Double-blind clinical trial of sertraline treatment for alcohol dependence.

Clinical studies that have evaluated serotonergic medications to reduce alcohol consumption have yielded conflicting results. These studies primarily treated patients with alcohol dependence, excluding those with a current depressive disorder, in an effort to differentiate any medication effects directly on drinking from those on mood. Yet despite the exclusion of current depression, a group of alcohol-dependent patients who are not depressed can be highly heterogeneous. For example, this subgroup can include those with a lifetime depressive disorder. If these patients were more sensitive to serotonergic medications than patients without a lifetime depressive disorder, medication effects in a subgroup of patients who were not depressed could be obscured. Thus, the purpose of this study was to examine the efficacy of sertraline for treating alcohol dependence in patient groups that were differentiated by the presence or absence of lifetime depression. This study examined the effectiveness of sertraline (200 mg/day) or placebo for 14 weeks in 100 alcohol-dependent subjects with (N = 53) or without (N = 47) a lifetime diagnosis of comorbid depression. Sertraline treatment seemed to provide an advantage in reducing drinking in alcohol-dependent patients without lifetime depression, illustrated best with a measure of drinking frequency during treatment. However, sertraline was no better than placebo in patients with a diagnosis of lifetime comorbid depression, and current depression did not change the results. Treatment with selective serotonin reuptake inhibitors may be useful in alcohol-dependent patients who are not depressed. Subtyping those with alcohol dependence on the basis of the absence versus the presence of a lifetime depressive disorder may help to resolve conflicting findings in the literature on the treatment of alcohol dependence with serotonergic medications.

6-beta-naltrexol reduces alcohol consumption in rats.

BACKGROUND: In humans, 6-beta-naltrexol is the major metabolite of naltrexone, and its effectiveness at suppressing alcohol consumption in any species has not been previously investigated. Naltrexone is an opiate antagonist that reduces excessive drinking in many species, including humans with alcohol dependence. Whether 6-beta-naltrexol is an active metabolite that contributes to the efficacy of naltrexone remains unknown. METHODS: Placebo and four doses of 6-beta-naltrexol were given by intraperitoneal injection to outbred Wistar rats and alcohol consumption was measured using a limited access model. RESULTS: 6-beta-Naltrexol reduced alcohol consumption in a dose-dependent manner. At doses 7.5, 12.5, and 25 mg/kg, 6-beta-naltrexol significantly decreased consumption of a 6% ethanol solution compared with saline control groups. CONCLUSIONS: These data suggest that there may be a potential clinical use for 6-beta-naltrexol in recovering alcoholics.

Gender and psychiatric comorbidity: impact on clinical presentation of alcohol dependence.

We examined differences in clinical presentation for outpatient alcohol treatment in: 1) males and females, considering comorbidity; and 2) three comorbid groups, considering gender. Drinking indices and emotional, physical, and sexual abuse reports were compared in 127 male and 69 female alcohol-dependent patients who have a current (36.2%) or lifetime (20.4%) psychiatric disorder or who never had a psychiatric disorder (43.4%). Females reported more emotional and physical abuse than males. Females reported drinking smaller volumes of alcohol but on more days than males. All with current comorbidity, irrespective of gender, reported more days of heavy drinking than other groups. When evaluating drinking status, gender and comorbidity should be considered.

Sertraline treatment for alcohol dependence: interactive effects of medication and alcoholic subtype.

BACKGROUND: Characteristic behaviors of some alcohol-dependent individuals, e.g., binge drinking, comorbid psychopathology, and some types of alcohol-related problems, have been linked to abnormalities in serotonergic neurotransmission. However, studies that have evaluated serotonergic pharmacotherapy for reducing drinking have yielded conflicting results. One explanation for these findings is a general failure to distinguish alcohol subgroups that may be differentiated on the basis of serotonergic abnormalities. However, in 1996, Kranzler and colleagues reported that Type B alcoholics, who are characterized by high levels of premorbid vulnerability, alcohol dependence severity, and comorbid psychopathology, showed less favorable drinking outcomes in response to treatment with fluoxetine, a serotonin reuptake inhibitor, than with placebo. This medication effect was not seen in Type A alcoholics, i.e., those with lower risk/severity of alcoholism and psychopathology. The aim of the present study was to explore the validity of differential responding by alcohol-dependent subtypes using the serotonin reuptake inhibitor, sertraline. METHODS: A k-means clustering procedure was applied to a sample of alcohol-dependent subjects enrolled in a 14-week, placebo-controlled trial of 200 mg/day of sertraline, classifying them into lower-risk/severity (Type A: n = 55) and higher-risk/severity (Type B: n = 45) subgroups. RESULTS: A significant interaction between alcoholic subtype and medication condition was found, confirming the findings of Kranzler and colleagues that alcoholic subtypes responded differentially to serotonergic medication. Somewhat at variance with their results, however, the present study showed that the lower risk/severity (Type A) subjects had more favorable outcomes when treated with sertraline compared to placebo. CONCLUSIONS: Alcoholic subtypes differentially responded to sertraline when used as a treatment to reduce alcohol drinking, with one subtype having more favorable outcomes. Subtyping alcoholics may help to resolve conflicting findings in the literature on serotonergic treatment of alcohol dependence.

Gender differences in comorbidly depressed alcohol-dependent outpatients.

UNLABELLED: Clinical profiles of alcohol-dependent male and female outpatients were evaluated at treatment entry to compare the level of clinical severity in alcoholics with a coexistent comorbid depressive disorder to alcoholics who have never been depressed. Due to a higher proportion of females than males in the depressed alcoholic population, selected patient groups were oversampled to create a study group with equivalent number of males and females with and without comorbid depression. Clinical severity was assessed by examining both the extent of alcohol problems, and depressive symptomatology at treatment entry with respect to gender differences (unrelated to depression), effects of comorbid depression (unrelated to gender), and effects from the interaction of gender and depression. There were 93 DSM-III-R alcohol-dependent outpatients (50 males, 43 females), half of whom had a current or lifetime DSM-III-R depressive disorder. The amount of drinking in the 90 days before treatment entry, the degree of alcohol severity, and the number of lifetime drinking-related consequences were collected in the first week after detoxification. Diagnoses of lifetime and current depression were determined via the Structured Clinical Interview for DSM-III-R, and depressive symptoms were evaluated with rating scales 1 week after detoxification. In most cases, a depressive disorder was diagnosed only if sometime in the patient's history depressive symptoms had either predated problem drinking or been present during a 6-month abstinent period. RESULTS: depressed males had a more severe clinical profile with respect to their alcoholism (i.e., more drinking, drinking-related problems, and alcohol severity than depressed females and never-depressed males). Surprisingly, females who had never been depressed (also no family history of depression) reported drinking the same quantities of alcohol in the 90 days before treatment and had comparable alcohol severity and number of consequences as males who had never been depressed. Depressed females, however, were more severely depressed (i.e., reported more intensive depressive symptoms than depressed male alcoholics). Thus, determining the type and extent of clinical severity at treatment entry in comorbidly depressed alcoholics depends on the gender of the patient The significant interaction between gender and the presence of comorbid depression that was found in this study may have important implications for predicting success in treatment.

Acute subjective responses to paroxetine in normal volunteers.

The purpose of this study was to compare the subjective effects of the selective serotonin reuptake inhibitor, paroxetine, to those of the prototypic stimulant, d-amphetamine. Ten healthy volunteers attended 5 sessions and received paroxetine (10, 20, 50 mg), d-amphetamine (20 mg), and placebo. Subjective effects were measured at regular intervals for 26-30 h. Paroxetine and d-amphetamine produced highly dissimilar effects on mood. For example, whereas d-amphetamine increased ratings of euphoria, drug high, and desire for drug, paroxetine produced no effects on these measures. Conversely, whereas paroxetine increased ratings of Confusion and Fatigue, d-amphetamine did not. These findings suggest that serotonin does not play a significant role in mediating the positive subjective effects of stimulant drugs.

Candida epididymitis: newly recognized opportunistic epididymal infection.

Epididymitis is common, yet it is rarely associated with fungal pathogens. We report a case of Candida albicans epididymitis in a diabetic which was ultimately treated by orchiectomy. Opportunistic infections of the genitourinary tract in immunosuppressed patients are becoming more prevalent; examples include fungal infections in patients with acquired immune deficiency syndrome or after organ transplant. The fact that opportunistic organisms can invade the epididymis and produce infection suggests that in cases of persistent epididymitis, which have failed to respond to conventional therapy, more aggressive diagnostic procedures should be considered. Needle aspiration with cultures for fungus and viral organisms should be performed. This is especially true in patients with preexisting chronic illness or an immune compromised state.