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At least one in six service members is on some form of psychiatric drug.

And many troops are taking more than one kind, mixing several pills in daily "cocktails" — for example, an antidepressant with an antipsychotic to prevent nightmares, plus an anti-epileptic to reduce headaches — despite minimal clinical research testing such combinations.

The drugs come with serious side effects: They can impair motor skills, reduce reaction times and generally make a war fighter less effective. Some double the risk for suicide, prompting doctors — and Congress — to question whether these drugs are connected to the rising rate of military suicides.

"It's really a large-scale experiment. We are experimenting with changing people's cognition and behavior," said Dr. Grace Jackson, a former Navy psychiatrist.

A Military Times investigation of electronic records obtained from the Defense Logistics Agency shows DLA spent $1.1 billion on common psychiatric and pain medications from 2001 to 2009. It also shows that use of psychiatric medications has increased dramatically — about 76 percent overall, with some drug types more than doubling — since the start of the current wars.

THE FULL INVESTIGATION:

* Could meds be responsible for suicides?

* Downrange: 'Any soldier can deploy on anything'

* How drugs enter the war zone

Troops and military health care providers also told Military Times that these medications are being prescribed, consumed, shared and traded in combat zones — despite some restrictions on the deployment of troops using those drugs.

The investigation also shows that drugs originally developed to treat bipolar disorder and schizophrenia are now commonly used to treat symptoms of post-traumatic stress disorder, such as headaches, nightmares, nervousness and fits of anger.

Such "off-label" use — prescribing medications to treat conditions for which the drugs were not formally approved by the FDA — is legal and even common. But experts say the lack of proof that these treatments work for other purposes, without fully understanding side effects, raises serious concerns about whether the treatments are safe and effective.

The DLA records detail the range of drugs being prescribed to the military community and the spending on them:

* Antipsychotic medications, including Seroquel and Risperdal, spiked most dramatically — orders jumped by more than 200 percent, and annual spending more than quadrupled, from $4 million to $16 million.

* Use of anti-anxiety drugs and sedatives such as Valium and Ambien also rose substantially; orders increased 170 percent, while spending nearly tripled, from $6 million to about $17 million.

* Antiepileptic drugs, also known as anticonvulsants, were among the most commonly used psychiatric medications. Annual orders for these drugs increased about 70 percent, while spending more than doubled, from $16 million to $35 million.

* Antidepressants had a comparatively modest 40 percent gain in orders, but it was the only drug group to show an overall decrease in spending, from $49 million in 2001 to $41 million in 2009, a drop of 16 percent. The debut in recent years of cheaper generic versions of these drugs is likely responsible for driving down costs.

Antidepressants and anticonvulsants are the most common mental health medications prescribed to service members. Seventeen percent of the active-duty force, and as much as 6 percent of deployed troops, are on antidepressants, Brig. Gen. Loree Sutton, the Army's highest-ranking psychiatrist, told Congress on Feb. 24.

In contrast, about 10 percent of all Americans take antidepressants, according to a 2009 Columbia University study.

Suicide risks

Many of the newest psychiatric drugs come with strong warnings about an increased risk for suicide, suicidal behavior and suicidal thoughts.

Doctors — and, more recently, lawmakers — are questioning whether the drugs could be responsible for the spike in military suicides during the past several years, an upward trend that roughly parallels the rise in psychiatric drug use.

From 2001 to 2009, the Army's suicide rate increased more than 150 percent, from 9 per 100,000 soldiers to 23 per 100,000. The Marine Corps suicide rate is up about 50 percent, from 16.7 per 100,000 Marines in 2001 to 24 per 100,000 last year. Orders for psychiatric drugs in the analysis rose 76 percent over the same period.

"There is overwhelming evidence that the newer antidepressants commonly prescribed by the military can cause or worsen suicidality, aggression and other dangerous mental states," said Dr. Peter Breggin, a psychiatrist who testified at the same Feb. 24 congressional hearing at which Sutton appeared.

Other side effects — increased irritability, aggressiveness and hostility — also could pose a risk.

"Imagine causing that in men and women who are heavily armed and under a great deal of stress," Breggin said.

He cited dozens of clinical studies conducted by drug companies and submitted to federal regulators, including one among veterans that showed "completed suicide rates were approximately twice the base rate following antidepressant starts in VA clinical settings."

But many military doctors say the risks are overstated and argue that the greater risk would be to fail to fully treat depressed troops.

For suicide, "depression is a big risk factor," too, said Army Reserve Col. (Dr.) Thomas Hicklin, who teaches clinical psychiatry at the University of Southern California. "To withhold the medications can be a huge problem."

Nevertheless, Hicklin said the risks demand strict oversight. "The access to weapons is a very big concern with someone who is feeling suicidal," he said. "It has to be monitored very carefully because side effects can occur."

Defense officials repeatedly have denied requests by Military Times for copies of autopsy reports that would show the prevalence of such drugs in suicide toxicology reports.

'Then it's over'

Spc. Mike Kern enlisted in 2006 and spent a year deployed in 2008 with the 4th Infantry Division as an armor crewman, running patrols out of southwest Baghdad.

Kern went to the mental health clinic suffering from nervousness, sleep problems and depression. He was given Paxil, an antidepressant that carries a warning label about increased risk for suicide.

A few days later, while patrolling the streets in the gunner's turret of a Humvee, he said he began having serious thoughts of suicide for the first time in his life.

"I had three weapons: a pistol, my rifle and a machine gun," Kern said. "I started to think, 'I could just do this and then it's over.' That's where my brain was: 'I can just put this gun right here and pull the trigger and I'm done. All my problems will be gone.'"

Kern said the incident scared him, and he did not take any more drugs during that deployment. But since his return, he has been diagnosed with PTSD and currently takes a variety of psychotropic medications.

Other side effects cited by troops who used such drugs in the war zones include slowed reaction times, impaired motor skills, and attention and memory problems.

One 35-year-old Army sergeant first class said he was prescribed the anticonvulsant Topamax to prevent the onset of debilitating migraines. But the drug left him feeling mentally sluggish, and he stopped taking it.

"Some people call it 'Stupamax' because it makes you stupid," said the sergeant, who asked not to be identified because he said using such medication carries a social stigma in the military.

Being slow — or even "stupid" — might not be a critical problem for some civilians. But it can be deadly for troops working with weapons or patrolling dangerous areas in a war zone, said Dr. John Newcomer, a psychiatry professor at Washington University in St. Louis and a former fellow at the American Psychiatric Association.

"A drug that is really effective and it makes you feel happy and calm and sleepy … might be a great medication for the general population," Newcomer said, "but that might not make sense for an infantryman in a combat arena.

"If it turns out that people on a certain combo are getting shot twice as often, you would start to worry if they were as 'heads up' as they should have been," Newcomer said. "There is so much on the line, you'd really like to have more specific military data to inform the prescribing."

Military doctors say they take a service member's mission into consideration before prescribing.

"Obviously, one would be concerned about what the person does," said Col. C.J. Diebold, chief of the Department of Psychiatry at Tripler Army Medical Center in Hawaii. "If they have a desk job, that may factor in what medication you may be recommending for the patient [compared with] if they are out there and they have to be moving around and reacting fairly quickly."

Off-label use

Little hard research has been done on such unique aspects of psychiatric drug usage in the military, particularly off-label usage.

A 2009 VA study found that 60 percent of veterans receiving antipsychotics were taking them for problems for which the drugs are not officially approved. For example, only two are approved for treating PTSD — Paxil and Zoloft, according to the Food and Drug Administration. But in actuality, doctors prescribe a range of drugs to treat PTSD symptoms.

To win FDA approval, drug makers must prove efficacy through rigorous and costly clinical trials. But approval determines only how a drug can be marketed; once a drug is approved for sale, doctors legally can prescribe it for any reason they feel appropriate.

Such off-label use comes with some risk, experts say.

"Patients may be exposed to drugs that have problematic side effects without deriving any benefit," said Dr. Robert Rosenheck, a professor of psychiatry at Yale University who studied off-label drug use among veterans. "We just don't know. There haven't been very many studies."

Some military psychiatrists are reluctant to prescribe off-label.

"It's a slippery slope," said Hicklin, the Army psychiatrist. "Medication can be overused. We need to use medication when indicated and we hope that we are all on the same page … with that."

Combinations of drugs pose another risk. Doctors note that most drugs are tested as a single treatment, not as one ingredient in a mixture of medications.

"In the case of poly-drug use - the 'cocktail' — where you are combining an antidepressant, an anticonvulsant, an antipsychotic, and maybe a stimulant to keep this guy awake — that has never been tested," Breggin said.

Newcomer agreed. "When we go to the literature and try to find support for these complex cocktails, we're not going to find it," he said. "As the number of medications goes up, the probability of adverse events like hospitalization or death goes up exponentially."

Looking for answers

Pinpointing the reasons for broad shifts in the military's drug use today is difficult. Each doctor prescribes medications for the patient'sindividual needs.

Nevertheless, many doctors in and outside the military point to several variables — some unique to the military, some not.

A close look at the data shows that use of the antipsychotic and anticonvulsant drugs, also known as "mood stabilizers," are growing much faster than antidepressants. That may correlate to the challenges that deployed troops face when they arrive back home and begin to readjust to civilian social norms and family life.

"The ultimate effect of both of these drugs is to take the heightened arousal — the hypervigilance and all the emotions that served you once you were deployed — and help to turn that back down," said Dr. Frank Ochberg, former associate director for the National Institute of Mental Health and a psychiatry professor at Michigan State University who reviewed the Military Times analysis.

Dr. Harry Holloway, a retired Army colonel and a psychiatry professor at the Uniformed Services University of the Health Sciences in Bethesda, Md., said the increased use of these medications is simply another sign of deployment stress on the force.

"For a long time, the ops tempo has been completely unrelieved and unrestrained," Holloway said. "When you have an increased ops tempo, and you have certain scheduling that will make it hard for everyone, you will produce a more symptomatic force. Most commanders understand that and they understand the tradeoffs."

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