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The Use of Naltrexone as an Adjunct to Cognitive Behavioral Therapy: A Literary Review


Mike Feyder

Date: 10/14/2006



            The purpose of the reviewed studies is to evaluate the efficacy of naltrexone as an adjunct to cognitive behavioral therapy.  After detoxification of an individual, current medical therapeutics involve behavioral treatments and pharmacotherapy.  Behavioral treatments include cognitive behavioral therapy (CBT), motivational enhancement therapy, Alcoholics Anonymous and analogous 12-step programs.  Current pharmacotherapy therapeutics approved by the Food and Drug Administration (FDA) includes disulfiram, which causes aversive reactions such as nausea and vomiting when consuming alcohol, naltrexone, an anti-craving medication that inhibits the pleasant affects of alcohol use, and acamprosate (Fuller and Hiller-Sturmhöfel, 1999).  The term “anti-craving” however is disputable because the exact psychopharmacological affects are unknown; however, multiple studies (O’Malley et al, 1992; Volpicelli et al, 1992) have shown that naltrexone reduces that rate of relapse in alcoholic even if the exact mechanism is unknown.  Clearly, the most beneficial combination of behavioral treatment and pharmacotherapy is desired.  The following studies investigated one possible combination by examining the affect of naltrexone in conjunction with CBT.



            Naltrexone was approved by the FDA after two landmark studies by O’Malley et al (1992) and Volpicelli et al (1992) revealed that the drug reduced relapse rates from 50 percent to 25 percent (Fuller and Hiller-Sturmhöfel, 1999).  Naltrexone is a competitive opioid antagonist that appears to reduce the pleasurable affects of alcohol and reduce cravings (  Rewarded behaviors, such as the ingestion of alcohol, result in the stimulation of dopamine release, particularly in the nucleus accumbens, the brain’s reward center.  Opiods, however, have been shown in animals to reduce the release of dopamine (  Therefore, the stimulating affects of dopamine release are modified by naltrexone, and the rewarded behavior is not as rewarding.  The theory is that if alcohol use is not as rewarding, the subject will not have the urge to drink and if he/she engages in drinking, will not experience the same ‘high.’


Cognitive Behavioral Therapy

            Cognitive behavioral therapy attempts to prevent the relapse of an alcoholic by modifying the behaviors that lead to alcohol use.  Factors such as cravings for alcohol, depression, social pressures, relationship problems, and negative life events may lead to relapse.  The goal of cognitive behavior is to make the patient away of these situations and to help him/her cope with such situations in order to prevent relapse. To prepare for these situations, patients engage in activities such as rehearsal as well as role-playing (Fuller and Hiller-Sturmhöfel, 1999).


Study I

            In a study published in the Australian and New England Journal of Psychiatry in 2004, Feeney at al concluded that use of naltrexone produced no significant effects in the self-reported health status or wellbeing of the patient.  The Rand Corporation Medical Outcomes Short Form 36 Health Survey (SF-36) was used to survey patients’ physical function, physical problems, bodily pain, general health perception, emotional problems, mental health, and vitality.  The General Health Questionnaire (GHQ-28) evaluates the patient’s somatic (bodily) concerns, anxiety, social dysfunction and depression.  Both groups also received eight hourly CBT sessions in twelve weeks.

            The CBT-only group showed significant improvement over the CBT+naltrexone in the anxiety subscale of the GHQ-28 but no difference for somatic concerns, social dysfunction, and depression.  However, at the end of the treatment program, both groups showed levels similar to the normal population in their overall GHQ-28 scores, illustrating the naltrexone in conjunction with CBT should no improvement in the health status of the patient, and may prevent improvement in anxiety.

            Also, only the control group showed improvements in the general health perception and vitality, measured by the SF-36 questionnaire, and no differences between groups in physical functioning, physical problems, bodily pain, social function, emotional problems, and mental health.  The results illustrate that naltrexone has no effect on the self-reported wellbeing of the patient.

            Finally, a higher percentage of those receiving naltrexone were significantly more likely to have more days abstinent (61.21 days and 29.51 days respectively, out of 84) and to finish the program abstinent (58.1% compared to 34.9% respectively).  It is important to note that this data was collected by the reports of the patient, and objective measures were not used to confirm these self-reports.


Study II

            In another study by Feeney et al in 2001, published in the Australian and New Zealand Journal of Psychiatry, the addition of naltrexone to CBT produced an increased in CBT attendance and completion of the 12-week program.  The naltrexone group was significantly more likely to attend CBT session over the 12 weeks than the control group (88% compared to 36%, respectively).  Furthermore, there was a significant difference between the groups in the percent of those remaining abstinent throughout the program (76% compared to 18%, respectively).  The results of the study suggest that naltrexone in conjunction with CBT increases therapy treatments and the probability of abstinence throughout the 12-week program duration.

            Although this study appears promising to the therapeutic benefits of naltrexone, the experimental design limits the validity of the results.  The study was not randomized, and all participants were administered naltrexone.  As a control, the experimenter used historical matches from previous data collected from CBT sessions of participants who did not receive naltrexone.  As a result, there was no placebo, and all patients knew that they were administered a drug that was intended to prevent relapse.  Furthermore, alcohol use was determined by self-reports and alcohol breathalysation at the time of each CBT screen.  Self-reports are subject to fabrication, and subjects may simply not tell the truth.  Brethalysation was only administered on the day of the session, which was once a week for the first 4 weeks and then once every two weeks for the remaining two months.  As long as the subject was not under the influence of alcohol at these times, the subject could potentially lie about his drinking habits if he/she had relapsed.  Although the findings may be accurate, the experimental flaws raise suspicions to the validity of the data.


Study III

            In a study by Anton et al in 1999, published in the respected American Journal of Psychiatry, naltrexone was shown to have a therapeutic effect when used in conjunction with CBT.  This study, unlike the previous one, employed a placebo control so that participants were unaware if they were medicated.  Furthermore, the study contained objective data on the subjects’ drinking habits.  Researchers collected carbohydrate-deficient transferin and g-glutamatransferase via blood collections at three points over the 12-week program (week 4, 8, and 12) to confirm patient’s verbal reports.

            The study measured three important variables in alcoholic drinking habits: time to first relapse (defined as the greater than five drinks for males and greater than 4 drinks for females), percentage of days abstinent, and drinks per day that the subject drank.  At the end of the study, 62% of the subjects taking naltrexone had not relapsed, as compared to 40% of those on placebo.  Also, medicated subjects had a higher percentage of days abstinent and reported fewer drinks when they did drink.  Finally, when medicated subjects did relapse, they experienced 14 days until the next heavy drinking day, whereas the control group experienced only 6 days until the next heavy drinking day.

            The results of this study provides strong evidence that naltrexone, when used in conjunction with CBT, provides a more therapeutic benefit than CBT alone.  The strong internal validity of the study, such as the presence of a control group and an independent validation of self-reported drinking habits, gives strong precedence to the results.



            The results of these studies suggest that naltrexone in conjunction with CBT may provide a more therapeutic benefit then CBT alone.  Although both experiments by Feeney (2001, 2004) show that naltrexone in conjunction with CBT produced longer periods until relapse, the two studies relied on the self-reporting of the patients.  Anton et al (1999), however, used an objective measure along with self-reports and produced similar results.  The difference in the relapse between the two groups in the Anton et al study was much smaller than in the Feeney study (2001) and may be attributed to the poor internal validity.  In addition, the Alton study showed improvements in the periods between relapses suggesting that the drug may reduce cravings and desire to drink.  Finally, the use of naltrexone in conjunction with CBT showed little benefit to the self-reported emotional and physical health status and wellbeing of the patient.  The increase in anxiety subscale for naltrexone does not appear to increase drinking habits because of the longer period of abstinence and longer duration between relapses.  In conclusion, there may be a slight benefit in the use of naltrexone in combination with CBT, such as longer periods until relapse, duration between first and second relapse, and total days abstinent and no benefit in the self-reported physical and emotional health of the user; however, more carefully controlled experiments are needed to provide stronger evidence for this effect.






Anton RF, Moak Sh, Waid R, Latham PK, Malcolm RJ, Dias JK. Naltrexone and cognitive behavioral therapy for the treatment of outpatient alcoholics: Results of a placebo-controlled trail. American Journal of Psychiatry. 156: 11, 1999.


Fuller RK, Hiller-Sturmhöfel S. Alcoholism treatment in the United States: An Overview. Alcohol Res Health 23(2):69-77, 1999.


O’Malley SS, Jaffe AJ, Chang G, Schottenfeld RS, Meyer RE, Rounsaville B. Naltrexone and coping skills therapy for alcohol dependence: A controlled study.  Archive of General Psychiatry 49(11):881-887, 1992.


Volpicelli JR, Alterman AI, Hayashida M, O’Brien CP. Naltrexone in the treatment of alcohol dependence. Archives of General Psychiatry. 49(11): 876-880, 1992.