Allegations of suppressed research, promotion of drugs for unapproved uses, payment of kickbacks to physicians, and ghostwriting of a major journal article surfaced recently when the Department of Justice unsealed a civil complaint against Forest Laboratories and Forest Pharmaceuticals, Inc.
Filed in the District Court in Massachusetts, the 34-page complaint charged that for more than half a decade, Forest illegally marketed Celexa (citalopram) and Lexapro (escitalopram) for off-label use in pediatric patients when both medications had been approved only for adult use. (The 2 drugs were licensed to Forest by H. Lundbeck A/S, a Danish company.)
The complaint also accused Forest of deceiving physicians by promoting the results of a positive study on pediatric use of citalopram(Drug information on citalopram),1 while failing to disclose the results of a contemporaneous negative study conducted in Europe for the same pediatric use (the Lundbeck study). Forest was also accused of using “illegal” inducements to physicians to get them to prescribe citalopram and escitalopram(Drug information on escitalopram).
“By knowingly and actively promoting these antidepressants for off-label pediatric use without disclosing the results of the negative pediatric study and by paying kickbacks, Forest caused false claims to be submitted to federal health care programs [Medicaid, TRICARE/CHAMPUS] in violation of the False Claims Act [FCA],” the complaint said.
Before filing its complaint, the government had intervened in 2 separate whistleblower actions against Forest brought by Christopher Gobble, a former Forest employee, and Joseph Piacentile, MD.
While the complaint has been unsealed, and Forest is aware of it, Frank Murdolo, Forest Laboratories’ vice president of investor relations, told Psychiatric Times that as of March 6, the company had not been served with the complaint.
In a statement posted on Forest Laboratories’ Web site—http://www. frx.com/news/PressRelease.aspx? ID=1260234—the company said it is “currently reviewing the complaint, [and] will respond to this action at the appropriate time” and that it understands 11 states along with the District of Columbia intend to intervene as plaintiffs in the action.
Murdolo added that as disclosed in its filings with the Securities and Exchange Commission (SEC), Forest “has been cooperating with the government investigation since 2004.”
Forest’s 10-Q filed November 10, 2008, noted that the US Attorney’s Office (USAO) had subpoenaed the company and requested documents from 1997 to the present related to the marketing and promotion of Celexa and Lexapro as well as Namenda (memantine) and Combunox (oxycodone and ibuprofen(Drug information on ibuprofen)).
In its statement, Forest added that the company is “committed to adhering to the highest ethical and legal standards, and off-label promotion and improper payments to medical providers have consistently been against Forest policy.”
Part of the controversy over the 2 citalopram studies emanates from governmental efforts to encourage drug manufacturers to conduct pediatric studies of drugs used in adults by offering an additional 6 months of patent exclusivity for previously approved, on-label drugs.
In 1999, according to the complaint, the FDA asked Forest to conduct 2 independent, well-controlled clinical trials in pediatric depression. Later that year, Forest submitted FDA protocol for 2 pediatric studies: a double-blind, placebo-controlled pediatric study being conducted in Europe by Lundbeck (the Lundbeck study) and a double-blind, placebo-controlled pediatric study to be conducted in this country. The principal investigator for the American study was Karen Dineen Wagner, MD, PhD, now Marie B. Gale Centennial Professor and vice chair of the department of psychiatry and behavioral sciences at the University of Texas Medical Branch (UTMB) at Galveston. Wagner serves on Psychiatric Times’ editorial board and writes columns on child and adolescent psychiatry.
The 8-week trial, conducted at 21 US centers, involved 174 outpatients (aged 7 to 17 years) who met DSM-IV criteria for major depressive disorder (MDD) and were randomized, 89 to citalopram and 85 to placebo. It showed that citalopram “produces a statistically and clinically significant reduction in depressive symptoms in children and adolescents” on the Children’s Depression Rating Scale–Revised (CDRS-R) and that “there were no serious adverse events observed in the citalopram group.”
The Lundbeck study, according to the complaint, was negative in that it did not show citalopram to be any more effective than placebo in treating pediatric depression. “Furthermore, 14 patients taking citalopram attempted suicide or reported suicidal ideation compared with 5 patients taking placebo,” the complaint said.