SSRI Treatment of Dual Diagnosis PTSD and Alcohol Dependence: A Test of the Serotonergic Hypothesis

Apr 06, 2015

Both PTSD and alcohol dependence are devastating disorders capable of destroying lives and disabling veterans and their families. Unfortunately, many veterans battle both problems at the same time. PTSD can spur the development of alcohol dependence, while heavy alcohol drinking can contribute to the development or worsening of PTSD symptoms. And when the two conditions come together, each is more difficult to overcome. Veterans who are diagnosed with both PTSD and alcohol use disorder have a worse prognosis than individuals just having a single diagnosis, highlighting the need to better understand the impact of one condition upon the other and to address both when designing treatment plans.

Regrettably, combined treatments are complicated and generally unavailable, but the STRONG STAR Consortium is examining how alcohol use disorder impacts the effectiveness of the only FDA-approved medication for the long-term treatment of PTSD: selective serotonin reuptake inhibitors (SSRIs). Under the direction of John Roache, PhD, of The University of Texas Health Science Center at San Antonio, the study’s ultimate goal is to identify baseline predictors of response to SSRI treatment, providing clinicians with a valuable tool to assess individuals who would benefit from such therapy and those who would be neutrally or even negatively affected by it. This would allow treating physicians to tailor patient therapy accordingly, without risking unnecessary or ineffective medication.

According to the VA/DoD Clinical Practice Guidelines for the Management Interventions Module Summary of Post Traumatic Stress published in 2007, SSRIs are the first-line medication treatment for PTSD and are a strongly recommended standard of care. However, a 2007 report by the Institute of Medicine concluded that the evidence for SSRI effectiveness is not certain. Given these mixed messages and uncertain evidence of benefit, it is important to know exactly for whom SSRI medication may be beneficial and for whom these medications are ineffective or cause unanticipated risk.

An explanation for the confusion over of the benefits of drug therapy

The central hypothesis of Dr. Roache’s STRONG STAR study suggests a possible explanation for the limited effectiveness of SSRIs: There are subgroups of patients who respond differently to SSRIs, such that some show benefits and others show either no effect or actual adverse responses. Furthermore, those subgroups relate to subtypes of alcoholism.

Research already has demonstrated that SSRIs show reduced effectiveness in the presence of co-occurring alcohol use disorder. There also is good evidence that individuals with different subtypes of alcohol use disorder respond differently to SSRI treatment, such that individuals with Type B or early onset alcoholism do worse on SSRI treatment than with placebo, while those with Type A or late onset alcoholism may benefit from SSRI treatment. A few key dimensions seem to predict Type B membership:

  • onset of problem drinking at an early age;
  • a family history of alcoholism (FH+); and
  • co-occurring anxiety or depression.


Dr. Roache and his research team have devised an experiment to reveal the impact of alcohol use disorder on the effectiveness of SSRI treatment in patients with PTSD. The experiment aims to provide treatment for veterans who experienced traumatic events during military service and who have been dually diagnosed with PTSD and alcohol use disorder. Treatment involves randomized assignment to receive sertraline or placebo and while patients receive manualized Cognitive Behavioral-based Therapy (CBT) for both PTSD and alcohol use disorder. Working with these patients, Dr. Roache seeks to determine whether multidimensional baseline measures are useful in classifying individuals with the comorbidities of PTSD and alcohol use disorder according to Type A and Type B subtypes of alcoholism. From here, he will examine whether the efficacy of the SSRI sertraline differs between subjects who fall under the Type A or Type B subtype classification.

Potential benefit for doctors and patients

Eventually, Dr. Roache and his STRONG STAR colleagues aim to provide clinicians with a set of baseline predictors of SSRI treatment response that can be used to design the best course of treatment for PTSD patients. With the necessary tools for classifying patients by appropriate subtypes, clinicians could offer SSRI treatment to those for whom it would be beneficial and forgo the drug therapy with individuals for whom it would be ineffective or contra-therapeutic.

Treatment of Chronic Stress Reaction and Chronic Pain after Traumatic Orthopedic Injury

Aug 18, 2010

Chronic pain after a traumatic orthopedic injury and posttraumatic stress disorder (PTSD) are each major concerns for the U.S. military in their own right. Both conditions have a direct impact on military readiness and are leading causes of medical discharges from active duty, as well as long-term VA disability, according to a 2006 report by the U.S. Department of Defense and the U.S. Department of Veterans Affairs. When these conditions become chronic, they can lead to a lifetime of pain and suffering for veterans and potentially contribute to an array of socioeconomic difficulties. In financial terms, the costs associated with the treatment of these conditions exceed hundreds of billions of dollars annually.

As different as these two conditions are, they are not necessarily separate problems that can be addressed in isolation from each other, because they frequently come together in one “unwanted package,” and each adversely affects the other. An increasing body of evidence from civilian studies suggests that individuals who experience physical trauma are likely to experience symptoms of significant psychosocial distress as well. In fact, one specific study published by A.J. Starr and colleagues in 2004 identified over half of a civilian sample of orthopedic trauma patients who met criteria for PTSD after their injury. To date, these studies have not been replicated in a military population, but it is suspected that the rates of comorbid orthopedic trauma and PTSD would be similar to those found in civilians, if not higher. The problem is not just that physical trauma can lead to the development of PTSD. Studies have also shown that PTSD affects patients’ reports of physical complaints, and PTSD is among the variables that are most predictive of functional outcome following injury.

Making matters worse, recent research by M.J. Bosse and colleagues suggests that individuals experiencing comorbid chronic pain and traumatic stress may respond poorly to treatment targeting only one diagnosis, contributing to the chronicity and severity of both PTSD and pain. On the positive side, data from other studies suggest that early interventions for orthopedic trauma pain and related traumatic stress can be effective in preventing chronic pain or PTSD syndromes.

The potential of cognitive therapy in treating both PTSD and pain: A STRONG STAR investigation

Robert Gatchel, PhD, of The University of Texas at Arlington hopes to build on these positive findings through a novel study he has designed for STRONG STAR to examine the effects of combining preventive pain and PTSD treatments for trauma patients. As part of their investigation, Dr. Gatchel and his co-investigators will identify the comorbidity of orthopedic trauma and traumatic stress in an active-duty military population, and they will evaluate a preventive behavioral health treatment strategy aimed at helping to retard or halt the development of PTSD and/or chronic pain syndromes. The study will examine the efficacy of multiple treatment options, utilizing a four-group randomized experimental design to measure the effects of cognitive behavioral therapies targeting pain treatment only, PTSD treatment only, and the treatment of both pain and PTSD compared to treatment as usual.

Evaluations of these four groups will be conducted at pretreatment, immediately at posttreatment, and at 6- and 12-month follow-up periods in order to determine differential outcomes on numerous variables. The investigators hypothesize that treating individuals with chronic pain and PTSD symptoms (e.g., lasting 12 weeks or more) through a proven psychosocial model will help to improve psychological, socioeconomic and physical symptoms of these chronic clinical syndromes. They further aim to demonstrate the efficacy of these early treatments in facilitating the return to active duty of military personnel living with pain and traumatic stress. Finally, they also expect to have a positive impact on other psychosocial and socioeconomic outcomes, such as work retention, additional health-care utilization, depression symptoms, health-related quality of life, and perceived disability.

The benefits of success

If Dr. Gatchel and his colleagues successfully demonstrate that integrating pain and PTSD treatments leads to improved outcomes for wounded warriors, the payoff will be substantial: affected military personnel could potentially enjoy a greatly improved quality of life; the U.S. Department of Defense could save billions of dollars in elevated treatment costs attributable to comorbid pain and PTSD; and thousands of civilian trauma patients could benefit from this improved treatment method.