is nine or 10 times greater than the risk on a sugar pill. According to experts, the drug company and U.S. and U.K. regulators have known about the data for 13 years. The report was broadcast last year by BBC, which subsequently received close to 1,400 e-mail reports and over 5,000 telephone calls mostly from people who had suffered drug withdrawal symptoms and thought they were alone. Along with reports from adults, BBC reported that they received 23 about children who had had bad experiences with Paxil. Although the drug has not been approved for use in people under 18 years of age in the U.K., doctors can prescribe it if they think it is necessary. In the United States, however, the Food and Drug Administration (FDA) has approved SSRIs for children. Moreover, according to BBC, the number of suicides linked to Paxil may be significantly underestimated, as the FDA receives reports for only one percent to 10 percent of actual adverse drug reactions. Despite the association, U.S. news media have averted their gaze and are not conducting an investigation that would shed light on the scope of the problem in America, where most of the psychotropic drugs--including SSRI antidepressants--are sold. Some speculate that the media may be reluctant to investigate the drug industry for fear that it may threaten their advertising revenue. The psychiatric community, including the American Psychiatric Associatio and the American College of Neuropsychopharmacology, has also remained silent on the problem of drug-induced suicide. According to experts, vital information is being suppressed and clinicians are prescribing these drugs without knowledge of their potentially lethal side effects, and millions of people who are taking the drugs, even for minor discomforts, are doing so without knowledge of the potential for harm. Research Protection May 21, 2003 Teen Sex, Linked to Depression & Suicide
Teenagers who engage in sexual intercourse are more likely to suffer from depression and attempt suicide than teens who are abstinent, according to a study.
The findings are especially significant for young girls. About 25 percent of sexually active girls say they are depressed all, most, or a lot of the time, compared to eight percent of girls who are not sexually active.
The study used selected federal data on 2,800 students aged between 14 and 17 years. The youth were not diagnosed as clinically depressed but rather rated their own “general state of continuing unhappiness.”
Researchers noted that they did not find a causal link between unhappiness and sexual activity, as that would be nearly impossible to prove.
The study found that about 14 percent of girls who have had intercourse have attempted suicide compared with five percent of girls who have not had intercourse.
About six percent of sexually active boys have attempted suicide compared with less than one percent of sexually inactive boys.
According to researchers, the findings send a different message from the one portrayed by popular culture, in which “all forms of non-marital sexual activity are wonderful and glorious, and the younger the teen the better.”
USA Today June 3, 2003 Heritage Foundation Study Appendix A: Explanation of Data Sources
Antidepressants Proven to Work Only Slightly Better Than Placebo
By Dr. Irving Kirsch Although antidepressant medication is widely regarded as effective, a recent meta-analysis of published clinical trials indicates that 75 percent of the response to antidepressants is duplicated by placebo. The report analyses the data submitted to the U.S. Food and Drug Administration (FDA) for approval of recent antidepressant medications. We analyzed the efficacy data submitted to the FDA for the six most widely prescribed antidepressants approved between 1987 and 1999: Results are reported from all well controlled efficacy trials of the use of these medications for the treatment of depression. FDA medical and statistical reviewers had access to the raw data and evaluated the trials independently. The findings of the primary medical and statistical reviewers were verified by at least one other reviewer, and the analysis was also assessed by an independent advisory panel. More important, the FDA data constitute the basis on which these medications were approved. Approval of these medications implies that these particular data are strong enough and reliable enough to warrant approval. To the extent that these data are flawed, the medications should not have been approved. In order to generalize the findings of the clinical trial to a larger patient population, FDA reviewers sought a completion rate of 70% or better for these typically 6-week trials. Only 4 of 45 trials, however, reached this objective. In clinical trials, the effect of the active drug is assumed to be the difference between the drug response and the placebo response. This report showed that the FDA clinical trials data indicate that 18% of the drug response is due to the pharmacological effects of the medication. Overall, the drug/placebo difference was less than 2 points on the HAM-D, a highly reliable physician-rated scale that has been reported to be more sensitive than patient-rated scales to drug/placebo differences. Although mean differences were small, most of them favored the active drug, and overall, the difference was statistically significant. There were only 4 trials in which mean improvement scores in the placebo condition were equal to or higher than those in the drug condition, and in no case was placebo significantly more effective than active drug. This may indicate a small but significant drug effect. However, it is also possible that this difference between drug and placebo is an enhanced placebo effect due to the breaking of blind. These data raise questions about the criteria used by the FDA in approving antidepressant medications. The FDA required positive findings from at least two controlled clinical trials, but the total number of trials can vary. Positive findings consist of statistically significant drug/placebo differences. The clinical significance of these differences is not considered. To summarize, the data submitted to the FDA reveal a small but significant difference between antidepressant drug and inert placebo. This difference may be a true pharmacological effect, or it may be an artifact associated with the breaking of blind by clinical trial patients and the psychiatrists who are rating the severity of their conditions. In any case, the difference is relatively small (about 2 points on the HAM-D), and its clinical significance is dubious. Research is therefore needed to assess the additivity of antidepressant drug and placebo effects. If there is a powerful antidepressant effect, then it is being masked by a nonadditive placebo effect, in which case current clinical trial methodology may be inappropriate for evaluating these medications, and alternate methodology need to be developed. Conversely, if the drug effect is as small as it appears when drug/placebo differences are estimated, then there may be little justification for the clinical use of these medications. The problem, then, would be to find an alternative, as the clinical response to both drug and placebo is substantial. Placebo treatment has the advantage of eliciting fewer side effects. However, the deception that is inherent in clinical administration of placebos inhibits their use. Thus, the development of nondeceptive methods of eliciting the placebo effect would be of great importance. Prevention & Treatment, Volume 5, Article 23, July 15, 2002 First Posted in Red Flags Weekly July 17, 2002
New warnings have surfaced about the risk of suicide from selective serotonin reuptake inhibitor (SSRI) antidepressant drugs, which include Paxil, Prozac and Zoloft.
Sexually Active Teenagers Are More Likely to Be Depressed
E-mail: irving.kirsch@uconn.edu
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Depressed? Consider Fish Oil |
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New research has found that people with depression who received a daily dose of 1 gram of an omega-3 fatty acid for 12 weeks experienced a decrease in their symptoms, such as sadness, anxiety and sleeping problems. The only side effect of the treatment appeared to be mild gastrointestinal problems. Previous researchers have suggested that the balance of omega-3 fatty acids in the brain may become skewed in people with depression, and earlier studies have shown that fish oil supplements can help alleviate the symptoms of schizophrenia and bipolar disorder, or manic depression. But depression isn't the only disease that may be affected by a person's levels of omega-3 fatty acids. Researchers have found that those who have been diagnosed with cardiovascular disease and other conditions associated with depression, have low levels of omega-3 fatty acids in their blood. The study included 70 depressed patients who took a daily dose of one to 4 grams of EPA or an inactive drug. The treatment lasted 12 weeks. The doses were either 1 gram, 2 grams or 4 grams of EPA. Those who took 1 gram experienced improvements akin to those given the inactive drug, in all the measurable aspects of depression, including sadness, anxiety, low sexual drive and suicidal tendencies. There was a significant improvement of those patients who took 1 gram of EPA daily: 69 percent of the patients achieved a 50 percent reduction in their symptoms, in contrast to those who took the inactive drug, where 25 percent of the patients saw improvement. The higher-dosage groups saw similar improvements, but no higher improvement than those who took the 1 gram daily dose. The study's authors surmise that this result may have had to do with the fact that a small amount of people took the 2 or 4 grams per day. They advised further trials to determine the efficacy of higher doses of EPA in treatment of depression. Archives of General Psychiatry October 2002; 59: 913-919 |