By Candice Leigh Helfand

ST. LOUIS, Mo. (CBS St. Louis/AP) – In 2010, a team of researchers investigated the possibility that some medications, due to the nature of their interactions with the human brain and body, could result in increased potential of violent or aggressive behavior.

Thomas J. Moore of the Institute for Safe Medication Practices in Virginia, Joseph Glenmullen of Cambridge Hospital at the Harvard Medical School in Massachusetts and Curt D. Furberg of the Wake Forest University School of Medicine in North Carolina collaborated on a study that specifically examined violence toward others as a result of taking certain medications, which they described in an abstract summary of their work as “a seldom-studied adverse drug event.”

“Acts of violence towards others are a genuine and serious adverse drug event associated with a relatively small group of drugs,” the group ultimately concluded. “Prospective studies to evaluate systematically this side effect are needed to establish the incidence, confirm differences among drugs and identify additional common features.”

Fast forward to earlier this month when Aaron Alexis, an information technology contractor who was said to have struggled with mental illness, perpetrated a mass shooting at the Washington Navy Yard on Sept. 16 that took the lives of 12 people and injured three more before he himself was killed by police fire.

Alexis had reportedly complained of insomnia during an Aug. 23 emergency room visit to the VA Medical Center in Providence, R.I. He was given sleep medication and advised to follow up with a doctor. He made a similar visit five days later to the VA hospital in Washington, when he again complained of not being able to sleep because of his work schedule. His medication was refilled.

Alexis appeared “alert and oriented” during the visits and denied feeling depressed or anxious or wanting to do harm, the VA said.

That statement, presented to lawmakers Wednesday, comes as investigators continue focusing on the erratic behavior of a 34-year-old man who law enforcement officials say was also grappling with paranoia and reported hearing voices and being followed.

Several mental health experts spoke with CBSDC recently regarding the increasingly pervasive stigma against people with mental illness that leads some to define them as inherently dangerous or violent – a school of thought that is said to be reinforced by the nature of news coverage and national debate following mass shootings such as the one committed by Alexis.

But what about the medications prescribed to treat those with mental health issues, or even medications that are intended for treatment of physical ailments but all the same affect a patient’s cognitive function? Could some drugs be, in part, responsible for violent behavior and, if so, could some tragedies be prevented through changes in the medications available or adjustments in dosages?

Some experts feel there might be a connection.

“Most psychiatric medications that we use do one of two things: alter levels of certain brain chemicals. The ones … that most drugs work on are serotonin, norepinephrine and dopamine – [or] … activate or block receptors on brain cells where brain chemicals work,” Dr. Brian Brennan, the associate director of the Translational Neuroscience research program at McLean Hospital in Belmont, Ma., explained to CBS St. Louis. “Those brain chemicals do have an impact on how people behave. That’s why they’re used.”

“One example [of a medication with such an effect] is … testosterone analogs, or anabolic steroids,” added Stephen R. Saklad, who is both a clinical pharmacologist at San Antonio State Hospital in Texas and the director of the psychiatric pharmacy program at the UT Health Science Center in San Antonio. “They increase relative aggression and, when provoked, anabolic steroid users retaliate much more than expected.”

He added, “The old medications like reserpine that are used to lower blood pressure deplete neurotransmitters … could make you very depressed and increase a chance of suicide … in someone who wasn’t depressed to begin with.”

The collaborative work done by Moore, Glenmullen and Furberg also cited the smoking cessation drug Varenicline  – more commonly known as Chantix – and “antidepressants with serotonergic effects” as medications that “were the most strongly and consistently implicated drugs” in their study’s findings.

In regards to Alexis specifically, Saklad told CBS St. Louis, “If there were some way of having him get the treatment he needed, that would probably have prevented [the shooting].”

He added, “In the United States, most people that are hospitalized for mental illness, usually a serious persistent mental illness (SPMI) … are usually involuntarily committed by a court for being a danger to themselves or to others.”

Others, however, felt different issues may come into play in regards to adverse reactions during treatment courses, including noncompliance by a given patient to take their medication properly.

Barbara Young, who serves as editor of AHFS Consumer Medication Information for the American Society of Health-System Pharmacists, told CBS St. Louis that more issues may result from patients who fail to follow prescription directions than from the act of taking the medication itself.

“If patients suddenly stop taking doses, [it can be problematic]. It needs to be communicated that they shouldn’t be doing that – it needs to be decreased slowly or tapered,” she said. “Often times in media coverage of recent events, reports may say a patient was prescribed ‘x’ drug. But compliance is a huge issue, particularly in anti-psychotic medications. They may be prescribed, but there may be uncertainty that [a patient is] taking it.”

Other issues may also arise in the process of diagnosing a patient with mental health issues.

Brennan noted, “Whereas you could easily do a blood test or … x-ray to accurately diagnose a disorder, our diagnoses are based solely on presenting symptoms, how people describe how they’re feeling, and often times, retrospective assessments. We don’t have objective tests, which makes the process … very difficult.”

In an effort to lower the likelihood of patients experiencing adverse effects to medications, the U.S. Food and Drug Administration explained that, at present, it has in place an ongoing system of checks and balances beginning with small-scale clinical trials and continuing with post-market research.

The FDA also allows for patients and clinicians alike to report adverse effects to medication.

“Ultimately, FDA faces a balancing act in evaluating a new drug. If it’s good for one person or a small group, will it be good for the whole population? Which safety risks are likely to be acceptable to patients who might take a drug and physicians who might prescribe it?” officials note on the official FDA website. “Once a drug is marketed and new information about its safety becomes available, FDA must revisit these questions continually over the drug’s life cycle.”

The site also states, “In the end, no matter how much data are available, we often have to make a judgment call, weighing the known benefits against known risks and the potential—and possibly unknown—risks.”

The FDA noted that there are several medications presently in circulation that carry government-issued warnings about increased risk of suicidality, including Chantix, as well as antidepressant medications and antipsychotic drugs.

Scott Vouri, Pharm.D., an assistant professor of pharmacy practice at the St. Louis College of Pharmacy, noted that there is “risk versus benefit with all medications.”

“If all medications that posed any risk to humans were removed, patients may have a limited supply of available medications to utilize for their conditions,” he told CBS St. Louis. “Physicians are trained on the efficacy – the positives – and the side effects – the negatives – and can work closely with their patient to determine if they should go forward with the prescribing plan.”

Other experts told CBS St. Louis that, while the one in place is not a perfect system, its allowance for updated warning labels and the ever-evaluative nature of it does have its merits.

“These drugs are … usually studied during … small- to medium-sized clinical trials where patients are carefully selected, usually omitting women, young people or the elderly,” Young observed. “So when [a drug] is approved and used in wider populations, and by people with other conditions who are taking other medications, it paints a different picture than what was initially reported.”

She added, “In regards to prescription drugs associated with violence, the FDA has coordinated a reporting program … to chronicle adverse effects [of drugs]. This has been one of the most commonly used voluntary systems for physicians or patients to report side effects. [However, i]t may take a while for reporting to catch up with what’s happening.”

Brennan said that the FDA’s process “does make sense.”

“[There has been] increasing concern about whether or not violent, more aggressive behavior associate with that family of medications as well. It’s hard to establish cause and effect,” he said. “There has been more scrutiny, especially with suicidal ideation, by the FDA these days. Each drug in development … is really highly scrutinized.”

Researchers posed several possible solutions to the issue of negative, even volatile effects stemming from taking certain drugs.

“If the Affordable Care Act can make good on its requirement for electronic health records that capture everyone’s data, then you could find many more adverse events because you know everything about everybody,” Saklad noted. “This could be done without violating anyone’s privacy as the information would be stripped of all personal identifiers. Other countries have some of this capability because they have a more advanced implementation of their electronic health records system.”

Vouri agreed, noting that “acquiring a medication history can determine which medication have and have not worked in the past and can be valuable in making a recommendation.”

Others felt that being mindful of the demographics into which a given patient falls, and where they are in the treatment process, may help avoid future complications.

“During critical times in starting therapy or increasing doses, there are periods where patients need to be more closely monitored, [especially] when medications are prescribed to be used by people who are not practicing psychiatrists,” Young noted. “Many experts are concerned about antidepressants prescribed by a family practitioner. They may be excellent clinicians, but it is not their area of expertise.”

“[T]here are certain medications which are not suggested in certain populations like Benadryl in the elderly … which need to be considered based on the individual patient before recommending in the case of pharmacists with over-the-counter products, or prescribing in the case of a physician,” Vouri additionally noted.

Saklad is also participating in research that may combat the issue of noncompliance in the form of long-lasting antipsychotic injectable medications, or LAI, which could stay in a patient’s system for up to one month.

Still, some said that beyond the medications themselves lie other complications that also need to be properly addressed.

Noted Brennan, “Patients have come to psychiatrists or therapists either because they or their families have concerns about what they are experiencing … the likelihood of aggression or violent behaviors is much, much, much higher in those populations than in the general public. It is much more likely that it’s the result of the illnesses themselves, rather than the medications they are taking.”

(TM and © Copyright 2013 CBS Radio Inc. and its relevant subsidiaries. CBS RADIO and EYE Logo TM and Copyright 2013 CBS Broadcasting Inc. Used under license. All Rights Reserved. This material may not be published, broadcast, rewritten, or redistributed. The Associated Press contributed to this report.)

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