In healing cocaine dependency, presently efforts are developing to emphasize the employment of pharmacological agents chosen for their effectiveness on such components of the withdrawal syndrome as depression. Because of the lack of assurance of therapeutic effects of these drugs on cocaine abuse, ethical as well as scientific considerations indicate the inclusion of a more proven therapeutic approach, i.e., counseling, in treatment studies.
O'Brien et al. (1, p. 17) point out that "a cocaine rehabilitation program should use a multidimensional approach, beginning with a detoxification procedure and proceeding to a variety of different models for preventing relapse." The detoxification phase often involves hospitalization, which can be quite costly. An obvious alternative is an outpatient treatment of sufficient intensity in which provisions are made for an array of therapeutic interventions aimed at attaining cessation of use as well as facilitating relapse prevention. While such a treatment program would obviously not be totally successful in achieving abstinence or relapse prevention, most participants could be expected to attain a range of favorable results, from decreased usage or better personal adjustment to permanent abstinence.
Antidepressants currently advocated in the treatment of cocaine abuse include tricyclics, some heterocyclics, and 5-HT reuptake inhibitors. One of the serotonergic antidepressants, fluoxetine, has been reported to markedly reduce cocaine reinforced behavior in rats in some laboratory studies but not in others. Cocaine-dependent methadone maintained patients have been reported to benefit from fluoxetine treatment. Fluoxetine has also been used with alcoholics.
The "gold standard" for outcome analyses in these types of studies has been the degree of reduction in actual frequency or amount of cocaine use achieved by study subjects who have adhered to the medication requirements of the protocol. While some investigators have used self-reports of drug use, others have relied exclusively on more objective measures such as urine toxicology surveillance in conditions controlled for tampering with the specimen. Mood measures are also important indicators of the effect of treatment in cocaine abuse, and some aspects of cravings intersect with depression and anxiety. Cravings may be in themselves sensitive outcome measures. Because of the ambiguity of the term "cravings" their measurement may require lengthy questionnaires. They may also be approached more simply in terms of "need" and "want" on analog scales, as has been our practice. All of these outcome measures were collected in the present study.
The present report utilizes three different stratifications of the sample to examine the efficacy of the combination of intensive "interpersonal" counseling with fluoxetine for cessation of cocaine use and relapse prevention in chronic cocaine abusers.
The first analysis compares the original medication assignment, "active placebo," fluoxetine 20, 40, or 60 mg. The second analysis looks more closely at medication compliance by comparing the placebo group to a group of all fluoxetine subjects who had detectable blood levels of fluoxetine and to a third group of those fluoxetine subjects without such blood levels. The third analysis examines relapse occurrence by comparing the urine status at the first treatment visit, i.e., cocaine positive and negative, with placebo and fluoxetine assignment.
The subjects for this study were self-referred chronic cocaine abusers seeking outpatient treatment at the National Institute on Drug Abuse, Addiction Research Center (ARC), located at the Francis Scott Key Medical Center in Baltimore, Maryland. They were recruited primarily through newspaper or radio advertisements, but some subjects were referred by friends or former ARC subjects and some from other treatment facilities or social agencies.
All applicants were screened by telephone. A counselor, following a standardized routine and script, described the treatment program and determined preliminary eligibility of each caller. All potentially eligible subjects were then offered appointments for further evaluation. Those found ineligible were offered referral to other treatment facilities in the area. Two hundred nine (75%) of the eligible individuals accepted appointments and 109 (52%) of those eligible attended their first appointment. The intake procedure extended over two half-day sessions in the course of a week. All subjects were interviewed by a drug abuse counselor who determined current DSM-III-R cocaine dependence and excluded those with other current substance dependencies, except nicotine. The level of cocaine use required to qualify for the study was a minimum of 1 gram of cocaine per week during the 12 weeks preceding intake. Additional exclusion criteria were illiteracy, current medical illness, pregnancy, and psychiatric conditions severe enough to need immediate psychiatric treatment. Persons with current legal problems were not excluded unless imprisonment was imminent.