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It was Britain's warning to physicians last year not to treat depression in young people with six antidepressant drugs that set off an international debate and gave impetus to U.S. health authorities who made similar recommendations this week, saying the drugs largely failed to treat depression in children and teenagers and led some to become suicidal. But the warnings by the Medicines and Healthcare Products Regulatory Agency, Britain's equivalent of the Food and Drug Administration, have left doctors here uncertain whether the rules protect patients from suicide or merely limit physicians' ability to treat them. The agency did exempt Prozac, made by Eli Lilly & Co., saying on its Web site that Prozac “appears to have a positive balance of risks and benefits in the treatment of depressive illness in the under-18s.” It said about half of the 30,000 to 40,000 British children and teenagers under 18 being treated for depression were being given Prozac. The British regulations, which were phased in from June to December 2003, do not ban the other antidepressants outright. While the agency counsels against prescribing them for patients under the age of 18, it leaves the decision to specialists in child psychiatry, who are deemed able to assess whether the antidepressants increase the risk of suicide or self-harm. The drugs are sold in the United States under the names Paxil, from GlaxoSmithKline; Zoloft, from Pfizer; Effexor, from Wyeth; Celexa and Lexapro, from Forest Laboratories Inc.; and Luvox, from Solvay. All but Effexor are selective serotonin reuptake inhibitors, or SSRIs; Effexor is a serotonin-norepinephrine inhibitor. Part of the debate in Britain revolves around statistics suggesting that while the use of antidepressants, particularly SSRIs, has grown rapidly, overall suicide rates related to overdoses of antidepressants have fallen. “There are two views,” said Dr. Mike McClure, the director of public education at the Royal College of Psychiatrists, a professional body. “One is that the use of certain SSRIs may lead to an increase in suicidal behavior and possible suicide itself. And then there are those who would say that the reduction of suicide rates in 10 years in the westernized world as a whole is in part due to better treatment with SSRIs.” For medical specialists, said Dr. Sue Bailey, an adolescent forensic psychiatrist at the University of Central Lancashire in Manchester, the new ruling has thrown the whole system into disarray. In practical terms, she said, family-practice doctors are referring more adolescent patients to specialists, rather than risk prescribing antidepressants other than Prozac. “What it has done is make us look at our own practices,” she said in a telephone interview. The new rules also seem to have provoked new demands from some specialists for greater openness on the part of pharmaceutical companies about their research trials. In a paper to be presented to child psychiatrists in Edinburgh next week, Bailey quotes from a letter she wrote to the government last month, on behalf of child and adolescent psychiatrists, demanding disclosure of data from such trials. “We do not believe in the current climate that drug companies can continue to argue against such openness on the basis of protecting themselves commercially when the health of the individual is at stake,” she wrote. Bailey says the restrictions on antidepressants for patients under 18 has stirred debate among physicians; some are persuaded that the rules are adding to their workloads and have limited their intervention abilities. Others, she says in the paper to be presented next week, argue that the restrictions have opened an opportunity to work with families and young people and to give them more sway in treatment choices and decisions. Before SSRIs were introduced in the late 1980s, an earlier form of antidepressants known as tricyclics were sometimes prescribed, and, of course, depressive illness, like other forms of psychiatric illnesses, has long been treated through psychotherapy. Discussing the SSRIs, Dr. David Healy, a specialist in psychological medicine at the University of Cardiff in Wales, said, “The sales of these drugs are pretty minor in Britain compared to the United States.” Indeed, up until the late 1990s, he said, parents and others tended to regard teenage depression as a temporary phase of adolescence. “Parents would not have thought that this was a thing that needed treatment. But we have all had the message handed to us that this does need treatment,” he said, blaming drug companies for shifting the prevailing wisdom toward the need for their products. He has called for more unbiased testing. The impact on the pharmaceutical companies also seems unclear, partly because some of the drugs at issue are also used to treat other illnesses, like obsessive compulsive disorder, and those uses are not addressed by the regulations. Chris Hunter-Ward, a spokesman for the drug giant GlaxoSmithKline, said the British regulations had had no discernible impact on prescriptions of Paxil, its paroxetine antidepressant, which is sold in Britain as Seroxat. A class-action suit filed in the United States this year accuses the company of suppressing critical research data about the drug. GlaxoSmithKline, which has denied covering up clinical trial results, settled a similar case filed by Eliot Spitzer, the New York attorney general, for $2.5 million. In a letter to physicians last December, the Medicines and Healthcare Products Regulatory Agency said that SSRI antidepressants other than Prozac should not be prescribed as new therapy for children and adolescents with depressive illness. But, it said, physicians could continue treating with the proscribed drugs “if your patient is being successfully treated with any of these products.” Any decision to use the drugs “should only be made with specialist advice and after careful consideration of all available information,” the regulators' letter said. It also warned that “no SSRI should be stopped abruptly.” “Gradual decrease in dose may be required.” By contrast, an advisory committee in the United States urged the FDA last week to mandate that the dangers of some antidepressants be highlighted in black-box warnings on the information sheet that physicians review when prescribing drugs. The American ruling played into a heated debate in Britain, where another government agency, the Office of National Statistics, produced figures in August charting the use of antidepressants among people of all ages and the prevalence of their use in overdose-induced suicides from 1993 to 2002 in England and Wales. In that period, prescriptions for all antidepressants, including both SSRIs and other forms of medication, rose from about 10 million to 26 million a year. Overall, the figures showed that suicides accounted for 78 percent of the 4,767 deaths involving antidepressant drugs from 1993 to 2002, and antidepressants were involved in 18 percent of all drug-poisoning deaths. In general, the statistics showed, average annual death rates related to antidepressants fell to 14 from 41 per million prescription items during this period. The statistics office did not give specific figures for those under 18 years of age. Its statistics related largely to drug poisonings rather than other forms of suicide. No figures were available on teenage suicides since the new regulations came into force last December, or on the frequency of prescriptions of antidepressants for young people. Professor Chris Hollis, a specialist at Queens Medical Center in Nottingham, said any decrease in prescribing antidepressants was most likely among family-practice physicians, known in Britain as general practitioners. The regulations, he suggested, had confirmed the view of some specialists that they ought to be consulted before antidepressants were prescribed for children and adolescents.
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