Antioxidant may help veterans suffering from PTSD and substance use disorders

A recent study shows the antioxidant N-acetylcysteine, or NAC, reduced post-traumatic stress disorder symptoms by 46 percent, substance use cravings by 81 percent and depression by 48 percent in veterans with PTSD and substance use disorder.

The randomized controlled pilot trial, conducted at the Medical University of South Carolina and the Ralph H. Johnson VA Medical Center, found that NAC, when combined with group cognitive behavioral therapy, reduced symptoms of PTSD, cravings and depression significantly more than therapy alone in veterans with both PTSD and substance use disorder, a particularly difficult to treat population.

This trial is the first to use NAC as a pharmacotherapy for PTSD and a broad range of substance use disorders. The results were published in a November edition of the Journal of Clinical Psychiatry.

The National Center for PTSD estimates that about 8 percent of Americans will have PTSD at some point. The numbers are even worse for veterans. It is estimated that 30 percent of Vietnam veterans will have experienced PTSD.  Between 40 to 50 percent of veterans with PTSD also have a substance use disorder.

“Addiction goes along with virtually every psychiatric disorder at a higher percentage than it does in the general population,” said Peter W. Kalivas, Ph.D., the senior author on the article and chairman of the Department of Neuroscience at MUSC. “People who are prone to psychiatric disorders are also prone to addiction.”

Currently, there are no well-explored pharmacological treatments for patients with co-occurring PTSD and substance use disorder. Although selective serotonin reuptake inhibitors, a class of drugs used as antidepressants, have been approved by the FDA for treatment of PTSD, pharmacological treatments for co-occurring conditions haven’t been as effective as some hoped for.

Groundbreaking basic science research by Kalivas has shown that levels of glutamate transporters in the brain are decreased in substance use disorders, and NAC can help restore those levels and guard against relapse in animal models of substance use disorder. Because evidence suggests that substance use disorder and PTSD share overlapping neurobiological pathways, Sudie Back, Ph.D., lead author on the article, hypothesized that NAC treatment with therapy would be a novel approach to treating the co-occurring conditions. Back is a professor in the Department of Psychiatry and Behavioral Sciences at MUSC and a staff psychologist at the Ralph H. Johnson VA Medical Center.

In the eight-week randomized controlled trial led by Back and Kalivas, 35 veterans with PTSD and substance use disorder, all of whom were receiving cognitive behavioral therapy, were randomized to either 2400 milligrams a day of NAC or a placebo. The average age of the veterans was 49 years, and many were veterans of the Vietnam War. To be included, veterans had to have abstained from substance use for at least seven days.

Back said of the veterans enrolled in the trial, 83 percent completed it, a very high rate for this difficult to treat population.

Veterans in the NAC-treated group showed a 46 percent reduction in PTSD symptoms, compared with a 25 percent reduction in the placebo group on the Clinical-Administered PTSD Scale (CAPS), which assesses trauma history and symptom severity. The threshold CAPS score for diagnosis of PTSD is 50.

“As a group, the NAC-treated veterans were below diagnostic level for PTSD at the end of treatment,” said Back. “For PTSD, these are some of the best outcomes we have seen in the literature for a medication.”

Craving and depression were also reduced in the NAC-treated group. The amount of craving was reduced by 81 percent and the frequency of craving by 71 percent in the NAC group, compared with 32 percent and 29 percent in the placebo group.

“Craving is a key component of substance use in relapse,” said Back. “If you have a medication that can really reduce craving, that will go a long way to helping people stay clean and sober.”

Depression, gauged using the Beck Depression Inventory, was reduced 48 percent in the NAC group versus 15 percent in the placebo group.

Veterans in the study had low rates of substance use during the trial, and the study found little effect of medication on use, perhaps due to the fact that all participants were receiving substance use disorder treatment and exhibiting low levels of use. Kalivas said this finding could also be due to the relatively limited number of participants or the chronic nature of the participants’ PTSD.

“This is a tough patient population with substance use disorder to work with,” said Kalivas. “We have Vietnam vets that have had PTSD for 15 to 20 years. This is not an easy to turn around population.”

Although these early, promising findings show that NAC reduced PTSD symptoms, craving, and depression, Back recommends that NAC not be used as a substitute for evidence-based behavioral treatment, but rather a therapy that enhances it. “We would not advocate using it instead of therapy,” said Back. “But this could be something to help prevent relapse when used alongside a behavioral treatment.”

NAC is available over the counter and does not cause side effects at the doses used in the study, but it degrades quickly when stored, is not considered safe for people with asthma and can cause nausea at higher doses. Back said it should always be taken with a doctor’s supervision.

The next steps in Back’s research are to run a longer-term trial of NAC in veterans with PTSD and substance use disorder and use magnetic resonance spectroscopy to better explore the effect of NAC on glutamate levels in patients with PTSD and substance use disorder.

Kalivas and Back both said the results are encouraging, especially given the link between PTSD and addiction and the difficulties of being able to treat PTSD in veterans once they already have become addicted to substances.

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