Department of Veterans Affairs doctors began raising red flags last year about whether the smoking-cessation drug Chantix was causing severe psychotic episodes among veterans, prompting a quiet investigation last fall but no warning for many months to the 32,000 retired service members prescribed the medication, according to internal agency documents reviewed by The Washington Times.
"Early reports" from doctors at VA medical centers were flowing in throughout 2007, well before the U.S. government and drug maker Pfizer Inc. issued public warnings late last year and earlier this year that Chantix had been linked to psychotic behavior, hallucinations and suicides, VA officials said.
By late November, VA officials began collecting data showing nearly one out of every 1,000 veterans taking the drug had been hospitalized for severe psychosis, a rate noticeably higher than for veterans trying to stop smoking with alternative treatments like nicotine replacement, the documents show.
VA officials told The Times that they decided to proceed with their normal process of studying their data for several months to determine whether the trend was "statistically significant" and did not issue immediate warnings.
In the interim, more veterans were prescribed the drug, including some suffering from post-traumatic stress disorder (PTSD) who were enrolled in a medical experiment in which VA officials acknowledged Monday that the number of severe side affects averaged nearly one problem for every two veterans taking Chantix. VA officials said they wished in retrospect that their warnings had been issued sooner and they are examining how to improve their communications process.
The House Veterans Affairs Committee is set to investigate the VA's conduct in prescribing Chantix at hearings Wednesday, and the committee's chairman said Monday that the inaction detailed in the documents obtained by The Times raised serious, new questions about whether the agency cared enough about the veterans it treats.
"When questioned, the VA immediately wants to defend 'the process,'" said Rep. Bob Filner, California Democrat. "When is the VA going to understand that it is not about the process, but about the veteran? Veterans don´t want to hear the VA defend its process. It´s time for the VA to defend our veterans, our heroes."
Doctors treating veterans were reporting last year into a medical surveillance database maintained by the VA numerous instances in which the patients were taking Chantix when they were hospitalized for serious psychotic episodes. By October, the VA changed its tracking of Chantix side effects to include psychosis because of the concerns raised by doctors. A month later, the VA began a formal review that took nearly four months to complete, gleaning from the database all reports of psychotic behavior that required hospitalization.
That review found that among 27 patients taking Chantix who were admitted to VA hospitals for psychiatric problems since the drug was approved for the market in 2006, 11 had attempted suicide, one attempted homicide, nine had suicidal thoughts, and six were suffering from hallucinations, according to an internal report completed on March 18.
Results "show a greater crude rate of severe psychosis with varenicline compared to nicotine or nicotine/bupropion but do not reach statistical significance," the report concluded. "These data show a signal for potential increased psychosis and warrant further examination to determine actual incidence and potential causality compared to control."
The study was never released to the public, but VA officials agreed to let The Times review it.
The VA internal analysis examined more than 100 hospitalizations for psychiatric episodes of VA patients who had just begun trying to quit smoking by taking either varenicline (Chantix), nicotine-replacement therapy, or nicotine-replacement therapy along with bupropion. It looked back at the time period between September 2006 and September 2007.
VA officials noted that patients in the other groups also were admitted to hospitals for similar episodes, including 73 veterans who were trying the nicotine-replacement therapy and seven who were trying nicotine-replacement therapy and bupropion.
But the rates of these events were highest among the Chantix group - 9.8 hospitalizations per 10,000 patients. For instance, veterans taking nicotine replacement were suffering psychotic episodes requiring hospitalizations at a lesser of rate 6.8 per 10,000 patients.
The report also found that nearly all of the patients in each of the three groups who were admitted to hospitals with psychiatric problems had histories of psychiatric problems, and more than half in each group had histories of some sorts of suicidal behaviors.
By the time the review was completed in March, the Food and Drug Administration (FDA) and Pfizer already had issued public warnings about Chantix.
Even then, VA officials conducting the review didn't urge that all veterans taking the medicine under the VA's care get warning letters. Instead, the review recommended that the FDA conduct a full epidemiological study of the drug at a cost of $250,000.
Virginia Torrise, VA's deputy chief consultant of Pharmacy Benefits Management, said agency officials were not able in their informal review "to actually correlate and say there was a causal effect" between any of the drugs or nicotine treatments and the psychiatric events and that is why they recommended a formal FDA study.
The VA began sending warning letters to all 32,000 veterans who have taken Chantix in late spring, nearly three months after the internal review was completed. The first letters were sent on May 30 and told veterans that they should be careful operating heavy machinery if they are taking Chantix, repeating a warning just days earlier from the Federal Aviation Administration when it banned pilots from taking the drug.
Updated guidelines for prescribing Chantix were posted on the VA Web site June 18, and the agency then sent out letters to all veterans taking the drug to specifically warn them that suicidal tendencies were a possible side effect.
Those actions were prompted by a joint investigative report by The Times and ABC News on June 17 that documented how the VA failed to warn more than 200 veterans suffering from PTSD who where participating in a smoking-cessation study of Chantix's possible side effects. During the delay, one of the Iraq war veterans, former Army sharpshooter James Elliott, in that study suffered a psychotic episode so severe that it led to a near lethal confrontation with police, The Times reported.
The VA initially reported that 143 veterans had taken Chantix in conjunction with the smoking-cessation study, and about two dozen had suffered some side effects. But on Monday, VA officials significantly raised those numbers, acknowledging that at least 241 veterans in the study had taken Chantix as of June 25, and that 114 serious adverse events were reported by 75 of those participants. Among the side effects, 22 involved psychiatric events.
The number of veterans now taking Chantix in that study has dropped to 40, officials said.
The description of the study's effort provided to The Times said that when the FDA approved Chantix, "the drug had not been studied in VA patients or patients with mental health conditions."
"VA received early reports of ... adverse drug reactions from various medical centers which signaled to VA the need for a pharmacovigilance effort that added psychosis to the events being tracked and ultimately analyzed and placed into a report," the VA said.
Wednesday's congressional hearing will review the VA process for handling human research subjects, the agency's responsibility to respond to the FDA´s advisories, and the relationship between pharmaceutical companies and researchers. Witnesses include VA Secretary James B. Peake; Dr. John D. Daigh, assistant inspector general; Mr. Elliott; and Lt. Col Roger Charles, editor of DefenseWatch.
Lawmakers are concerned because the VA's alerts about Chantix side effects lagged those of the drug maker and the FDA.
For instance, Pfizer updated its Chantix label in January to warn of possible "serious neuropsychiatric symptoms, including changes in behavior, agitation, depressed mood, suicidal ideation and suicidal behavior."
The FDA first issued a notice about possible additional side effects of Chantix in November and issued a health alert on Feb. 1, warning that Chantix could result in changes in behavior, agitation, depressed mood, suicidal thoughts and attempted suicide.