Combination Therapy for PTSD Provides No Added Benefit

CHICAGO — The combination of antidepressants and psychotherapy is not more effective than either treatment alone for posttraumatic stress disorder (PTSD), new research suggests.

The Prolonged Exposure and Sertraline (PROGRESS) trial is the first head-to-head comparison of these first-line treatment options in a military population.

In PROGRESS, which included more than 200 service people or veterans with PTSD, those who received the selective serotonin reuptake inhibitor sertraline (Zoloft, Pfizer) plus prolonged exposure therapy for 6 months showed no significant benefit compared with those who only received sertraline or who only underwent prolonged exposure therapy.

"We found PTSD symptoms decreased significantly and [found] very large treatment effects over the 24 weeks. However, the slopes did not differ by treatment arms," lead author Sheila A. M. Rauch, PhD, Emory University School of Medicine, Atlanta, Georgia, told attendees here at the Anxiety and Depression Association of America (ADAA) 2019.

Although the study was published in the February issue of JAMA Psychiatry, this was the first live presentation of the findings and included additional results.

First Head-to-Head Trial

Trauma-focused psychotherapies, particularly prolonged exposure therapy, have traditionally shown stronger treatment effects in patients with PTSD compared with treatment with antidepressants. However, head-to-head trials comparing the treatment approaches have been lacking, particularly in military populations, note the investigators.

For PROGRESS, 223 service members or veterans of the Iraq/Afghanistan wars were enrolled at four sites. All were experiencing combat-related PTSD and had significant impairment, defined as a score of 50 or higher on the Clinician-Administered PTSD Scale (CAPS), of at least 3 months' duration.

Participants were randomly assigned to one of three treatments: prolonged exposure therapy plus placebo; prolonged exposure therapy plus treatment with sertraline; or sertraline combined with enhanced medication management. The latter consisted of additional psychoeducation and discussion with patients to boost adherence.

Those in the prolonged exposure group completed up to 13 90-minute sessions by week 24. Sertraline doses were titrated over 10 weeks and were then maintained until week 24.

Of the 223 participants, 149 (87% men; mean age, 34.5 years) completed the 24-week study.

In a modified intent-to-treat analysis of 207 participants, significant decreases were observed in all three groups in CAPS scores over 24 weeks. There was a change of 33.8 points in the sertraline plus enhanced medication management group, 32.7 points in the prolonged exposure therapy plus sertraline group, and 29.4 points in the prolonged exposure therapy plus placebo group (for all, P < .001).

However, there were no significant differences between the treatment arms (P = .81).

Although the investigators had speculated that the group that received combination therapy would demonstrate greater improvements than the others, they said they were not surprised by the results.

Importantly, the improvements in the patients who received sertraline with enhanced medication management were significantly greater than are typically found with PTSD in the military, Rauch said.

"We ended up with a very strong medication effect in the veteran population — much larger than is found in most clinical trials," she noted. "I think that's largely a function of this operationalized medication management that really helped people to stay on the medication long enough to see the benefits and to titrate to a dose that's going to be effective."

Flexible Treatment Choice

Commenting on the findings for Medscape Medical News, Paula P. Schnurr, PhD, professor of psychiatry at the Dartmouth Geisel School of Medicine, Hanover, New Hampshire, and executive director of the VA National Center for PTSD, White River Junction, Vermont, said that although there's an ongoing debate on the benefits of psychotherapy vs medication for patients with PTSD, these new findings suggest clinicians can have relative confidence in either choice.

The study also has important clinical implications, noted Schnurr, who was not involved with the research.

"It suggests that if a patient prefers medication, then that is a good strategy that is equivalent to prolonged exposure. On the other hand, if a person prefers psychotherapy and they are very depressed, there may be no additional benefit from putting them on an antidepressant immediately," she said.

Rauch agreed with Schnurr that the findings show that physicians can be confident in choosing either treatment without fear of compromising patient care.

"With my patients, I've long said we should start with one type of treatment, and then if the patient is not responding or only partially responding, we could switch to the other instead of starting with both at once," Rauch said.

She noted that this is important because when patients are first treated with medication and psychotherapy, they may misattribute the results.

"They may attribute a lot of the changes happening in their life to the pill instead of to the changes they're bringing about themselves. And that's not helpful to the therapeutic process, because in the long run, the more competent they feel in handling affect, the better they're going to do," she said.

Schnurr noted that PTSD clinical guidelines from the US Department of Veterans Affairs recommend trauma-focused psychotherapy, including prolonged exposure, as the first-line treatment. Medication is an option for patients who prefer it.

"The bulk of the evidence generally points toward larger and more durable effects with psychotherapy," she said.

Schnurr added that for studies such the this one, it is difficult to have an effective placebo group.

"We don't have good placebos, so we use control groups that are more or less active, such as patients on a wait list or not having much done therapeutically; but more rigorous controls are needed," she said.

"So I do believe these data, but I don't think they tell the whole story yet," she said.

The study was supported by the US Department of Defense through the US Army Medical Research and Materiel Command and by the National Center for Advancing Translational Sciences of the National Institutes of Health. Rauch reports having received support from the Wounded Warrior Project, the Department of Veterans Affairs, the National Institutes of Health, the Woodruff Foundation, and the Department of Defense and having received royalties from Oxford University Press. Schnurr is on the scientific advisory board for Noblis Therapeutics.

Anxiety and Depression Association of America (ADAA) 2019: Abstract 1250. Presented March 30, 2019.

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