Healthy Skepticism Library item: 12465

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Publication type: news

Busko M.
FDA Warnings Did Not Herald Closer Pediatric SSRI Supervision or Drastic Drop in Prescribing
Medscape Medical News 2008 Jan 17
http://www.medscape.com/viewarticle/568909?src=mpnews

Full text:

Following US Food and Drug Administration (FDA) warnings about pediatric suicidality risk with selective serotonin-reuptake inhibitors (SSRIs), patient monitoring did not increase and prescribing dipped modestly, according to 2 studies.

The first study, which looked at provider contact following initial antidepressant prescribing, is published in the January issue of the American Journal of Psychiatry. The second study, which examines trends in prescribing antidepressants, appears in the January issue of Archives of General Psychiatry.

Follow-up Falls Short

The FDA’s October 2003 public health advisory described reports of suicidal ideation and suicide attempts in pediatric patients taking antidepressants and advised “close supervision” of such patients, the researchers from the American Journal of Psychiatry study, led by Elaine H. Morrato, DrPH, from the University of Colorado Health Sciences Center, in Denver, explain.

“We expected [the FDA advisory] to cause . . . increased monitoring by physicians of patients and increased contacts, but we did not find that; it stayed very similar to how it was before the warnings,” corresponding author Robert J. Valuck, PhD, from the University of Colorado Health Sciences Center, told Medscape Psychiatry.

To date, the way that this FDA advisory affected the frequency of provider contact for patients newly prescribed antidepressants had not been reported, the group writes. They performed a retrospective study to evaluate this, using data from the PharMetrics claims database of more than 85 managed-care plans, representing more than 47 million individuals throughout the United States.

The researchers created 2 study cohorts: pediatric patients (age 5 to 18 years) and adult patients who had a new episode of depression between October 1998 and March 2005 and who received antidepressant medication within 30 days of their diagnosis. A total of 27,370 pediatric patients and 475,838 adult patients met the study criteria.

The investigators evaluated adherence to 2 standards of recommended physician contact following initiation of an antidepressant medication:

Health Plan Employer Data and Information Set (HEDIS) criteria: 3 or more contacts with a practitioner (1 contact could be a phone call) in the first 3 months.
FDA-recommended physician visits: weekly during the first month of antidepressant therapy, biweekly in the second month, and again at 12 weeks, for a total of 7 visits.
HEDIS criteria, based on expert consensus, have been tracked by the National Committee on Quality Assurance (NCQA) since 1998.

Before the FDA advisory, less than 5% of all patients met the FDA physician contact recommendations, although more patients (60% of children and 40% of adults) met the HEDIS follow-up recommendations. These rates remained unchanged following the FDA advisory.

Among pediatric patients, 80% seen by psychiatrists vs 60% seen by pediatricians and 54% seen by primary care physicians met HEDIS follow-up contact criteria. Among adults, 65% seen by psychiatrists vs 37% seen by primary care physicians met these criteria.

Barriers to care or a lack of knowledge of the recommended monitoring might explain the lower-than-expected frequency of follow-up, Dr. Valuck suggested. Since their paper was submitted, the FDA has removed the recommendation for 7 visits and instead only recommends close supervision and monitoring of these patients, he noted.

“There is no real evidence base to be able to say what the right intensity of monitoring is,” he said. There is a need to determine whether increased surveillance actually improves outcomes, and if so, what the follow-up frequency should be, the group concludes.

“Changes Are Needed”

“The data provided in the paper by Morrato et al are important in identifying the fact that changes are needed to improve clinical monitoring of antidepressant treatment,” writes Graham J. Emslie, MD, from the University of Texas Southwestern Medical Center, in Dallas, in an accompanying editorial.

He points out that although the discussion about treatment of depression in youth has focused on which treatments are effective and safe, “a major concern usually missed in this controversy is that less than 50% of children and adolescents with depression receive treatment.”

For young patients with depression who are being treated, there is a need to evaluate barriers to implementing guidelines in clinical settings and to articulate realistic goals for implementing evidence-based care to improve patient outcomes, he concludes.

Prescribing Growth Halted

The Archives of General Psychiatry study of antidepressant prescribing around this time reports that FDA warnings appeared to have slowed the growth in antidepressant treatment of children and adults.

“Given anecdotal clinical reports and early studies that focused on month-to-month crude numbers of antidepressant prescriptions without a defined population or denominator, we expected to find that the warnings had a profound impact on antidepressant use,” lead author Mark Olfson, MD, from Columbia University College of Physicians and Surgeons, in New York, told Medscape Psychiatry. “In this sense, it was surprising and reassuring to learn that collectively physicians responded in a measured way to the FDA warnings.”

The group sought to determine how prescribing of antidepressants was affected by 2 events:

The June 19, 2003 FDA warning that recommended that paroxetine not be used to treat depression in children and adolescents because of a possible increased rate of suicidal behavior.
The October 15, 2004 FDA black-box warning that all antidepressants pose significant risks of suicidality in children and adolescents and that these patients should be watched closely for these risks.
They examined data from the Medco database, one of the largest pharmacy benefit management services in the United States, representing roughly 60 million Americans.

Cohorts of more than 2 million Medco members were examined in each of 3 study periods:

Prewarning (May 1, 2002 to June 19, 2003).
Paroxetine warning (June 20, 2003 to October 15, 2004).
Black-box warning (October 16, 2004 to December 31,2005).
The patients were classed as youth (age 6 to 17 years), adults (age 18 to 64 years), and older adults (65 years or older). Antidepressants were divided into 4 subgroups: paroxetine, other SSRIs, tricyclics, and other.

The researchers found that among youth, antidepressant use increased significantly by 36% per year during the prewarning study period, and this was followed by nonsignificant decreases of 0.8% per year and 9.6% per year during the paroxetine warning and the black-box warning study periods, respectively.

After the paroxetine warning, there was a significant absolute decline in use of paroxetine but not in the use of other antidepressants among young patients. Similar, though less pronounced, declines occurred in paroxetine treatment of older patients.

Changes in prescribing were less pronounced in adults than in youth. Among older adults, antidepressant use increased significantly (8.1% per year) during the black-box study period.

“The paroxetine and black-box warnings had modest, targeted effects in the intended populations,” the group concludes, adding that these changes, which were greatest for youth, were broadly consistent with the FDA warnings and the scientific literature.

“Practicing clinicians appear to have taken the FDA warnings seriously,” Dr. Olfson said. “The warnings likely contributed to stopping the previous rapid growth in antidepressant treatment of young people.”

The American Journal of Psychiatry study was supported by an unrestricted investigator-initiated research grant from Eli Lilly that funded the access fees to the independent PharMetrics database and salary support for the investigators. Dr. Morrato has received research support from Janssen and Pfizer. Dr. Valuck is an advisory board member for Eli Lilly and has received research support from Pfizer. The financial disclosures for the other authors are listed in the paper. The author of the American Journal of Psychiatry editorial, Dr. Emslie, has received research support from Eli Lilly, Organon, Shire, Somerset Pharmaceuticals, BioBehavioral Diagnostics, and Forest Laboratories. He has consulted for Eli Lilly, GlaxoSmithKline, Wyeth-Ayerst, Shire, and BioBehavioral Diagnostics and is on the speakers’ bureau for McNeil.

The Archives of General Psychiatry study was supported by a grant from the Agency for Healthcare Research and Quality and from the Carmel Hill Fund, and data were provided by Medco Health Solutions. Dr. Olfson has received grant support from Eli Lilly, Bristol-Myers Squibb, and AstraZeneca. He has been a consultant for Pfizer, McNeil, and Eli Lilly and has been on the advisory board for Eli Lilly and Bristol-Myers Squibb. He is on the speakers’ bureau for Janssen. The financial disclosures for the other authors are listed in the paper.

Am J Psychiatry. 2008; 165:42-50 Abstract, 1-3. Abstract

Arch Gen Psychiatry. 2008; 65:94-101. Abstract