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Safety of intravenous methamphetamine administration during treatment with bupropion

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Abstract

Rationale

Methamphetamine dependence is a growing problem for which no medication treatments have proven effective.

Objectives

We evaluated bupropion, an antidepressant with beneficial effects for the treatment of nicotine dependence, in patients with methamphetamine dependence, to assess the safety and tolerability of methamphetamine administration during bupropion treatment.

Methods

Twenty-six participants entered the study and 20 completed the protocol. Participants received intravenous methamphetamine (0, 15, and 30 mg) before and after randomization to twice-daily bupropion (150 mg SR) or matched placebo. Dependent measures included cardiovascular effects of methamphetamine, methamphetamine and amphetamine pharmacokinetics, and peak and trough plasma concentrations of bupropion and its metabolites.

Results

Bupropion treatment was well tolerated, with bupropion- and placebo-treated groups reporting similar rates of adverse events. Methamphetamine administration was associated with expected stimulant cardiovascular effects, and these were not accentuated by bupropion treatment. Instead, there was a trend for bupropion to reduce methamphetamine-associated increases in blood pressure and a statistically significant reduction in methamphetamine-associated increases in heart rate. Pharmacokinetic analysis revealed that bupropion treatment reduced the plasma clearance of methamphetamine and also reduced the appearance of amphetamine in the plasma. Methamphetamine administration did not alter the peak and trough plasma concentrations of bupropion or its metabolites.

Conclusions

Methamphetamine administration was well tolerated during bupropion treatment. There was no evidence of additive cardiovascular effects when the drugs were coadministered. This study provides initial evidence for the safety of prescribing bupropion for the treatment of methamphetamine abuse and dependence. The impact of bupropion treatment in patients who abuse larger doses of methamphetamine remains undetermined.

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References

  • Aubin HJ (2002) Tolerability and safety of sustained-release bupropion in the management of smoking cessation. Drugs 62(Suppl 2):45–52

    Article  PubMed  CAS  Google Scholar 

  • Azzaro AJ, Rutledge CO (1973) Selectivity of release of norepinephrine, dopamine and 5-hydroxytryptamine by amphetamine in various regions of rat-brain. Biochem Pharmacol 22:2801–2813

    Article  PubMed  CAS  Google Scholar 

  • Belson MG, Kelley TR (2002) Bupropion exposures: clinical manifestations and medical outcome. J Emerg Med 23:223–230

    Article  PubMed  Google Scholar 

  • De La Garza R II, Newton TF, Elkashef A, Smith P, Bloch D, Holmes T (2004) Physiologic and subjective effects of methamphetamine in the presence of selegiline in methamphetamine dependent patients. Annual meeting of the College on Problems of Drug Dependence, San Juan, Puerto Rico

  • Derlet RW, Albertson TE, Rice P (1990) Antagonism of cocaine, amphetamine, and methamphetamine toxicity. Pharmacol Biochem Behav 36:745–749

    Article  PubMed  CAS  Google Scholar 

  • Fischer JF, Cho AK (1979) Chemical-release of dopamine from striatal homogenates-evidence for an exchange diffusion-model. J Pharmacol Exp Ther 208:203–209

    PubMed  CAS  Google Scholar 

  • Galloway GP, Newmeyer J, Knapp T, Stalcup SA, Smith D (1994) Imipramine for the treatment of cocaine and methamphetamine dependence. J Addict Dis 13:201–216

    Article  PubMed  CAS  Google Scholar 

  • Galloway GP, Newmeyer J, Knapp T, Stalcup SA, Smith D (1996) A controlled trial of imipramine for the treatment of methamphetamine dependence. J Subst Abuse Treat 13:493–497

    Article  PubMed  CAS  Google Scholar 

  • Gibaldi M, Perrier D (1982) Pharmacokinetics, 2nd edn. Marcel Dekker, New York

    Google Scholar 

  • Guzey C, Norstrom A, Spigset O (2002) Change from the CYP2D6 extensive metabolizer to the poor metabolizer phenotype during treatment with bupropion. Ther Drug Monit 24:436–437

    Article  PubMed  Google Scholar 

  • Huber A, Ling W, Shoptaw S, Gulati V, Brethen P, Rawson R (1997) Integrating treatments for methamphetamine abuse: a psychosocial perspective. J Addict Dis 16:41–50

    Article  PubMed  CAS  Google Scholar 

  • Huber A, Shoptaw S, Gulati V, Gonzales R (2000) Sertraline and contingency management as treatments for methamphetamine dependence. Drug Alcohol Depend 60:S95

    Google Scholar 

  • Kim S, Westphalen R, Callahan B, Hatzidimitriou G, Yuan J, Ricaurte GA (2000) Toward development of an in vitro model of methamphetamine-induced dopamine nerve terminal toxicity. J Pharmacol Exp Ther 293:625–633

    PubMed  CAS  Google Scholar 

  • Kleven MS, Seiden LS (1992) Methamphetamine-induced neurotoxicity: structure activity relationships. Ann N Y Acad Sci 654:292–301

    Article  PubMed  CAS  Google Scholar 

  • Liang NY, Rutledge CO (1982) Evidence for carrier-mediated efflux of dopamine from corpus striatum. Biochem Pharmacol 31:2479–2484

    Article  PubMed  CAS  Google Scholar 

  • Lin LY, Di Stefano EW, Schmitz DA, Hsu L, Ellis SW, Lennard MS, Tucker GT, Cho AK (1997) Oxidation of methamphetamine and methylenedioxymethamphetamine by CYP2D6. Drug Metab Dispos 25:1059–1064

    PubMed  CAS  Google Scholar 

  • Marek GJ, Vosmer G, Seiden LS (1990) Dopamine uptake inhibitors block long-term neurotoxic effects of methamphetamine upon dopaminergic neurons. Brain Res 513:274–279

    Article  PubMed  CAS  Google Scholar 

  • Margolin A, Kosten TR, Avants SK, Wilkins J, Ling W, Beckson M, Arndt IO, Cornish J, Ascher JA, Li SH et al (1995) A multicenter trial of bupropion for cocaine dependence in methadone-maintained patients. Drug Alcohol Depend 40:125–131

    Article  PubMed  CAS  Google Scholar 

  • McCann UD, Wong DF, Yokoi F, Villemagne V, Dannals RF, Ricaurte GA (1998) Reduced striatal dopamine transporter density in abstinent methamphetamine and methcathinone users: evidence from positron emission tomography studies with [11C]WIN-35,428. J Neurosci 18:8417–8422

    PubMed  CAS  Google Scholar 

  • Muley MP, Joshi MA, Manekar MS (1984) Effect of bupropion on dopamine and 5-hydroxytryptamine-mediated behaviour in mice. J Pharm Pharmacol 36:208–210

    PubMed  CAS  Google Scholar 

  • Rauhut AS, Neugebauer N, Dwoskin LP, Bardo MT (2003) Effect of bupropion on nicotine self-administration in rats. Psychopharmacology (Berl) 169:1–9

    Article  CAS  Google Scholar 

  • Rawson R, McCann M, Huber A, Shoptaw S (1999) Contingency management and relapse prevention as stimulant abuse treatment interventions. Motivating behavior change among illicit-drug abusers: research on contingency management interventions. American Psychological Association, Washington, DC, pp 57–74

    Book  Google Scholar 

  • Richmond R, Zwar N (2003) Review of bupropion for smoking cessation. Drug Alcohol Rev 22:203–220

    Article  PubMed  Google Scholar 

  • SAMHSA (2004) Summary of findings from the National Household Survey of Drug Abuse. SAMHSA, Office of Applied Studies, National Household Survey on Drug Abuse, Washington, DC

    Google Scholar 

  • Sekine Y, Minabe Y, Ouchi Y, Takei N, Iyo M, Nakamura K, Suzuki K, Tsukada H, Okada H, Yoshikawa E, Futatsubashi M, Mori N (2003) Association of dopamine transporter loss in the orbitofrontal and dorsolateral prefrontal cortices with methamphetamine-related psychiatric symptoms. Am J Psychiatry 160:1699–1701

    Article  PubMed  Google Scholar 

  • Shoptaw S, Rawson RA, McCann MJ, Obert JL (1994) The matrix model of outpatient stimulant abuse treatment: evidence of efficacy. J Addict Dis 13:129–141

    Article  PubMed  CAS  Google Scholar 

  • Stahl SM, Pradko JF, Haight BR, Modell JG, Rockett CB, Learned-Coughlin S (2004) A review of the neuropharmacology of bupropion, a dual norepinephrine and dopamine reuptake inhibitor. Prim Care Companion J Clin Psychiat 6:159–166

    Google Scholar 

  • Volkow ND, Chang L, Wang GJ, Fowler JS, Franceschi D, Sedler M, Gatley SJ, Miller E, Hitzemann R, Ding YS, Logan J (2001) Loss of dopamine transporters in methamphetamine abusers recovers with protracted abstinence. J Neurosci 21:9414–9418

    PubMed  CAS  Google Scholar 

  • Wilson JM, Kalasinsky KS, Levey AI, Bergeron C, Reiber G, Anthony RM, Schmunk GA, Shannak K, Haycock JW, Kish SJ (1996) Striatal dopamine nerve terminal markers in human, chronic methamphetamine users. Nat Med 2:699–703

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

This project was supported by contracts from NIDA (DA-18185, DA-00388, DA-08804, and RR-00865).

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Correspondence to Thomas F. Newton.

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Newton, T.F., Roache, J.D., De La Garza, R. et al. Safety of intravenous methamphetamine administration during treatment with bupropion. Psychopharmacology 182, 426–435 (2005). https://doi.org/10.1007/s00213-005-0102-8

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  • DOI: https://doi.org/10.1007/s00213-005-0102-8

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