Influence of antisocial personality subtypes on drug abuse treatment response.

This methodological study examined the impact of antisocial personality disorder (APD) and other psychiatric comorbidity on drug use and treatment retention in 513 new admissions to methadone maintenance treatment. Patients were classified into one of four groups: APD ONLY, APD plus other psychiatric disorder (APD MIXED), other psychiatric disorder, and no psychiatric disorder. Patients completed research assessments and were then followed for 1 year of treatment. Patients with APD had longer histories of heroin and cocaine use than non-APD patients and were more likely to meet criteria for cocaine dependence. Distinct clinical profiles emerged that differentiated APD ONLY from APD MIXED. APD ONLY patients exhibited higher rates of cocaine and heroin use, whereas those with APD MIXED exhibited higher rates of benzodiazepine use. Self-report measures supported urinalysis results, but group differences did not affect treatment retention. These differences in clinical profiles should be considered when evaluating treatment performance in substance abusers with APD.

Short-term stability of NEO-PI-R personality trait scores in opioid-dependent outpatients.

The present study examined the short-term stability of personality trait scores from the Revised NEO Personality Inventory (NEO-PI-R) among 230 opioid-dependent outpatients. The NEO-PI-R is a 240-item empirically developed measure of the five-factor model of personality (Neuroticism, Extraversion, Openness, Agreeableness, and Conscientiousness). Participants completed the NEO-PI-R at admission and again approximately 19 weeks later. Results indicated fair to good stability for all NEO-PI-R factor domain scores, with coefficients ranging from .68 to .74. Stability of NEO-PI-R scores was decreased among potentially invalid response patterns but was not significantly affected by drug-positive versus drug-negative status at follow-up.

Effects of buprenorphine/naloxone in opioid-dependent humans.

RATIONALE: Buprenorphine is a partial mu opioid agonist under development as a sublingual (SL) medication for opioid dependence treatment in the United States. Because buprenorphine may be abused, tablets combining buprenorphine with naloxone in a 4:1 ratio have been developed to reduce that risk. Low doses of injected buprenorphine/naloxone have been tested in opioid-dependent subjects, but higher doses (more than 2 mg of either medication) and direct comparisons to SL buprenorphine/naloxone have not been examined. OBJECTIVES: To assess and compare the effects of intramuscular (i.m.) versus SL buprenorphine/naloxone in opioid-dependent volunteers. METHODS: Opioid-dependent volunteers were maintained on 40 mg per day of oral hydromorphone while on a residential research ward. After safety testing in two pilot subjects, participants (n = 8) were tested with both i.m. and SL buprenorphine/naloxone (1/0.25, 2/0.5, 4/1, 8/2, 16/4 mg); i.m. hydromorphone (10 mg) and naloxone (0.25 mg); both i.m. and SL buprenorphine alone (8 mg); and placebo. Test sessions were twice per week; dosing was double-blind. RESULTS: Intramuscular buprenorphine/naloxone produced dose-related increases on indices of opioid antagonist effects. Effects were consistent with naloxone-precipitated withdrawal, and were short-lived. As withdrawal effects dissipated, euphoric opioid agonist effects from buprenorphine did not appear. Sublingual buprenorphine/naloxone produced neither opioid agonist nor antagonist effects. CONCLUSIONS: Intramuscular injection of buprenorphine/naloxone precipitates withdrawal in opioid dependent persons; therefore, the combination has a low abuse potential by the injection route in this population. Sublingual buprenorphine/naloxone by tablet is well tolerated in opioid dependent subjects, and shows neither adverse effects (i.e., precipitated withdrawal) nor a high abuse potential (i.e., opioid agonist effects).

Influence of psychiatric comorbidity on HIV risk behaviors: changes during drug abuse treatment.

This study evaluated whether psychiatric comorbidity is related to change in HIV high risk behaviors during outpatient drug abuse treatment. Participants were opioid abusers entering methadone treatment. Psychiatric and substance use diagnoses were determined at intake. Information on HIV high risk drug use and sexual behaviors, psychosocial functioning, and urine toxicology was assessed at intake and at month six. Subjects were divided into those with versus without a lifetime comorbid non-substance use psychiatric disorder. The comorbid group reported more injection equipment sharing, lower rates of condom use, and higher rates of alcohol use at intake and follow-up. Overall injection drug use behavior decreased over the follow-up period for both groups, however. Methadone treatment had a beneficial effect on HIV risk behaviors, and though some risk behaviors improved signiticantly for both groups, comorbid subjects continued to have higher rates of HIV risk factors than noncomorbid subjects.

A controlled study of flumazenil-precipitated withdrawal in chronic low-dose benzodiazepine users.

RATIONALE: Preclinical studies of the benzodiazepine antagonist flumazenil (Romazicon) have contributed to the understanding of the physical dependence associated with chronic benzodiazepine use; when administered to animals chronically pretreated with benzodiazepines, flumazenil precipitates a withdrawal syndrome. However, few controlled clinical studies have been conducted. OBJECTIVES: The objective was to characterize the effects of flumazenil in long-term users of therapeutic doses of benzodiazepines. METHODS: The acute physiological, participant-rated, and observer-rated effects of intravenously administered flumazenil (1 mg/70 kg) and caffeine (300 mg/70 kg; active drug control) were evaluated in an experimental group of 13 long-term users (mean 4.6 years) of low therapeutic doses (mean 11.2 mg/day diazepam equivalent) relative to a matched group of 13 volunteers without prior exposure to benzodiazepines in a double-blind, placebo-controlled, mixed design. RESULTS: Whereas the experimental group did not differ from the control group with respect to the effects of placebo, and both groups showed some changes in response to caffeine (e.g., increased blood pressure and anxiety scores), only the experimental group showed considerable changes in physiological measures, participant ratings (e.g., increased ratings of dizziness, blurred vision, heart pounding, feelings of unreality, pins and needles, nausea, sweatiness, noises louder than usual, jitteriness, things moving, sensitivity to touch), and observer ratings in response to flumazenil; in addition, four participants developed panic attacks. CONCLUSIONS: This study clearly demonstrates that flumazenil can precipitate symptoms commonly associated with benzodiazepine withdrawal in chronic low-dose benzodiazepine users.

Attention deficit hyperactivity disorder and treatment outcome in opioid abusers entering treatment.

Symptoms of DSM-IV attention-deficit hyperactivity disorder (ADHD) were determined in patients entering methadone maintenance treatment. The relationship of ADHD to psychiatric and substance abuse comorbidity, attention testing, and treatment outcome was analyzed; 19% of patients had a history of ADHD, and 88% of these had current symptoms. Continuous Performance Testing indicated poorer attention in patients with ADHD. The only substance use disorder more common in the ADHD group was clonidine. There was significantly more current axis I, dysthymic disorder, anxiety disorder (including social phobia), and antisocial personality disorder in the ADHD patients. There was no difference between groups at the 1-year follow-up for illicit drug use, treatment retention, or treatment performance. The ADHD diagnosis did not convey significant prognostic implications for methadone maintenance treatment. A strong psychiatric assessment and treatment focus in the treatment program may help to explain the good treatment outcome.

Predictive validity of cocaine, sedative, and alcohol dependence diagnoses.

This study examined the predictive validity of Structured Clinical Interview for DSM-III-R (Spitzer, Williams, Gibbon, & First, 1990) based substance dependence diagnoses (i.e., cocaine, sedative, and alcohol) for 518 opioid-dependent outpatients entering methadone maintenance. Patients were followed over 1 year of treatment, which involved daily methadone substitution supplemented by individual and group counseling. Urine specimens were tested randomly 1-4 times per month. Patients diagnosed with current cocaine, sedative, or alcohol dependence were more likely to use these drugs than were patients with past only or no dependence syndrome. Current cocaine dependence predicted early treatment dropout. The results demonstrate the predictive and discriminant validity of several substance dependence diagnoses common among patients in substance abuse or other psychiatric treatment settings.