Efficacy screening trials of paroxetine, pentoxifylline, riluzole, pramipexole and venlafaxine in cocaine dependence.
OBJECTIVE
The two studies presented here were conducted to assess the efficacy of paroxetine, pentoxifylline, riluzole, venlafaxine and pramipexole as medications for the treatment of cocaine dependence.


METHODS
A multi-arm, modified blinded, placebo-controlled design was used.


METHODS
The studies were conducted at the Boston VA Healthcare System and the Boston University School of Medicine Medication Development Research Unit (MDRU).


METHODS
Participants met criteria for cocaine dependence during a 2-week screening period.


METHODS
Following random assignment to one of the treatment groups, subjects received active medication or placebo for 8 weeks in combination with cognitive behavioral counseling. In the first study the efficacy of the antidepressant paroxetine (20 mg daily), the phosphodiesterase inhibitor pentoxifylline (1200 mg daily) and the glutamate release inhibitor riluzole (100 mg daily) was assessed. The antidepressant venlafaxine (150 mg daily) and the dopamine agonist pramipexole (1.5 mg daily) were evaluated in the second study.


METHODS
Urine benzoylecgonine (BE) concentrations, self-report of cocaine use and global impression scores served as primary outcome measures. Secondary measures included assessments of cocaine craving and psychiatric functioning. Adverse events were monitored during the treatment period.


RESULTS
None of the active medications produced greater reductions in urine BE concentrations over the treatment period than did placebo. There were trends for BE levels to become reduced in the pentoxifylline group during the first 4 weeks of treatment and for Addiction Severity Index (ASI) drug composite scores to be lower in the pentoxyfylline group at end-point compared to the placebo group. Significant within-group reductions in reported cocaine use and craving were found for all treatment groups, but none of the active medications were superior to placebo on these measures. The accuracy of self-reported cocaine use declined over the study period. Overall, the active medications were well tolerated.


CONCLUSIONS
This study does not support the use of paroxetine, pentoxifylline, riluzole, venlafaxine or pramipexole for the treatment of cocaine dependence. However, these results need to be interpreted with caution because of the small size and lack of homogeneity of the experimental groups.
Ciraulo
Domenic A
DA
Division of Psychiatry, Boston University School of Medicine, VA Boston Healthcare System Medication Development Research Unit (MDRU), Boston, MA, USA. dciraulo@bu.edu
Sarid-Segal
Ofra
O
Knapp
Clifford M
CM
Ciraulo
Ann Marie
AM
LoCastro
Joseph
J
Bloch
Daniel A
DA
Montgomery
Margaret A
MA
Leiderman
Deborah B
DB
Elkashef
Ahmed
A
D000293:Adolescent; D000328:Adult; D000928:Antidepressive Agents / Q000008:administration & dosage*; D052160:Benzothiazoles; D019970:Cocaine-Related Disorders / Q000534:rehabilitation*; D003511:Cyclohexanols / Q000008:administration & dosage; D018491:Dopamine Agonists / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D017374:Paroxetine / Q000008:administration & dosage; D010431:Pentoxifylline / Q000008:administration & dosage; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage*; D000077487:Pramipexole; D019782:Riluzole / Q000008:administration & dosage; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage*; D013844:Thiazoles / Q000008:administration & dosage; D000069470:Venlafaxine Hydrochloride
D000928:Antidepressive Agents; D052160:Benzothiazoles; D003511:Cyclohexanols; D018491:Dopamine Agonists; D018696:Neuroprotective Agents; D017374:Paroxetine; D010431:Pentoxifylline; D010726:Phosphodiesterase Inhibitors; D000077487:Pramipexole; D019782:Riluzole; D017367:Selective Serotonin Reuptake Inhibitors; D013844:Thiazoles; D000069470:Venlafaxine Hydrochloride