Psychotherapy, alone or in combination with medication, appears to be the optimal treatment for posttraumatic stress disorder (PTSD) to produce the best long-term outcomes, new research suggests.

A meta-analysis conducted by investigators at the University of Basel, Switzerland, shows treating PTSD with pharmacologic, psychotherapeutic or a combination of these approaches leads to similar short-term results. However, psychotherapy is superior when it comes to longer-term outcomes.

The findings, investigators note, support multiple treatment guidelines that endorse psychotherapeutic approaches as first-line treatments.

Dr Heike Gerger

"Clinicians should have a conversation with patients about what they can expect from which treatment, in the short-term and in the long-term, and then make an informed decision with the patient," study investigator Heike Gerger, PhD, a research fellow in the Division of Clinical Psychology and Psychotherapy at the University of Basel in Switzerland, told Medscape Medical News.

The study was published online June 12 in JAMA Psychiatry.

Debilitating, Common Disorder

A highly debilitating disorder, PTSD is characterized by psychological and behavioral symptoms, including reexperiencing the culprit trauma, avoiding stimuli associated with the trauma, negative alterations in cognition and mood, and hyperarousal. The lifetime prevalence of PTSD among adults is estimated to be about 8%.

Drug treatments for PTSD include selective serotonin reuptake inhibitors (SSRIs) and, in some cases, 3,4-methylenedioxymethamphetamine (MDMA).

Psychotherapeutic approaches include cognitive behavioral therapy, prolonged exposure therapy, and eye movement desensitization and reprocessing.

Recommendations for treatment vary from country to country, but most guidelines suggest psychotherapy as a first-line approach followed by a trial of medication in cases where patients fail to respond.

The investigators conducted a search for studies that directly compared psychotherapeutic and pharmacologic treatments for PTSD as monotherapy and in combination. Psychotherapy had to be individualized talk therapy focusing on PTSD symptoms, said Gerger.

The final meta-analysis included 12 published randomized controlled trials (RCTs) with a total of 922 participants who had a variety of trauma types.

Researchers used network meta-analyses and standard pairwise meta-analyses. They decided to use both approaches because of the small number of studies, said Gerger.

An advantage of network meta-analyses over pairwise meta-analyses is that they facilitate indirect comparisons of multiple interventions that have not been tested in a head-to-head fashion, she noted.

Slight Edge for Combo Therapy

All 12 studies were included in the end-of-treatment analysis. The studies ranged in duration from 8 to 24 weeks. Six studies contributed data for the longer-term analysis, which extended between 2 and 12 months after treatment termination.

Researchers determined confidence intervals (CIs) and standard mean differences (SMDs). SMDs less than 0 and odds ratios (ORs) less than 1 indicated superiority of psychotherapy over pharmacologic treatment and of combined treatment over either approach alone.

At the end of treatment, none of the therapies showed significant superiority. The amount of overall heterogeneity in the analysis was small and there was no indication of inconsistency either within or between study designs.

Sensitivity analyses confirmed the robustness of the SMDs and contributed to explaining heterogeneity and inconsistency, said the authors.

The pairwise meta-analyses confirmed the lack of superiority of either approach at the end of treatment. Heterogeneity was low in all pairwise comparisons.

The researchers' longer-term follow-up produced different results. At the longest available follow-up, psychotherapeutic treatments were significantly more beneficial than pharmacologic treatments (SMD –0.83; 95% CI, –1.59 to –0.07).

Combined treatments were slightly, but not significantly, superior to psychotherapeutic treatment alone (SMD –0.13; 95% CI, –1.12 to 0.87), but the combined treatments were significantly more beneficial than pharmacologic treatments alone (SMD –0.96; 95% CI, –1.87 to –0.04).

There was high overall heterogeneity at the last available follow-up, a finding that was mainly explained by inconsistency between designs, the authors note. After detaching single designs in the full design-by-treatment interaction model, inconsistency was reduced but still significant.

Sensitivity analyses confirmed the magnitude of the SMDs, but did not explain heterogeneity or inconsistency.

More Durable Effect With Psychotherapy

The pairwise meta-analyses confirmed the statistically significant superiority of psychotherapeutic over pharmacologic treatments at the last available follow-up, as well as a large but nonsignificant benefit of combined treatments over pharmacologic treatment alone.

"It appears that with psychotherapy, there's a bigger chance of maintaining the improvements patients showed during treatment," said Gerger.

The results do not show which form of psychotherapy is best. However, the researchers carried out another meta-analysis, published about 5 years ago, that showed that in "higher quality studies" different types of psychotherapies produced similar outcomes, Gerger noted.

While the meta-analysis showed no long-term superiority for pharmacotherapy, it did suggest that medications are beneficial, at least in the short-term.

"If you're really upset and need help now because you have to get work done or have family issues or other problems, then it's good to have the medication because it does help in the short-term," said Gerger.

There were no significant differences in patient acceptability of different treatment approaches. This finding, the investigators note, "diverged from previous meta-analyses showing a significantly higher dropout rate for pharmacologic compared with psychotherapeutic treatments."

A limitation of the study was the relatively small number of included studies. Although the results were consistent in the short-term analysis, conclusions "are constrained with respect to long-term findings," the authors note.

They emphasized that the substantial superiority of psychotherapeutic over pharmacologic treatments in the network meta-analysis needs to be confirmed by high-quality, direct comparison studies.

A potential future study should assess combination treatments in which a placebo is added to psychotherapy, said Gerger. She noted that research shows that a placebo can have a significant effect in this patient population.

Beyond Head-to-Head Comparisons

In an accompanying editorial, Murray B. Stein, MD, and Sonya B. Norman, PhD, Department of Psychiatry, University of California San Diego, note that by including all available studies in the network meta-analysis, the authors amalgamated data from studies that had vastly differing objectives.

"Deciding which studies to include in a network meta-analysis — or whether the available studies are suitable for network meta-analysis at all — is a crucial undertaking that involves consideration of factors such as sample size, likelihood of bias, and heterogeneity," they write.

Stein and Norman, who is also at the National Center for PTSD, White River Junction, Vermont, point out that numerous studies have found trauma-focused psychotherapies such as prolonged exposure and cognitive processing therapy are effective; these treatments, they say, have the highest recommendation across all clinical practice guidelines for PTSD.

"Yet this network meta-analysis made no distinction between trauma-focused or other psychotherapies," Stein and Norman write, "which may explain why it failed to see differences between pharmacotherapy and psychotherapy at the end of treatment."

In addition, the editorialists point out that the network meta-analysis did not distinguish between FDA-approved drugs (administered at therapeutic doses and duration) from augmentation trials for patients who did not respond to treatment from one-time administration of experimental agents.

Clinicians still have no idea what to do when the first treatment fails, the editorialists note.

"The field needs to get beyond the trope of asking 'Which is better, psychotherapy or pharmacotherapy?' and ask clinically meaningful questions, such as, 'What do you do after a patient with PTSD has not experienced improvement with their first evidence-based treatment? Do you add a second treatment? (Which one?) Do you switch to another evidence-based treatment?' "

Also commenting on the findings, Elspeth Cameron Ritchie, MD, a retired military psychiatrist with expertise in PTSD among combat veterans who has published a book on the subject, said the meta-analysis confirms what is already known — but more research on this topic is always welcome.

Ritchie often recommends both treatment approaches together.

"The medications help in the short-term and they also may help the psychotherapy work better, because if you're less bothered by symptoms, you'll be able to focus more on the psychotherapy," she said.

Ritchie noted that some patients are leery of medications because of potential side effects, while others are wary of psychotherapy because they don't want to have to relive the trauma.

In addition to drugs and/or psychotherapy, yoga, meditation, and exercise have been shown to be helpful in this patient population, Ritchie said.

Gerger reported finishing a 1-year training in solution-focused brief therapy. Stein reports he has consulted for Actelion, Aptinyx, Bionomics, Dart Neuroscience, Healthcare Management Technologies, Janssen, Jazz Pharmaceuticals, Neurocrine Biosciences, Oxeia Biopharmaceuticals, Pfizer, and Resilience Therapeutics. He has stock options in Oxeia Biopharmaceuticals. Ritchie has disclosed no relevant financial relationships.

JAMA Psychiatry. Published online June 12, 2019. Abstract, Editorial

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