Drug Effectiveness

The VA/DoD program will conduct clinical studies of a variety of FDA-approved pharmacotherapies to identify alternate indications for their use in PTSD, Wynn said.

“While there is anecdotal evidence [and] small studies that support the use of these drugs, there aren't large, well-controlled studies to show whether they are truly effective,” he said. The program initially will evaluate trazodone, quetiapine and eszopiclone, all drugs frequently used to help PTSD patients with sleep difficulties.

Coley’s memo noted that quetiapine and other atypical antipsychotics have not been subjected to the same level of testing as respiridone but “carry similar clinical concerns.” Consequently, Army healthcare providers, “who use these medications for off-label indications must clearly document their rationale for concluding that the potential benefits outweigh the known risks and that informed consent has been conducted,” the memo said.

“It’s important to understand that these concerns do not mean that benzodiazepines and atypical antipsychotics should never be used,” retired Col. Charles  W. Hoge, MD, U.S. Army Neuropsychiatry Research Consultant, told U.S. Medicine. “Sometimes the physician is between a rock and a hard place; the patient is not getting better, and other options have proved ineffective. The clinical practice guidelines are not prescriptive. They leave a lot up to the clinician because of the difference in patients with PTSD.”

Hoge noted that, while only traditional antidepressants have “A” level recommendations for treatment of PTSD, adjunctive use of other drugs may be quite effective for specific patients.

“One good example is Minipress [prazosin], a blood pressure medication that reduces the physiological hyper-arousal associated with nightmares. By blocking the physiological reaction, it can improve sleep in patients with PTSD,” he said.

While the Army has no plans to restrict prescriptions of antipsychotics to psychiatrists, primary-care providers who prescribe the drugs will be seeing increased levels of monitoring and training, according to Labadie.

“The Army is in the process of developing a policy to help us better monitor these drugs,” she explained. “We’ll be talking with providers about offering the lowest risk medication or non-medication therapy for sleep, anger management and other issues, as well as requiring informed consent for off-label use.”

The Army also will track how often specific medications are prescribed for off-label uses. “If we see a trend for certain providers, there may be additional training or peer review to remind them to do due diligence before prescribing” atypical antipsychotics, Labadie said, adding that, as part of the monitoring plan, “We’re trying to identify some outcome measures and we hope to publish those within about 60 days.”

Labadie noted that some changes in the Army’s polypharmacy policy also are in process.

“Today, we define polypharmacy as a patient on four or more medications, one of which is an antipsychotic or central nervous system depressant narcotic,” she noted.

That description, however, can turn up patients on two cholesterol drugs who are taking Vicodin or Tylenol with codeine for dental work, for example. Consequently, she said, “we’re looking now to change the definition to better identify high-risk patients by adding a diagnosis of traumatic brain injury or PTSD and whether they are on pain medication and an atypical antipsychotic. In a population of 20,000 patients, perhaps 6,000 are on four or more drugs, but just 1,300 would meet the additional criteria.”

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[1] Woodson, Jonathan. Guidance for Providers Prescribing Atypical Antipsychotic Medication. 22 February 2012. http://cdn.govexec.com/media/gbc/docs/pdfs_edit/051712bb1_policy.pdf

[1] Coley, Herbert. Policy Guidance on the Assessment and Treatment of Post-Traumatic Stress Disorder (PTSD). 10 April 2012. http://cdn.govexec.com/media/gbc/docs/pdfs_edit/042312bb1.pdf