Letters to the Editors
4. Preskorn S, Ereshefsky L, Chiu YY, et al. Effect of food on the pharmacokinetics of lurasidone: results of two randomized, open-label, crossover studies. Hum Psychopharmacol. 2013;28:495Y505. 5. Meyer JM, Loebel AD, Schweizer E. Lurasidone: a new drug in development for schizophrenia. Expert Opin Investig Drugs. 2009;18:1715Y1726. 6. Hussar DA. New drugs 2012 part I. Nursing. 2012;42:38Y45. 7. Kane JM. Lurasidone: a clinical overview. J Clin Psychiatry. 2011;72(suppl 1):24Y28. 8. Drug development and drug interactions: table of substrates, inhibitors and inducers [US Food and Drug Administration Web site]. September 16, 2011. Available at: http://www.fda.gov/drugs/ developmentapprovalprocess/ developmentresources/druginteractionslabeling/ ucm093664.htm#classInhibit. Accessed June 16, 2014. 9. Hopkins CR. ACS chemical neuroscience molecule spotlight on Latuda (lurasidone; SM-13,496). ACS Chem Neurosci. 2011;2:58Y59. 10. Citrome L, Cucchiaro J, Sarma K, et al. Long-term safety and tolerability of lurasidone in schizophrenia: a 12-month double blind, active controlled study. Int Clin Psychopharmacol. 2012;27:165Y176. 11. Stahl SM. Stahl’s Essential Psychopharmacology: the Prescriber’s Guide. 4th ed. New York, NY: Cambridge University Press; 2011. 12. Physicians’ Desk Reference. 67th ed. Montvale, NJ: Thomson PDR; 2013.
Adding to Antidepressant Augmentation To the Editors: iterally, the term augmentation refers to the act of enlarging, increasing something. In psychopharmacology, this term is widely used to designate therapeutic strategies that aim at maximizing the efficacy of a monotherapy by adding a second drug. The accepted definition of antidepressant augmentation, validated by international guidelines,1 assumes that augmentation of antidepressants involves adding a second drug, other than an antidepressant, to the treatment regimen when no response or only partial response has been achieved, with the goal of enhancing treatment. Although enhancing the effectiveness of one another, the adding of an antidepressant to an ongoing antidepressant treatment is designated by the neutral generalist terms: association or combination. To test this definition against the literature, we performed a computerized
L
770
www.psychopharmacology.com
Journal of Clinical Psychopharmacology
literature search (National Library of Medicine/Medline) using the following words: ‘‘augmentation’’ and ‘‘antidepressant.’’ Articles included were both in English and non-English and up to January 2014. Abstracts of all retrieved occurrences were carefully read by F.M., F.H., and O.D. The corresponding publications were extracted and scrutinized when necessary. Articles retained had to deal with antidepressant combination strategies in treating depression as well as psychotic or anxiety disorders in humans. We ensured that the use of the term augmentation was not related to a translation error of nonEnglish articles. A total of 1388 occurrences were retrieved, and 531 were excluded as nonrelevant. In 768 publications, the use of the term augmentation was in accordance with the current definition. In 91 studies, the term augmentation was used to designate the combination of 2 antidepressants. The added antidepressant was bupropion in 32 articles, a tricyclic antidepressant in 21 articles, mirtazapine in 16 articles, an selective serotonin reuptake inhibitor (SSRI) in 8 articles, each of mianserin, agomelatine, and trazodone, as well as an monoamine oxidase inhibitor in 3 articles. Augmentation of an SSRI with nortriptyline was reported in 1 article. Although widely accepted as the definition of combining an antidepressant to another drug that is not an antidepressant, the concept of augmentation is used, in some cases, to designate the association of 2 antidepressants. The ‘‘augmenting’’ agent either adds a different mechanism of action (pharmacodynamic augmentation) or affects plasma concentration of the ongoing treatment by modifying its metabolism (pharmacokinetic augmentation). When added to an SSRI, bupropion augmentation is mainly pharmacodynamic because bupropion adds to serotonin reuptake inhibition, norepinephrine reuptake inhibition, and dopamine reuptake inhibition. Even for SSRIs, we could hardly omit that these drugs actually display different mechanisms of action. Fluoxetine is not only a serotonin reuptake inhibitor but also a potent 5-HT2C antagonist.2 Besides serotonin reuptake inhibition properties, paroxetine has mild anticholinergic (M1 receptor antagonism) and weak norepinephrine reuptake inhibition actions.2 Theoretically, adding fluoxetine to paroxetine enhances its antidepressant effectiveness by adding new pharmacodynamics mechanisms. Thus, paroxetine and fluoxetine combination should, theoretically, be considered as an augmentation strategy. With a view toward the development of a new antidepressant with innovating
&
Volume 34, Number 6, December 2014
mechanism of action and for the sake of clarity, we suggest that the term augmentation should be used whenever the combination of 2 antidepressants results in the enhancement of pharmacodynamic or pharmacokinetic action of the ongoing treatment. AUTHOR DISCLOSURE INFORMATION The authors declare no conflicts of interest. Fayc¸al Mouaffak, MD, PhD Department of Psychiatry Biceˆtre University Hospital and Faculte´ de Me´decine Universite´ Paris XI Paris, France [email protected]
Franz Hozer, MD Olivia Delomel, MD Patrick Hardy, MD Department of Psychiatry Biceˆtre University Hospital and Faculte´ de Me´decine Universite´ Paris XI Paris, France
REFERENCES 1. Bauer M, Whybrow PC, Angst J, et al. World Federation of Societies Biological Psychiatry Task Force on Treatment Guidelines for Unipolar Depressive D. World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Unipolar Depressive Disorders, Part 1: acute and continuation treatment of major depressive disorder. World J Biol Psychiatry. 2002;3(1):5Y43. 2. Stahl SM. Stahl’s Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. Cambridge, England: Cambridge University Press; 2013.
Atomoxetine-Associated Akathisia A Case Report To the Editors: tomoxetine is the first nonstimulant drug approved by the Food and Drug Administration for the treatment of attentiondeficit/hyperactivity disorder (ADHD) in patients older than 6 years.1 It works by blocking the presynaptic norepinephrine transporter, which leads to increased norepinephrine levels in the presynaptic gap.2 Common adverse effects of atomoxetine include nausea, vomiting, constipation, loss of appetite, weight loss, stomach pain, dizziness, headache, irritability, aggression, fatigue, and somnolence.3,4 In this
A
* 2014 Lippincott Williams & Wilkins
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
4. Preskorn S, Ereshefsky L, Chiu YY, et al. Effect of food on the pharmacokinetics of lurasidone: results of two randomized, open-label, crossover studies. Hum Psychopharmacol. 2013;28:495Y505. 5. Meyer JM, Loebel AD, Schweizer E. Lurasidone: a new drug in development for schizophrenia. Expert Opin Investig Drugs. 2009;18:1715Y1726. 6. Hussar DA. New drugs 2012 part I. Nursing. 2012;42:38Y45. 7. Kane JM. Lurasidone: a clinical overview. J Clin Psychiatry. 2011;72(suppl 1):24Y28. 8. Drug development and drug interactions: table of substrates, inhibitors and inducers [US Food and Drug Administration Web site]. September 16, 2011. Available at: http://www.fda.gov/drugs/ developmentapprovalprocess/ developmentresources/druginteractionslabeling/ ucm093664.htm#classInhibit. Accessed June 16, 2014. 9. Hopkins CR. ACS chemical neuroscience molecule spotlight on Latuda (lurasidone; SM-13,496). ACS Chem Neurosci. 2011;2:58Y59. 10. Citrome L, Cucchiaro J, Sarma K, et al. Long-term safety and tolerability of lurasidone in schizophrenia: a 12-month double blind, active controlled study. Int Clin Psychopharmacol. 2012;27:165Y176. 11. Stahl SM. Stahl’s Essential Psychopharmacology: the Prescriber’s Guide. 4th ed. New York, NY: Cambridge University Press; 2011. 12. Physicians’ Desk Reference. 67th ed. Montvale, NJ: Thomson PDR; 2013.
Adding to Antidepressant Augmentation To the Editors: iterally, the term augmentation refers to the act of enlarging, increasing something. In psychopharmacology, this term is widely used to designate therapeutic strategies that aim at maximizing the efficacy of a monotherapy by adding a second drug. The accepted definition of antidepressant augmentation, validated by international guidelines,1 assumes that augmentation of antidepressants involves adding a second drug, other than an antidepressant, to the treatment regimen when no response or only partial response has been achieved, with the goal of enhancing treatment. Although enhancing the effectiveness of one another, the adding of an antidepressant to an ongoing antidepressant treatment is designated by the neutral generalist terms: association or combination. To test this definition against the literature, we performed a computerized
L
770
www.psychopharmacology.com
Journal of Clinical Psychopharmacology
literature search (National Library of Medicine/Medline) using the following words: ‘‘augmentation’’ and ‘‘antidepressant.’’ Articles included were both in English and non-English and up to January 2014. Abstracts of all retrieved occurrences were carefully read by F.M., F.H., and O.D. The corresponding publications were extracted and scrutinized when necessary. Articles retained had to deal with antidepressant combination strategies in treating depression as well as psychotic or anxiety disorders in humans. We ensured that the use of the term augmentation was not related to a translation error of nonEnglish articles. A total of 1388 occurrences were retrieved, and 531 were excluded as nonrelevant. In 768 publications, the use of the term augmentation was in accordance with the current definition. In 91 studies, the term augmentation was used to designate the combination of 2 antidepressants. The added antidepressant was bupropion in 32 articles, a tricyclic antidepressant in 21 articles, mirtazapine in 16 articles, an selective serotonin reuptake inhibitor (SSRI) in 8 articles, each of mianserin, agomelatine, and trazodone, as well as an monoamine oxidase inhibitor in 3 articles. Augmentation of an SSRI with nortriptyline was reported in 1 article. Although widely accepted as the definition of combining an antidepressant to another drug that is not an antidepressant, the concept of augmentation is used, in some cases, to designate the association of 2 antidepressants. The ‘‘augmenting’’ agent either adds a different mechanism of action (pharmacodynamic augmentation) or affects plasma concentration of the ongoing treatment by modifying its metabolism (pharmacokinetic augmentation). When added to an SSRI, bupropion augmentation is mainly pharmacodynamic because bupropion adds to serotonin reuptake inhibition, norepinephrine reuptake inhibition, and dopamine reuptake inhibition. Even for SSRIs, we could hardly omit that these drugs actually display different mechanisms of action. Fluoxetine is not only a serotonin reuptake inhibitor but also a potent 5-HT2C antagonist.2 Besides serotonin reuptake inhibition properties, paroxetine has mild anticholinergic (M1 receptor antagonism) and weak norepinephrine reuptake inhibition actions.2 Theoretically, adding fluoxetine to paroxetine enhances its antidepressant effectiveness by adding new pharmacodynamics mechanisms. Thus, paroxetine and fluoxetine combination should, theoretically, be considered as an augmentation strategy. With a view toward the development of a new antidepressant with innovating
&
Volume 34, Number 6, December 2014
mechanism of action and for the sake of clarity, we suggest that the term augmentation should be used whenever the combination of 2 antidepressants results in the enhancement of pharmacodynamic or pharmacokinetic action of the ongoing treatment. AUTHOR DISCLOSURE INFORMATION The authors declare no conflicts of interest. Fayc¸al Mouaffak, MD, PhD Department of Psychiatry Biceˆtre University Hospital and Faculte´ de Me´decine Universite´ Paris XI Paris, France [email protected]
Franz Hozer, MD Olivia Delomel, MD Patrick Hardy, MD Department of Psychiatry Biceˆtre University Hospital and Faculte´ de Me´decine Universite´ Paris XI Paris, France
REFERENCES 1. Bauer M, Whybrow PC, Angst J, et al. World Federation of Societies Biological Psychiatry Task Force on Treatment Guidelines for Unipolar Depressive D. World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Unipolar Depressive Disorders, Part 1: acute and continuation treatment of major depressive disorder. World J Biol Psychiatry. 2002;3(1):5Y43. 2. Stahl SM. Stahl’s Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. Cambridge, England: Cambridge University Press; 2013.
Atomoxetine-Associated Akathisia A Case Report To the Editors: tomoxetine is the first nonstimulant drug approved by the Food and Drug Administration for the treatment of attentiondeficit/hyperactivity disorder (ADHD) in patients older than 6 years.1 It works by blocking the presynaptic norepinephrine transporter, which leads to increased norepinephrine levels in the presynaptic gap.2 Common adverse effects of atomoxetine include nausea, vomiting, constipation, loss of appetite, weight loss, stomach pain, dizziness, headache, irritability, aggression, fatigue, and somnolence.3,4 In this
A
* 2014 Lippincott Williams & Wilkins
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
