SNRI 'Shows Promise' for Comorbid ADHD, PTSD

Fran Lowry

March 22, 2021

Atomoxetine, a selective norepinephrine reuptake inhibitor (SNRI), may improve outcomes for patients with both attention-deficit/hyperactivity disorder (ADHD) and posttraumatic stress disorder (PTSD), new research suggests.

A pilot trial of veterans with comorbid ADHD/PTSD showed that atomoxetine significantly reduced ADHD symptoms and moderately improved PTSD treatment outcomes and quality of life in comparison with placebo.

Dr Zhewu Wang

The two disorders often occur together, study investigator Zhewu Wang, MD, Charleston VA Medical Center, and professor, Medical University of South Carolina, Charleston, South Carolina, told Medscape Medical News. He noted that in the study, more than 30% of the participants with PTSD symptoms met diagnostic criteria for ADHD.

"Physicians treating PTSD should be aware that ADHD is a common comorbidity and that it may have a significant impact on PTSD treatment outcomes if it is not treated simultaneously," Wang said.

The research was presented in a poster session at the Anxiety and Depression Association of America (ADAA) 2021.

Significant Symptom Reduction

Combat veterans with PTSD often have impaired attention, working memory, executive function, and inhibitory control, Wang noted. In addition, these cognitive symptoms of ADHD are often associated with PTSD psychopathology and poorer treatment outcomes.

Atomoxetine is not classified as a stimulant and is particularly useful for patients at risk for substance abuse, including adolescents and young adults and those with PTSD. It is currently the only nonstimulant medication indicated for the treatment of both children and adults with ADHD.

The randomized, placebo-controlled, double-blind, crossover trial included 36 veterans with comorbid ADHD/PTSD. Patients received atomoxetine 80 mg or placebo daily for 4 weeks. All participants also received treatment as usual for PTSD, including prolonged exposure therapy.

Patients were assessed at weeks 1, 2, and 4. They then entered the crossover phase of the study for an additional 4 weeks.

At each visit, researchers administered the Conners' Adult ADHD Resting Scales–Self-Report: Short Version (CAARS-S:S), the Adult ADHD Quality of Life–29, and the Clinician Administered PTSD Scale.

Results showed that atomoxetine produced a statistically significant reduction of symptoms compared with placebo, as measured by CAARS-S:S (P = .017).

A larger clinical trial is planned to further investigate the efficacy of amoxetine for patients with comorbid ADHD/PTSD, Wang said. That trial will focus on improvement of cognitive function,

Promising Findings

Commenting on the findings for Medscape Medical News, Charles B. Nemeroff, MD, PhD, Matthew P. Nemeroff Professor and chair, Dell Medical School, the University of Texas at Austin, noted that because atomoxetine is approved by the US Food and Drug Administration for treating ADHD, there was "an interesting question as to whether it would improve ADHD symptoms in PTSD."

Dr Charles Nemeroff

Nemeroff, who is also president-elect of the ADAA, was not involved with the research.

He noted that having an effective nonstimulant medication to treat ADHD in the presence of PTSD is particularly important because of the high rate of comorbid substance abuse with PTSD.

"The researchers note that atomoxetine numerically improved PTSD symptoms and quality of life, but we can't make much of that because it's not statistically significant," Nemeroff said.

"So I wouldn't be wildly enthusiastic about atomoxetine as a treatment for PTSD; but in terms of this comorbid ADHD/PTSD population, it certainly is promising," he added.

He noted that it would be interesting to evaluate whether atomoxetine, as an SNRI, is also effective for treating the depression that often occurs with PTSD.

"There is a very high comorbidity rate between PTSD and major depression, and [the investigators] didn't speak to how many of these patients had major depression. Norepinephrine reuptake inhibitors can exert antidepressant effects. Although atomoxetine is not approved for depression, that would have been of interest," Nemeroff said.

The study was funded by a VA merit review award. Wang and Nemeroff have reported no relevant financial relationships.

Anxiety and Depression Association of America (ADAA) 2021: Abstract S1-054. Presented March 18, 2021.

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