Great Britain issues warnings on adult use of antidepressants
■ U.S. physicians hope any action here balances concern about side effects with the risk that patients in need might become unwilling to take the drugs.
By Victoria Stagg Elliott — Posted Feb. 7, 2005
Recommendations by Britain's health agency that physicians restrict and monitor SSRI prescriptions for adults have U.S. doctors wondering if the Food and Drug Administration will follow suit.
The United Kingdom's Medicines and Healthcare products Regulatory Agency issued the new advice in December 2004. The agency warned that selective serotonin reuptake inhibitors should not be used to treat mild depression, that young adults older than 18 who are taking these drugs be closely monitored, that the lowest possible dose be used and that the drugs be discontinued slowly to avoid withdrawal reactions.
The recommendations build on advice the agency announced in December 2003 against the use of most of these drugs, except Prozac (fluoxetine), by those younger than 18 because of a lack of evidence of effectiveness in this age group and data suggesting significant side effects, including possible suicide risk.
In its most recent guidance, the U.K. agency concluded that these drugs were effective for adults and that the benefits outweighed the risk for those with major depressive disorder. "SSRIs are an important group of medicines, which help patients who suffer depressive illness," said Dr. Kent Woods, chief executive of the MHRA. "The benefits of SSRIs in adults are still considered to outweigh the risk of adverse drug reactions."
Many U.S. physicians are eager to see what the FDA will do in light of the MHRA's recommendations.
In March 2004, the FDA called on SSRI manufacturers to include stronger cautions on the labels regarding the possibility of suicidal thoughts among children and adolescents and a worsening of depression. In January of this year, it issued new medication guides and revised labeling warning that children and adolescents on the drugs should be monitored closely, particularly when initiating treatment. The new labeling also suggests that these risks could apply to adults.
These actions likely are not the end of the story. Experts expect the FDA to closely scrutinize studies looking at adult SSRI use to determine if additional recommendations are needed.
Physicians are keenly interested in SSRI issues. The American Medical Association's Council on Scientific Affairs has been charged with writing a review of scientific data pertaining to the safety and efficacy of these drugs in children and adolescents.
Many doctors cautioned that a decision about whether to use the drugs should be based on the needs of the patient. Doctors also noted that many of the British government's recommendations are in line with what is already common medical practice here.
"We need to ensure that patients of all ages have a comprehensive evaluation and accurate diagnosis prior to any treatment," said David Fassler, MD, clinical associate professor of psychiatry at the University of Vermont College of Medicine and a member of the American Academy of Child and Adolescent Psychiatry and of the AMA House of Delegates. "We also try to use all medications at the lowest dosages effective, but these decisions really need to be individualized."
Physicians also expressed concern that patients not be deterred from taking medications they might need.
"The FDA should study [antidepressants] very closely," said Julio Licinio, MD, professor of psychiatry and endocrinology at the University of California, Los Angeles. "Untreated depression is the leading cause of suicide, and the FDA should be very careful not to make treatment more difficult and keep people away from treatment when it could be life-saving."
These questions and concerns regarding SSRI use highlight the need for more evidence-based medicine to determine the most effective treatment strategies, experts said.
Toward this end, scientists published a study in the Jan. 19 issue of JAMA saying that a quality improvement initiative in primary care clinics could improve outcomes for depressed adolescents. The program featured additional doctor education on depression and the involvement of a care manager who could initiate and manage a treatment plan. Treatment included cognitive behavior therapy, and, in some cases, SSRI drugs.
"Our study should create a sense of hope and optimism in the face of the recent public and scientific controversy because our data really suggest that clinicians can do something to treat the disorder," said Joan Rosenbaum Asarnow, PhD, lead author and a professor of psychiatry and biobehavioral sciences at the University of California, Los Angeles.
Researchers say efforts in this area are particularly key, not just because of the recent debate over the use of antidepressants in this age group, but also because of studies suggesting that depressed adolescents are likely to become depressed adults. Most recently, a study in the January issue of the Archives of General Psychiatry suggested that adolescents with mild depression were just as likely as those with the severe form of the disease to have problems with depression and suicidal thoughts as they grew up.
"The good news is that we really can help most people who suffer from psychiatric illnesses, including depression," Dr. Fassler said. "The real tragedy is that there are still so many people of all ages who don't receive the effective and appropriate intervention that they need and deserve."
While doctors are struggling to determine the best treatment strategy, scientists are taking a closer look at genetic predispositions and which genes might determine if an SSRI will be effective. One study in the December 2004 issue of Neuron said variants in TPH2 could put a person at increased risk of depression and inhibit medication response. Another in the December 2004 Molecular Psychiatry found that those who had a variant of the CRH gene (CRHR1) were more likely to benefit from antidepressants. The studies' authors hope that this science eventually will lead to tests that will guide more effective prescribing.
"Right now, treatment is a trial-and-error experiment," said Dr. Licinio, lead author of the paper in Molecular Psychiatry. "It's a little too early to bring it to the clinic, but that's the ultimate goal."