DoD cracks down on off-label drug use
By
Patricia Kime - Staff writer
Posted : Thursday Jun 14, 2012 10:01:04 EDT
A letter landed in Stan White’s mailbox in Cross Lanes, W.Va., in April.
It began: “On behalf of the men and women of the U.S. Armed Forces … I extend my sincerest and deepest sympathy for the loss of your sons.”
But the note wasn’t simply a condolence. The message from Air Force Lt. Gen. Brooks Bash informed White that U.S. Central Command had decided in March to remove the powerful antipsychotic drug Seroquel from its approved formulary list.
Under the new rules, CENTCOM doctors now must request a waiver if they write a prescription for Seroquel, also known as quetiapine.
The change is a small victory for White, who had already lost one son to combat and has sought restrictions on the drug he believes contributed to the death of a younger son.
Marine Cpl. Andrew White died Feb. 12, 2008, at age 23 from a lethal combination of medications prescribed for post-traumatic stress disorder, mainly clonazepam, quetiapine and paroxetine — the latter two known to sometimes affect the heart’s regular rhythm.
“I have never been one to say I’m opposed to medication — I’m just opposed to these medications, which have a side effect of causing cardiac arrest,” White said June 6.
Off-label use soars
Prescriptions for Seroquel have exploded in the past decade, especially in the armed forces, where it often is prescribed off-label as a sleep aid.
In 2003, service members were diagnosed with insomnia at a rate of 30 per 10,000; by 2009, the rate had risen to 226 per 10,000. Prescriptions for Seroquel, or quetiapine, have subsequently soared, multiplying 27-fold in the same time period.
The drug is known to cause drowsiness and chase away nightmares associated with post-traumatic stress disorder.
Navy Capt. Mike Colston of the Office of the Assistant Secretary of Defense for Health Affairs said medications become popular as providers learn about them and as they receive new approvals for use by the Food and Drug Administration — in the case of quetiapine, as an add-on therapy for antidepressants.
Yet questions have been raised over whether its off-label use for insomnia was more than a grass-roots movement by physicians. In April 2010, manufacturer Astra-Zeneca agreed to pay $520 million to the federal government to settle a civil suit alleging that it illegally marketed Seroquel for a host of off-label uses such as Alzheimer’s disease, anxiety, PTSD and sleeplessness.
According to The Associated Press, in 2009, the Pentagon spent $8.6 million on the drug, while the Veterans Affairs Department spent $125.4 million.
Recent moves by the Pentagon to restrict prescriptions for atypical antipsychotic drugs were the result of a search for safe, proven therapies for troops, Colston said.
“We aim to … discourage the use of off-label medication treatments with antipsychotic medications before established evidence-based strategies have been implemented,” he said.
Earlier this year, Assistant Secretary of Defense for Health Affairs Dr. Jonathan Woodson asked the military services to monitor prescriptions for atypical antipsychotic medications, a class of drugs that includes quetiapine.
The medications are approved by the Food and Drug Administration for treating schizophrenia and bipolar disorder. But in the past decade, their popularity has soared for off-label use, including for treating PTSD and insomnia.
A 2011 study of 692 patients prescribed quetiapine at Madigan Army Medical Center, Wash., showed just 9.4 percent received it for an FDA-approved use, while 57 percent received it for insomnia.
In 2011, the services issued 54,581 prescriptions for Seroquel alone, the most for any antipsychotic medication — more than 2.5 times the number of prescriptions for the second-most prescribed atypical antipsychotic, Abilify, and nearly four times the number for risperidone, according to information obtained by a Military Times under a Freedom of Information Act request.
A growing alarm
Quetiapine has the strongest somnolent effect of all atypical antipsychotics, and is commonly prescribed troops for relieving nightmares.
But as its popularity has grown, evidence has mounted pointing to links between atypical antipsychotics and irregular heartbeat and even death — prompting critics and physicians, including Woodson, to sound the alarm on frequent prescriptions.
“Providers should use caution when these agents are used as sleep aids in service members struggling with substance use disorders, especially given the risk of such side effects as glucose dysregulation and cardiac effects,” Woodson wrote Feb. 22.
A study in the January 2009 New England Journal of Medicine found the rate of sudden cardiac death doubled for those taking atypical antipsychotic drugs, and there were three such deaths per year for every 1,000 patients taking the medication.
The risk of a fatal heart event also increased with dosage, and study author and Vanderbilt University researcher Wayne Ray said mixing these medications with others that cause irregular heartbeat, known medically as QT prolongation, could worsen the issue and possibly cause death.
“We saw this strong relationship between the antipsychotics and sudden death … and all the information we had pointed to the drugs as the cause,” Ray said after the study was published. “Our findings … would suggest avoiding other medications that prolong QT whenever possible because when you give two together, you’re … increasing the patient’s risk.”
The Madigan study, conducted by Army Lt. Col. Vincent Mysliwiec and presented last June at a meeting of the American Academy of Sleep Medicine, showed that of 692 patients who took quetiapine, 126 were monitored for heart arrhythmia within six months of starting on the drug, and of those, 11 showed an abnormal heart rhythm.
Ten of those cases were directly attributed to quetiapine; when the medication was stopped, their heart rhythm returned to normal, according to Psychiatric News.
Through an Army spokesman, Mysliwiec declined to release the study but said it was available to Defense Department physicians on request.
A 2008 Dutch study also showed patients taking more than one QT-interval-prolonging drug had 4.8 times the risk of cardiac arrest.
‘He just died’
White attributes his son’s death, and those of at least three others from West Virginia — Army Pfc. Derick Johnson, 22; Army National Guard Sgt. Eric Layne, 29; and Marine Cpl. Nicholas Endicott, 24 — to at least two heart-rhythm-altering drugs, quetiapine and paroxetine.
Since their cases were publicized, others have stepped forward, including Alicia McElroy, whose husband, Army National Guard Staff Sgt. James McElroy, 30, was found dead in his barracks while receiving treatment for PTSD at Fort Benning, Ga.
She said that among his many medications were Paxil, Seroquel and Klonopin.
“This wasn’t a long, slow death. It wasn’t an overdose. He wasn’t found unconscious. He just died,” said Alicia McElroy, who is still awaiting autopsy results. Her husband died June 6, 2011.
Seroquel maker AstraZeneca stands behind the safety record of its medication, which it made exclusively until March 2012, when the patent expired.
“Patient safety is a priority for AstraZeneca, and we think Seroquel is safe and effective when it’s used as recommended,” Stephanie Andrzejewski said.
She added the company does not condone prescribing Seroquel for off-label uses.
“We trust doctors to use medical judgment in … determining when it is appropriate to prescribe medications,” she said.
In July 2011, the FDA required AstraZeneca to add a warning to the drug’s label regarding its potential cardiac risk.
The services take action
The service surgeons general have responded to Woodson’s request for their policy guidance on atypical antipsychotics, Defense Department spokesman Navy Capt. Michael Colston said June 4. According to documents released by Colston:
• The Army decided risperidone should not be prescribed because its risks outweigh its benefits, and providers who prescribe other such drugs, including quetiapine, “must clearly document their rationale” and receive informed consent from the patient.
• The Navy Department agreed to monitor providers and flag those who prescribe the most atypical antipsychotics off-label for additional review.
• The Air Force, which prescribes atypical antipsychotics to “fewer than 0.15 percent of airmen,” will review provider prescribing practices and counsel those who show a pattern.
• The Washington, D.C., area medical command will conduct periodic evaluations of drugs prescribed to patients with PTSD and follow-up evaluations to see whether further monitoring is needed.
White, who had another son, Army Sgt. Robert White, killed in combat, said he is glad the military is moving away from medications for PTSD.
“I know people who have died from medication,” he said. “I don’t know anyone who’s ever been killed by counseling.”
Staff writer Andrew Tilghman contributed to this report.
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for further reading on this topic Pharmalot has written a related article
The US Military And Off-Label Antipsychotic Use
By Ed Silverman //
June 14th, 2012
But growing concern over links between antipsychotics – especially Seroquel, which is the most widely prescribed antipscyhotic by the US military – and irregular heartbeats is prompting moves to restrict usage. For instance, a retrospective review of 692 patients who were prescribed Seroquel at the Madigan Army Medical Center in 2007 and 2008 found that only 3.4 percent received the drug for an approved use, which would also include adjunct treatment for depression.
However, 60 percent received the drug for insomnia, 19 percent for anxiety, 12 percent for mood disorders and 8 percent for post-traumatic stress disorder. Yet, only 18 percent were screened for irregular heartbeats and 126 underwent an EKG, with 11 percent showing abnormal heart rhythms, according to a presentation at the American Academy of Sleep Medicine annual meeting (
here is the presentation – see page A179).
Such findings underscore the concerns. Last year, the armed services issued 54,581 prescriptions for Seroquel alone, the most for any antipsychotic — and more than 2.5 times the number of prescriptions for the second-most prescribed atypical antipsychotic, Abilify, and nearly four times the number for Risperdal, according to information obtained by
Military Times under a Freedom of Information Act request.
In 2003, Military Times reports, service members were diagnosed with insomnia at a rate of 30 per 10,000. By 2009, the rate had jumped to 226 per 10,000. Prescriptions for Seroquel rose 27-fold in the same time period. And according to The Associated Press, in 2009, the Pentagon spent $8.6 million on the drug, while the Veterans Affairs Department spent $125.4 million. That same year, results of a proof-of-concept study showed Seroquel benefited patients with post-traumatic stress disorder (see
this and
this).
Meanwhile, a 2008 study in the British Journal of Clinical Pharmacology showed patients taking more than one drug that can cause irregular heartbeats had 4.8 times the risk of cardiac arrest (
look here). A study the following year in The New England Journal of Medicine found the rate of sudden cardiac death doubled for those taking atypical antipsychotics, and there were three such deaths each year for every 1,000 patients taking such a drug (
here is the abstract). The risk of a fatal heart event also increased with dosage, the Military Times notes.
Moreover, mixing antipsychotics with others that cause irregular heartbeat, known medically as QT prolongation, could cause more harm and, possibly, death.
**read full article at the link provided above**
Stirling said the Attorney General's Office sued on behalf of the state and the state agencies that paid additional funds because of the medication side effects.
