Ondansetron for reduction of drinking among biologically predisposed alcoholic patients: A randomized controlled trial.

CONTEXT: Early-onset alcoholism differs from late-onset alcoholism by its association with greater serotonergic abnormality and antisocial behaviors. Thus, individuals with early-onset alcoholism may be responsive to treatment with a selective serotonergic agent. OBJECTIVE: To test the hypothesis that drinking outcomes associated with early vs late-onset alcoholism are differentially improved by the selective 5-HT(3) (serotonin) antagonist ondansetron. DESIGN: Double-blind, randomized, placebo-controlled clinical trial. SETTINGS: University of Texas Health Science Center in Houston (April 1995-June 1998) and University of Texas Health Science Center in San Antonio (July 1998-December 1999). PARTICIPANTS: A total of 321 patients with diagnosed alcoholism (mean age, 40.6 years; 70.5% male; 78.6% white) were enrolled, 271 of whom proceeded to randomization. INTERVENTIONS: After 1 lead-in week of single-blind placebo, patients were randomly assigned to receive 11 weeks of treatment with ondansetron, 1 microg/kg (n = 67), 4 microg/kg (n = 77), or 16 microg/kg (n = 71) twice per day; or identical placebo (n = 56). All patients also participated in weekly standardized group cognitive behavioral therapy. MAIN OUTCOME MEASURES: Self-reported alcohol consumption (drinks per day, drinks per drinking day, percentage of days abstinent, and total days abstinent per study week); and plasma carbohydrate deficient transferrin (CDT) level, an objective and sensitive marker of transient alcohol consumption. RESULTS: Patients with early-onset alcoholism who received ondansetron (1, 4, and 16 microg/kg twice per day) compared with those who were administered placebo, had fewer drinks per day (1.89, 1.56, and 1.87 vs 3.30; P =.03, P =.01, and P =.02, respectively) and drinks per drinking day (4.75, 4.28, and 5.18 vs 6.90; P =.03, P =.004, and P =.03, respectively). Ondansetron, 4 microg/kg twice per day, was superior to placebo in increasing percentage of days abstinent (70.10 vs 50.20; P =.02) and total days abstinent per study week (6.74 vs 5.92; P =.03). Among patients with early-onset alcoholism, there was a significant difference in the mean log CDT ratio between those who received ondansetron (1 and 4 microg/kg twice per day) compared with those who received the placebo (-0.17 and -0.19 vs 0.12; P =.03 and P =.01, respectively). CONCLUSION: Our results suggest that ondansetron (particularly the 4 microg/kg twice per day dosage) is an effective treatment for patients with early-onset alcoholism, presumably by ameliorating an underlying serotonergic abnormality. JAMA. 2000;284:963-971

Age of onset as a discriminator between alcoholic subtypes in a treatment-seeking outpatient population.

Subtyping alcoholics may provide a more accurate guide as to the course and character of the disease. Classifications of different ages of onset of problem drinking have so far resulted in categorical inconsistencies. In the past, hospital-based alcoholics have over-represented those most severely ill, and comprehensive evaluations of psychopathology for discriminating between alcoholic subtypes have been infrequent. In a heterogeneous treatment-seeking, outpatient, alcoholic population, we tested the hypothesis that age of onset represents a continuum of disease, and that greater severity of psychopathology is associated with lower ages of onset. Using a standard questionnaire, 253 male and female treatment-seeking alcoholics were stratified according to specific ages of onset: a) < 20 years; b) 20-25 years, and c) > 25 years. These age of onset groups were compared on alcohol severity and craving, family history, childhood behavior, personality, hostility, overt aggression, mood, and social functioning. Symptom severity and age of onset were negatively correlated, and the 20-25-year onset group usually had intermediate scores. The < 20 year onset group was characterized by greater severity of alcohol-related problems, family history, childhood behavioral problems, craving, hostility, antisocial traits, mood disturbance, and poor social functioning. Alcoholics with an earlier age of onset have relatively greater psychopathology than those of later onset. While the preponderance of psychopathology among those in the < 20-year onset group could be conceptualized as a clinical "subtype," such a characterization would not define an entirely homogeneous category. Yet, this clinical characterization would be clinically important if specific age of onset levels were found to be differentially sensitive to pharmacological and/or psychological treatments.

Effects of isradipine, a dihydropyridine-class calcium channel antagonist, on d-methamphetamine-induced reduction in hunger.

1. The authors studied the effects of isradipine, a dihydropyridine-class calcium channel antagonist, on d-methamphetamine-induced changes in somatic and psychological perceptions of hunger state using a placebo-controlled, double-blind, Latin Square, cross-over design in 18 healthy volunteers. 2. D-methamphetamine significantly decreased these subjective ratings of hunger, presumably by increasing monoaminergic turnover. 3. Effects on hunger are hypothesized to be mediated by norepinephrine primarily, while dopamine plays only a modest role. Isradipine alone, an inhibitor of dopamine release, had no significant effect on the hunger measures. Additionally, isradipine pretreatment did not significantly alter d-methamphetamine's anorexic effects. 4. Isradipine may, therefore, not significantly modify the control of hunger in humans.

Isradipine, a dihydropyridine-class calcium channel antagonist, attenuates some of d-methamphetamine's positive subjective effects: a preliminary study.

RATIONALE: Dopamine (DA) pathways in the midbrain mediate d-methamphetamine's rewarding effects associated with its abuse liability. Isradipine, a dihydropyridine-class calcium channel antagonist, reduces the rewarding effects of psychostimulants such as cocaine and d-amphetamine, presumably by antagonizing these central DA pathways. This is the first experiment to test the hypothesis that the rewarding effects of d-methamphetamine, like other psychostimulants, can be reduced by isradipine. OBJECTIVE: We studied the effects of high dose isradipine (0.21 mg/kg orally), on the positive subjective effects associated with the abuse liability of low and high dose d-methamphetamine (0.21 mg/kg and 0.42 mg/kg orally, respectively). METHODS: Using a double-blind, double-dummy, placebo-controlled, Latin-Square, cross-over design, 18 healthy male and female volunteers received each of the following six treatments separated by a rest period of 2-7 days: a) placebo+placebo; b) low-dose d-methamphetamine+placebo); c) high-dose d-methamphetamine+placebo; d) high dose isradipine+placebo); e) low-dose d-methamphetamine+high dose isradipine, and f) high-dose d-methamphetamine+high dose isradipine. RESULTS: d-Methamphetamine produced orderly increases in positive subjective measures of both stimulation and mood. Pre-treatment with isradipine significantly reduced some of these positive subjective effects and craving for d-methamphetamine. CONCLUSION: Isradipine as an anti-reward or craving reducing medication is a promising therapeutic agent for the treatment of d-methamphetamine dependence.

Evaluating outpatient behavior therapy of sex offenders. A pretest-posttest study.

This study compared the entrance and exit scores of 16 patients completing treatment at the Highland Institute for Behavioral Change (HIBC), an outpatient program specializing in the behavioral treatment of sex offenders. Outcome measures included the Minnesota Multiphasic Personality Inventory (MMPI), the Multiphasic Sexual Inventory, and recidivism (rearrest record) posttreatment. Statistically significant and clinical improvements were obtained on a number of these measures. One of the 16 graduates reoffended during the average follow-up period of 26 months (he is now incarcerated). These data are supportive of the contention that outpatient behavior therapy can be effective in reducing deviant sexual arousal and in enhancing appropriate consensual sexual behavior.

Cocaine craving: an evaluation across treatment phases.

This study examined the relationship between verbal reports of craving and actual cocaine use across different treatment phases using a longitudinal design. Participants (n = 32) were cocaine-dependent patients who completed an inpatient chemical dependency program and then participated in an 8-week outpatient relapse prevention program. Craving ratings and urine samples were collected during hospitalization, at 12 weekly outpatient treatment sessions, and at 1, 2, 4, 8, 12, and 24-week follow-up. Craving increased significantly from inpatient to outpatient treatment. Cocaine-abstinent participants reported lower craving across outpatient treatment and follow-up compared to moderate and heavy cocaine users. The overall relationship between craving and total proportion of cocaine positive urines was highly significant. Implications of these findings for advancing our theoretical and practical knowledge about craving and cocaine use, are explored.

Treatment outcome of cocaine-alcohol dependent patients.

Cocaine dependent patients (n = 27) with and without concurrent alcohol dependence disorder were compared on measures of substance use, addiction severity (ASI), coping, and psychopathology taken before, during, and after outpatient relapse prevention treatment for cocaine dependence. At pre-treatment, the cocaine-alcohol (CA) group reported more frequent alcohol use, and more severe alcohol and family/social problems compared to the cocaine-only (CO) group. By the end of treatment, both groups reported significantly fewer days of alcohol and cocaine use, with sustained reductions observed at 24 weeks following treatment. On most of the addiction severity and psychiatric symptomatology scales, results indicated overall improvement as a function of time, however scores remained relatively 'worse' in the CA group. Implication of these findings and the need for specific programming in the treatment of dual drug use are explored.

Evaluating improvement over the course of adult psychiatric hospitalization.

This paper describes an evaluation of the potential efficacy of adult in-patient psychiatric treatment provided at a private general hospital. Using a simple pretest-posttest group design, 78 consecutively admitted patients, and a valid measure of psychiatric symptomatology (Symptom Checklist-90-R), it was found that the diverse group of patients were statistically significantly improved at discharge, relative to their admission status. This study illustrates a practical effort by social workers to integrate simple evaluative efforts into routine clinical services provided by mental health facilities, efforts consistent with managed care, the demands of third-party-payers, and the profession's initiatives in the direction of empirically-based practice.

Feather picking disorder and trichotillomania: an avian model of human psychopathology.

Animal models of psychopathology have been extremely valuable in conceptualizing various human disorders. The human condition known as trichotillomania (compulsive hair pulling) has considerable similarities with an avian disorder called feather picking, with respect to analogous behavior, proposed etiologies, evoking cues, response to behavior therapy, and response to pharmacological treatments based on serotonin re-uptake inhibitors. We suggest that feather picking disorder has the potential to be a useful animal model of trichotillomania, and lends itself to studies on the experimental psychopathology of compulsive hair pulling.