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Naltrexone and therapy reduce relapse in comorbid alcohol dependence, PTSD

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Small sample size, poor retention

The findings certainly shed light on treatment for comorbid alcohol dependence and PTSD but must be considered in the context of the study’s limitations, said Katherine Mills, Ph.D.


Dr. Katherine Mills

The sample size was relatively small, especially considering that this was a four-group, randomized controlled trial. And the retention rate was particularly low, with only 56% completing the posttreatment and follow-up interviews. "This is not surprising given the nature of the research, in which participants are asked to confront some of the most terrifying events that have ever happened to them, and simultaneously try to abstain from using alcohol and other drugs, which are often the only means by which they have felt that they could cope with the consequences of those events," she noted. Still, the study "provides hope that the gap in treatment provision for this population may begin to narrow."

Dr. Mills is with the National Health and Medical Research Council Centre of Research Excellence in Mental Health and Substance Use at the University of New South Wales, Sydney. She reported no relevant financial conflicts of interest. These remarks were taken from her editorial accompanying Dr. Foa’s report (JAMA 2013;310:482-3).


 

FROM JAMA

Patients with comorbid alcohol dependence and posttraumatic stress disorder might benefit from naltrexone therapy, either alone or in combination with prolonged exposure therapy, according to a report published online Aug. 6 in JAMA.

In a study examining the relative benefits of naltrexone alone, prolonged exposure therapy alone, and both treatments in combination, as compared with supportive counseling, participants who received naltrexone either alone or in combination therapy had significantly fewer days drinking and reported a significantly lower level of craving for alcohol up to 6 months after treatment ended, said Edna B. Foa, Ph.D., of the department of psychiatry at the University of Pennsylvania, Philadelphia, and her associates.

Although prolonged exposure therapy did not improve PTSD symptoms in this study, the combination of the therapy plus naltrexone did reduce the rate of relapse of alcohol dependence during the 6 months after treatments were discontinued.

Just as important, prolonged exposure therapy did not exacerbate drinking or alcohol craving, "a concern that has been voiced by some investigators," Dr. Foa and her colleagues said (JAMA 2013;310:488-95 [doi:10.1001/jama.2013.8268]).

"This finding contradicts the common view that trauma-focused therapy is contraindicated for individuals with alcohol dependence and PTSD because it may exacerbate PTSD symptoms and thereby lead to increased alcohol use," they noted.

After screening 657 potential study participants, the investigators enrolled 165 patients with comorbid PTSD and alcohol dependence over the course of 8 years. All had clinically significant PTSD symptoms, as reflected by scores of 15 or more on the PTSD Symptom Scale-Interview (possible range, 0-51, with higher scores indicating more severe symptoms). All patients also reported drinking heavily during the preceding 30 days on to the Timeline Follow-Back Interview.

The median length of the interval since the traumatic experience occurred was approximately 5 years.

All of the study subjects completed outpatient medical detoxification at baseline. All also received supportive counseling because of the concern about their safety in the face of debilitating impairment and multiple life difficulties such as homelessness.

These patients were randomly assigned to one of four treatment groups for the 6-month duration of the intervention phase of the study: naltrexone plus prolonged exposure therapy (40 patients), placebo plus prolonged exposure therapy (40 patients), naltrexone plus supportive counseling only (42 patients), or placebo plus supportive counseling only (43 patients).

The naltrexone groups were to receive the opiate antagonist at a target dose of 100 mg/d for 6 months.

The prolonged exposure therapy involved 12 weekly 90-minute sessions of repeated imaginal exposure in which patients revisited and recounted their traumatic memories, as well as discussed their thoughts and feelings. These study subjects also listened at home repeatedly to a recording of their recounting of the traumatic experience and repeatedly exposed themselves to safe situations that they previously had avoided because of trauma-related distress.

The supportive counseling focused on medication management and enhancement of patient compliance. Patients were to participate in 18 30- to 45-minute sessions with a study nurse who also provided education about alcoholism and offered support and advice concerning drinking.

All of the study subjects were evaluated for PTSD symptoms, alcohol use, and cravings every month during the intervention phase of the study, as well as at the conclusion of treatment (at 6 months) and at 6 months after discontinuation of treatment (at 12 months).

A total of 53 participants, 32% of the entire study population, dropped out of the study before completing the treatment phase. The dropout rate was similar across the four treatment groups.

Twelve patients were withdrawn because of serious adverse events that were not deemed to be related to the study interventions. These included seven patients with serious suicidal ideation, three with serious medical illness, one with psychotic symptoms, and one who died.

The subjects assigned to prolonged exposure therapy completed a mean of approximately six sessions.

Regarding alcohol dependence, patients in every study group reported some reduction in the percentage of days drinking during the intervention phase of the study, but after treatment ended, only patients who had taken naltrexone reported significantly fewer days of drinking, Dr. Foa and her associates said.

Similarly, all of the study groups reported reductions in alcohol cravings during treatment, but only patients in the two naltrexone groups reported such reductions after the intervention ended.

Patients who received prolonged exposure therapy reported a 3.6% reduction in the percentage of days during which they drank alcohol, while those who did not receive prolonged exposure therapy had a mean increase of 15.9% in the percentage of days during which they drank. This difference, however, did not reach statistical significance.

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