In the Journals

Different combinations of PTSD medications may be equally effective

Shelia Rauch, PhD
Sheila Rauch

Although treatment with sertraline plus enhanced medication management, prolonged exposure plus placebo, and prolonged exposure plus sertraline resulted in significant reductions in PTSD symptoms and symptom severity, there were no differences in change in these measures across the groups at 24 weeks, according to study findings.

“Clinical practice guidelines for posttraumatic stress disorder have presented both trauma-focused psychotherapies and selective serotonin reuptake inhibitors as effective, strongly recommended treatments,” Sheila A.M. Rauch, PhD, department of psychiatry and behavioral sciences, Emory University School of Medicine, and colleagues wrote. “The American Psychological Association, Veterans Affairs and Department of Defense recommended trauma-focused psychotherapy vs. medication for the treatment of PTSD based on meta-analyses comparing effect sizes across studies that rarely involved direct head-to-head comparisons of psychotherapy vs. medication. Without direct comparisons, effect sizes across studies may not accurately reflect efficacy, owing to differences in study designs and comparators.”

In this randomized, double-blind 24-week clinical trial, researchers compared the efficacy of prolonged exposure therapy plus placebo, prolonged exposure therapy plus sertraline hydrochloride, and sertraline plus enhanced medication management for the treatment of PTSD. They measured change in symptom severity of PTSD in the past month using the Clinician-Administered PTSD Scale score at week 24.

Service members or veterans of the Iraq and/or Afghanistan wars with combat-related PTSD who had at least 3 months of significant impairment completed up to thirteen 90-minute sessions of prolonged exposure therapy from week 0 (intake) through week 24. The investigators titrated sertraline therapy during a 10-week period and treatment continued until week 24. Researchers also manualized medication management. Participants were assessed at weeks 0, 6, 12, 24 and 52 (follow-up).

At 24 weeks, 149 participants completed the study and 207 were included in the intent-to-treat analysis. Results revealed a significant reduction in PTSD symptoms during the 24 weeks across all treatment groups (beta = –9.39; 95% CI, –11.62 to –7.16):

  • 33.8 points for sertraline plus enhanced medication management;
  • 32.7 points for prolonged exposure therapy plus sertraline; and
  • 29.4 points for prolonged exposure therapy plus placebo.

However, there was no difference in slopes by treatment group at 24 weeks:

  • –9.39 for prolonged exposure therapy plus placebo;
  • –10.37 for sertraline plus enhanced medication management; and
  • –9.99 for prolonged exposure therapy plus sertraline.

“The high rates of clinically meaningful change observed among veterans in this trial (eg, ranging from 52% to 62%) are noteworthy, given the proportion of participants with chronic treatment-resistant PTSD,” the researchers wrote.

Furthermore, the results showed no significant differences in response rates or remission rates across treatment groups.

“Contrary to our hypotheses, while sertraline plus enhanced medication management performed better than expected, in the purist effectiveness comparison of prolonged exposure therapy plus sertraline vs. prolonged exposure therapy plus placebo, there was no evidence for added benefit for active medication,” Rauch and colleagues wrote. “These results require additional replication and may suggest changes to future clinical guidelines, particularly when [selective serotonin reuptake inhibitors] are administered under similar conditions to this study.”

According to Debra L. Kaysen, PhD, department of psychiatry and behavioral sciences, University of Washington, and colleagues, this study showed that prolonged exposure, sertraline and enhanced medication management likely have efficacy in treating combat-associated PTSD.

“It provides crucial information that combining these therapies while adding burden does not increase efficacy in this population,” they wrote in a related comment. “Further research is needed on mixed-trauma samples in both veterans and community members. Most importantly, we need further research about ways to retain patients and make these effective treatments more broadly accessible.” – by Savannah Demko

Disclosures: Rauch reports receiving support from the DoD, NIH, the VA, Woodruff Foundation and the Wounded Warrior Project, as well as royalties from Oxford University Press. Please see the study for all other authors’ relevant financial disclosures. Kaysen reports support from the DoD, NIH, and the U.S. Agency for International Development. Please see the editorial for all other authors’ relevant financial disclosures.

Shelia Rauch, PhD
Sheila Rauch

Although treatment with sertraline plus enhanced medication management, prolonged exposure plus placebo, and prolonged exposure plus sertraline resulted in significant reductions in PTSD symptoms and symptom severity, there were no differences in change in these measures across the groups at 24 weeks, according to study findings.

“Clinical practice guidelines for posttraumatic stress disorder have presented both trauma-focused psychotherapies and selective serotonin reuptake inhibitors as effective, strongly recommended treatments,” Sheila A.M. Rauch, PhD, department of psychiatry and behavioral sciences, Emory University School of Medicine, and colleagues wrote. “The American Psychological Association, Veterans Affairs and Department of Defense recommended trauma-focused psychotherapy vs. medication for the treatment of PTSD based on meta-analyses comparing effect sizes across studies that rarely involved direct head-to-head comparisons of psychotherapy vs. medication. Without direct comparisons, effect sizes across studies may not accurately reflect efficacy, owing to differences in study designs and comparators.”

In this randomized, double-blind 24-week clinical trial, researchers compared the efficacy of prolonged exposure therapy plus placebo, prolonged exposure therapy plus sertraline hydrochloride, and sertraline plus enhanced medication management for the treatment of PTSD. They measured change in symptom severity of PTSD in the past month using the Clinician-Administered PTSD Scale score at week 24.

Service members or veterans of the Iraq and/or Afghanistan wars with combat-related PTSD who had at least 3 months of significant impairment completed up to thirteen 90-minute sessions of prolonged exposure therapy from week 0 (intake) through week 24. The investigators titrated sertraline therapy during a 10-week period and treatment continued until week 24. Researchers also manualized medication management. Participants were assessed at weeks 0, 6, 12, 24 and 52 (follow-up).

At 24 weeks, 149 participants completed the study and 207 were included in the intent-to-treat analysis. Results revealed a significant reduction in PTSD symptoms during the 24 weeks across all treatment groups (beta = –9.39; 95% CI, –11.62 to –7.16):

  • 33.8 points for sertraline plus enhanced medication management;
  • 32.7 points for prolonged exposure therapy plus sertraline; and
  • 29.4 points for prolonged exposure therapy plus placebo.

However, there was no difference in slopes by treatment group at 24 weeks:

  • –9.39 for prolonged exposure therapy plus placebo;
  • –10.37 for sertraline plus enhanced medication management; and
  • –9.99 for prolonged exposure therapy plus sertraline.

“The high rates of clinically meaningful change observed among veterans in this trial (eg, ranging from 52% to 62%) are noteworthy, given the proportion of participants with chronic treatment-resistant PTSD,” the researchers wrote.

Furthermore, the results showed no significant differences in response rates or remission rates across treatment groups.

“Contrary to our hypotheses, while sertraline plus enhanced medication management performed better than expected, in the purist effectiveness comparison of prolonged exposure therapy plus sertraline vs. prolonged exposure therapy plus placebo, there was no evidence for added benefit for active medication,” Rauch and colleagues wrote. “These results require additional replication and may suggest changes to future clinical guidelines, particularly when [selective serotonin reuptake inhibitors] are administered under similar conditions to this study.”

According to Debra L. Kaysen, PhD, department of psychiatry and behavioral sciences, University of Washington, and colleagues, this study showed that prolonged exposure, sertraline and enhanced medication management likely have efficacy in treating combat-associated PTSD.

“It provides crucial information that combining these therapies while adding burden does not increase efficacy in this population,” they wrote in a related comment. “Further research is needed on mixed-trauma samples in both veterans and community members. Most importantly, we need further research about ways to retain patients and make these effective treatments more broadly accessible.” – by Savannah Demko

Disclosures: Rauch reports receiving support from the DoD, NIH, the VA, Woodruff Foundation and the Wounded Warrior Project, as well as royalties from Oxford University Press. Please see the study for all other authors’ relevant financial disclosures. Kaysen reports support from the DoD, NIH, and the U.S. Agency for International Development. Please see the editorial for all other authors’ relevant financial disclosures.