DHEAS and POMS measures identify cocaine dependence treatment outcome.

UNLABELLED: Early attrition is a significant problem in the treatment of cocaine dependence, but it is unclear why some patients succeed in treatment while others relapse or drop out of treatment without a demonstrated relapse. The goal of this study was to determine whether baseline levels of select hormones, including the adrenal hormone and excitatory neurosteroid dehydroepiandrosterone sulfate (DHEAS), would distinguish between treatment outcome groups. Based on the literature, completion of 90 days of treatment was established as a key outcome variable. METHODS: Quantitative urine levels of the cocaine metabolite benzoylecgonine (BE) and other substance of abuse analytes, plasma levels of DHEAS, DHEA, cortisol, and prolactin, and the profile of mood states (POMS) were serially measured in 38 male cocaine-dependent (DSM-IV) patients and in 28 controls of similar gender and age over a six month study. Exclusion criteria for the patients and controls included Axis I mood, anxiety or psychotic disorders. The patients could not manifest substance dependence except to cocaine. The patients and controls received remuneration for urine and blood collection. Blood samples for hormone levels were obtained between 8 and 10 a.m. on days 1, 14 and 21 of a 21-day inpatient treatment program and throughout 6 months of outpatient study visits at 45-day intervals. RESULTS: Attrition from treatment and study appointments occurred predominately at the junction between inpatient and outpatient programs. Forty percent of patients made the transition to outpatient treatment and remained abstinent and in treatment for a median of 103 days (ABST). Forty-two percent of patients dropped out of treatment during the inpatient stay or never returned after completing the inpatient program (DO) and 18% had a documented relapse either during, or within the first week after, the inpatient stay (REL). POMS total scores were elevated at treatment entry for both the ABST and DO groups. Plasma DHEAS levels in the DO patients were decreased compared to controls and increased in the ABST patients. POMS total scores for the REL patients at baseline were at control levels. Baseline cortisol levels were not statistically different between the outcome groups, though they were elevated for all cocaine patient groups. When treatment outcome was collapsed into whether patients completed (ABST) or did not complete 90 days of treatment (90N), ABST plasma DHEAS and cortisol were significantly elevated compared to the 90N patients and controls across the first 3 weeks of cocaine withdrawal. CONCLUSIONS: At treatment entry, each of the three patient outcome groups was identified by levels of circulating DHEAS and distressed mood. In the ABST patients, distressed mood during withdrawal may have been mitigated through antidepressant-like actions of enhanced endogenous DHEAS activity, thus contributing to improved abstinence and treatment retention. Patients, such as the DO group, with high levels of distressed mood at treatment entry and low DHEAS levels may benefit from adjunctive pharmacotherapy that targets DHEAS and POMS measures. Patients, such as the REL group, who lack distressed mood at treatment entry, may require intense application of motivational approaches plus residential treatment.

Ultrafiltration using the Amicon MPS-1 for assessing methadone plasma protein binding.

The percent of protein-free and protein-bound methadone were separated in methadone-spiked bank and artificial plasma, and in plasma samples taken from methadone-maintained patients using the Amicon MPS-1 ultrafiltration device. Following the separation procedure, protein-bound and protein-free methadone were extracted from the protein-bound and free fractions, and their respective concentrations were determined by gas chromatography and nitrogen-phosphorus detection. Eighty-five patient samples from 38 men and 10 women receiving methadone maintenance were collected and subjected to the ultrafiltration methodology. Two independent procedures demonstrated that, following the ultrafiltration process, no proteins were measurable in the filtrate. In addition, the ultrafiltration process was found to function independently of the concentration of methadone and the volume of sample, assuming the amount filtered never exceeded 40% of the original volume. In the patient samples, the %-free methadone varied sixfold across all patients. Female patients were found to have a mean +/- SD %-free methadone of 11.9 +/- 3.8% vs. 10.1 +/- 3.4% for men. Pearson correlation values suggest that steady-state protein-free methadone levels (r = 0.521) and total methadone levels (r = 0.491) rise as methadone dose is increased. Corresponding to these results, free methadone levels are highly correlated with total methadone levels (Pearson r = 0.85). The Amicon MPS-1 ultrafiltration device appears to be a reliable and relatively easy system to use for separating protein-free from protein-bound methadone, though further study is required to clarify the clinical applications of free methadone levels.

Absence of acute cocaine interactions with the MAO-B inhibitor selegiline.

Selegiline, an irreversible monoamine oxidase-B (MAO-B) inhibitor, is under investigation as a treatment for cocaine relapse prevention. To evaluate its safety, human volunteers (n = 5) received intravenous cocaine (0, 20 and 40 mg, 1 h apart) following treatment with placebo or selegiline (10 mg, p.o.). Cocaine increased heart rate, blood pressure, pupil diameter and subjective indices of euphoria and craving. Selegiline produced no measureable effects, except for miosis, and did not alter the effects of cocaine. These data suggest that selegiline may be safely administered in combination with cocaine, and that selegiline is unlikely to increase reinforcing effects of cocaine.

Lipoperoxides in sebum of substance users and controls.

Sebum was collected from forehead skin in five compulsive heroin and/or cocaine (substance) users and in five controls over three consecutive periods, each lasting three hours. The participants were adult black and white men similar in age and smoking habits, who did not consume alcohol. Lipoperoxides were determined in sebum as malondialdehyde by high performance liquid chromatography. Two participants were excluded in the control group: in both, urinary lipoperoxides were elevated; in one, urine tested positive for delta-9 tetrahydrocannabinol (THC). All other participants had negative urine drug screening tests. Relative to the controls, all substance users had elevated concentrations of lipoperoxides in urine. Compared to the controls, the rate of sebum excretion in the last collecting period was higher in substance users, but sebum had significantly lower lipoperoxide concentration. It is assumed that compulsive drug use may influence lipoperoxidation of incipient sebum, possibly by altered tissue perfusion.

Discrepancies between patient report, clinical assessment, and urine analysis in psychiatric patients during inpatient admission.

Self-report and clinical assessment of substance use were compared with urine analysis results in 56 male patients consecutively admitted for inpatient psychiatric treatment. All subjects received DSM-III-R Axis I diagnosis and were classified into diagnostic groups. Urine samples were tested for cocaine, marijuana, opiates, phencyclidine (PCP), amphetamines, and barbiturates. Thirty-five of the 56 patients (62%) produced urine samples that were positive for at least 1 substance of abuse. Of this group, 15 patients (27% of total sample) denied substance use during the week prior to admission. In addition, the admitting physician did not identify intoxication in 23 of the 35 patients (66%) with positive urines. The admitting physician's assessment matched the patient's answers regarding recent substance use in 79 percent of the patients. This association was especially apparent with the 26 patients who denied recent substance use, all but one of whom received a drug-negative assessment from the admitting physician.