Faculty Bibliography

The authors prospectively followed patients with treatment-resistant obsessive-compulsive disorder (OCD). Between 1988 and 1995, 56 patients with a history of inadequate response to oral clomipramine received 14 infusions of intravenous clomipramine. The follow-up period ranged from 4 to 11 years after treatment. Of the 44 subjects interviewed at follow-up, 70.5% had current OCD and 29.5% had sub-threshold OCD. Almost half reported feeling much improved or very much improved compared to their state prior to treatment with intravenous clomipramine

Ketamine is a schedule III drug with a well-established safety profile that has been used extensively as an anesthetic for close to 4 decades. It has long been described as a drug of abuse and has become known as one of the 'club drugs,' used by adolescents and young adults in rave and circuit party settings. Ketamine is a congener of phencyclidine and acts as a noncompetitive N-methyl-D-aspartate (NMDA) antagonist. Through a complicated and not completely understood process, NMDA antagonism increases dopamine levels in reward-related areas such as the ventral tegmental area and the nucleus accumbens. In addition to its addictive liability, there is also evidence to suggest that ketamine might have anti-addictive properties when used as an adjunct to psychotherapy that takes advantage of its ability to produce spiritually oriented altered states of consciousness. This technique has been applied to patients with alcohol and opiate use disorders. Ketamine's potential anti-addictive properties can be understood by looking at biologic and psycho-spiritual models

We report here on the feasibility of implementing a semiautomated performance improvement system-Patient Feedback (PF)-that enables real-time monitoring of patient ratings of therapeutic alliance, treatment satisfaction, and drug/alcohol use in outpatient substance abuse treatment clinics. The study was conducted in six clinics within the National Institute on Drug Abuse Clinical Trials Network. It involved a total of 39 clinicians and 6 clinic supervisors. Throughout the course of the study (consisting of five phases: training period [4 weeks], baseline [4 weeks], intervention [12 weeks], postintervention assessment [4 weeks], sustainability [1 year]), there was an overall collection rate of 75.5% of the clinic patient census. In general, the clinicians in these clinics had very positive treatment satisfaction and alliance ratings throughout the study. However, one clinic had worse drug use scores at baseline than other participating clinics and showed a decrease in self-reported drug use at postintervention. Although the implementation of the PF system proved to be feasible in actual clinical settings, further modifications of the PF system are needed to enhance any potential clinical usefulness

BACKGROUND: Existing data indicate that 12-step program involvement is associated with improved outcomes in the dually diagnosed, but there are questions concerning the magnitude and mechanisms of this effect in various dually diagnosed populations. METHODS: Publications identified in a comprehensive review of the literature pertaining to 12-step programs and patients with addictions and co-occurring psychiatric disorders were reviewed for any content relevant to understanding the process of change involving dually diagnosed patients involved with 12-step programs. RESULTS: Dually diagnosed individuals attend 12-step programs at rates comparable to the nondually diagnosed, although specific diagnoses may have some effect on attendance. The benefits of 12-step attendance do not appear to be markedly different for those with psychiatric disorders. Specialized 12-step programs could have benefits for the dually diagnosed over and above those of traditional 12-step programs. Existing data suggest that nonspecific change mechanisms (self-efficacy, social support) are similar to those found in the general AA literature. CONCLUSIONS: Based on existing data, the change mechanisms are broadly similar to those found in the general 12-step literature, but additional factors related to mental illness may also play a significant role. Further work is necessary to test the components of this model and to achieve a firm empirical foundation for understanding the processes of 12-step recovery in the dually diagnosed.

OBJECTIVES: To determine seroprevalence and correlates of exposure to HPV 16, 18, and 53 among 15- to 30-year-old drug users in Baltimore, MD. STUDY DESIGN: Young, newly initiated injection and noninjection drug users underwent a behavioral risk assessment and HPV serology testing. Sex-specific analyses were performed comparing seropositive and seronegative participants using chi2, Mann-Whitney tests, and logistic regression. RESULTS: Participants (n = 553) were 43.0% female, 40.2% African American, and median age was 24 years. HPV seroprevalence among females and males, respectively, was: HPV-16, 38.2% and 7.0%; HPV-18, 42.4% and 7.3%; and HPV-53, 27.7% and 5.1%. Correlates of HPV seropositivity among females included being African American and anal sex, and among males, having had sex with another male. CONCLUSIONS: HPV seroprevalence was high among young drug users and significantly higher among females than males, supporting previous findings. Further research is required to fully understand HPV risk factors among men and the contribution of anal transmission in women.

Cigarette smoking is widely prevalent among individuals in treatment for drug or alcohol dependence; however, the treatment of nicotine addiction in this population has numerous obstacles at both programmatic and patient levels. Despite these difficulties, recent studies have demonstrated moderate success in implementing smoking cessation treatment in drug rehabilitation programs. The National Drug Abuse Treatment Clinical Trials Network sponsored a smoking cessation study in 13 community-based outpatient substance abuse rehabilitation programs across the country. The study evaluated the effectiveness of smoking cessation treatment provided as an adjunct to substance abuse treatment-as-usual. This report summarizes the practical and clinical experiences encountered at each of the study sites with regard to implementing the smoking cessation treatment intervention. Smoking behavior of the treatment clientele was assessed by anonymous survey at each site. In addition, sites were systematically characterized by using program review and assessment tools completed by the respective staff and program directors at the site. Survey and recruitment data indicated that cigarette smoking is more prevalent and that smoking cessation treatment is more feasible, in methadone maintenance treatment programs. Other factors associated with smoking behavior and with the recruitment of drug- and alcohol-dependent individuals into the smoking cessation treatment study are described.

Chronic food restriction (FR) increases behavioral sensitivity to drugs of abuse in animal models and is associated with binge eating, which shares comorbidity with drug abuse, in clinical populations. Behavioral, biochemical and molecular studies conducted in this laboratory to elucidate the functional and mechanistic bases of these phenomena are briefly reviewed. Results obtained to date indicate that FR increases the reward magnitude and locomotor-activating effects of abused drugs, and direct dopamine (DA) receptor agonists, as a result of neuroadaptations rather than changes in drug disposition. Changes in striatal DA dynamics, and postsynaptic cell signaling and gene expression in response to D-1 DA receptor stimulation have been observed. Of particular interest is an upregulation of NMDA receptor-dependent MAP kinase and CaM Kinase II signaling, CREB phosphorylation, and immediate-early and neuropeptide gene expression in nucleus accumbens (NAc) which may facilitate reward-related learning, but also play a role in the genesis of maladaptive goal-directed behaviors. Covariation of altered drug reward sensitivity with body weight loss and recovery suggests a triggering role for one of the endocrine adiposity hormones. However, neither acute nor chronic central infusions of leptin or the melanocortin 3/4 receptor agonist, MTII, have attenuated d-amphetamine reward or locomotor activation in FR rats. Interestingly, chronic intracerebroventricular leptin infusion in ad libitum fed (AL) rats produced a sustained decrease in food intake and body weight that was accompanied by a reversible potentiation of rewarding and locomotor-activating effects of d-amphetamine. This raises the interesting possibility that rapid progressive weight loss is sufficient to increase behavioral sensitivity to drugs of abuse. Whether weight loss produced by leptin infusion produces the same neuroadaptations as experimenter-imposed FR, and whether any of the observed neuroadaptations are necessary for expression of increased behavioral responsiveness to acute drug challenge remain to be investigated

INTRODUCTION: Although several studies have identified abnormal rates of neurological soft signs (NSS) as a manifestation of CNS dysfunction in schizophrenia, differences in sample populations have contributed to a discrepancy in empirical findings. Furthermore, little is known about the potential of NSS to predict a clinical response to antipsychotic medications. The present study tests the associations between NSS and schizophrenia symptomatology and examines NSS as a potential marker for predicting treatment response. METHODS: Nineteen unmedicated male schizophrenia patients were treated prospectively with haloperidol for six weeks. The subjects were assessed for pre and post-treatment NSS and schizophrenia symptomatology (Brief Psychiatric Rating Scale, BPRS). RESULTS: NSS at baseline were significantly associated with baseline symptoms on the Positive, Negative, and Psychological Discomfort BPRS subscales. NSS showed a strong trend toward improvement during six weeks of a prospective haloperidol trial. Hierarchical linear regression analyses indicated that more severe baseline NSS predicted poorer response to haloperidol treatment as measured by post-treatment BPRS Total subscale scores. DISCUSSION: NSS at untreated baseline are associated with baseline symptom severity, and elevated NSS are predictive of a smaller degree of improvement in symptoms after antipsychotic treatment. These findings are consistent with the hypothesis that NSS are linked to the neuropathology that underlies schizophrenia symptomatology and course