Opening Statement: The following case was chosen for presentation at the Naltrexone Usage Study Investigators Meeting because it addresses two aspects of naltrexone treatment for alcoholism that have not yet been systematically studied: (1) duration of treatment and (2) concomitant pharmacotherapy for major a depressive disorder.
Naltrexone has been shown to be a safe and effective medication for the treatment of alcohol dependence in clinical trials of three months, duration. However, alcohol dependence is a chronic, relapsing disorder, and the safety and efficacy of naltrexone treatment of alcoholism over longer durations has been studied less comprehensively. For example, it is unknown whether tolerance to medication effects develops over time, requiring higher dose levels, or whether side effects emerge with chronic treatment that were not present in the acute treatment phase. The patient presented in this case study has successfully completed week 44 of naltrexone treatment for alcoholism. He is maintaining a negative baseline urine drug screen. The patient's medical history was significant for predisposition to gastrointestinal distress, including diarrhea, nausea, and vomiting, that occurred almost every time he drank. The patient's baseline ALT (SGPT) was slightly elevated (51, ref 6-37 U/L), as was his GGT (106, ref 7-64-U/L)--and total protein (8.2, ref 6.0-8.0 mg/dL). All other laboratory tests were unremarkable. A complete physical workup, including HIV testing, was negative. The patient had been self-prescribing diphenhydramine hydrochloride (Benadryl) for sleep since March 1992. There were no additional concomitant medications at study baseline.
The patient had been referred to the (treatment center name omitted) from the Crisis Unit in (Hospital name omitted), where he presented in alcohol withdrawal. He had been drinking an average of 117 drinks per week prior to entering treatment. He reported 13 years of heavy drinking, with onset of alcohol use at age 12. He had one 7-day inpatient detoxification treatment 1 year ago, after which he abstained from alcohol and attended AA meetings for 4 months. Alcohol-related symptoms included one alcohol-related seizure 1 year ago, frequent blackouts, withdrawal symptoms, feelings of panic that a drink may not be available when he needed it, repeated relapse after a period of abstinence, and repeated attempts to cut down on drinking that failed.
Naltrexone Treatment and Results: The patient began treatment with 50 mg per day of naltrexone, and has been maintained at this dose level for 44 weeks without change. Throughout this treatment period, the patient episodically complained of mild to moderate fatigue, depression, diarrhea, nausea, and headaches, which is consistent with his complaints prior to treatment. The patient initiated complete abstinence at the time of his treatment for alcohol withdrawal 2 weeks prior to study baseline, and has maintained complete abstinence for the 44 weeks of naltrexone treatment. Self report of abstinence is corroborated by liver function tests (LFTS) returning to within the normal range within 4 weeks after initiation of complete abstinence. Subsequent repeat LFTS remain within the normal range. Breathalyzer readings are obtained at every study visit, and have consistently been negative throughout the treatment duration. Self reports of craving, using a 0- to 10-point visual analogue scale, decreased gradually from 8 at baseline to 1 at week 44. The patient also reported increasing ease in saying "no" if offered an alcoholic beverage. Repeat urine screens for drugs of abuse are consistently negative. The patient received weekly coping skills relapse-prevention therapy for the first 16 weeks of study, and weekly psychotherapy for the comorbid affective disorder for the study duration. The patient began 50 mg per day of Zoloft. for treatment of comorbid depression, 9 days after initiation of naltrexone treatment for alcoholism. The dose of Zoloft was increased to 100 mg per day after 3 weeks. There were no treatment emergent signs or symptoms with onset of Zoloft treatment. Symptoms of depression and anxiety showed clinically significant improvement by week 8 of study (week 6 of Zoloft). The patient states that his sense of emotional well-being has increased and sleep has improved in response to treatment. He also reports increased sexual pleasure, and feels his general physical health has improved, with a corresponding decrease in use of over-the-counter medications. The number of hours spent watching TV or videos per week has decreased from 60 at baseline to 3 at week 44. The patient's body weight (155 lbs), appetite, intake of sweets, and cigarette consumption (50 per day) remained unchanged from baseline. Caffeine consumption has increased from 10 to 15 drinks per day, and represents the only evidence of possible symptom substitution. The patient is currently enrolled full-time in college, and the 44-week naltrexone treatment period represents the longest period of complete abstinence since the patient first began abusing alcohol at age 12.