N-acetylcysteine (NAC) is a powerful antioxidant used in both conventional and alternative medicine and is particularly known for its role in treating patients with acetaminophen overdose.
Now a new study shows that when combined with group cognitive-behavioral therapy (CBT), NAC is able to reduce symptoms of post-traumatic stress disorder (PTSD), cravings, and depression significantly more than CBT alone in veterans with co-occurring PTSD and substance use disorder (SUD).
The study, conducted by researchers at the Medical University of South Carolina (MUSC) and the Ralph H. Johnson VA Medical Center, is the first to use NAC as a pharmacotherapy for PTSD and a broad range of SUDs.
The results are published in the Journal of Clinical Psychiatry.
It is estimated that 30 percent of Vietnam veterans will have experienced PTSD at some point in their life, and about 40 to 50 percent of veterans with PTSD also have a substance use disorder (SUD).
“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 chair of the Department of Neuroscience at MUSC. “People who are prone to psychiatric disorders are also prone to addiction.”
“This is a tough patient population with SUD to work with. We have Vietnam vets that have had PTSD for 15 to 20 years. This is not an easy-to-turn-around population.”
Currently, there are no well-explored pharmacological treatments for patients with co-occurring PTSD/SUD. Although selective serotonin reuptake inhibitors (SSRIs) have been approved by the FDA for treatment of PTSD, they have demonstrated suboptimal results for patients with a combination of PTSD/SUD.
Previous research by Kalivas has shown that levels of glutamate transporters are decreased in SUDs and that administration of the antioxidant NAC can help restore those levels and guard against relapse in animal models of SUD.
Because evidence suggests that SUDs and PTSD share overlapping neurobiological pathways, that NAC treatment with CBT would be a novel approach to treat co-occurring PTSD and SUD, said Sudie E. Back, Ph.D., lead author on the article. 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.
For the study, 35 veterans with PTSD and SUD, all of whom were receiving CBT for their SUD, were randomized to either 2400 mg/day of NAC or placebo. The average age of the veterans was 49 years. To be included, veterans had to have abstained from substance use for at least seven days. Of the veterans enrolled in the trial, 83 percent completed it, a very high rate for this difficult-to-treat population.
The NAC-treated group showed a 46 percent reduction in PTSD symptoms, compared with a 25 percent reduction in the placebo group.
“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 significantly 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 was also reduced 48 percent in the NAC group vs. 15 percent in the placebo group.
Although these early, promising findings show that NAC reduced PTSD symptoms, craving, and depression, NAC should not be used as a monotherapy or substitute for evidence-based behavioral treatment, but instead be seen as an adjunct 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 contraindicated in patients with asthma, and can cause nausea at higher doses; it should always be obtained and administered under a physician’s supervision.