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Biomedical subjects

Michael Kotlyar

Publications and source records attributed to Michael Kotlyar.

12 recordsLinked to original sources
PubMed2006

Effect of bupropion on physiological measures of stress in smokers during nicotine withdrawal.

Studies suggest that among cigarette smokers trying to quit, stress undermines abstinence. Little research has assessed if therapies that increase smoking cessation rates impact physiological measures of stress response. Forty-three subjects completed this repeated-measures study in which a laboratory assessment was completed at baseline and after 17 days of treatment with either placebo (n=15), bupropion sustained release (150 mg twice daily) (n=14) or bupropion with stress reduction counseling (n=14). All subjects quit smoking 3 days prior to the second laboratory assessment. At each laboratory assessment physiological measures of stress (i.e. blood pressure, heart rate, plasma epinephrine, norepinephrine and cortisol concentrations) were measured during rest periods and in response to a speech, a math and a cold pressor task. Among subjects taking placebo, physiological measures of stress were generally lower at rest and during the stressors after smoking cessation. In those taking bupropion these measures were equivalent at the two assessments. Additionally, compared to placebo, those on bupropion had a greater diastolic blood pressure response to the speech stressor and greater systolic blood pressure response to the math stressor during the second laboratory session. This study suggests that bupropion may be maintaining physiological measures of stress during the nicotine withdrawal period.

Adult↗
PubMed2005

Effects of paroxetine on cardiovascular response to mental stress in subjects with a history of coronary artery disease and no psychiatric diagnoses.

RATIONALE: Paroxetine may decrease mental stress-induced cardiovascular responses and so benefit individuals with heart disease, even those with no psychiatric illness. OBJECTIVES: The effects of paroxetine on cardiovascular measures during a speech task were evaluated in psychiatrically healthy subjects with a history of coronary artery disease (CAD). METHODS: Eight subjects completed this double-blind, placebo-controlled, cross-over study in which each subject took 1 month of paroxetine and 4 weeks of placebo in random order. While on each study, medication, blood pressure, heart rate, and plasma norepinephrine concentrations were measured during a period of relaxation and during a mental stressor. The mental stressor consisted of thinking about a stressful topic, speaking about the topic, and listening to a tape-recorded replay of the speech. RESULTS: While on paroxetine, systolic blood pressure and diastolic blood pressure were 10-15% lower (p < 0.005) during the stressor, relative to measures obtained while on placebo. Pulse and plasma norepinephrine concentrations during stress trended lower during paroxetine treatment but did not reach statistical significance. CONCLUSION: Paroxetine has antihypertensive properties during periods of psychological stress in psychiatrically healthy subjects with a history of CAD, and so should be evaluated for potential cardio-protective qualities.

Aged↗
PubMed2005

Inhibition of CYP2D6 activity by bupropion.

The purpose of this study was to assess the effect of bupropion on cytochrome P450 2D6 (CYP2D6) activity. Twenty-one subjects completed this repeated-measures study in which dextromethorphan (30-mg oral dose) was administered to smokers at baseline and after 17 days of treatment with either bupropion sustained-release (150 mg twice daily) or matching placebo. Subjects quit smoking 3 days before the second dextromethorphan administration. To assess CYP2D6 activity, urinary dextromethorphan/dextrorphan metabolic ratios were calculated after an 8-hour urine collection. Thirteen subjects received bupropion, and 8 received placebo. In those receiving active medication, the dextromethorphan/dextrorphan ratio increased significantly at the second assessment relative to the first (0.012 +/- 0.012 vs. 0.418 +/- 0.302; P < 0.0004). No such change was observed in those randomized to placebo (0.009 +/- 0.010 vs. 0.017 +/- 0.015; P = NS). At baseline, all subjects were phenotypically extensive CYP2D6 metabolizers (metabolic ratio <0.3); after treatment, 6 of 13 subjects receiving bupropion, but none of those receiving placebo, had metabolic ratios consistent with poor CYP2D6 metabolizers. Bupropion is therefore a potent inhibitor of CYP2D6 activity, and care should be exercised when initiating or discontinuing bupropion use in patients taking drugs metabolized by CYP2D6.

Adult↗
PubMed2005

Effects of cigarette reduction on cardiovascular risk factors and subjective measures.

STUDY OBJECTIVES: To assess the effect of continued smoking and smoking reduction on cardiovascular biomarkers (eg, WBC count, cholesterol concentrations, BP, heart rate). DESIGN, SETTING, AND PARTICIPANTS: This study, conducted at the University of Minnesota, randomized smokers interested in significantly reducing cigarette use but not quitting to either start 12 weeks of smoking reduction immediately (n = 102), assisted by nicotine replacement therapy, or to a 6-week wait list (n = 49). Those starting smoking reduction were required to reduce smoking by 25% for 2 weeks, 50% for 2 weeks, and 75% during the final 2 weeks. After 6 weeks, the subjects were asked to maintain a 50% reduction or quit. Nicotine gum and, if necessary, nicotine patch were used to achieve reduction goals. The wait list group (n = 49) smoked ad libitum for 6 weeks and then reduced smoking as previously described. MEASUREMENTS AND RESULTS: Cardiovascular biomarkers (eg, WBC count, cholesterol concentrations, BP, heart rate) were assessed at several time points after enrollment. During ad libitum smoking, cardiovascular biomarkers remained relatively stable with correlation coefficients across the various time measurements, ranging from 0.44 to 1.00 (p < 0.01 for all measures). Among successful nonabstinent reducers (64 of 151 subjects), significant improvements were found in many biomarkers (eg, hemoglobin, hematocrit, RBC and WBC counts, lipids, BP, heart rate, respiratory symptoms, all p < 0.0167). CONCLUSIONS: These results show the availability of reliable and dose-sensitive biomarkers and that reduction in smoking can lead to significant but only modest changes in cardiovascular risk factors in healthy smokers. It is not known whether the reductions in cardiovascular risk factors observed after smoking reduction are also associated with reduced disease risk. Additional research is necessary to address this issue.

Adolescent↗
PubMed2005

Update on drug-induced depression in the elderly.

BACKGROUND: Depression is a common disorder in the elderly. Use of certain medications may be a potentially preventable cause of new-onset depression or worsening of established depression. OBJECTIVE: This paper reviews recent publications evaluating medications commonly used in the elderly as potential causes of depressive symptoms. METHODS: Relevant articles examining the association between medication use and symptoms of depression were identified through searches of MEDLINE (1996-March 2005) and International Pharmaceutical Abstracts (1996-March 2005) using the MeSH heading depression and the subheading chemically induced. Included articles were limited to those that discussed medications commonly used in the elderly and that employed a rigorous study design. RESULTS: A wide variety of medications have been implicated as potential causes of depressive symptoms in numerous reports, although many of these reports relied on data obtained from observational rather than experimental studies. The most extensively studied agents include anti hypertensives, lipid-lowering drugs, and selective estrogen-receptor modulators. The data on antihypertensive agents were contradictory; however, most studies found no association between use of the newer lipid-lowering drugs (statins) or selective estrogen-receptor modulators and the emergence of depressive symptoms. Corticosteroids, although not studied recently, generally have been associated with depressive symptoms in the older literature. CONCLUSIONS: The recent data evaluating whether medications can induce or worsen symptoms of depression are largely contradictory. This reflects a relative lack of controlled studies of this association and the difficulties in determining whether depressive symptoms are caused by a particular medication or by other factors. Nonetheless, when new or worsening symptoms of depression occur, medications should be considered a potential cause and withdrawn as appropriate. Nonpharmacologic and/or pharmacologic treatment is indicated for those whose depressive symptoms do not resolve.

Adrenal Cortex Hormones↗
PubMed2004

Effects of sustained-release bupropion among persons interested in reducing but not quitting smoking.

PURPOSE: To determine whether sustained-release bupropion promotes smoking reduction leading to smoking cessation among persons who wish to reduce their amount of smoking, but who are unwilling to quit or who perceive themselves as being unable to quit. METHODS: Current smokers were assigned randomly to receive either sustained-release bupropion (150 mg twice daily) or matching placebo. During an initial 6-month smoking reduction phase, those who were willing to quit entered a 7-week cessation phase, during which study medication was continued. RESULTS: Four-week continuous abstinence rates were 14% (41/295) in the bupropion group and 8% (25/299) in the placebo group (P = 0.02) during treatment. However, this benefit did not continue after treatment was stopped; subsequent continuous abstinence rates were 7% (20/295) in the bupropion group and 5% (16/299) in the placebo group (P = 0.50). Similar proportions of subjects entered the cessation phase in both treatment groups (38% [n = 113] of those in the bupropion group and 34% [n = 101] of those in the placebo group), although the time until a cessation attempt was shorter for those taking bupropion (median, 64 days vs. 118 days, P = 0.008). The extent of smoking reduction (measured by urinary cotinine concentrations) among the 327 subjects who did not enter the cessation phase was significantly greater (P <0.05) in those treated with bupropion during the reduction treatment phase, but not during the month 12 follow-up visit (P = 0.25). CONCLUSION: Sustained-release bupropion, when used in smokers initially not willing to make a cessation attempt, can help sustain smoking reduction while subjects are on active medication, reduce the time until the next cessation attempt, and increase short-term abstinence rates. However, these benefits were modest and not sustained after bupropion was discontinued.

Adult↗
PubMed2004

Harm reduction approaches to reducing tobacco-related mortality.

Tobacco harm reduction approaches are gaining increased attention. Much of this attention is due to a growing concern that significant populations of smokers either do not want to quit or believe they are unable to quit smoking, and to a concern over tobacco-industry attempts to produce tobacco products that claim to result in less toxin exposure. Decreasing tobacco toxin exposure as a method for reducing mortality and morbidity may be a reasonable tobacco control strategy. However, the impact of this strategy must be explored both on individual and population levels. A significant amount of independent research is needed to inform policy decisions. Regulatory authority over potential reduced exposure products is also essential.

Harm Reduction↗
PubMed2004

Lack of a fluoxetine effect on prednisolone disposition and cortisol suppression.

STUDY OBJECTIVE: To evaluate the potential effect of fluoxetine, a cytochrome P450 isoenzyme inhibitor, on prednisolone disposition and cortisol suppression. DESIGN: Sequential, two-phase, crossover, open-label pharmacokinetic study. SETTING: General clinical research center. SUBJECTS: Fourteen healthy volunteers. INTERVENTION: A single intravenous dose of prednisolone 40 mg before and after 14 days of treatment with fluoxetine 20 mg/day for 5 days followed by 60 mg/day for 9 days to achieve steady-state concentrations. MEASUREMENTS AND MAIN RESULTS: Pharmacokinetic parameters of the prednisolone and resulting pharmacodynamic effects on the time course of plasma cortisol suppression before and after fluoxetine administration were evaluated. No significant differences were observed for the mean +/- SD area under the prednisolone concentration-time curve (3739 +/- 992 vs 3498 +/- 797 microg x hr/L, respectively), clearance (8.58 +/- 2.62 vs 8.92 +/- 2.05 L/hr, respectively), volume of distribution (39.5 +/- 12.4 vs 38.2 +/- 9.9 L, respectively), elimination half-life (3.32 +/- 0.83 vs 3.05 +/- 0.80 hrs, respectively), or duration of plasma cortisol suppression (23.5 +/- 3.1 vs 22.0 +/- 4.2 hrs, respectively). CONCLUSION: Fluoxetine administration did not significantly affect prednisolone disposition or prolong cortisol suppression. This finding suggests that coadministration of these agents is unlikely to result in clinically important pharmacokinetic or pharmacodynamic drug interactions. Prednisolone may be a useful alternative for patients who require both glucocorticoid and fluoxetine therapy.

Adolescent↗
PubMed2003

Nefazodone inhibits methylprednisolone disposition and enhances its adrenal-suppressant effect.

Nefazodone is a potent and selective inhibitor of cytochrome P450 3A4 (CYP3A4), an enzyme pathway responsible for the biotransformation of a number of steroid compounds. The potential therefore exists that nefazodone inhibits the disposition of methylprednisolone. In this open label, repeated measures study, the effect of 9 days of nefazodone administration on the pharmacokinetic disposition of a single 0.6 mg/kg intravenous dose of methylprednisolone was assessed. Additionally the effect of concomitant nefazodone use on duration of cortisol suppression after methylprednisolone administration was assessed. Eight healthy volunteers completed the study. Following nefazodone administration, the mean (+/-SD) area under the methylprednisolone concentration-time curve was significantly higher (1393 +/- 343 vs. 2966 +/- 928 ug*h/L; P < 0.005), apparent clearance was lower (28.7 +/- 7.2 vs. 14.6 +/- 7.8 L/h; P < 0.02) and the terminal elimination half-life was longer (2.28 +/- 0.49 vs. 3.32 +/- 0.95 hours; P < 0.02). The duration of cortisol suppression after methylprednisolone administration was longer (> or =32 vs. 23.3 +/- 3.43 hours) during nefazodone administration.

Adrenal Cortex↗
PubMed2003

Premature ejaculation associated with citalopram withdrawal.

OBJECTIVE: To report a case of premature ejaculation occurring subsequent to citalopram discontinuation. CASE SUMMARY: A 43-year-old white man being treated for depression with citalopram wished to discontinue treatment. Four or 5 days after stopping citalopram he reported that, during sexual intercourse, his genitals seemed to be extremely sensitive and orgasm was achieved within approximately 1 minute. These symptoms continued over the next 3-4 weeks and remitted after citalopram was restarted. Several subsequent attempts to discontinue citalopram resulted in a return of these symptoms despite using a slow tapering regimen. An objective causality assessment revealed a probable relationship between drug withdrawal and the observed symptoms. DISCUSSION: The ability of selective serotonin-reuptake inhibitors (SSRIs) to delay ejaculation has been well documented; however, discontinuation of these agents generally results in a return to baseline function. Although discontinuation of SSRI therapy has been associated with a number of withdrawal symptoms, this is the first report (MEDLINE, September 2003), to our knowledge, of the emergence of sexual adverse effects in someone with no previous history of these symptoms. CONCLUSIONS: Premature ejaculation is a possible withdrawal effect after SSRI discontinuation. Since patients are usually reluctant to spontaneously report sexual adverse effects, it is important to specifically inquire about them both when starting and stopping treatment with an SSRI.

Adult↗
PubMed2002

Managing nicotine addiction.

Nicotine addiction has been identified as the primary contributor to continued widespread tobacco use worldwide. Although the health benefits of smoking cessation are well publicized, few smokers successfully quit on a long-term basis. A number of pharmacological agents have been shown to approximately double long-term smoking cessation rates and have, therefore, been recommended as first-line therapy for the treatment of nicotine dependence in the clinical practice guidelines recently released by the Agency for Healthcare Research and Quality (AHRQ). These include the currently available dosage forms of nicotine replacement therapy (gum, patch, nasal spray, and inhaler) and bupropion. Other agents that have exhibited some efficacy in increasing smoking cessation rates are nortriptyline and clonidine. All pharmacological treatments are most effective in conjunction with behavioral therapy. Other approaches to treating tobacco use disorder now being investigated include additional ways to administer nicotine, a vaccine to prevent nicotine from crossing the blood-brain barrier, and agents that alter the metabolism of nicotine. This review summarizes the characteristics of nicotine addiction, reviews the pharmacological agents currently used to treat tobacco use disorder, and describes possible approaches to treat nicotine dependence in the future.

Administration, Inhalation↗