I. Differences in Effectiveness of Atypical Antipsychotics in Patients with Co-Occurring Psychotic and Substance Abuse Disorders

II. GABA Agonists as Putative Pharmacotherapies for Cocaine Abuse: Results From Human Laboratory Experiments

III. Treatment Response of Opium Smoking Hmong Refugees to Methadone Maintenance

IV. Substance Abuse Field: The State of the Art

V. Predictors for Residential Rehabilitation and Treatment No-Show in High-Frequency Cocaine Users: Validation of the American Society of Addiction Medicine (ASAM) Criteria

The Circle Program is a 30-bed, 90-day intense cognitive/behavioral-based, fully integrated, inpatient dual diagnosis treatment for patients between the ages of 18 and 60 years. The program is abstinence based, including being totally tobacco free. Successful completion is difficult to achieve and averages 58% for all diagnoses. Successful completion of the program includes

A retrospective review of patients with psychotic disorder diagnoses treated between January 2001 and May 2002 was conducted to compare outcome measures with the primary antipsychotic medication prescribed.

Outcome measures included length of stay in treatment, successful completion of the program, level in the program at the time of discharge and changes in body mass index (BMI) during the time of treatment. The program had three levels: precontemplation, contemplation and action or ownership.

The study included 50 patients: 26 had schizophrenia, 19 had schizoaffective disorder and five had psychotic disorder NOS. All had one or more chemical dependence diagnosis.

Olanzapine was the most frequently prescribed atypical antipsychotic — 17 or 34% of patients were taking olanzapine, and the mean dose was 18.7 mg/day. Eleven patients, or 22%, were taking ziprasidone, and the mean dose was 118 mg/day. Ten patients, or 20%, were taking risperidone, and the mean dose was 3.8 mg/day. An additional 10 patients, or 20%, were taking typical depot. One patient was taking clozapine, and one patient was taking quetiapine.

There was no significant difference in frequency of other medication use in patients on any antipsychotic, and there was no significant difference in frequency of other medication use on length of stay, program completion or level achieved at discharge. Differences in effectiveness were observed between atypicals. Patients experienced less sedation with risperidone and ziprasidone. There was less cognitive clouding with risperidone and ziprasidone. Patients were able to lose weight on ziprasidone with improved self-esteem, and an improvement was seen in serum lipids on ziprasidone.

Patients were more likely to remain in treatment longer when taking ziprasidone compared with olanzapine or typicals and when taking risperidone compared with olanzapine. Seventy-three percent of ziprasidone patients and 70% of risperidone patients successfully completed the program, while only 24% of those on olanzapine and 20% of those on typicals successfully completed the program. Change in BMI was significant for those on ziprasidone compared to those on olanzapine, risperidone and typicals, with a significant decrease in weight in those on ziprasidone compared to those on olanzapine and risperidone.

The study concluded that ziprasidone and risperidone were significantly more effective medications than olanzapine or depot typicals in this population. Ziprasidone was effective in patients losing weight and in decreasing lipids when switching from olanzapine with improvement in sedation and cognition while maintaining psychiatric stability.

Cocaine abuse and dependence are significant public health concerns. Between 2001 and 2002, the number of people reporting cocaine use in the previous 30 days increased by approximately 38%. Because of the public health concerns, identifying an effective pharmacotherapy for the management of cocaine abuse and dependence is a priority for the National Institute on Drug Abuse (NIDA).

Preclinical studies have demonstrated that GABA agonists attenuate the effects of cocaine under a variety of experimental arrangements. GABA systems might be targeted for the development of medications to treat cocaine abuse.

Three experiments were conducted. In the first experiment, 10 volunteers with recent history of cocaine use participated. The effects of oral cocaine (0 and 300 mg) were assessed following pretreatment with GABA_A agonist triazolam (0 and 0.5 mg). Volunteers received all possible cocaine-triazolam combinations. Subjective and physiological responses were measured.

The second experiment included seven volunteers with histories of recent cocaine use. In this experiment, the effects of intranasal cocaine (0 and 45 mg) were assessed following pretreatment with the GABA_B agonist baclofen (0, 10, 20 and 30 mg). Volunteers received all possible cocaine-baclofen combinations. Subjective and physiological responses were measured. Neither triazolam nor baclofen blocked the effects of cocaine.

The third study is ongoing. Four volunteers have completed the protocol, and an additional four will be enrolled. In this experiment, volunteers are taught to discriminate 15-mg d-amphetamine. Following the acquisition of this discrimination, a range of doses of d-amphetamine (0, 2.5, 5, 10 and 15 mg) is tested alone and following pretreatment with alprazolam (0 and 0.5 mg). Each of the 10 d-amphetamine-alprazolam combinations was tested once. Discriminative, subject-rated and physiological responses were measured. Alprazolam blocked the discriminative-stimulus effects of d-amphetamine.

The results of these studies provide some support for the utility of GABA_A agonists as pharmacotherapies for stimulant abuse. Future research should test the effects of GABA agonists in volunteers trained to discriminative cocaine.

Hmong are tribal people mainly from southern China. In the late 1800s, there was an uprising in China. Hmong then moved to Laos, Vietnam and Thailand. They have since migrated to the United States, France, Canada and Australia. In 2000, there were approximately 169,000 Hmong in the United States.

The purpose of this study was to examine the outcome of methadone treatment in opium-dependent Hmong refugees.

Medical records were reviewed for Hmong patients in methadone treatment between January 1995 and September 1997. History, diagnosis, laboratory evaluations and co-morbid medical conditions were extracted. Assessments included the Addiction Severity Index (ASI), urine toxicology screens and outcome criteria established by the Drug Abuse Research Project (DARP). Patients’ progress was assessed over 9 months.

The study included 40 Hmong patients — 33 men and seven women. Their mean age was 47.7 years. The majority (93%) were married, 27% were employed, 77% were in the military. Their mean age at first opium use was 22.3 years. They had used opium for a mean of 16 years. The mean number of opium pipes smoked per day was 105.

At admission, 100% met the DSM-IV criteria for opium dependence, 75% had a major depressive disorder and 68% had PTSD. All patients exclusively smoked opium. Thirty-six percent were positive for hepatitis C, and all were HIV negative. Their average methadone dose was 45 mg per day.

The average number of urine samples was 27 per patient over 9 months, with only four of 27 positive for opiates, mostly in the first 3 months. The ASI composite score improved from 3.9 at admission to 2.1 at 9 months (p<0.01) with subscales of employment/support status changing from 4.4 to 1.5 (p<0.01), drug use from 8.0 to 4.6 (p<0.01), family/social relationships from 4.5 to 1.7 (p<0.01) and psychiatric status from 6.2 to 4.5 (p<0.01).

Using outcome criteria modified from the Drug Abuse Research Project, 70% were highly successful, 15% were moderately successful, 5% were moderately unsuccessful and 10% were highly unsuccessful.

These study findings suggest that Hmong opium-dependent patients can show marked improvement while in methadone treatment.

Possible factors responsible for the positive outcome include the patients’ exclusive use of opium, most were married, they had no legal issues, they received comprehensive services, their compliance with psychotropics and the methadone program and the use of a Hmong addiction counselor.

The American Society of Addiction Medicine (ASAM) Patient Placement Criteria (PPC) has four levels that are associated with the location of treatment. Location describes the intensity of the treatment. Of these four levels of care, Level IV is the most intensive. These patients are medically managed 24 hours a day, such as in a hospital. Level III is residential treatment. Level II is intensive outpatient, and Level I is outpatient therapy.

Psychiatrists can determine which patients should receive which level of care by using six dimensions of measurement to assess the patient. The six dimensions are

1. intoxication and withdrawal

2. medical complications

3. psychiatric or behavior complications

4. readiness for change

5. relapse potential

6. recovery environment

To determine whether these criteria will save money or improve treatment response, nine studies have been conducted with more than 3,000 patients participating.

The most rigorous test would be a randomized, controlled trial. It should test matched versus mismatched assignments comparing at least two different levels. It would be unethical to randomize patients who need hospital care. Additionally, it is difficult to randomize people who only need outpatient care because they don’t want to go to residential treatment.

A computer algorithm was used because it is hard to use these rules. An inter-rater reliability test was conducted using eight counselors trained to use the criteria through this computerized mechanism. Seventy-seven percent of the time, two counselors agreed on the same level of care for the patient, which is good reliability.

In addition to inter-rater reliability, the criteria were found to have applicability. It was feasible to administer the criteria in less than 1 hour. The patients included in the study were indigent and on Medicaid.

The study included 700 patients; 70% were recruited from residential detox. They were followed up at months 1, 3, 6 and 12 and were asked for face-to-face interviews.

Of the 700 patients, 52% showed up on the first day, leaving 366 patients. Most (87%) had at least one follow-up interview. In the first month, ASI scores dropped by more than 50% and stayed that way for the rest of the year.

These data, on a substantial sample of 366 patients, support the ASAM patient placement criteria as a staging system for addictions. In some ways, this is a breakthrough. It’s not a breakthrough because it tells physicians what the treatment should be. This is not the final answer, because we’d like to know that matching is valid with these criteria.

Mismatching outcomes showed that patients needing Level III treatment who get less treatment than needed do marginally worse on alcohol, medical, family/social and psychiatric outcome measures and on global assessment of function. Additionally, they had significantly worse treatment engagement. Differences persist even over 12 months and through general and public treatment.

The finding that high-frequency cocaine users (HFCU) (i.e., those with more than 8 days of use in the previous 30 days) were preferentially placed into a residential level of care (LOC) (Level-III = residential rehabilitation vs. L-II = day treatment) by the ASAM Patient Placement Criteria (PPC) prompted an examination of what factors were most influential in determining placement and if these were associated with differential outcomes.

Subjects (n=700) were randomly assigned into either Level II or III and were analyzed in two groups: those placed in their adequate LOC or higher and those who were mismatched to a lower LOC. Matching was performed using a comprehensive computerized assessment implementing all six ASAM PPC dimensions.

HFCU were found to be statistically distinct with regard to certain demographics, Addiction Severity Index (ASI), Recovery Attitude and Treatment Evaluator (RAATE), and Global Assessment of Functioning (GAF) scores and were more likely to qualify for Level III (77%) by the ASAM PPC (p<0.01). Deconstruction analysis of the ASAM PPC identified six specific rules as substantially contributing to Level III placement. A regression analysis showed that four of these rules were in fact predictors of residential rehabilitation placement by the ASAM PPC (p<0.01). None of these rules by themselves significantly predicted no-show rate. However, a consistent predictor of overall no-show to treatment for this population of HFCU was being mismatched to lower level of care status (p<0.001). One of the six rules was also statistically significant in its association with a higher show rate specifically for adequately matched subjects (p<0.05).

This blind, randomized, controlled study indicates that placement according to the ASAM PPC would yield better show rates for HFCU through its complex combinations of hierarchical decision rules. Particular patient characteristics predicting differential placement by the ASAM criteria and associated with higher show rates can also be identified. Such characteristics may be very valuable in the diagnosis, prognosis and treatment planning for cocaine users.