HOW BEST TO TREAT POSTTRAUMATIC STRESS DISORder (PTSD) is a long-standing question. Treatments for PTSD, which began in the late 19th century, have varied greatly. In the current era, numerous PTSD treatments are available, some with a strong evidence base. In this issue of JAMA, the findings of 2 randomized controlled trials of interventions for PTSD expand the boundaries of treatment to relatively underserved populations: the trial by Mills et al assesses interventions in persons with PTSD and substance dependence, and the trial by Monson et al assesses interventions in couples in which 1 partner has PTSD. The trial by Mills et al evaluated Concurrent Treatment of PTSD and Substance Use Disorders Using Prolonged Exposure (COPE) plus usual treatment for substance dependence (n=55) vs usual treatment for substance dependence alone (n=48). COPE involved an individual modality treatment totaling 19.5 hours, whereas usual treatment was any type of substance use treatment available in the patient’s community, including counseling, detoxification, residential rehabilitation, and pharmacotherapy. Prolonged exposure therapy is a type of cognitive-behavioral therapy that exposes patients to memories and reminders of traumatic events associated with intense negative emotions such as anxiety, anger, and sadness. Although this is the first published randomized controlled trial using prolonged exposure in patients with PTSD and substance use disorder, trials of other models for concurrent treatment of PTSD and substance use disorders have shown positive findings. Prolonged exposure therapy is an evidence-based treatment for PTSD currently being implemented on a large scale within the US Veterans Affairs Healthcare System; thus, results of this trial of prolonged exposure for co-occurring PTSD and substance dependence are of immediate interest. Patients with PTSD have been treated with prolonged exposure therapy since the 1990s, and several variants of this therapy have been developed. Although the evidence base for prolonged exposure therapy is strong, previous clinical trials have consistently excluded many of the complex PTSD cases that clinicians routinely encounter, such as patients with suicidal ideation; histories of self-harm, homelessness, and intimate partner violence; and comorbid conditions such as psychosis and substance use disorder. In fact, patients with substance use disorders have been excluded from most PTSD treatment trials. For exposure-based models in particular, PTSD experts indicated that the treatment was not appropriate for patients with comorbid PTSD and substance use disorders until patients attained substantial recovery from substances. In recent years, pilot studies have evaluated exposure-based treatments for patients with PTSD and substance use disorders, with no finding of exacerbation of symptoms and with improvements in various domains, but the study by Mills et al is the first randomized controlled trial to assess the efficacy of prolonged exposure for co-occurring PTSD and substance use disorder, specifically substance dependence, the more severe form of the disorder. It is thus a welcome addition to the PTSD literature. However, the results of the study by Mills et al showed no differences between patients in the COPE plus usual treatment condition and those in the usual treatment alone condition in outcomes for any substance use variable, depression, or anxiety at any point. For the outcome of PTSD symptoms, there were no differences between conditions at 3 months, which was the point with the greatest number of patients still participating and would be the typical end-oftreatment point for a 13-session treatment such as COPE. However, the investigators allowed a time frame of 9 months so that study participants had more time to attend treatment sessions. At 9 months, compared with baseline, PTSD had significantly improved in both study conditions, but there was a greater reduction in PTSD symptoms in the COPE group. The strengths of this trial comprise inclusion of welltrained clinicians, monitoring of treatment quality, measurement of the amount of therapies provided as usual treatment, validated measures of patient outcomes, and appropriate statistical analyses. The investigators conducted the study in a substance abuse treatment setting, and the trial included a broad range of patients typically excluded in studies of prolonged exposure therapy, such as