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Intravenous challenges with placebo and cocaine doses ranging from 0.125 to 0.5 mg/kg were administered to five subjects using a within subjects design during placebo and active desipramine (DMI) maintenance at a fixed dose of 150 mg daily for at least 10 days. The "high" reported after cocaine infusion was not altered by DMI, but "desire for cocaine" after a single dose was attenuated. Together with the results of clinical trials of DMI for cocaine abuse, these laboratory results suggest that DMI may reduce cocaine craving both during and between cocaine binges. Physiologically, baseline heart rate was higher on DMI, but the incremental heart rate response to cocaine was attenuated.

We conducted a double-blind, random assignment, six-week comparison of desipramine hydrochloride (n = 24), lithium carbonate (n = 24), and placebo (n = 24) treatments for cocaine dependence. Subjects were 72 outpatient cocaine abusers who met DSM-III-R dependence criteria for cocaine but not for other substance abuse. Subjects in each treatment group were similar in history of cocaine and other substance abuse, cocaine craving, sociodemographics, and other psychiatric comorbidity. Desipramine, compared with both other treatments, substantially decreased cocaine use. Lithium treatment outcome did not differ from that of placebo. Desipramine-treated subjects attained contiguous periods of abstinence substantially more frequently than subjects receiving lithium or placebo. Fifty-nine percent of the desipramine-treated subjects were abstinent for at least three to four consecutive weeks during the six-week study period, compared with 17% for placebo and 25% for lithium. Cocaine craving reductions were also substantially greater in the desipramine-treated subjects. Establishment of initial abstinence is the first stage in recovery from cocaine dependence. Our findings indicate that desipramine is an effective general treatment, for this first treatment stage, in actively cocaine-dependent outpatients.