Letters to the Editors
Kenji Fukui, MD, PhD Department of Psychiatry Graduate School of Medical Science Kyoto Prefectural University of Medicine Kyoto, Japan
Journal of Clinical Psychopharmacology
body dysmorphic disorder. Clin Drug Investig. 2010;30:707Y710.
REFERENCES
14. Huang M, Luo B, Hu J, et al. Combination of citalopram plus paliperidone is better than citalopram alone in the treatment of somatoform disorder: results of 6-week randomized study. Int Clin Psychopharmacol. 2012;27:151Y158.
1. Abramowitz JS, Braddock AE. Hypochondriasis: conceptualization, treatment, and relationship to obsessive-compulsive disorder. Psychiatr Clin North Am. 2006;29:503Y519.
15. Masi G, Pfanner C, Millepiedi S, et al. Aripiprazole augmentation in 39 adolescents with medication-resistant obsessive-compulsive disorder. J Clin Psychopharmacol. 2010;30:688Y693.
2. Castle DJ, Phillips KA. Obsessive-compulsive spectrum of disorders: a defensible construct? Aust N Z J Psychiatry. 2006;40:114Y120.
16. Matsunaga H, Hayashida K, Maebayashi K, et al. A case series of aripiprazole augmentation of selective serotonin reuptake inhibitors in treatment-refractory obsessive compulsive disorder. Int J Psychiatry Clin Pract. 2011;15: 263Y269.
3. Bartz JA, Hollander E. Is obsessive-compulsive disorder an anxiety disorder? Prog Neuropsychopharmacol Biol Psychiatry. 2006;30:338Y352. 4. Greeven A, van Balkom AJ, Visser S, et al. Cognitive behavior therapy and paroxetine in the treatment of hypochondriasis: a randomized controlled trial. Am J Psychiatry. 2007;164:91Y99.
17. Delle Chiaie R, Scarciglia P, Pasquini M, et al. Aripiprazole augmentation in patients with resistant obsessive compulsive disorder: a pilot study. Clin Pract Epidemiol Ment Health. 2011;7:107Y111.
5. Fallon BA, Petkova E, Skritskaya N, et al. A double-masked, placebo-controlled study of fluoxetine for hypochondriasis. J Clin Psychopharmacol. 2008;28:638Y645.
18. Muscatello MR, Bruno A, Pandolfo G, et al. Effect of aripiprazole augmentation of serotonin reuptake inhibitors or clomipramine in treatment-resistant obsessive-compulsive disorder: a double-blind, placebo-controlled study. J Clin Psychopharmacol. 2011; 31:174Y179.
6. Noyes R Jr, Happel RL, Muller BA, et al. Fluvoxamine for somatoform disorders: an open trial. Gen Hosp Psychiatry. 1998;20:339Y344. 7. Muller JE, Wentzel I, Koen L, et al. Escitalopram in the treatment of multisomatoform disorder: a double-blind, placebo-controlled trial. Int Clin Psychopharmacol. 2008;23:43Y48. 8. Bloch MH, Landeros-Weisenberger A, Kermendi B, et al. A systematic review: antipsychotic augmentation with treatment refractory obsessive-compulsive disorder. Mol Psychiatry. 2006;11:622Y632. 9. Skapinakis P, Papatheodorou T, Mavreas V. Antipsychotic augmentation of serotonergic antidepressants in treatment-resistant obsessive-compulsive disorder: a meta-analysis of the randomized controlled trials. Eur Neuropsychopharmacol. 2007;17: 79Y93. 10. Phillips KA, Albertini RS, Siniscalchi JM, et al. Effectiveness of pharmacotherapy for body dysmorphic disorder: a chart-review study. J Clin Psychiatry. 2001;62:721Y727. 11. Phillips KA. Olanzapine augmentation of fluoxetine in body dysmorphic disorder. Am J Psychiatry. 2005;162:1022Y1023. 12. Nakaaki S, Murata Y, Furukawa TA. Efficacy of olanzapine augmentation of paroxetine therapy in patients with severe body dysmorphic disorder. Psychiatry Clin Neurosci. 2008;62:370. 13. Uzun O, Ozdemir B. Aripiprazole as an augmentation agent in treatment-resistant
398
www.psychopharmacology.com
19. Sayyah M, Sayyah M, Boostani H, et al. Effects of aripiprazole augmentation in treatment-resistant obsessive-compulsive disorder (a double blind clinical trial). Depress Anxiety. 2012;29:850Y854.
Plasma Levels and Cerebrospinal Fluid Penetration of Venlafaxine in a Patient With a Nonfatal Overdose During a Suicide Attempt To the Editors:
CASE REPORT Variability in response to psychotropic drugs is due to genetic and environmental factors. Cytochrome P450 (CYP) isoforms are involved in the metabolism of drugs, whereas the P-glycoprotein transporter (P-gp), encoded by the ABCB1 gene, may influence both blood and cerebrospinal fluid (CSF) drug concentrations. We report the case of a genotyped 37-year-old female inpatient surviving a severe suicide attempt with 15 g of venlafaxine (VEN) without long-lasting negative effects. Therapeutic drug monitoring of VEN and
&
Volume 34, Number 3, June 2014
O-desmethylvenlafaxine (ODV) revealed extraordinary high drug levels in both plasma and CSF. Ms. A. is a 37-year-old female inpatient suffering from a severe episode of major depressive disorder (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition: 296.23, International Classification of Diseases, 10th Revision: F32.2) treated with a daily dose of 150 mg of VEN since the day of her admission. In suicidal ideation, she ingested 100 tablets of 150 mg VEN extended release equivalent to a total amount of 15 g. Shortly hereafter, she was found unconscious in her room with foam around the mouth, suggesting an epileptic seizure. Blood oxygen saturation was 92%, blood glucose level was 76 mg/dL, and pulse rate was accelerated to 130 beats/min. Starting basic life support, she had another epileptic seizure of 30 seconds’ duration and was intubated because of circulatory instability and respiratory insufficiency. Intracranial pathology and encephalitis as reasons for unconsciousness were excluded by computed tomography scan and lumbar puncture. Cerebrospinal fluid analysis 5 hours after intoxication revealed normal leukocyte count and physiological protein, glucose, and lactate levels. Therapeutic drug monitoring, using highperformance liquid chromatography, showed plasma levels for VEN of 18,138 ng/mL, ODV 2955 ng/mL (active moiety [VEN + ODV] 21,093 ng/mL; reference range, 100Y400 ng/mL).1 Cerebrospinal fluid levels were found to be 6488 ng/mL for VEN and 2154 ng/mL for ODV. The active moiety plasma/CSF ratio was 2.44. After some days at the ICU, the patient recovered well until she was readmitted to the psychiatric department where she then signed a written informed consent to do genetic testing on CYP isoenzymes and on ABCB1 genotype to get a deeper understanding of the pharmacokinetics and CSF penetration of VEN. For P450 2D6, she was found to be an extensive metabolizer with the genotype *1/*1, for CYP2C9 genetic testing revealed *1/*3 (intermediate metabolizer), and the genotype for CYP2C19 was *1/*1 (extensive metabolizer). Concerning the ABCB1 C3435T genotype, she was found to be CT, reflecting an intermediate phenotype, which is the most common one. For 2677, her genotype consists of GG, which corresponds to a higher activity, but there is an incomplete linkage disequilibrium between 2677 and 3435.
DISCUSSION The clinical efficacy of systemically administered drugs acting on the central nervous system depends on their ability to pass the blood-brain barrier, a process that is regulated * 2014 Lippincott Williams & Wilkins
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Journal of Clinical Psychopharmacology
&
Volume 34, Number 3, June 2014
Letters to the Editors
TABLE 1. Drug Concentrations in Plasma and CSF 5 Hours After Intake of 15,000 mg of Venlafaxine Drug Concentration in Plasma VEN, ng/mL ODV, ng/mL VEN + ODV, ng/mL VEN + ODVVplasma/CSF ratio
18,138 2955 21,093 2.44
Drug Concentration in CSF VEN, ng/mL ODV, ng/mL VEN + ODV, ng/mL
6488 2154 8642
Michael Paulzen, MD Department of Psychiatry Psychotherapy and Psychosomatics RWTH Aachen University and JARAYTranslational Brain Medicine Aachen, Germany [email protected]
Karsten Henkel, MD Department of Psychiatry Psychotherapy and Psychosomatics RWTH Aachen University and JARAYTranslational Brain Medicine Aachen, Germany
Simone Tauber, MD Arno Reich, MD Department of Neurology RWTH Aachen University Aachen, Germany
by transporter molecules such as ABCB1, encoding P-gp, BCRP (breast cancer resistance protein), or MRP (multidrug resistance protein). P-glycoprotein located at the blood-brain barrier regulates intracerebral concentrations of substances and may thereby affect the clinical response of central nervous systemYtargeting drugs that are substrates of this transporter. However, the molecular mechanisms keeping drugs out of or clearing drugs rapidly from the CSF are not yet clearly understood. Although VEN is known to be both a P-gp substrate and an inducer of P-gp,2 the ratio of plasma to CSF levels is very low (2.44; Table 1), reflecting a high penetration rate into CSF. This is in contrast to other psychotropic drugs such as duloxetine.3 Consistent with the literature, classifying VEN as lower toxicity among different antidepressants,4 the toxicity of the extraordinarily high plasma and CSF levels of VEN + ODV in our patient was comparably low. Nonetheless, a laboratory alert level for VEN defined as a plasma level at or above which the laboratory should immediately inform the treating physician in daily routine of antidepressant treatment is defined at 800 ng/mL active moiety.1 In our case, this level was exceeded more than 26-fold. As information about serious consequences of VEN intoxications in the literature is lacking and only 1 single case describes a severe hypoglycemia following a VEN intoxication with measured plasma levels of 9800 ng/mL for VEN and 4200 ng/mL for ODV, respectively,5 general conclusions about its toxicity cannot be drawn. By genotyping the patient for the ABCB1 gene, we hoped to find a reason for the high penetration rate into the CSF, but it seems impossible to predict the consequence of a genetic ABCB1 polymorphism disregarding that the high levels of VEN and ODV possibly resulted in a saturation of the P-gp pumps. Apparently, ABCB1 genotyping explains only part of the variability of P-gp activity in humans. * 2014 Lippincott Williams & Wilkins
Finally, it is important to notice that VEN is chiral. It is known that the different enantiomers display different pharmacodynamic profiles in inhibiting presynaptic reuptake at different target structures (R[j]VEN inhibits noradrenaline and serotonin reuptake; S[+]-VEN primarily inhibits serotonin reuptake).6 A difference in the distribution of the enantiomers according to CYP2D6 metabolizer status7 might be of importance when interpreting the results; however, a chiral analysis has not been performed in the present case. An enantioselective analysis of VEN and its metabolites could in this regard assist in the interpretation of the distribution pattern between plasma and CSF.
AUTHOR DISCLOSURE INFORMATION Dr. Gru¨nder has served as a consultant for AstraZeneca (London, UK), BristolMyers Squibb (New York, NY), Cheplapharm (Greifswald, Germany), Eli Lilly (Indianapolis, IN), Johnson & Johnson (Beerse, Belgium), and Otsuka (Rockville, MD). He has served on the speakers’ bureau of AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen Cilag, Otsuka, Pfizer, Servier (Paris, France), and Wyeth. He has received grant support from Alkermes, Bristol-Myers Squibb, Eli Lilly, and Johnson & Johnson. He is cofounder of Pharma-ImageYMolecular Imaging Technologies GmbH (Du¨sseldorf, Germany). Dr. Eap received research support from AstraZeneca (2000), Eli Lilly (2007), Fujisawa (2003), Janssen-Cilag (1997, 2005), Novartis (2003), Sandoz (1997), SmithKline Beecham (1998, 2000), Bristol-Myers Squibb (2008), and Wyeth (1997). He received honoraria for conferences or teaching CME courses from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Essex Chemie, GlaxoSmithKline, JanssenCilag, Lundbeck, Novo Nordisk, Organon, Sandoz, and Advisis. The other authors declare no conflicts of interest.
Chin B. Eap, PhD Unit of Pharmacogenetics and Clinical Psychopharmacology Centre for Psychiatric Neuroscience Department of Psychiatry University Hospital Lausanne Prilly-Lausanne, Switzerland
Gerhard Gru¨nder, MD Department of Psychiatry Psychotherapy and Psychosomatics RWTH Aachen University and JARAYTranslational Brain Medicine Aachen, Germany
REFERENCES 1. Hiemke C, Baumann P, Bergemann N, et al. AGNP consensus guidelines for therapeutic drug monitoring in psychiatry: update 2011. Pharmacopsychiatry. 2011;44(6):195Y235. 2. Bachmeier CJ, Beaulieu-Abdelahad D, Ganey NJ, et al. Induction of drug efflux protein expression by venlafaxine but not desvenlafaxine. Biopharm Drug Dispos. 2011;32(4):233Y244. 3. Paulzen M, Hiemke C, Gru¨nder G. Plasma levels and cerebrospinal fluid penetration by duloxetine in a patient with a non-fatal overdose during a suicide attempt. Int J Neuropsychopharmacol. 2009;12(10):1431Y1432. 4. Reis M, Aamo T, Ahlner J, et al. Reference concentrations of antidepressants. A compilation of postmortem and therapeutic levels. J Anal Toxicol. 2007;31(5):254Y64. 5. Meertens JH, Monteban-Kooistra WE, Ligtenberg JJ Severe hypoglycemia following venlafaxine intoxication: a case report. J Clin Psychopharmacol. 2007;27(4):414Y415. 6. Holliday SM, Benfield P. VenlafaxineVa review of its pharmacology and therapeutic potential in depression. Drugs. 1995;49:280Y294. 7. Eap CB, Lessard E, Baumann P. Role of CYP2D6 in the stereoselective disposition of venlafaxine in humans. Pharmacogenetics. 2003;13(1):39Y47.
www.psychopharmacology.com
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
399
Kenji Fukui, MD, PhD Department of Psychiatry Graduate School of Medical Science Kyoto Prefectural University of Medicine Kyoto, Japan
Journal of Clinical Psychopharmacology
body dysmorphic disorder. Clin Drug Investig. 2010;30:707Y710.
REFERENCES
14. Huang M, Luo B, Hu J, et al. Combination of citalopram plus paliperidone is better than citalopram alone in the treatment of somatoform disorder: results of 6-week randomized study. Int Clin Psychopharmacol. 2012;27:151Y158.
1. Abramowitz JS, Braddock AE. Hypochondriasis: conceptualization, treatment, and relationship to obsessive-compulsive disorder. Psychiatr Clin North Am. 2006;29:503Y519.
15. Masi G, Pfanner C, Millepiedi S, et al. Aripiprazole augmentation in 39 adolescents with medication-resistant obsessive-compulsive disorder. J Clin Psychopharmacol. 2010;30:688Y693.
2. Castle DJ, Phillips KA. Obsessive-compulsive spectrum of disorders: a defensible construct? Aust N Z J Psychiatry. 2006;40:114Y120.
16. Matsunaga H, Hayashida K, Maebayashi K, et al. A case series of aripiprazole augmentation of selective serotonin reuptake inhibitors in treatment-refractory obsessive compulsive disorder. Int J Psychiatry Clin Pract. 2011;15: 263Y269.
3. Bartz JA, Hollander E. Is obsessive-compulsive disorder an anxiety disorder? Prog Neuropsychopharmacol Biol Psychiatry. 2006;30:338Y352. 4. Greeven A, van Balkom AJ, Visser S, et al. Cognitive behavior therapy and paroxetine in the treatment of hypochondriasis: a randomized controlled trial. Am J Psychiatry. 2007;164:91Y99.
17. Delle Chiaie R, Scarciglia P, Pasquini M, et al. Aripiprazole augmentation in patients with resistant obsessive compulsive disorder: a pilot study. Clin Pract Epidemiol Ment Health. 2011;7:107Y111.
5. Fallon BA, Petkova E, Skritskaya N, et al. A double-masked, placebo-controlled study of fluoxetine for hypochondriasis. J Clin Psychopharmacol. 2008;28:638Y645.
18. Muscatello MR, Bruno A, Pandolfo G, et al. Effect of aripiprazole augmentation of serotonin reuptake inhibitors or clomipramine in treatment-resistant obsessive-compulsive disorder: a double-blind, placebo-controlled study. J Clin Psychopharmacol. 2011; 31:174Y179.
6. Noyes R Jr, Happel RL, Muller BA, et al. Fluvoxamine for somatoform disorders: an open trial. Gen Hosp Psychiatry. 1998;20:339Y344. 7. Muller JE, Wentzel I, Koen L, et al. Escitalopram in the treatment of multisomatoform disorder: a double-blind, placebo-controlled trial. Int Clin Psychopharmacol. 2008;23:43Y48. 8. Bloch MH, Landeros-Weisenberger A, Kermendi B, et al. A systematic review: antipsychotic augmentation with treatment refractory obsessive-compulsive disorder. Mol Psychiatry. 2006;11:622Y632. 9. Skapinakis P, Papatheodorou T, Mavreas V. Antipsychotic augmentation of serotonergic antidepressants in treatment-resistant obsessive-compulsive disorder: a meta-analysis of the randomized controlled trials. Eur Neuropsychopharmacol. 2007;17: 79Y93. 10. Phillips KA, Albertini RS, Siniscalchi JM, et al. Effectiveness of pharmacotherapy for body dysmorphic disorder: a chart-review study. J Clin Psychiatry. 2001;62:721Y727. 11. Phillips KA. Olanzapine augmentation of fluoxetine in body dysmorphic disorder. Am J Psychiatry. 2005;162:1022Y1023. 12. Nakaaki S, Murata Y, Furukawa TA. Efficacy of olanzapine augmentation of paroxetine therapy in patients with severe body dysmorphic disorder. Psychiatry Clin Neurosci. 2008;62:370. 13. Uzun O, Ozdemir B. Aripiprazole as an augmentation agent in treatment-resistant
398
www.psychopharmacology.com
19. Sayyah M, Sayyah M, Boostani H, et al. Effects of aripiprazole augmentation in treatment-resistant obsessive-compulsive disorder (a double blind clinical trial). Depress Anxiety. 2012;29:850Y854.
Plasma Levels and Cerebrospinal Fluid Penetration of Venlafaxine in a Patient With a Nonfatal Overdose During a Suicide Attempt To the Editors:
CASE REPORT Variability in response to psychotropic drugs is due to genetic and environmental factors. Cytochrome P450 (CYP) isoforms are involved in the metabolism of drugs, whereas the P-glycoprotein transporter (P-gp), encoded by the ABCB1 gene, may influence both blood and cerebrospinal fluid (CSF) drug concentrations. We report the case of a genotyped 37-year-old female inpatient surviving a severe suicide attempt with 15 g of venlafaxine (VEN) without long-lasting negative effects. Therapeutic drug monitoring of VEN and
&
Volume 34, Number 3, June 2014
O-desmethylvenlafaxine (ODV) revealed extraordinary high drug levels in both plasma and CSF. Ms. A. is a 37-year-old female inpatient suffering from a severe episode of major depressive disorder (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition: 296.23, International Classification of Diseases, 10th Revision: F32.2) treated with a daily dose of 150 mg of VEN since the day of her admission. In suicidal ideation, she ingested 100 tablets of 150 mg VEN extended release equivalent to a total amount of 15 g. Shortly hereafter, she was found unconscious in her room with foam around the mouth, suggesting an epileptic seizure. Blood oxygen saturation was 92%, blood glucose level was 76 mg/dL, and pulse rate was accelerated to 130 beats/min. Starting basic life support, she had another epileptic seizure of 30 seconds’ duration and was intubated because of circulatory instability and respiratory insufficiency. Intracranial pathology and encephalitis as reasons for unconsciousness were excluded by computed tomography scan and lumbar puncture. Cerebrospinal fluid analysis 5 hours after intoxication revealed normal leukocyte count and physiological protein, glucose, and lactate levels. Therapeutic drug monitoring, using highperformance liquid chromatography, showed plasma levels for VEN of 18,138 ng/mL, ODV 2955 ng/mL (active moiety [VEN + ODV] 21,093 ng/mL; reference range, 100Y400 ng/mL).1 Cerebrospinal fluid levels were found to be 6488 ng/mL for VEN and 2154 ng/mL for ODV. The active moiety plasma/CSF ratio was 2.44. After some days at the ICU, the patient recovered well until she was readmitted to the psychiatric department where she then signed a written informed consent to do genetic testing on CYP isoenzymes and on ABCB1 genotype to get a deeper understanding of the pharmacokinetics and CSF penetration of VEN. For P450 2D6, she was found to be an extensive metabolizer with the genotype *1/*1, for CYP2C9 genetic testing revealed *1/*3 (intermediate metabolizer), and the genotype for CYP2C19 was *1/*1 (extensive metabolizer). Concerning the ABCB1 C3435T genotype, she was found to be CT, reflecting an intermediate phenotype, which is the most common one. For 2677, her genotype consists of GG, which corresponds to a higher activity, but there is an incomplete linkage disequilibrium between 2677 and 3435.
DISCUSSION The clinical efficacy of systemically administered drugs acting on the central nervous system depends on their ability to pass the blood-brain barrier, a process that is regulated * 2014 Lippincott Williams & Wilkins
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Journal of Clinical Psychopharmacology
&
Volume 34, Number 3, June 2014
Letters to the Editors
TABLE 1. Drug Concentrations in Plasma and CSF 5 Hours After Intake of 15,000 mg of Venlafaxine Drug Concentration in Plasma VEN, ng/mL ODV, ng/mL VEN + ODV, ng/mL VEN + ODVVplasma/CSF ratio
18,138 2955 21,093 2.44
Drug Concentration in CSF VEN, ng/mL ODV, ng/mL VEN + ODV, ng/mL
6488 2154 8642
Michael Paulzen, MD Department of Psychiatry Psychotherapy and Psychosomatics RWTH Aachen University and JARAYTranslational Brain Medicine Aachen, Germany [email protected]
Karsten Henkel, MD Department of Psychiatry Psychotherapy and Psychosomatics RWTH Aachen University and JARAYTranslational Brain Medicine Aachen, Germany
Simone Tauber, MD Arno Reich, MD Department of Neurology RWTH Aachen University Aachen, Germany
by transporter molecules such as ABCB1, encoding P-gp, BCRP (breast cancer resistance protein), or MRP (multidrug resistance protein). P-glycoprotein located at the blood-brain barrier regulates intracerebral concentrations of substances and may thereby affect the clinical response of central nervous systemYtargeting drugs that are substrates of this transporter. However, the molecular mechanisms keeping drugs out of or clearing drugs rapidly from the CSF are not yet clearly understood. Although VEN is known to be both a P-gp substrate and an inducer of P-gp,2 the ratio of plasma to CSF levels is very low (2.44; Table 1), reflecting a high penetration rate into CSF. This is in contrast to other psychotropic drugs such as duloxetine.3 Consistent with the literature, classifying VEN as lower toxicity among different antidepressants,4 the toxicity of the extraordinarily high plasma and CSF levels of VEN + ODV in our patient was comparably low. Nonetheless, a laboratory alert level for VEN defined as a plasma level at or above which the laboratory should immediately inform the treating physician in daily routine of antidepressant treatment is defined at 800 ng/mL active moiety.1 In our case, this level was exceeded more than 26-fold. As information about serious consequences of VEN intoxications in the literature is lacking and only 1 single case describes a severe hypoglycemia following a VEN intoxication with measured plasma levels of 9800 ng/mL for VEN and 4200 ng/mL for ODV, respectively,5 general conclusions about its toxicity cannot be drawn. By genotyping the patient for the ABCB1 gene, we hoped to find a reason for the high penetration rate into the CSF, but it seems impossible to predict the consequence of a genetic ABCB1 polymorphism disregarding that the high levels of VEN and ODV possibly resulted in a saturation of the P-gp pumps. Apparently, ABCB1 genotyping explains only part of the variability of P-gp activity in humans. * 2014 Lippincott Williams & Wilkins
Finally, it is important to notice that VEN is chiral. It is known that the different enantiomers display different pharmacodynamic profiles in inhibiting presynaptic reuptake at different target structures (R[j]VEN inhibits noradrenaline and serotonin reuptake; S[+]-VEN primarily inhibits serotonin reuptake).6 A difference in the distribution of the enantiomers according to CYP2D6 metabolizer status7 might be of importance when interpreting the results; however, a chiral analysis has not been performed in the present case. An enantioselective analysis of VEN and its metabolites could in this regard assist in the interpretation of the distribution pattern between plasma and CSF.
AUTHOR DISCLOSURE INFORMATION Dr. Gru¨nder has served as a consultant for AstraZeneca (London, UK), BristolMyers Squibb (New York, NY), Cheplapharm (Greifswald, Germany), Eli Lilly (Indianapolis, IN), Johnson & Johnson (Beerse, Belgium), and Otsuka (Rockville, MD). He has served on the speakers’ bureau of AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen Cilag, Otsuka, Pfizer, Servier (Paris, France), and Wyeth. He has received grant support from Alkermes, Bristol-Myers Squibb, Eli Lilly, and Johnson & Johnson. He is cofounder of Pharma-ImageYMolecular Imaging Technologies GmbH (Du¨sseldorf, Germany). Dr. Eap received research support from AstraZeneca (2000), Eli Lilly (2007), Fujisawa (2003), Janssen-Cilag (1997, 2005), Novartis (2003), Sandoz (1997), SmithKline Beecham (1998, 2000), Bristol-Myers Squibb (2008), and Wyeth (1997). He received honoraria for conferences or teaching CME courses from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Essex Chemie, GlaxoSmithKline, JanssenCilag, Lundbeck, Novo Nordisk, Organon, Sandoz, and Advisis. The other authors declare no conflicts of interest.
Chin B. Eap, PhD Unit of Pharmacogenetics and Clinical Psychopharmacology Centre for Psychiatric Neuroscience Department of Psychiatry University Hospital Lausanne Prilly-Lausanne, Switzerland
Gerhard Gru¨nder, MD Department of Psychiatry Psychotherapy and Psychosomatics RWTH Aachen University and JARAYTranslational Brain Medicine Aachen, Germany
REFERENCES 1. Hiemke C, Baumann P, Bergemann N, et al. AGNP consensus guidelines for therapeutic drug monitoring in psychiatry: update 2011. Pharmacopsychiatry. 2011;44(6):195Y235. 2. Bachmeier CJ, Beaulieu-Abdelahad D, Ganey NJ, et al. Induction of drug efflux protein expression by venlafaxine but not desvenlafaxine. Biopharm Drug Dispos. 2011;32(4):233Y244. 3. Paulzen M, Hiemke C, Gru¨nder G. Plasma levels and cerebrospinal fluid penetration by duloxetine in a patient with a non-fatal overdose during a suicide attempt. Int J Neuropsychopharmacol. 2009;12(10):1431Y1432. 4. Reis M, Aamo T, Ahlner J, et al. Reference concentrations of antidepressants. A compilation of postmortem and therapeutic levels. J Anal Toxicol. 2007;31(5):254Y64. 5. Meertens JH, Monteban-Kooistra WE, Ligtenberg JJ Severe hypoglycemia following venlafaxine intoxication: a case report. J Clin Psychopharmacol. 2007;27(4):414Y415. 6. Holliday SM, Benfield P. VenlafaxineVa review of its pharmacology and therapeutic potential in depression. Drugs. 1995;49:280Y294. 7. Eap CB, Lessard E, Baumann P. Role of CYP2D6 in the stereoselective disposition of venlafaxine in humans. Pharmacogenetics. 2003;13(1):39Y47.
www.psychopharmacology.com
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
399
