Journal of Clinical Psychopharmacology
Chappell et al
20. Omiya Y, Yuzurihara M, Suzuki Y, et al. Role of alpha2-adrenoceptors in enhancement of antinociceptive effect in diabetic mice. Eur J Pharmacol. 2008;592:62Y66. 21. Thor KB, Kirby M, Viktrup L. Serotonin and noradrenaline involvement in urinary incontinence, depression and pain: scientific basis for overlapping clinical efficacy from a single drug, duloxetine. Int J Clin Pract. 2007;61:1349Y1355. 22. Vincent S, Bieck PR, Garland EM, et al. Clinical assessment of norepinephrine transporter blockade through biochemical and pharmacological profiles. Circulation. 2004;109:3202Y3207.
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Volume 34, Number 1, February 2014
31. Eisenhofer G, Goldstein DS, Stull R, et al. Simultaneous liquid-chromatographic determination of 3,4-dihydroxyphenylglycol, catecholamines, and 3,4-dihydroxyphenylalanine in plasma, and their responses to inhibition of monoamine oxidase. Clin Chem. 1986;32:2030Y2033. 32. Lobo ED, Quinlan T, O’Brien L, et al. Population pharmacokinetics of orally administered duloxetine in patients: implications for dosing recommendation. Clin Pharmacokinet. 2009;48:189Y197. 33. Meyer JH, Wilson AA, Ginovart N, et al. Occupancy of serotonin transporters by paroxetine and citalopram during treatment of depression: a [(11)C]DASB PET imaging study. Am J Psychiatry. 2001;158:1843Y1849.
23. Goldstein DS, Eisenhofer G, Stull R, et al. Plasma dihydroxyphenylglycol and the intraneuronal disposition of norepinephrine in humans. J Clin Invest. 1988;81:213Y220. 24. Eisenhofer G. The role of neuronal and extraneuronal plasma membrane transporters in the inactivation of peripheral catecholamines. Pharmacol Ther. 2001;91:35Y62. 25. Chappell JC, Kovacs R, Haber H, et al. Evaluation of the effects of duloxetine and escitalopram on 24-hour heart rate variability: a mechanistic study using heart rate variability as a pharmacodynamic measure. J Clin Psychopharmacol. 2013;33:236Y239. 26. Owens MJ, Krulewicz S, Simon JS, et al. Estimates of serotonin and norepinephrine transporter inhibition in depressed patients treated with paroxetine or venlafaxine. Neuropsychopharmacology. 2008;33:3201Y3212. 27. Gilmor ML, Owens MJ, Nemeroff CB. Inhibition of norepinephrine uptake in patients with major depression treated with paroxetine. Am J Psychiatry. 2002;159:1702Y1710. 28. Davidson J, Watkins L, Owens M, et al. Effects of paroxetine and venlafaxine XR on heart rate variability in depression. J Clin Psychopharmacol. 2005;25:480Y484. 29. Owens MJ, Knight DL, Nemeroff CB. Second-generation SSRIs: human monoamine transporter binding profile of escitalopram and R-fluoxetine. Biol Psychiatry. 2001;50:345Y350. 30. Lantz RJ, Gillespie TA, Rash TJ, et al. Metabolism, excretion, and pharmacokinetics of duloxetine in healthy human subjects. Drug Metab Dispos. 2003;31:1142Y1150.
34. Meyer JH, Wilson AA, Sagrati S, et al. Serotonin transporter occupancy of five selective serotonin reuptake inhibitors at different doses: an [11C]DASB positron emission tomography study. Am J Psychiatry. 2004;161:826Y835. 35. Koch S, Hemrick-Luecke SK, Thompson LK, et al. Comparison of effects of dual transporter inhibitors on monoamine transporters and extracellular levels in rats. Neuropharmacology. 2003;45:935Y944. 36. Wong DT, Bymaster FP, Mayle DA, et al. LY248686, a new inhibitor of serotonin and norepinephrine uptake. Neuropsychopharmacology. 1993;8:23Y33. 37. Maletic V, Raison CL. Neurobiology of depression, fibromyalgia and neuropathic pain. Front Biosci. 2009;14:5291Y5338. 38. Kalk NJ, Nutt DJ, Lingford-Hughes AR. The role of central noradrenergic dysregulation in anxiety disorders: evidence from clinical studies. J Psychopharmacol. 2011;25:3Y16. 39. Eisenhofer G. Sympathetic nerve functionVassessment by radioisotope dilution analysis. Clin Auton Res. 2005;15:264Y283. 40. Baumert M, Lambert GW, Dawood T, et al. Short-term heart rate variability and cardiac norepinephrine spillover in patients with depression and panic disorder. Am J Physiol Heart Circ Physiol. 2009;297:H674YH679.
Editor’s Note: Clinical Trial Designs and Statistics Made Easy The randomized, placebo-control trial has been considered the criterion standard for the development of new chemical entities for more than 50 years. In recent years, because of growing costs, increasing regulations, and difficulties in recruiting patients, the search has been on for ways to modify and perhaps even improve on the standard randomized, placebo-control trial model. As I was trying to better understand various alternative models, I came across a book by Professor David L. Streiner of McMaster University and the University of Toronto. In his 396-page book entitled A Guide for the Statistically Perplexed: Selected Readings for Clinical Researchers,1 Streiner uses plain language, humor, and analogies to bring clarity to the statistical issues involved in clinical trials. After reading his book, I contacted Dr Streiner and asked him to write a series of commentaries for us on newer approaches to clinical trials. In the first of his essays, Streiner takes on the subject of adaptive trial designs.2 We would appreciate reader feedback on these essays. Do they do their intended job? Do you take issue with it in any way? REFERENCES 1. Streiner DL. A Guide for the Statistically Perplexed: Selected Readings for Clinical Researchers. Toronto, Ontario, Canada: University of Toronto Press, Scholarly Publishing Division; 2013. 2. Streiner DL. Adaptive randomization. Commentary. J Clin Psychopharmacol. 2014;34:7–8.
Richard I. Shader, MD Editor-in-Chief
16
www.psychopharmacology.com
* 2014 Lippincott Williams & Wilkins
Copyright © 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Chappell et al
20. Omiya Y, Yuzurihara M, Suzuki Y, et al. Role of alpha2-adrenoceptors in enhancement of antinociceptive effect in diabetic mice. Eur J Pharmacol. 2008;592:62Y66. 21. Thor KB, Kirby M, Viktrup L. Serotonin and noradrenaline involvement in urinary incontinence, depression and pain: scientific basis for overlapping clinical efficacy from a single drug, duloxetine. Int J Clin Pract. 2007;61:1349Y1355. 22. Vincent S, Bieck PR, Garland EM, et al. Clinical assessment of norepinephrine transporter blockade through biochemical and pharmacological profiles. Circulation. 2004;109:3202Y3207.
&
Volume 34, Number 1, February 2014
31. Eisenhofer G, Goldstein DS, Stull R, et al. Simultaneous liquid-chromatographic determination of 3,4-dihydroxyphenylglycol, catecholamines, and 3,4-dihydroxyphenylalanine in plasma, and their responses to inhibition of monoamine oxidase. Clin Chem. 1986;32:2030Y2033. 32. Lobo ED, Quinlan T, O’Brien L, et al. Population pharmacokinetics of orally administered duloxetine in patients: implications for dosing recommendation. Clin Pharmacokinet. 2009;48:189Y197. 33. Meyer JH, Wilson AA, Ginovart N, et al. Occupancy of serotonin transporters by paroxetine and citalopram during treatment of depression: a [(11)C]DASB PET imaging study. Am J Psychiatry. 2001;158:1843Y1849.
23. Goldstein DS, Eisenhofer G, Stull R, et al. Plasma dihydroxyphenylglycol and the intraneuronal disposition of norepinephrine in humans. J Clin Invest. 1988;81:213Y220. 24. Eisenhofer G. The role of neuronal and extraneuronal plasma membrane transporters in the inactivation of peripheral catecholamines. Pharmacol Ther. 2001;91:35Y62. 25. Chappell JC, Kovacs R, Haber H, et al. Evaluation of the effects of duloxetine and escitalopram on 24-hour heart rate variability: a mechanistic study using heart rate variability as a pharmacodynamic measure. J Clin Psychopharmacol. 2013;33:236Y239. 26. Owens MJ, Krulewicz S, Simon JS, et al. Estimates of serotonin and norepinephrine transporter inhibition in depressed patients treated with paroxetine or venlafaxine. Neuropsychopharmacology. 2008;33:3201Y3212. 27. Gilmor ML, Owens MJ, Nemeroff CB. Inhibition of norepinephrine uptake in patients with major depression treated with paroxetine. Am J Psychiatry. 2002;159:1702Y1710. 28. Davidson J, Watkins L, Owens M, et al. Effects of paroxetine and venlafaxine XR on heart rate variability in depression. J Clin Psychopharmacol. 2005;25:480Y484. 29. Owens MJ, Knight DL, Nemeroff CB. Second-generation SSRIs: human monoamine transporter binding profile of escitalopram and R-fluoxetine. Biol Psychiatry. 2001;50:345Y350. 30. Lantz RJ, Gillespie TA, Rash TJ, et al. Metabolism, excretion, and pharmacokinetics of duloxetine in healthy human subjects. Drug Metab Dispos. 2003;31:1142Y1150.
34. Meyer JH, Wilson AA, Sagrati S, et al. Serotonin transporter occupancy of five selective serotonin reuptake inhibitors at different doses: an [11C]DASB positron emission tomography study. Am J Psychiatry. 2004;161:826Y835. 35. Koch S, Hemrick-Luecke SK, Thompson LK, et al. Comparison of effects of dual transporter inhibitors on monoamine transporters and extracellular levels in rats. Neuropharmacology. 2003;45:935Y944. 36. Wong DT, Bymaster FP, Mayle DA, et al. LY248686, a new inhibitor of serotonin and norepinephrine uptake. Neuropsychopharmacology. 1993;8:23Y33. 37. Maletic V, Raison CL. Neurobiology of depression, fibromyalgia and neuropathic pain. Front Biosci. 2009;14:5291Y5338. 38. Kalk NJ, Nutt DJ, Lingford-Hughes AR. The role of central noradrenergic dysregulation in anxiety disorders: evidence from clinical studies. J Psychopharmacol. 2011;25:3Y16. 39. Eisenhofer G. Sympathetic nerve functionVassessment by radioisotope dilution analysis. Clin Auton Res. 2005;15:264Y283. 40. Baumert M, Lambert GW, Dawood T, et al. Short-term heart rate variability and cardiac norepinephrine spillover in patients with depression and panic disorder. Am J Physiol Heart Circ Physiol. 2009;297:H674YH679.
Editor’s Note: Clinical Trial Designs and Statistics Made Easy The randomized, placebo-control trial has been considered the criterion standard for the development of new chemical entities for more than 50 years. In recent years, because of growing costs, increasing regulations, and difficulties in recruiting patients, the search has been on for ways to modify and perhaps even improve on the standard randomized, placebo-control trial model. As I was trying to better understand various alternative models, I came across a book by Professor David L. Streiner of McMaster University and the University of Toronto. In his 396-page book entitled A Guide for the Statistically Perplexed: Selected Readings for Clinical Researchers,1 Streiner uses plain language, humor, and analogies to bring clarity to the statistical issues involved in clinical trials. After reading his book, I contacted Dr Streiner and asked him to write a series of commentaries for us on newer approaches to clinical trials. In the first of his essays, Streiner takes on the subject of adaptive trial designs.2 We would appreciate reader feedback on these essays. Do they do their intended job? Do you take issue with it in any way? REFERENCES 1. Streiner DL. A Guide for the Statistically Perplexed: Selected Readings for Clinical Researchers. Toronto, Ontario, Canada: University of Toronto Press, Scholarly Publishing Division; 2013. 2. Streiner DL. Adaptive randomization. Commentary. J Clin Psychopharmacol. 2014;34:7–8.
Richard I. Shader, MD Editor-in-Chief
16
www.psychopharmacology.com
* 2014 Lippincott Williams & Wilkins
Copyright © 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
