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


Examine how alcohol use disorder impacts the effectiveness of selective serotonin reuptake inhibitor (SSRI) antidepressants used as the only FDA-approved medication for the treatment of PTSD. Specifically, identify patient characteristics predicting the response to SSRI treatment, which would give clinicians a valuable tool to assess who would or would not benefit from such treatment.

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.

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