TUESDAY, Aug. 2, 2011 (HealthDay News) -- An antipsychotic drug widely used to treat soldiers with post-traumatic stress disorder (PTSD) may not be as effective as once thought.
A new study in the Aug. 3 issue of the Journal of the American Medical Association found that six months' treatment with risperidone did not reduce veterans' PTSD symptoms, including anxiety, paranoia and depression, or improve their quality of life.
"Obviously, this gives us pause" about using risperidone to treat patients who aren't responding to antidepressants, said study author Dr. John H. Krystal, director of the clinical neuroscience division at the Veterans Administration's National Center for PTSD.
Some 10 percent to 20 percent of soldiers returning from war zones such as Iraq and Afghanistan develop PTSD -- a condition marked by emotional numbing, nightmares, flashbacks of terrifying events and severe anxiety -- with very few of them receiving effective treatment, according to an accompanying editorial.
Only two drugs are approved for the condition -- Zoloft (sertraline) and Paxil (paroxetine) -- and both belong to the class of antidepressants known as selective serotonin reuptake inhibitors (SSRIs). The SSRIs appear to be less effective in men than in women, however, and less effective in chronic PTSD than in acute PTSD, the study authors wrote.
"Here you have a common disorder that has only one validated medication treatment," said Krystal, who is also chair and professor of psychiatry at Yale University. "There is a significant treatment effectiveness gap between what the SSRIs is can provide and what the real need is among patients."
In the absence of other approved alternatives, physicians have turned to other possibilities, notably risperidone, a second-generation antipsychotic which is used to treat schizophrenia, bipolar disorder and the irritability associated with autism in children and teens.
Risperidone is prescribed off-label for PTSD, since the U.S. Food and Drug Administration has not approved its use for the treatment of PTSD.
"Since we still don't understand the biological basis for [PTSD], we are still in in the 'use it if it works'" era," said Keith A. Young, director of the Neuropsychiatry Research Program at Texas A&M Health Science Center College of Medicine.
This is the first large-scale trial of adding risperidone to other treatment for chronic military-related PTSD symptoms that have not responded to SSRIs, Krystal said.
The study assigned 250 mostly male veterans with SSRI-resistant PTSD to randomly receive either risperidone (up to 4 milligrams once daily) or a placebo for six months. Some were also taking other medications.
There were virtually no differences in depression, anxiety, paranoia/psychosis or quality of life between the two groups.
The small differences that were noted "would probably have been invisible to the average clinician," Krystal said.
Risperidone has been associated with several serious side effects, including diabetes, involuntary and repetitive movements and a rare but life-threatening nervous system disorder. The study authors reported that the side effects in the study, although low and not in the serious category, were more common with risperidone than with the placebo.
The side effects included weight gain (15.3 percent in the risperidone group vs. 2 percent in the placebo group), fatigue (13.7 percent vs. 0 percent), extreme drowsiness (9.9 vs. 1.5) and hypersalivation (9.9 vs. 0.8).
"Overall, the data do not provide strong support for the current widespread prescription of risperidone" to vets suffering from PTSD who doesn't respond to SSRI treatment, the study authors wrote.
One positive note is that there was a hint that risperidone might have improved nightmares, flashbacks, intrusive thoughts and arousal symptoms like jumpiness or startling, they added.
Again, it's not clear if clinicians could see that improvement, they noted, but it raises the possibility that some patients may actually benefit from the drug.
"Our data would suggest that in some cases it might make sense to very cautiously and carefully see whether people still need risperidone on a case-by-case basis," said Krystal. "We wouldn't want [current patients] to stop taking the medication willy nilly, nor would we want to not prescribe it to people who had these symptoms quite prominently."
"There may still be a place for atypical antipsychotics, but more work will be needed," added Young, who is also core leader for neuroimaging and genetics at the Center of Excellence for Research on Returning War Veterans in Temple.
The findings also can't be generalized to non-veterans with PTSD or to women.
An editorial accompanying the article called for more innovative approaches to treating military PTSD, including combining psychotherapy with acupuncture, mindfulness meditation, yoga and other innovative approaches.
More information
The U.S. National Center for PTSD has more on this condition.
