Efficacy screening trials of paroxetine, pentoxifylline, riluzole, pramipexole and venlafaxine in cocaine dependence

Authors

  • Domenic A. Ciraulo,

    Corresponding author
    1. Division of Psychiatry, Boston University School of Medicine and VA Boston Healthcare System Medication Development Research Unit (MDRU), Boston, MA, USA,
      Domenic A. Ciraulo
      Boston University School of Medicine
      Doctors Office Building
      Suite 914
      720 Harrison Avenue
      Boston
      MA 02118
      USA
      E-mail: dciraulo@bu.edu
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  • Ofra Sarid-Segal,

    1. Division of Psychiatry, Boston University School of Medicine and VA Boston Healthcare System Medication Development Research Unit (MDRU), Boston, MA, USA,
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  • Clifford M. Knapp,

    1. Division of Psychiatry, Boston University School of Medicine and VA Boston Healthcare System Medication Development Research Unit (MDRU), Boston, MA, USA,
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  • Ann Marie Ciraulo,

    1. Division of Psychiatry, Boston University School of Medicine and VA Boston Healthcare System Medication Development Research Unit (MDRU), Boston, MA, USA,
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  • Joseph LoCastro,

    1. Division of Psychiatry, Boston University School of Medicine and VA Boston Healthcare System Medication Development Research Unit (MDRU), Boston, MA, USA,
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  • Daniel A. Bloch,

    1. Department of Health and Research Policy, Division of Biostatistics, Stanford University School of Medicine, Stanford, CA, USA,
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  • Margaret A. Montgomery,

    1. Center for Drug Evaluation and Research, Food and Drug Administration, Rockville, MD, USA and
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  • Deborah B. Leiderman,

    1. Center for Drug Evaluation and Research, Food and Drug Administration, Rockville, MD, USA and
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  • Ahmed Elkashef

    1. National Institute on Drug Abuse Medications Development Division, Bethesda, MD, USA
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Domenic A. Ciraulo
Boston University School of Medicine
Doctors Office Building
Suite 914
720 Harrison Avenue
Boston
MA 02118
USA
E-mail: dciraulo@bu.edu

ABSTRACT

Aims  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.

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

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

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

Intervention  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.

Measurements  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.

Findings  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.

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