Nefazodone treatment of cocaine dependence with comorbid depressive symptoms

In the current study, nefazodone, an antidepressant with dual action on serotonin and norepinephrine reuptake as well as 5-HT(2A) receptor antagonist effects, was studied in subjects with cocaine dependence and depressive symptoms, to determine its efficacy in reducing cocaine use.

An 8-week, double blind, placebo-controlled design was used.

The study was conducted at the Medication Development Research Unit (MDRU) at the VA Boston Healthcare System and the Manhattan Department of Veterans Affairs (DVA) Medical Center.

Subjects (n = 69) met Diagnostic and Statistical Manual version IV (DSM-IV) criteria for cocaine dependence and had Hamilton Depression Scores of 12 or higher.

Subjects were assigned randomly to receive nefazodone 200 mg twice daily (n = 34) or matching placebo (n = 35). All subjects received individual counseling.

Urinary measurements of benzoylecgonine (BE, three times per week) and self-reports of cocaine use were the primary outcome measures. Secondary outcome measures included assessments of psychiatric functioning, cocaine craving and social functioning.

Median weekly BE declined more rapidly in the nefazodone than in the placebo group. Median urine BE at baseline was, however, significantly greater in nefazodone than in the placebo group. Scores for strength of cocaine craving also decreased more rapidly in the nefazodone group compared to the placebo group. Both groups had equivalent improvement in mood, psychosocial functioning and self-reported cocaine use.

These results suggest that nefazodone administration can reduce cocaine craving after it has been administered for several weeks. Although the nefazodone group had a greater rate of decrease in BE levels than the placebo group, the interpretation of this finding is obscured by significant group differences in baseline BE levels.