The Alpha-1 Adrenergic Antagonist Doxazosin for Treatment of Cocaine Dependence: A Pilot Study

Overview

Journal Drug Alcohol Depend

Publisher Elsevier

Specialty Psychiatry

Date 2013 Jan 12

PMID 23306096

Citations 31

Authors

D Shorter

J A Lindsay

T R Kosten

Affiliations

Soon will be listed here.

Abstract

Background: Medications decreasing central noradrenergic activity have been associated with attenuation of cocaine effects.

Aims: This pilot study examined the efficacy of doxazosin versus placebo for reducing cocaine use in treatment-seeking cocaine dependent persons.

Methods: We screened 108 cocaine dependent subjects and assigned 35 participants to receive either doxazosin (8mg/day) or placebo for 13 weeks. Participants were titrated on the study medication according to two different schedules. During the initial phase of the study, patients were titrated onto the study medication over an 8-week period (DOX-slow). After reviewing data from our human laboratory study, a second phase was initiated, wherein titration was accelerated to a 4-week period (DOX-fast). All participants received weekly cognitive behavioral therapy. Urine toxicology was performed thrice weekly.

Results: Baseline subject characteristics were comparable. Thirty subjects entered the study: 8 subjects in DOX-slow, 9 subjects in DOX-fast, and 13 subjects in placebo. Total number of cocaine-negative urines was significantly increased in the DOX-fast group; and percentage of total cocaine-negative urines by group were 10% for DOX-slow group, 35% for DOX-fast group, and 14% for placebo (χ(2)=36.3, df=2, p<0.0001). The percentage of participants achieving two or more consecutive weeks of abstinence by group was 0% for DOX-slow group, 44% for DOX-fast group, and 7% for placebo (χ(2)=7.35, df=2, p<0.023).

Conclusions: This pilot study suggests the potential efficacy of doxazosin when rapidly titrated in reducing cocaine use.

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References

Sofuoglu M, Sewell R . Norepinephrine and stimulant addiction. Addict Biol. 2008; 14(2):119-29. PMC: 2657197. DOI: 10.1111/j.1369-1600.2008.00138.x. View

Sheehan D, Lecrubier Y, Sheehan K, Amorim P, Janavs J, Weiller E . The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry. 1999; 59 Suppl 20:22-33;quiz 34-57. View

Bourdelat-Parks B, Anderson G, Donaldson Z, Weiss J, Bonsall R, Emery M . Effects of dopamine beta-hydroxylase genotype and disulfiram inhibition on catecholamine homeostasis in mice. Psychopharmacology (Berl). 2005; 183(1):72-80. DOI: 10.1007/s00213-005-0139-8. View

Hirschfeld R, Baker J, Wozniak P, Tracy K, Sommerville K . The safety and early efficacy of oral-loaded divalproex versus standard-titration divalproex, lithium, olanzapine, and placebo in the treatment of acute mania associated with bipolar disorder. J Clin Psychiatry. 2003; 64(7):841-6. DOI: 10.4088/jcp.v64n0717. View

Linner L, Endersz H, Ohman D, Bengtsson F, Schalling M, Svensson T . Reboxetine modulates the firing pattern of dopamine cells in the ventral tegmental area and selectively increases dopamine availability in the prefrontal cortex. J Pharmacol Exp Ther. 2001; 297(2):540-6. View

Mulvaney F, Alterman A, BOARDMAN C, Kampman K . Cocaine abstinence symptomatology and treatment attrition. J Subst Abuse Treat. 1999; 16(2):129-35. DOI: 10.1016/s0740-5472(98)00017-8. View

Gossop M, Best D, Marsden J, Strang J . Test-retest reliability of the Severity of Dependence Scale. Addiction. 1997; 92(3):353. DOI: 10.1111/j.1360-0443.1997.tb03205.x. View

Newton T, De La Garza 2nd R, Brown G, Kosten T, Mahoney 3rd J, Haile C . Noradrenergic α₁ receptor antagonist treatment attenuates positive subjective effects of cocaine in humans: a randomized trial. PLoS One. 2012; 7(2):e30854. PMC: 3272014. DOI: 10.1371/journal.pone.0030854. View

Sofuoglu M, Brown S, Babb D, Pentel P, Hatsukami D . Carvedilol affects the physiological and behavioral response to smoked cocaine in humans. Drug Alcohol Depend. 2000; 60(1):69-76. DOI: 10.1016/s0376-8716(99)00143-x. View

10.

Gawin F, KLEBER H . Cocaine abuse treatment. Open pilot trial with desipramine and lithium carbonate. Arch Gen Psychiatry. 1984; 41(9):903-9. DOI: 10.1001/archpsyc.1984.01790200085011. View

11.

Zhang X, Kosten T . Previous exposure to cocaine enhances cocaine self-administration in an alpha 1-adrenergic receptor dependent manner. Neuropsychopharmacology. 2006; 32(3):638-45. DOI: 10.1038/sj.npp.1301120. View

12.

Paladini C, Williams J . Noradrenergic inhibition of midbrain dopamine neurons. J Neurosci. 2004; 24(19):4568-75. PMC: 6729397. DOI: 10.1523/JNEUROSCI.5735-03.2004. View

13.

Devlin R, Henry J . Clinical review: Major consequences of illicit drug consumption. Crit Care. 2008; 12(1):202. PMC: 2374627. DOI: 10.1186/cc6166. View

14.

Blanc G, Trovero F, Vezina P, Herve D, Godeheu A, Glowinski J . Blockade of prefronto-cortical alpha 1-adrenergic receptors prevents locomotor hyperactivity induced by subcortical D-amphetamine injection. Eur J Neurosci. 1994; 6(3):293-8. DOI: 10.1111/j.1460-9568.1994.tb00272.x. View

15.

Jaillon P . Clinical pharmacokinetics of prazosin. Clin Pharmacokinet. 1980; 5(4):365-76. DOI: 10.2165/00003088-198005040-00004. View

16.

Wellman P, Ho D, Cepeda-Benito A, Bellinger L, Nation J . Cocaine-induced hypophagia and hyperlocomotion in rats are attenuated by prazosin. Eur J Pharmacol. 2002; 455(2-3):117-26. DOI: 10.1016/s0014-2999(02)02616-x. View

17.

Schroeder J, Cooper D, Schank J, Lyle M, Gaval-Cruz M, Ogbonmwan Y . Disulfiram attenuates drug-primed reinstatement of cocaine seeking via inhibition of dopamine β-hydroxylase. Neuropsychopharmacology. 2010; 35(12):2440-9. PMC: 2956132. DOI: 10.1038/npp.2010.127. View

18.

Gossop M, Darke S, Griffiths P, Hando J, Powis B, Hall W . The Severity of Dependence Scale (SDS): psychometric properties of the SDS in English and Australian samples of heroin, cocaine and amphetamine users. Addiction. 1995; 90(5):607-14. DOI: 10.1046/j.1360-0443.1995.9056072.x. View

19.

Kosten T, Jatlow P . Disulfiram effects on acute cocaine administration. Drug Alcohol Depend. 1998; 52(1):27-39. DOI: 10.1016/s0376-8716(98)00050-7. View

20.

Petrakis I, Carroll K, Nich C, Gordon L, Frankforter T, Rounsaville B . Disulfiram treatment for cocaine dependence in methadone-maintained opioid addicts. Addiction. 2000; 95(2):219-28. DOI: 10.1046/j.1360-0443.2000.9522198.x. View