uab.edu

The objective of this study was to determine whether the aminoketone antidepressant bupropion has beneficial effects in orgasmic dysfunction. DESIGN: Single-blind, sequential treatment order of three weeks each: placebo, bupropion-SR 150 mg/day, bupropion-SR 300 mg/day. SUBJECTS: Nondepressed women (n = 20) and men (n = 10) having nonphysiologic orgasmic delay or inhibition. MAIN OUTCOME MEASURES: Reported difficulty or delay in achieving orgasm, satisfaction with orgasm and erectile function, and subjective impressions of drug effect. RESULTS: In the women, there were significant improvements relative to baseline (p < .01) on both doses of bupropion-SR in all measured aspects of sexual function, and significant improvements relative to placebo (p < .05) in overall sexual satisfaction on both doses and satisfaction with intensity of orgasm on 150 mg/day (300 mg/day, p = .10). In the men, significant improvements over baseline (p < .01) were observed with both doses in overall sexual satisfaction, ability to achieve an erection, and delay in reaching orgasm/ejaculation; significant improvements relative to placebo (p < .05) were observed in overall sexual satisfaction on both doses, ability to achieve erection on 150 mg/day, and delay in orgasm/ejaculation on 150 mg/day. Seventy percent of subjects reported improvement in libido, arousal, or orgasmic function during bupropion administration. CONCLUSIONS: Bupropion-SR may be a useful agent for treating orgasmic delay and inhibition, and possibly disorders of sexual arousal. The results argue against bupropion's apparent prosexual effect in depressed patients being simply a result of its antidepressant activity.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10929571&dopt=Abstract Bupropion Wellbutrin




Am J Health Syst Pharm. 2000 Aug 1;57(15):1421-9.
Economic model of sustained-release bupropion hydrochloride in health plan and work site smoking-cessation programs.

Halpern MT, Khan ZM, Young TL, Battista C.

Glaxo Wellcome Inc., Research Triangle Park, NC, USA.

The development and application of an economic model designed to assess the specific costs and benefits of health plan coverage of smoking-cessation programs involving sustained-release bupropion hydrochloride are described. A cohort of 100,000 employees or health plan members and 60,000 adult dependents was followed from the start of the model to either retirement at age 65 or death at age 85. The model was used to compare outcomes for coverage versus no coverage of sustained-release bupropion hydrochloride as a component of a smoking-cessation benefit under four managed care plan scenarios and four employer scenarios. For the managed care scenarios involving coverage of bupropion sustained-release the overall decrease in health care costs over a 20-year period ranged from $7.9 million to $8.8 million; for every dollar spent covering smoking cessation, $4.10-$4.69 in health care costs was saved. For the employer scenarios, health care costs over 20 years decreased by $8.3 million to $14.0 million, and smoking-related indirect costs decreased an additional $5.1 million to $7.7 million; for every dollar spent covering smoking cessation, $5.04-$6.48 was saved. A model developed to assess the specific costs and benefits of covering sustained release bupropion hydrochloride as a component of a smoking-cessation benefit indicated cost savings for health plans and employers.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10938982&dopt=Abstract Bupropion Wellbutrin




Ann Pharmacother. 2000 Sep;34(9):1007-12.
Increased rate of trazodone prescribing with bupropion and selective serotonin-reuptake inhibitors versus tricyclic antidepressants.

Clark NA, Alexander B.

College of Pharmacy, University of Iowa, Iowa City, USA.

OBJECTIVE: To determine whether trazodone is prescribed significantly more often with selective serotonin-reuptake inhibitors (SSRIs) and bupropion than with tricyclic antidepressants (TCAs). METHODS: A retrospective analysis of Iowa City Department of Veteran's Affairs prescription records from March 1, 1995, to March 1, 1998, was performed. Antidepressants prescribed only by psychiatrists were included. Concomitant use was defined as trazodone prescribed on the same date or up to 42 days after the fill date of the primary antidepressant. STATISTICS: All comparisons used 2 x 2 chi 2 contingency table. Significance level was set at p < 0.05. RESULTS: Significantly more patients were prescribed trazodone concurrently with bupropion and SSRI antidepressants than with TCAs. Trazodone was prescribed significantly more often for patients receiving an SSRI (p = 0.0001, chi 2 = 14.59) or bupropion (p = 0.0295, chi 2 = 4.74) than for patients receiving a TCA. There was no significant difference in trazodone use between the patients taking SSRIs or bupropion. The percent of patients that received an SSRI, bupropion, or a TCA in combination with trazodone was 27%, 23%, and 13%, respectively. Overall, 23.7% of patients received trazodone concomitantly with a primary antidepressant. DISCUSSION: The effects of antidepressants on sleep and on sleep scores of depression rating scales are reviewed. The clinical implications of these findings are discussed. The literature addressing the effects of antidepressants on sleep and on sleep scores of depression rating scales is summarized. Although sleep studies suggest that SSRIs may not improve sleep as well as a TCA, clinical studies do not often support these findings. Several studies report that bupropion m




J Pharmacol Exp Ther. 2000 Oct;295(1):321-7.
Bupropion is a nicotinic antagonist.

Slemmer JE, Martin BR, Damaj MI.

Department of Pharmacology and Toxicology, Medical College of Virginia of Virginia Commonwealth University, Richmond, Virginia, USA.

Neuronal nicotinic receptors are ligand-gated ion channels of the central and peripheral central nervous system that regulate synaptic activity from both pre- and postsynaptic sites. The present study establishes the acute interaction of bupropion, an antidepressant agent that is also effective in nicotine dependence, with nicotine and nicotinic receptors using different in vivo and in vitro tests. Bupropion was found to block nicotine's antinociception (in two tests), motor effects, hypothermia, and convulsive effects with different potencies in the present investigation, suggesting that bupropion possesses some selectivity for neuronal nicotinic receptors underlying these various nicotinic effects. In addition, bupropion blocks nicotine activation of alpha(3)beta(2), alpha(4)beta(2), and alpha(7) neuronal acetylcholine nicotinic receptors (nAChRs) with some degree of selectivity. It was approximately 50 and 12 times more effective in blocking alpha(3)beta(2) and alpha(4)beta(2) than alpha(7.) This functional blockade was noncompetitive, because it was insurmountable by increasing concentration of ACh in the nAChRs subtypes tested. Furthermore, bupropion at high concentration failed to displace brain [(3)H]nicotine binding sites, a site largely composed of alpha(4)beta(2) subunit combination. Given the observation that bupropion inhibition of alpha(3)beta(2) and alpha(4)beta(2) receptors exhibits voltage-independence properties, bupropion may not be acting as an open channel blocker. These effects may explain in part bupropion's efficacy in nicotine dependence. Our present findings suggest that functional blockade of neuronal nAChRs are useful in nicotine dependence treatment.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10991997&dopt=Abstract Bupropion Wellbutrin




Drug Metab Dispos. 2000 Oct;28(10):1176-83.
CYP2B6 mediates the in vitro hydroxylation of bupropion: potential drug interactions with other antidepressants.

Hesse LM, Venkatakrishnan K, Court MH, von Moltke LL, Duan SX, Shader RI, Greenblatt DJ.

Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, and the Division of Clinical Pharmacology, New England Medical Center, Boston, Massachusetts, USA.

The in vitro biotransformation of bupropion to hydroxybupropion was studied in human liver microsomes and microsomes containing heterologously expressed human cytochromes P450 (CYP). The mean (+/-S.E.) K(m) in four human liver microsomes was 89 (+/-14) microM. In microsomes containing cDNA-expressed CYPs, hydroxybupropion formation was mediated only by CYP2B6 at 50 microM bupropion (K(m) 85 microM). A CYP2B6 inhibitory antibody produced more than 95% inhibition of bupropion hydroxylation in four human livers. Bupropion hydroxylation activity at 250 microM was highly correlated with S-mephenytoin N-demethylation activity (yielding nirvanol), another CYP2B6-mediated reaction, in a panel of 32 human livers (r = 0.94). The CYP2B6 content of 12 human livers highly correlated with bupropion hydroxylation activity (r = 0.96). Thus bupropion hydroxylation is mediated almost exclusively by CYP2B6 and can serve as an index reaction reflecting activity of this isoform. IC(50) values for inhibition of a CYP2D6 index reaction (dextromethorphan O-demethylation) by bupropion and hydroxybupropion were 58 and 74 microM, respectively. This suggests a low inhibitory potency versus CYP2D6, the clinical importance of which is not established. Since bupropion is frequently coadministered with other antidepressants, IC(50) values (microM) for inhibition of bupropion hydroxylation were determined as follows: paroxetine (1.6), fluvoxamine (6.1), sertraline (3.2), desmethylsertraline (19.9), fluoxetine (59.5), norfluoxetine (4.2), and nefazodone (25.4). Bupropion hydroxylation was only we