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Menger Chung - One of the best experts on this subject based on the ideXlab platform.
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Desipramine pharmacokinetics when coadministered with paroxetine or sertraline in extensive metabolizers
Journal of Clinical Psychopharmacology, 1997Co-Authors: Jeffrey Alderman, Sheldon H. Preskorn, Wilma Harrison, David J Greenblatt, Darryl Penenberg, Janet Allison, Menger ChungAbstract:In vitro studies have shown that fluoxetine and paroxetine are more potent inhibitors of cytochrome CYP2D6 than sertraline. The pharmacokinetics of Desipramine when coadministered with the selective serotonin reuptake inhibitors (SSRIs) paroxetine and sertraline were studied in 24 healthy male volunteers (CYP2D6 extensive metabolizers). Desipramine (50 mg/day) was administered for 23 days in each phase of the crossover study with a 7-day drug-free period between phases. In addition, subjects were randomly assigned to receive concomitant paroxetine (20 mg/day on days 8 through 17 followed by 30 mg/day on days 18 through 20) or sertraline (50 mg/day on days 8 through 17 and 100 mg/day on days 18 through 20). SSRI treatments were switched between phases. After 10 days of coadministration at the lower dose, mean Desipramine maximum concentration in plasma (Cmax) relative to baseline increased from 37.8 to 173 ng/mL (+358%) with paroxetine versus from 36.1 to 51.9 ng/mL (+44%) with sertraline; the mean Desipramine 24-hour area under the concentration-time curve (AUC[24]) increased from 634 to 3,305 ng x h/mL (+421%) with paroxetine versus from 611 to 838 ng x h/mL (+37%) with sertraline; and the mean Desipramine trough value (C0) increased from 18.5 to 113 ng/mL (+511%) with paroxetine versus from 18.3 to 21.8 ng/mL (+19%) with sertraline (all increases, p < 0.001). An approximately 10-fold increase in the Cmax and AUC(24) of paroxetine and an approximately 2-fold increase in these parameters for sertraline occurred simultaneously with the Desipramine concentration changes. Thus, when coadministered with 50 mg/day Desipramine, sertraline had significantly less pharmacokinetic interaction than paroxetine with Desipramine at the recommended starting dosages of 50 mg/day and 20 mg/day, respectively.
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Pharmacokinetics of Desipramine coadministered with sertraline or fluoxetine.
Journal of clinical psychopharmacology, 1994Co-Authors: Sheldon H. Preskorn, Jeffrey Alderman, Menger Chung, Wilma Harrison, Michael Messig, Stuart HarrisAbstract:The pharmacokinetic interactions of sertraline and fluoxetine with the tricyclic antidepressant Desipramine were studied in 18 healthy male volunteers phenotyped as extensive metabolizers of dextromethorphan. Concentrations in plasma were determined after 7 days of Desipramine (50 mg/day) dosing alone, during the 21 days of Desipramine and selective serotonin reuptake inhibitor (SSRI) coadministration (fluoxetine, 20 mg/day; sertraline, 50 mg/day), and for 21 days of continued Desipramine administration after SSRI discontinuation. Desipramine Cmax was increased 4.0-fold versus 31% and AUC0-24 was increased 4.8-fold versus 23% for fluoxetine versus sertraline, respectively, relative to baseline after 3 weeks of coadministration. Desipramine trough concentrations approached baseline within 1 week of sertraline discontinuation but remained elevated for the 3-week follow-up period after fluoxetine discontinuation. Concentrations of SSRIs and their metabolites correlated significantly with Desipramine concentration changes (for fluoxetine/norfluoxetine, r = 0.94 to 0.96; p < 0.001; for sertraline/desmethylsertraline, r = 0.63; p < 0.01). Thus, sertraline had less pharmacokinetic interaction with Desipramine than did fluoxetine at their respective, minimum, usually effective doses.
Sheldon H. Preskorn - One of the best experts on this subject based on the ideXlab platform.
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Desipramine pharmacokinetics when coadministered with paroxetine or sertraline in extensive metabolizers
Journal of Clinical Psychopharmacology, 1997Co-Authors: Jeffrey Alderman, Sheldon H. Preskorn, Wilma Harrison, David J Greenblatt, Darryl Penenberg, Janet Allison, Menger ChungAbstract:In vitro studies have shown that fluoxetine and paroxetine are more potent inhibitors of cytochrome CYP2D6 than sertraline. The pharmacokinetics of Desipramine when coadministered with the selective serotonin reuptake inhibitors (SSRIs) paroxetine and sertraline were studied in 24 healthy male volunteers (CYP2D6 extensive metabolizers). Desipramine (50 mg/day) was administered for 23 days in each phase of the crossover study with a 7-day drug-free period between phases. In addition, subjects were randomly assigned to receive concomitant paroxetine (20 mg/day on days 8 through 17 followed by 30 mg/day on days 18 through 20) or sertraline (50 mg/day on days 8 through 17 and 100 mg/day on days 18 through 20). SSRI treatments were switched between phases. After 10 days of coadministration at the lower dose, mean Desipramine maximum concentration in plasma (Cmax) relative to baseline increased from 37.8 to 173 ng/mL (+358%) with paroxetine versus from 36.1 to 51.9 ng/mL (+44%) with sertraline; the mean Desipramine 24-hour area under the concentration-time curve (AUC[24]) increased from 634 to 3,305 ng x h/mL (+421%) with paroxetine versus from 611 to 838 ng x h/mL (+37%) with sertraline; and the mean Desipramine trough value (C0) increased from 18.5 to 113 ng/mL (+511%) with paroxetine versus from 18.3 to 21.8 ng/mL (+19%) with sertraline (all increases, p < 0.001). An approximately 10-fold increase in the Cmax and AUC(24) of paroxetine and an approximately 2-fold increase in these parameters for sertraline occurred simultaneously with the Desipramine concentration changes. Thus, when coadministered with 50 mg/day Desipramine, sertraline had significantly less pharmacokinetic interaction than paroxetine with Desipramine at the recommended starting dosages of 50 mg/day and 20 mg/day, respectively.
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Pharmacokinetics of Desipramine coadministered with sertraline or fluoxetine.
Journal of clinical psychopharmacology, 1994Co-Authors: Sheldon H. Preskorn, Jeffrey Alderman, Menger Chung, Wilma Harrison, Michael Messig, Stuart HarrisAbstract:The pharmacokinetic interactions of sertraline and fluoxetine with the tricyclic antidepressant Desipramine were studied in 18 healthy male volunteers phenotyped as extensive metabolizers of dextromethorphan. Concentrations in plasma were determined after 7 days of Desipramine (50 mg/day) dosing alone, during the 21 days of Desipramine and selective serotonin reuptake inhibitor (SSRI) coadministration (fluoxetine, 20 mg/day; sertraline, 50 mg/day), and for 21 days of continued Desipramine administration after SSRI discontinuation. Desipramine Cmax was increased 4.0-fold versus 31% and AUC0-24 was increased 4.8-fold versus 23% for fluoxetine versus sertraline, respectively, relative to baseline after 3 weeks of coadministration. Desipramine trough concentrations approached baseline within 1 week of sertraline discontinuation but remained elevated for the 3-week follow-up period after fluoxetine discontinuation. Concentrations of SSRIs and their metabolites correlated significantly with Desipramine concentration changes (for fluoxetine/norfluoxetine, r = 0.94 to 0.96; p < 0.001; for sertraline/desmethylsertraline, r = 0.63; p < 0.01). Thus, sertraline had less pharmacokinetic interaction with Desipramine than did fluoxetine at their respective, minimum, usually effective doses.
B. Timothy Walsh - One of the best experts on this subject based on the ideXlab platform.
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Side effects of Desipramine and age.
Journal of child and adolescent psychopharmacology, 2002Co-Authors: Cathryn A. Galanter, Carina Bilich, B. Timothy WalshAbstract:Introduction: The treatment response of children and adolescents to tricyclic antidepressants differs from that of adults. Few data exist on the impact of age on side effects. This study compares Desipramine-associated side effects in children, adolescents, and adults. Methods: Data from three trials of Desipramine were combined to produce a sample of 148 subjects, aged 7 to 66 years. Pulse and blood pressure were measured at baseline and while participants were receiving Desipramine. Side effects were rated by a clinician. For data analysis, subjects were divided into two groups, younger patients (18 and younger) and older patients (19 and older). Group means of side effect ratings and vital signs were compared. Results were also analyzed covarying for plasma levels of Desipramine. Results: There were significant differences between younger and older patients in pulse and blood pressure at baseline, on Desipramine, and in changes in vital signs between baseline and medicated states. Younger patients had ...
Jeffrey Alderman - One of the best experts on this subject based on the ideXlab platform.
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Desipramine pharmacokinetics when coadministered with paroxetine or sertraline in extensive metabolizers
Journal of Clinical Psychopharmacology, 1997Co-Authors: Jeffrey Alderman, Sheldon H. Preskorn, Wilma Harrison, David J Greenblatt, Darryl Penenberg, Janet Allison, Menger ChungAbstract:In vitro studies have shown that fluoxetine and paroxetine are more potent inhibitors of cytochrome CYP2D6 than sertraline. The pharmacokinetics of Desipramine when coadministered with the selective serotonin reuptake inhibitors (SSRIs) paroxetine and sertraline were studied in 24 healthy male volunteers (CYP2D6 extensive metabolizers). Desipramine (50 mg/day) was administered for 23 days in each phase of the crossover study with a 7-day drug-free period between phases. In addition, subjects were randomly assigned to receive concomitant paroxetine (20 mg/day on days 8 through 17 followed by 30 mg/day on days 18 through 20) or sertraline (50 mg/day on days 8 through 17 and 100 mg/day on days 18 through 20). SSRI treatments were switched between phases. After 10 days of coadministration at the lower dose, mean Desipramine maximum concentration in plasma (Cmax) relative to baseline increased from 37.8 to 173 ng/mL (+358%) with paroxetine versus from 36.1 to 51.9 ng/mL (+44%) with sertraline; the mean Desipramine 24-hour area under the concentration-time curve (AUC[24]) increased from 634 to 3,305 ng x h/mL (+421%) with paroxetine versus from 611 to 838 ng x h/mL (+37%) with sertraline; and the mean Desipramine trough value (C0) increased from 18.5 to 113 ng/mL (+511%) with paroxetine versus from 18.3 to 21.8 ng/mL (+19%) with sertraline (all increases, p < 0.001). An approximately 10-fold increase in the Cmax and AUC(24) of paroxetine and an approximately 2-fold increase in these parameters for sertraline occurred simultaneously with the Desipramine concentration changes. Thus, when coadministered with 50 mg/day Desipramine, sertraline had significantly less pharmacokinetic interaction than paroxetine with Desipramine at the recommended starting dosages of 50 mg/day and 20 mg/day, respectively.
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Pharmacokinetics of Desipramine coadministered with sertraline or fluoxetine.
Journal of clinical psychopharmacology, 1994Co-Authors: Sheldon H. Preskorn, Jeffrey Alderman, Menger Chung, Wilma Harrison, Michael Messig, Stuart HarrisAbstract:The pharmacokinetic interactions of sertraline and fluoxetine with the tricyclic antidepressant Desipramine were studied in 18 healthy male volunteers phenotyped as extensive metabolizers of dextromethorphan. Concentrations in plasma were determined after 7 days of Desipramine (50 mg/day) dosing alone, during the 21 days of Desipramine and selective serotonin reuptake inhibitor (SSRI) coadministration (fluoxetine, 20 mg/day; sertraline, 50 mg/day), and for 21 days of continued Desipramine administration after SSRI discontinuation. Desipramine Cmax was increased 4.0-fold versus 31% and AUC0-24 was increased 4.8-fold versus 23% for fluoxetine versus sertraline, respectively, relative to baseline after 3 weeks of coadministration. Desipramine trough concentrations approached baseline within 1 week of sertraline discontinuation but remained elevated for the 3-week follow-up period after fluoxetine discontinuation. Concentrations of SSRIs and their metabolites correlated significantly with Desipramine concentration changes (for fluoxetine/norfluoxetine, r = 0.94 to 0.96; p < 0.001; for sertraline/desmethylsertraline, r = 0.63; p < 0.01). Thus, sertraline had less pharmacokinetic interaction with Desipramine than did fluoxetine at their respective, minimum, usually effective doses.
Joseph Biederman - One of the best experts on this subject based on the ideXlab platform.
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a double blind comparison of Desipramine and placebo in children and adolescents with chronic tic disorder and comorbid attention deficit hyperactivity disorder
Archives of General Psychiatry, 2002Co-Authors: Thomas J. Spencer, Joseph Biederman, Barbara J Coffey, Daniel Geller, Margaret Crawford, Sarah Kate Bearman, Reem Tarazi, Stephen V. FaraoneAbstract:Background Currently, there is no consensus on the best therapeutic approach to chronic tic disorders and comorbid attention-deficit/hyperactivity disorder(ADHD). To address this issue, we evaluated the tolerability and efficacy of the noradrenergic tricyclic antidepressant Desipramine hydrochloride in the treatment of children and adolescents with chronic tic disorders and comorbid ADHD. Methods Forty-one children and adolescents with chronic tic disorders, including Tourette disorder and comorbid ADHD, were studied in a 6-week, double-blind, placebo-controlled, parallel trial. Desipramine was titrated weekly up to3.5 mg/kg per day. We rated ADHD and tic symptoms weekly and monitored adverse effects, laboratory findings, and cardiovascular parameters. Results Treatment with Desipramine (mean total daily dose, 3.4 mg/kg per day) was well tolerated without meaningful adverse effects. Desipramine significantly reduced core symptoms of ADHD (ADHD Rating Scale; 42% decrease from baseline relative to placebo, P P P P P P Conclusions Treatment with Desipramine was well tolerated and was associated with robust clinically significant reductions in tic and ADHD symptoms in children and adolescents with chronic tic disorders and ADHD diagnoses.
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Absence of Effect of Stimulants on the Pharmacokinetics of Desipramine in Children
Pharmacotherapy, 1999Co-Authors: Louise Glassner Cohen, Jefferson B. Prince, Joseph Biederman, Timothy E. Wilens, Stephen V. Faraone, Sabrina Whitt, Eric Mick, Thomas J. Spencer, Michele C. Meyer, David PolisnerAbstract:We conducted a retrospective chart review to examine the pharmacokinetic interaction between Desipramine and the stimulants methylphenidate and dexedrine using routinely monitored Desipramine serum concentrations in children receiving Desipramine either alone or with a stimulant. Subjects were 142 children and adolescents (age 6-17 yrs; 113 taking Desipramine, 29 taking Desipramine-stimulants) in whom 401 dose- and weight-normalized serum concentrations were evaluated (333 Desipramine, 68 Desipramine-stimulants). Desipramine pharmacokinetic parameters were similar for both groups, including mean weight-corrected dose (3.66+/-1.36 mg/kg, Desipramine; 3.66+/-1.09 mg/kg, Desipramine-stimulants; p=0.97), weight- and dose-normalized serum concentrations (47.26+/-39.26 [microg/L]/[mg/kg], Desipramine, 39.02+/-19.92 [microg/L]/[mg/kg], Desipramine-stimulants; p=0.09), and clearance (0.690+/-0.913 [L/kg]/hr, Desipramine; 0.613+/-0.514 [L/kg]/hr, Desipramine-stimulants; p=0.499). When stratified by age, gender, and type of stimulant, no difference was detected (p>0.05) between groups. Our findings indicate the absence of a clinically significant interaction between Desipramine and stimulants.
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estimation of the association between Desipramine and the risk for sudden death in 5 to 14 year old children
The Journal of Clinical Psychiatry, 1995Co-Authors: Joseph Biederman, Ronald A Thisted, Laurence L Greenhill, Neal D RyanAbstract:BACKGROUND Four cases of sudden death in children 12 years or younger during Desipramine treatment were identified between 1986 and 1992. We evaluated whether these events support the hypothesis that exposure to therapeutic doses of Desipramine contributes to the risk for sudden death in otherwise healthy children. METHOD The National Center for Health Statistics provided the baseline number of sudden unexplained deaths in children 5 to 14 years old. Data from the National Disease and Therapeutic Index were used to estimate the exposure to Desipramine in children in the same age group. Since two of the four deaths were identified by 1987, we used the post-1987 experience as if it were a prospective period in which a causal association could be examined. RESULTS The number of sudden deaths in Desipramine-exposed children did not increase from 1986 to 1992 despite a marked increase in exposure. By using 4 to 6 months as the average lifetime of a Desipramine prescription and a baseline rate of sudden death of 4.2 deaths/million/year in this population, the post-1987 period would account for 162,000 to 242,000 person-years of Desipramine exposure. Although not statistically significant, this level of exposure corresponds to a relative risk of 2.1 (95% CI = 0.5 to 15) to 3.1 (95% CI = 0.8 to 22). CONCLUSION Although, based on our estimates, the evidence for an association between Desipramine and sudden death in children aged 5 to 14 years appears weak, replication of our findings is needed with a more precise numerator (total number of deaths) and denominator (the appropriate conversion from drug appearance to actual exposure) before a firm conclusion on this subject can be drawn. Until then, even if remote, the possibility of an association between Desipramine and sudden death in children stresses the importance of assessing risks and benefits when Desipramine is used in pediatric patients.
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Fluoxetine inhibits Desipramine metabolism.
Archives of general psychiatry, 1992Co-Authors: Timothy E. Wilens, Joseph Biederman, Ross J. Baldessarini, Stephen P. Mcdermott, James G. FloodAbstract:To the Editor.— We read with interest the article by Nelson et al 1 on the treatment of depression with fluoxetine and Desipramine, particularly regarding effects of fluoxetine on serum levels of Desipramine and its major active metabolite, 2-hydroxyDesipramine. Fluoxetine can elevate blood concentrations and the risk of toxic effects of tricyclic antidepressants unless their dose is greatly restricted. 2,3 This interaction probably reflects competition for enzymatic oxidation. 4 Although ring-hydroxylation to 2-hydroxyDesipramine is a major route of metabolism of Desipramine, assessment of effects of fluoxetine on 2-hydroxyDesipramine is very limited. 2-4 In a retrospective comparison of 14 adults with depression given Desipramine and fluoxetine and 52 patients given Desipramine alone, Nelson et al 1 found serum Desipramine levels to be similar in both groups despite an approximate reduction of 30% in Desipramine dose with fluoxetine. In their data, we find (eg, at 4 weeks of fixed-dose treatment) lower mean
