A powerful antipsychotic drug given to tens of thousands of veterans suffering from post-traumatic stress disorder is no more effective than a placebo against PTSD, according to a study released Wednesday.
The study, published in the Journal of the American Medical Association, could diminish the widespread use of second-generation antipsychotics to treat PTSD, said Dr. John H. Krystal, who led the study as director of the clinical neuroscience division of the Veterans Affairs’ National Center for PTSD.
When antidepressants fail to help servicemembers with PTSD, the drugs are often supplemented with second-generation antipsychotics prescribed “off label” — meaning their use in treating PTSD patients has not been approved by the U.S. Food and Drug Administration.
“I do think doctors and patients and family members are going to see the study, and all are going to have some questions about the use of these second-generation antipsychotics,” Krystal said.
In 2009, more than 80,000 veterans with PTSD were prescribed second-generation antipsychotics, Krystal and his colleagues said in the journal. Risperidone, which the FDA approves only for schizophrenic and bipolar patients, was thought to be the most effective drug in this class.
But the new study — the largest of its kind — found that veterans with PTSD who were given risperidone fared no better than those who received a placebo.
Krystal’s team looked at 267 patients at 23 VA outpatient medical centers from 2007 to 2010. Placebos were given to 134 patients, and 133 were given up to 4 milligrams of risperidone daily.
Patients’ PTSD symptoms were gauged using various scales and surveys, including a clinically administered measurement called CAPS — a 30-item interview that is the gold standard in PTSD assessment, according to the VA.
An analysis of the data showed that there was “no statistically significant difference between risperidone and placebo in reducing CAPS total scores,” the researchers wrote.
“I think this has implications for a large number of veterans who have been on risperidone for a long time where the benefit might not be so clear,” Krystal said.
What’s more, the drug did not reduce PTSD symptoms in terms of quality of life, depression, anxiety or paranoia.
Risperidone-treated patients also complained of several of the drug’s common side effects, including fatigue, sleepiness, increased saliva and weight gain. The findings do not leave doctors entirely without drug options for PTSD.
Selective serotonin reuptake inhibitors — a widely used class of antidepressants — are approved for PTSD. Also, risperidone showed a small ability to help calm nerves and aid sleep. Other drugs that target those symptoms, such as prazosin, may prove to be more beneficial, he said.
Krystal said more research is needed to examine the underlying brain chemistry of PTSD.
“All these medications were developed for other mental disorders,” he said.
In an article accompanying Krystal’s study, Dr. Charles Hoge, a senior scientist and adviser at the Walter Reed Army Institute of Research, warned that there are many long-term adverse health effects associated with second-generation antipsychotics, including heart issues and glucose regulation.
The study “has the potential to change clinical practice,” he said in a phone interview.
In addition to prescribing medications, Hoge said, mental health professionals must tailor treatments to servicemembers’ needs, keeping in mind that many of the symptoms of PTSD, such as hypervigilance, are normal responses to being in combat.
Hoge emphasized that clinicians need to find new ways to reach servicemembers with PTSD, to ensure that they get and continue therapy and other treatments. Currently, only one-half of veterans who need mental health services are getting them, he said.