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Antidepressants

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Applied Clinical Pharmacokinetics and Pharmacodynamics of Psychopharmacological Agents

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Abstract

Antidepressants have made major contributions towards the treatment of anxiety and mood disorders. A variety of pharmacologic classes of these agents emerged since the 1960s. Tricyclics and monoamine oxidase inhibitors were early agents developed and remain in use today. Plasma concentration monitoring for therapeutic effects were initiated with the tricyclic agents. However, safety concerns persisted with these agents and the selective serotonin reuptake inhibitors (SSRIs) arose. Since the introduction of the SSRIs, these agents became the foremost prescribed medications for depression and anxiety disorders. The SSRIs have also expanded the understanding of cytochrome P450 (CYP) metabolism, drug transporters, and drug-drug interaction mechanisms. Serotonin norepinephrine reuptake inhibitors (SNRIs) joined the SSRIs but with a dual pharmacologic mechanism of action. Various other pharmacologic types of antidepressants have been fostered such as bupropion, vilazodone, mirtazapine, and vortioxetine. Persons with polymorphic CYP metabolism (e.g., poor or ultrarapid metabolizers) may explain the occurrence of adverse events despite modest drug dosages or the lack of efficacy regardless of the appropriate doses. Pharmacokinetic and pharmacodynamics studies have been conducted for all the antidepressants, exploring the potential association of plasma concentrations with therapeutic outcomes (efficacy and toxicity) but routine therapeutic drug monitoring (TDM) is only recommended for a few agents. There is reason to believe, however, that the incorporation of pharmacogenetic information with TDM practices may ultimately lead to enhanced efficacy, reduced toxicity, and minimized risk for drug interactions.

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References

  1. Gram L (1994) Fluoxetine. N Engl J Med 331(20):1354–1361

    Article  CAS  PubMed  Google Scholar 

  2. Prozac (fluoxetine capsules) (2014) Prescribing information. Eli Lilly and Company, Inc., Indianapolis

    Google Scholar 

  3. DeVane CL, Jarecke R (1992) Cyclic antidepressants. In: Evans WE, Schentag JJ, Jusko WJ (eds) Applied pharmacokinetics, principles of therapeutic drug monitoring, 3rd edn. Applied Therapeutics, Vancouver

    Google Scholar 

  4. Preskorn SH, Dorey RC, Jerkovich GS (1988) Therapeutic drug monitoring of tricyclic antidepressants. Clin Chem 34(5):822–828

    CAS  PubMed  Google Scholar 

  5. DeVane CL (1999) Metabolism and pharmacokinetics of selective serotonin reuptake inhibitors. Cell Mol Neurobiol 19(4):443–466

    Article  CAS  PubMed  Google Scholar 

  6. Rudorfer MV, Potter WZ (1999) Metabolism of tricyclic antidepressants. Cell Mol Neurobiol 19(3):373–409

    Article  CAS  PubMed  Google Scholar 

  7. Young RC (1991) Hydroxylated metabolites of antidepressants. Psychopharmacol Bull 27(4):521–532

    CAS  PubMed  Google Scholar 

  8. Kupfer DJ, Hanin I, Spiker DG, Grau T, Coble P (1977) Amitriptyline plasma levels and clinical response in primary depression. Clin Pharmacol Ther 22(6):904–911

    Article  CAS  PubMed  Google Scholar 

  9. Ziegler VE, Co BT, Taylor JR, Clayton PJ, Biggs JT (1976) Amitriptyline plasma levels and therapeutic response. Clin Pharmacol Ther 19(6):795–801

    Article  CAS  PubMed  Google Scholar 

  10. Takeuchi H, Yokota S, Shimada S, Ohtani Y, Miura S, Kubo H (1993) Pharmacokinetics of amoxapine and its active metabolites in healthy subjects. Curr Ther Res 53:427–434

    Article  CAS  Google Scholar 

  11. Golden RN, De Vane CL, Laizure SC, Rudorfer MV, Sherer MA, Potter WZ (1988) Bupropion in depression. II. The role of metabolites in clinical outcome. Arch Gen Psychiatry 45(2):145–149

    Article  CAS  PubMed  Google Scholar 

  12. Preskorn SH (1991) Should bupropion dosage be adjusted based upon therapeutic drug monitoring? Psychopharmacol Bull 27(4):637–643

    CAS  PubMed  Google Scholar 

  13. Mendlewicz J (2001) Optimising antidepressant use in clinical practice: towards criteria for antidepressant selection. Br J Psychiatry Suppl 42:S1–S3

    Article  CAS  PubMed  Google Scholar 

  14. Reisby N, Gram LF, Bech P et al (1979) Clomipramine: plasma levels and clinical effects. Commun Psychopharmacol 3(5):341–351

    CAS  PubMed  Google Scholar 

  15. Traskman L, Asberg M, Bertilsson L et al (1979) Plasma levels of chlorimipramine and its demethyl metabolite during treatment of depression. Clin Pharmacol Ther 26(5):600–610

    Article  CAS  PubMed  Google Scholar 

  16. Stern RS, Marks IM, Mawson D, Luscombe DK (1980) Clomipramine and exposure for compulsive rituals: II. Plasma levels, side effects and outcome. Br J Psychiatry 136:161–166

    Article  CAS  PubMed  Google Scholar 

  17. Nelson JC, Jatlow P, Quinlan DM, Bowers MB Jr (1982) Desipramine plasma concentration and antidepressant response. Arch Gen Psychiatry 39(12):1419–1422

    Article  CAS  PubMed  Google Scholar 

  18. Linnoila M, Seppala T, Mattila MJ, Vihko R, Pakarinen A, Skinner T 3rd (1980) Clomipramine and doxepin in depressive neurosis. Plasma levels and therapeutic response. Arch Gen Psychiatry 37(11):1295–1299

    Article  CAS  PubMed  Google Scholar 

  19. Lundmark J, Reis M, Bengtsson F (2000) Therapeutic drug monitoring of sertraline: variability factors as displayed in a clinical setting. Ther Drug Monit 22(4):446–454

    Article  CAS  PubMed  Google Scholar 

  20. Reisby N, Gram LF, Bech P et al (1977) Imipramine: clinical effects and pharmacokinetic variability. Psychopharmacology (Berl) 54(3):263–272

    Article  CAS  Google Scholar 

  21. Glassman AH, Perel JM, Shostak M, Kantor SJ, Fleiss JL (1977) Clinical implications of imipramine plasma levels for depressive illness. Arch Gen Psychiatry 34(2):197–204

    Article  CAS  PubMed  Google Scholar 

  22. Gwirtsman HE, Ahles S, Halaris A, DeMet E, Hill MA (1983) Therapeutic superiority of maprotiline versus doxepin in geriatric depression. J Clin Psychiatry 44(12):449–453

    CAS  PubMed  Google Scholar 

  23. Glassman AH (1985) Tricyclic antidepressants – blood level measurements and clinical outcome – an APA-Task-Force report. Am J Psychiat 142(2):155–162

    Article  Google Scholar 

  24. Montgomery S, Braithwaite R, Dawling S, Mcauley R (1978) High plasma nortriptyline levels in treatment of depression. 1. Clin Pharmacol Ther 23(3):309–314

    Article  CAS  PubMed  Google Scholar 

  25. Putzolu S, Pecknold JC, Baiocchi L (1976) Proceedings: Trazodone: clinical and biochemical studies II. Blood levels and therapeutic responsiveness. Psychopharmacol Bull 12(1):40–41

    CAS  PubMed  Google Scholar 

  26. Mann JJ, Georgotas A, Newton R, Gershon S (1981) A controlled study of trazodone, imipramine, and placebo in outpatients with endogenous depression. J Clin Psychopharmacol 1(2):75–80

    Article  CAS  PubMed  Google Scholar 

  27. Suckow RF, Cooper TB (1984) Determination of trimipramine and metabolites in plasma by liquid chromatography with electrochemical detection. J Pharm Sci 73(12):1745–1748

    Article  CAS  PubMed  Google Scholar 

  28. Mika J, Jurga AM, Starnowska J et al (2015) Effects of chronic doxepin and amitriptyline administration in naive mice and in neuropathic pain mice model. Neuroscience 294:38–50

    Article  CAS  PubMed  Google Scholar 

  29. Wang YQ, Takata Y, Li R et al (2015) Doxepin and diphenhydramine increased non-rapid eye movement sleep through blockade of histamine H1 receptors. Pharmacol Biochem Behav 129:56–64

    Article  CAS  PubMed  Google Scholar 

  30. Bergstrom RF, Lemberger L, Farid NA, Wolen RL (1988) Clinical pharmacology and pharmacokinetics of fluoxetine: a review. Br J Psychiatry Suppl 3:47–50

    PubMed  Google Scholar 

  31. Strauss WL, Layton ME, Hayes CE, Dager SR (1997) 19F magnetic resonance spectroscopy investigation in vivo of acute and steady-state brain fluvoxamine levels in obsessive-compulsive disorder. Am J Psychiatry 154(4):516–522

    Article  CAS  PubMed  Google Scholar 

  32. von Moltke LL, Greenblatt DJ, Duan SX et al (1997) Human cytochromes mediating N-demethylation of fluoxetine in vitro. Psychopharmacology (Berl) 132(4):402–407

    Article  Google Scholar 

  33. Walden M, Carrier CT (2003) Sleeping beauties: the impact of sedation on neonatal development. J Obstet Gynecol Neonatal Nurs (JOGNN/NAACOG) 32(3):393–401

    Article  Google Scholar 

  34. Hicks JK, Bishop JR, Sangkuhl K et al (2015) Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6 and CYP2C19 genotypes and dosing of selective serotonin reuptake inhibitors. Clin Pharmacol Ther 98(2):127–134

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Stevens JC, Wrighton SA (1993) Interaction of the enantiomers of fluoxetine and norfluoxetine with human liver cytochromes P450. J Pharmacol Exp Ther 266(2):964–971

    CAS  PubMed  Google Scholar 

  36. Sager JE, Lutz JD, Foti RS, Davis C, Kunze KL, Isoherranen N (2014) Fluoxetine- and norfluoxetine-mediated complex drug-drug interactions: in vitro to in vivo correlation of effects on CYP2D6, CYP2C19, and CYP3A4. Clin Pharmacol Ther 95(6):653–662

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Weiss J, Dormann SM, Martin-Facklam M, Kerpen CJ, Ketabi-Kiyanvash N, Haefeli WE (2003) Inhibition of P-glycoprotein by newer antidepressants. J Pharmacol Exp Ther 305(1):197–204

    Article  CAS  PubMed  Google Scholar 

  38. Altamura AC, Moro AR, Percudani M (1994) Clinical pharmacokinetics of fluoxetine. Clin Pharmacokinet 26(3):201–214

    Article  CAS  PubMed  Google Scholar 

  39. Hughes ZA, Starr KR, Langmead CJ et al (2005) Neurochemical evaluation of the novel 5-HT1A receptor partial agonist/serotonin reuptake inhibitor, vilazodone. Eur J Pharmacol 510(1–2):49–57

    Article  CAS  PubMed  Google Scholar 

  40. Zoloft (sertraline) (2014) Prescribing information. Pfizer, Inc., New York

    Google Scholar 

  41. Ronfeld RA, Tremaine LM, Wilner KD (1997) Pharmacokinetics of sertraline and its N-demethyl metabolite in elderly and young male and female volunteers. Clin Pharmacokinet 32(Suppl 1):22–30

    Article  CAS  PubMed  Google Scholar 

  42. Wang JH, Liu ZQ, Wang W et al (2001) Pharmacokinetics of sertraline in relation to genetic polymorphism of CYP2C19. Clin Pharmacol Ther 70(1):42–47

    Article  CAS  PubMed  Google Scholar 

  43. Hicks JK, Bishop JR, Sangkuhl K et al (2015) Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6 and CYP2C19 genotypes and dosing of selective serotonin reuptake inhibitors. Clin Pharmacol Ther. doi:10.1002/cpt.147. [Epub ahead of print]

    Google Scholar 

  44. Warrington SJ (1992) Clinical implications of the pharmacology of serotonin reuptake inhibitors. Int Clin Psychopharmacol 7(Suppl 2):13–19

    Article  PubMed  Google Scholar 

  45. Owens MJ, Morgan WN, Plott SJ, Nemeroff CB (1997) Neurotransmitter receptor and transporter binding profile of antidepressants and their metabolites. J Pharmacol Exp Ther 283(3):1305–1322

    CAS  PubMed  Google Scholar 

  46. Rogowsky D, Marr M, Long G, Moore C (1994) Determination of sertraline and desmethylsertraline in human serum using copolymeric bonded-phase extraction, liquid chromatography and gas chromatography-mass spectrometry. J Chromatogr B Biomed Appl 655(1):138–141

    Article  CAS  PubMed  Google Scholar 

  47. Crewe HK, Lennard MS, Tucker GT, Woods FR, Haddock RE (1992) The effect of selective serotonin re-uptake inhibitors on cytochrome P4502D6 (CYP2D6) activity in human liver microsomes. Br J Clin Pharmacol 34(3):262–265

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Hiemke C, Baumann P, Bergemann N et al (2011) AGNP consensus guidelines for therapeutic drug monitoring in psychiatry: update 2011. Pharmacopsychiatry 44(6):195–235

    Article  Google Scholar 

  49. Alfaro CL, Lam YW, Simpson J, Ereshefsky L (1999) CYP2D6 status of extensive metabolizers after multiple-dose fluoxetine, fluvoxamine, paroxetine, or sertraline. J Clin Psychopharmacol 19(2):155–163

    Article  CAS  PubMed  Google Scholar 

  50. Paxil (paroxetine hydrochloride) (2003) Prescribing information. GlaxoSmithKline, Research Triangle Park

    Google Scholar 

  51. Dechant KL, Clissold SP (1991) Paroxetine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in depressive illness. Drugs 41(2):225–253

    Article  CAS  PubMed  Google Scholar 

  52. Lund J, Christensen JA, Bechgaard E, Molander L, Larsson H (1979) Pharmacokinetics of femoxetine in man. Acta Pharmacol Toxicol (Copenh) 44(3):177–184

    Article  CAS  Google Scholar 

  53. Kaye CM, Haddock RE, Langley PF et al (1989) A review of the metabolism and pharmacokinetics of paroxetine in man. Acta Psychiatr Scand Suppl 350:60–75

    Article  CAS  PubMed  Google Scholar 

  54. Bartoszyk GD, Hegenbart R, Ziegler H (1997) EMD 68843, a serotonin reuptake inhibitor with selective presynaptic 5-HT1A receptor agonistic properties. Eur J Pharmacol 322(2-3):147–153

    Article  CAS  PubMed  Google Scholar 

  55. Nemeroff CB, DeVane CL, Pollock BG (1996) Newer antidepressants and the cytochrome P450 system. Am J Psychiatry 153(3):311–320

    Article  CAS  PubMed  Google Scholar 

  56. Sangkuhl K, Klein TE, Altman RB (2011) PharmGKB summary: citalopram pharmacokinetics pathway. Pharmacogenet Genomics 21(11):769–772

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Page ME, Cryan JF, Sullivan A et al (2002) Behavioral and neurochemical effects of 5-(4-[4-(5-Cyano-3-indolyl)-butyl)-butyl]-1-piperazinyl)-benzofuran-2-carboxamide (EMD 68843): a combined selective inhibitor of serotonin reuptake and 5-hydroxytryptamine(1A) receptor partial agonist. J Pharmacol Exp Ther 302(3):1220–1227

    Article  CAS  PubMed  Google Scholar 

  58. Celexa (citalopram hydrobromide) (2014) Prescribing information. Forest Phamaceuticals, Inc., St. Louis

    Google Scholar 

  59. Kragh-Sorensen P, Overo KF, Petersen OL, Jensen K, Parnas W (1981) The kinetics of citalopram: single and multiple dose studies in man. Acta Pharmacol Toxicol (Copenh) 48(1):53–60

    Article  CAS  Google Scholar 

  60. Caccia S (2004) Metabolism of the newest antidepressants: comparisons with related predecessors. IDrugs (The Investigational Drugs Journal) 7(2):143–150

    CAS  Google Scholar 

  61. Rao N (2007) The clinical pharmacokinetics of escitalopram. Clin Pharmacokinet 46(4):281–290

    Article  CAS  PubMed  Google Scholar 

  62. Viibryd (vilazodone hydrochloride) (2011–2015) Prescribing information. Forest Pharmaceuticals, Inc. Subsidiary of Forest Laboratories, LLC, Cincinnati

    Google Scholar 

  63. Lexapro (escitalopram oxalate) (2009) Prescribing information. Forest Pharmaceuticals, Inc., St Louis

    Google Scholar 

  64. Sogaard B, Mengel H, Rao N, Larsen F (2005) The pharmacokinetics of escitalopram after oral and intravenous administration of single and multiple doses to healthy subjects. J Clin Pharmacol 45(12):1400–1406

    Article  CAS  PubMed  Google Scholar 

  65. van Harten J (1995) Overview of the pharmacokinetics of fluvoxamine. Clin Pharmacokinet 29(Suppl 1):1–9

    Article  PubMed  Google Scholar 

  66. Mandrioli R, Mercolini L, Saracino MA, Raggi MA (2012) Selective serotonin reuptake inhibitors (SSRIs): therapeutic drug monitoring and pharmacological interactions. Curr Med Chem 19(12):1846–1863

    Article  CAS  PubMed  Google Scholar 

  67. Orlando R, De Martin S, Andrighetto L, Floreani M, Palatini P (2010) Fluvoxamine pharmacokinetics in healthy elderly subjects and elderly patients with chronic heart failure. Br J Clin Pharmacol 69(3):279–286

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Nichols AI, Focht K, Jiang Q, Preskorn SH, Kane CP (2011) Pharmacokinetics of venlafaxine extended release 75 mg and desvenlafaxine 50 mg in healthy CYP2D6 extensive and poor metabolizers: a randomized, open-label, two-period, parallel-group, crossover study. Clin Drug Investig 31(3):155–167

    Article  CAS  PubMed  Google Scholar 

  69. Schweizer E, Feighner J, Mandos LA, Rickels K (1994) Comparison of venlafaxine and imipramine in the acute treatment of major depression in outpatients. J Clin Psychiatry 55(3):104–108

    CAS  PubMed  Google Scholar 

  70. Klamerus KJ, Maloney K, Rudolph RL, Sisenwine SF, Jusko WJ, Chiang ST (1992) Introduction of a composite parameter to the pharmacokinetics of venlafaxine and its active O-desmethyl metabolite. J Clin Pharmacol 32(8):716–724

    Article  CAS  PubMed  Google Scholar 

  71. Effexor (venlafaxine hydrochloride) (2004) Prescribing information. Wyeth Pharmaceuticals, Philadelphia

    Google Scholar 

  72. Troy SM, Schultz RW, Parker VD, Chiang ST, Blum RA (1994) The effect of renal disease on the disposition of venlafaxine. Clin Pharmacol Ther 56(1):14–21

    Article  CAS  PubMed  Google Scholar 

  73. Klamerus KJ, Parker VD, Rudolph RL, Derivan AT, Chiang ST (1996) Effects of age and gender on venlafaxine and O-desmethylvenlafaxine pharmacokinetics. Pharmacotherapy 16(5):915–923

    CAS  PubMed  Google Scholar 

  74. Ehret MJ, Levin GM, Narasimhan M, Rathinavelu A (2007) Venlafaxine induces P-glycoprotein in human Caco-2 cells. Hum Psychopharmacol 22(1):49–53

    Article  CAS  PubMed  Google Scholar 

  75. Nichols AI, Abell M, Chen Y, Behrle JA, Frick G, Paul J (2013) Effects of desvenlafaxine on the pharmacokinetics of desipramine in healthy adults. Int Clin Psychopharmacol 28(2):99–105

    Article  PubMed  Google Scholar 

  76. Pristiq (desvenlafaxine) (2014) Prescribing information. Wyeth Pharmaceuticals Inc., Subsidiary of Pfizer Inc., New York

    Google Scholar 

  77. Parker GB, Brotchie HL, Hyett M (2011) Tolerance to desvenlafaxine in rapid metabolizing depressed patients. Int Clin Psychopharmacol 26(2):84–87

    Article  PubMed  Google Scholar 

  78. Baird-Bellaire S, Behrle JA, Parker VD, Patat A, Paul J, Nichols AI (2013) An open-label, single-dose, parallel-group study of the effects of chronic hepatic impairment on the safety and pharmacokinetics of desvenlafaxine. Clin Ther 35(6):782–794

    Article  CAS  PubMed  Google Scholar 

  79. Boinpally R, Henry D, Gupta S, Edwards J, Longstreth J, Periclou A (2014) Pharmacokinetics and safety of vilazodone in hepatic impairment. Am J Ther 22(4):269–277

    Article  Google Scholar 

  80. Patroneva A, Connolly SM, Fatato P et al (2008) An assessment of drug-drug interactions: the effect of desvenlafaxine and duloxetine on the pharmacokinetics of the CYP2D6 probe desipramine in healthy subjects. Drug Metab Dispos 36(12):2484–2491

    Article  CAS  PubMed  Google Scholar 

  81. Patat A, Baird-Bellaire S, Behrle J et al (2007) Lack of clinically relevant effect of pharmacokinetic interaction between ketoconazole on desvenlafaxine-SR pharmacokinetics. Clin Pharmacol Ther 81(Suppl 1):64–71

    Google Scholar 

  82. Cymbalta (duloxetine hydrochloride) (2004) Prescribing information. Eli Lilly and Company, Indianapolis

    Google Scholar 

  83. Lobo ED, Bergstrom RF, Reddy S et al (2008) In vitro and in vivo evaluations of cytochrome P450 1A2 interactions with duloxetine. Clin Pharmacokinet 47(3):191–202

    Article  CAS  PubMed  Google Scholar 

  84. Boinpally R, Gad N, Gupta S, Periclou A (2014) Influence of CYP3A4 induction/inhibition on the pharmacokinetics of vilazodone in healthy subjects. Clin Ther 36(11):1638–1649

    Article  CAS  PubMed  Google Scholar 

  85. Skinner MH, Kuan HY, Pan A et al (2003) Duloxetine is both an inhibitor and a substrate of cytochrome P4502D6 in healthy volunteers. Clin Pharmacol Ther 73(3):170–177

    Article  CAS  PubMed  Google Scholar 

  86. Tianmei S, Knadler MP, Lim MT et al (2007) Pharmacokinetics and tolerability of duloxetine following oral administration to healthy Chinese subjects. Clin Pharmacokinet 46(9):767–775

    Article  PubMed  Google Scholar 

  87. Suri A, Reddy S, Gonzales C, Knadler MP, Branch RA, Skinner MH (2005) Duloxetine pharmacokinetics in cirrhotics compared with healthy subjects. Int J Clin Pharmacol Ther 43(2):78–84

    Article  CAS  PubMed  Google Scholar 

  88. Remeron (mirtazapine) tablets (2015) Prescribing information. Merck & Co, Inc., Whitehouse Station

    Google Scholar 

  89. Fetzima (levomilnacipran) (2014) Prescribing information. Forest Phamaceuticals, Inc., St. Louis

    Google Scholar 

  90. Chen L, Boinpally R, Greenberg WM, Wangsa J, Periclou A, Ghahramani P (2014) Effect of hepatic impairment on the pharmacokinetics of levomilnacipran following a single oral dose of a levomilnacipran extended-release capsule in human participants. Clin Drug Investig 34(5):351–359

    Article  CAS  PubMed  Google Scholar 

  91. Findlay JW, Van Wyck FJ, Smith PG et al (1981) Pharmacokinetics of bupropion, a novel antidepressant agent, following oral administration to healthy subjects. Eur J Clin Pharmacol 21(2):127–135

    Article  CAS  PubMed  Google Scholar 

  92. Wellbutrin SR (bupropion hydrochloride) (2015) Prescribing information. GlaxoSmithKline, LLC, Research Triangle Park

    Google Scholar 

  93. Wellbutrin XL (bupropion hydrochloride) (2015) Prescribing information. GlaxoSmithKline, LLC, Research Triangle Park

    Google Scholar 

  94. Schroeder DH (1983) Metabolism and kinetics of bupropion. J Clin Psychiatry 44(5 Pt 2):79–81

    CAS  PubMed  Google Scholar 

  95. Dwoskin LP, Rauhut AS, King-Pospisil KA, Bardo MT (2006) Review of the pharmacology and clinical profile of bupropion, an antidepressant and tobacco use cessation agent. CNS Drug Rev 12(3-4):178–207

    Article  PubMed  Google Scholar 

  96. Laizure SC, DeVane CL, Stewart JT, Dommisse CS, Lai AA (1985) Pharmacokinetics of bupropion and its major basic metabolites in normal subjects after a single dose. Clin Pharmacol Ther 38(5):586–589

    Article  CAS  PubMed  Google Scholar 

  97. Pollock BG, Sweet RA, Kirshner M, Reynolds CF 3rd (1996) Bupropion plasma levels and CYP2D6 phenotype. Ther Drug Monit 18(5):581–585

    Article  CAS  PubMed  Google Scholar 

  98. Zhu AZ, Zhou Q, Cox LS, Ahluwalia JS, Benowitz NL, Tyndale RF (2014) Gene variants in CYP2C19 are associated with altered in vivo bupropion pharmacokinetics but not bupropion-assisted smoking cessation outcomes. Drug Metab Dispos 42(11):1971–1977

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  99. Hsyu PH, Singh A, Giargiari TD, Dunn JA, Ascher JA, Johnston JA (1997) Pharmacokinetics of bupropion and its metabolites in cigarette smokers versus nonsmokers. J Clin Pharmacol 37(8):737–743

    Article  CAS  PubMed  Google Scholar 

  100. Worrall SP, Almond MK, Dhillon S (2004) Pharmacokinetics of bupropion and its metabolites in haemodialysis patients who smoke. A single dose study. Nephron Clin Pract 97(3):c83–c89

    Article  CAS  PubMed  Google Scholar 

  101. Hesse LM, Venkatakrishnan K, Court MH et al (2000) CYP2B6 mediates the in vitro hydroxylation of bupropion: potential drug interactions with other antidepressants. Drug Metab Dispos 28(10):1176–1183

    CAS  PubMed  Google Scholar 

  102. Jefferson JW, Pradko JF, Muir KT (2005) Bupropion for major depressive disorder: pharmacokinetic and formulation considerations. Clin Ther 27(11):1685–1695

    Article  CAS  PubMed  Google Scholar 

  103. Kotlyar M, Brauer LH, Tracy TS et al (2005) Inhibition of CYP2D6 activity by bupropion. J Clin Psychopharmacol 25(3):226–229

    Article  CAS  PubMed  Google Scholar 

  104. Reese MJ, Wurm RM, Muir KT, Generaux GT, St John-Williams L, McConn DJ (2008) An in vitro mechanistic study to elucidate the desipramine/bupropion clinical drug-drug interaction. Drug Metab Dispos 36(7):1198–1201

    Article  CAS  PubMed  Google Scholar 

  105. Watanabe MD, Winter ME (2004) Tricyclic antidepressants: amitriptyline, despiramine, imipramine, and nortriptyline. In: Winter ME (ed) Basic clinical pharmacokinetics, 4th edn. Lippincott Williams and Wilkins, Baltimore, pp 423–437

    Google Scholar 

  106. Baldessarini RJ (2006) Drug therapy of depression and anxiety disorders. In: Brunton LL, Lazo JS, Parker KL (eds) Goodman and Gilman’s the pharmacologic basis of therapeutics, 11th edn. McGraw-Hill Medical Publishing Division, New York, pp 429–459

    Google Scholar 

  107. Piafsky KM, Borga O (1977) Plasma protein binding of basic drugs. II. Importance of alpha 1-acid glycoprotein for interindividual variation. Clin Pharmacol Ther 22(5 Pt 1):545–549

    Article  CAS  PubMed  Google Scholar 

  108. Freilich DI, Giardina EG (1984) Imipramine binding to alpha-1-acid glycoprotein in normal subjects and cardiac patients. Clin Pharmacol Ther 35(5):670–674

    Article  CAS  PubMed  Google Scholar 

  109. Emsam (selegiline transdermal patch) (2015) Prescribing Information. Mylan Specialty L.P, Basking Ridge

    Google Scholar 

  110. Reynolds GP, Elsworth JD, Blau K, Sandler M, Lees AJ, Stern GM (1978) Deprenyl is metabolized to methamphetamine and amphetamine in man. Br J Clin Pharmacol 6(6):542–544

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Nickel B, Schulze G, Szelenyi I (1990) Effect of enantiomers of deprenyl (selegiline) and amphetamine on physical abuse liability and cortical electrical activity in rats. Neuropharmacology 29(11):983–992

    Article  CAS  PubMed  Google Scholar 

  112. Roberts C, Hagan JJ, Bartoszyk GD, Kew JN (2005) Effect of vilazodone on 5-HT efflux and re-uptake in the guinea-pig dorsal raphe nucleus. Eur J Pharmacol 517(1–2):59–63

    Article  CAS  PubMed  Google Scholar 

  113. Khan A (2009) Vilazodone, a novel dual-acting serotonergic antidepressant for managing major depression. Expert Opin Investig Drugs 18(11):1753–1764

    Article  CAS  PubMed  Google Scholar 

  114. Boinpally R, Alcorn H, Adams MH, Longstreth J, Edwards J (2013) Pharmacokinetics of vilazodone in patients with mild or moderate renal impairment. Clin Drug Investig 33(3):199–206

    Article  CAS  PubMed  Google Scholar 

  115. Welch LP, Leader WG, Chandler MH (1993) Predicting vancomycin pharmacokinetics by using aminoglycoside pharmacokinetics. Clin Pharm 12(12):909–913

    CAS  PubMed  Google Scholar 

  116. Kelder J, Funke C, De Boer T, Delbressine L, Leysen D, Nickolson V (1997) A comparison of the physicochemical and biological properties of mirtazapine and mianserin. J Pharm Pharmacol 49(4):403–411

    Article  CAS  PubMed  Google Scholar 

  117. Delbressine LP, Moonen ME, Kaspersen FM et al (1998) Pharmacokinetics and biotransformation of mirtazapine in human volunteers. Clin Drug Investig 15(1):45–55

    Article  CAS  PubMed  Google Scholar 

  118. Stormer E, von Moltke LL, Shader RI, Greenblatt DJ (2000) Metabolism of the antidepressant mirtazapine in vitro: contribution of cytochromes P-450 1A2, 2D6, and 3A4. Drug Metab Dispos 28(10):1168–1175

    CAS  PubMed  Google Scholar 

  119. Okubo M, Murayama N, Miura J, Chiba Y, Yamazaki H (2015) Effects of cytochrome P450 2D6 and 3A5 genotypes and possible coadministered medicines on the metabolic clearance of antidepressant mirtazapine in Japanese patients. Biochem Pharmacol 93(1):104–109

    Article  CAS  PubMed  Google Scholar 

  120. Liang J, Liu X, Zheng J, Yu S (2013) Effect of amitriptyline on tetrodotoxin-resistant Nav1.9 currents in nociceptive trigeminal neurons. Mol Pain 9:31

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Areberg J, Luntang-Jensen M, Sogaard B, Nilausen DO (2012) Occupancy of the serotonin transporter after administration of Lu AA21004 and its relation to plasma concentration in healthy subjects. Basic Clin Pharmacol Toxicol 110(4):401–404

    Article  CAS  PubMed  Google Scholar 

  122. Uldam HK, Juhl M, Pedersen H, Dalgaard L (2011) Biosynthesis and identification of an N-oxide/N-glucuronide metabolite and first synthesis of an N-O-glucuronide metabolite of Lu AA21004. Drug Metab Dispos 39(12):2264–2274

    Article  CAS  PubMed  Google Scholar 

  123. Hvenegaard MG, Bang-Andersen B, Pedersen H, Jorgensen M, Puschl A, Dalgaard L (2012) Identification of the cytochrome P450 and other enzymes involved in the in vitro oxidative metabolism of a novel antidepressant, Lu AA21004. Drug Metab Dispos 40(7):1357–1365

    Article  CAS  PubMed  Google Scholar 

  124. Chen G, Lee R, Hojer AM, Buchbjerg JK, Serenko M, Zhao Z (2013) Pharmacokinetic drug interactions involving vortioxetine (Lu AA21004), a multimodal antidepressant. Clin Drug Investig 33(10):727–736

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Kulaksiz-Erkmen G, Dalmizrak O, Dincsoy-Tuna G, Dogan A, Ogus IH, Ozer N (2013) Amitriptyline may have a supportive role in cancer treatment by inhibiting glutathione S-transferase pi (GST-pi) and alpha (GST-alpha). J Enzyme Inhib Med Chem 28(1):131–136

    Article  CAS  PubMed  Google Scholar 

  126. White PF, Ham J, Way WL, Trevor AJ (1980) Pharmacology of ketamine isomers in surgical patients. Anesthesiology 52(3):231–239

    Article  CAS  PubMed  Google Scholar 

  127. Bergman SA (1999) Ketamine: review of its pharmacology and its use in pediatric anesthesia. Anesth Prog 46(1):10–20

    CAS  PubMed  PubMed Central  Google Scholar 

  128. Walker FR (2013) A critical review of the mechanism of action for the selective serotonin reuptake inhibitors: do these drugs possess anti-inflammatory properties and how relevant is this in the treatment of depression? Neuropharmacology 67:304–317

    Article  CAS  PubMed  Google Scholar 

  129. Andrews JM, Nemeroff CB (1994) Contemporary management of depression. Am J Med 97(6A):24S–32S

    Article  CAS  PubMed  Google Scholar 

  130. Auerbach SB, Lundberg JF, Hjorth S (1995) Differential inhibition of serotonin release by 5-HT and NA reuptake blockers after systemic administration. Neuropharmacology 34(1):89–96

    Article  CAS  PubMed  Google Scholar 

  131. Rush AJ, Trivedi MH, Wisniewski SR et al (2006) Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression. N Engl J Med 354(12):1231–1242

    Article  CAS  PubMed  Google Scholar 

  132. Stahl SM (2013) Mechanism of action of ketamine. CNS Spectr 18(4):171–174

    Article  PubMed  Google Scholar 

  133. Wolkowitz OM, Wolf J, Shelly W et al (2011) Serum BDNF levels before treatment predict SSRI response in depression. Prog Neuropsychopharmacol Biol Psychiatry 35(7):1623–1630

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Iadarola ND, Niciu MJ, Richards EM et al (2015) Ketamine and other N-methyl-D-aspartate receptor antagonists in the treatment of depression: a perspective review. Ther Adv Chronic Dis 6(3):97–114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Kroeze Y, Zhou H, Homberg JR (2012) The genetics of selective serotonin reuptake inhibitors. Pharmacol Ther 136(3):375–400

    Article  CAS  PubMed  Google Scholar 

  136. Meyer JH (2007) Imaging the serotonin transporter during major depressive disorder and antidepressant treatment. J Psychiatry Neurosci 32(2):86–102

    PubMed  PubMed Central  Google Scholar 

  137. Cipriani A, Furukawa TA, Salanti G et al (2009) Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis. Lancet 373(9665):746–758

    Article  CAS  PubMed  Google Scholar 

  138. Papakostas GI, Thase ME, Fava M, Nelson JC, Shelton RC (2007) Are antidepressant drugs that combine serotonergic and noradrenergic mechanisms of action more effective than the selective serotonin reuptake inhibitors in treating major depressive disorder? A meta-analysis of studies of newer agents. Biol Psychiatry 62(11):1217–1227

    Article  CAS  PubMed  Google Scholar 

  139. Thase ME (2003) Effectiveness of antidepressants: comparative remission rates. J Clin Psychiatry 64(Suppl 2):3–7

    CAS  Google Scholar 

  140. Richelson E (2001) Pharmacology of antidepressants. Mayo Clin Proc 76(5):511–527

    Article  CAS  PubMed  Google Scholar 

  141. Debonnel G, Saint-Andre E, Hebert C, de Montigny C, Lavoie N, Blier P (2007) Differential physiological effects of a low dose and high doses of venlafaxine in major depression. Int J Neuropsychopharmacol 10(1):51–61

    Article  CAS  PubMed  Google Scholar 

  142. Deecher DC, Beyer CE, Johnston G et al (2006) Desvenlafaxine succinate: a new serotonin and norepinephrine reuptake inhibitor. J Pharmacol Exp Ther 318(2):657–665

    Article  CAS  PubMed  Google Scholar 

  143. Hunziker ME, Suehs BT, Bettinger TL, Crismon ML (2005) Duloxetine hydrochloride: a new dual-acting medication for the treatment of major depressive disorder. Clin Ther 27(8):1126–1143

    Article  CAS  PubMed  Google Scholar 

  144. Trivedi MH, Desaiah D, Ossanna MJ, Pritchett YL, Brannan SK, Detke MJ (2008) Clinical evidence for serotonin and norepinephrine reuptake inhibition of duloxetine. Int Clin Psychopharmacol 23(3):161–169

    Article  PubMed  Google Scholar 

  145. Asnis GM, Henderson MA (2015) Levomilnacipran for the treatment of major depressive disorder: a review. Neuropsychiatr Dis Treat 11:125–135

    Article  PubMed  PubMed Central  Google Scholar 

  146. Learned-Coughlin SM, Bergstrom M, Savitcheva I, Ascher J, Schmith VD, Langstrom B (2003) In vivo activity of bupropion at the human dopamine transporter as measured by positron emission tomography. Biol Psychiatry 54(8):800–805

    Article  CAS  PubMed  Google Scholar 

  147. Dong J, Blier P (2001) Modification of norepinephrine and serotonin, but not dopamine, neuron firing by sustained bupropion treatment. Psychopharmacology (Berl) 155(1):52–57

    Article  CAS  Google Scholar 

  148. Redolat R, Gomez MC, Vicens P, Carrasco MC (2005) Bupropion effects on aggressiveness and anxiety in OF1 male mice. Psychopharmacology (Berl) 177(4):418–427

    Article  CAS  Google Scholar 

  149. Birmaher B, Brent D, Issues AWGoQ et al (2007) Practice parameter for the assessment and treatment of children and adolescents with depressive disorders. J Am Acad Child Adolesc Psychiatry 46(11):1503–1526

    Article  PubMed  Google Scholar 

  150. Dalmizrak O, Kulaksiz-Erkmen G, Ozer N (2011) The inhibition characteristics of human placental glutathione S-transferase-pi by tricyclic antidepressants: amitriptyline and clomipramine. Mol Cell Biochem 355(1–2):223–231

    Article  CAS  PubMed  Google Scholar 

  151. Araneda R, Andrade R (1991) 5-Hydroxytryptamine2 and 5-hydroxytryptamine 1A receptors mediate opposing responses on membrane excitability in rat association cortex. Neuroscience 40(2):399–412

    Article  CAS  PubMed  Google Scholar 

  152. Celada P, Puig M, Amargos-Bosch M, Adell A, Artigas F (2004) The therapeutic role of 5-HT1A and 5-HT2A receptors in depression. J Psychiatry Neurosci 29(4):252–265

    PubMed  PubMed Central  Google Scholar 

  153. Rabiner EA, Gunn RN, Wilkins MR et al (2000) Drug action at the 5-HT(1A) receptor in vivo: autoreceptor and postsynaptic receptor occupancy examined with PET and [carbonyl-(11)C]WAY-100635. Nucl Med Biol 27(5):509–513

    Article  CAS  PubMed  Google Scholar 

  154. Artigas F, Celada P, Laruelle M, Adell A (2001) How does pindolol improve antidepressant action? Trends Pharmacol Sci 22(5):224–228

    Article  CAS  PubMed  Google Scholar 

  155. Koch H, Nanev D (2012) Important interaction between mirtazapine and ondansetron. Afr J Psychiatry (Johannesbg) 15(3):160

    CAS  Google Scholar 

  156. Lozano R (2013) Mirtazapine and ondansetron: a dual pharmacodynamic and pharmacokinetic interaction. Afr J Psychiatry (Johannesbg) 16(1):56

    CAS  Google Scholar 

  157. Bang-Andersen B, Ruhland T, Jorgensen M et al (2011) Discovery of 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine (Lu AA21004): a novel multimodal compound for the treatment of major depressive disorder. J Med Chem 54(9):3206–3221

    Article  CAS  PubMed  Google Scholar 

  158. Mork A, Pehrson A, Brennum LT et al (2012) Pharmacological effects of Lu AA21004: a novel multimodal compound for the treatment of major depressive disorder. J Pharmacol Exp Ther 340(3):666–675

    Article  CAS  PubMed  Google Scholar 

  159. Westrich L, Haddjeri N, Dkhissi-Benyahya O, Sanchez C (2015) Involvement of 5-HT(7) receptors in vortioxetine’s modulation of circadian rhythms and episodic memory in rodents. Neuropharmacology 89:382–390

    Article  CAS  PubMed  Google Scholar 

  160. Areberg J, Sogaard B, Hojer AM (2012) The clinical pharmacokinetics of Lu AA21004 and its major metabolite in healthy young volunteers. Basic Clin Pharmacol Toxicol 111(3):198–205

    CAS  PubMed  Google Scholar 

  161. Stenkrona P, Halldin C, Lundberg J (2013) 5-HTT and 5-HT(1A) receptor occupancy of the novel substance vortioxetine (Lu AA21004). A PET study in control subjects. Eur Neuropsychopharmacol 23(10):1190–1198

    Article  CAS  PubMed  Google Scholar 

  162. Pehrson AL, Leiser SC, Gulinello M et al (2015) Treatment of cognitive dysfunction in major depressive disorder–a review of the preclinical evidence for efficacy of selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors and the multimodal-acting antidepressant vortioxetine. Eur J Pharmacol 753:19–31

    Article  CAS  PubMed  Google Scholar 

  163. Sanchez C, Asin KE, Artigas F (2015) Vortioxetine, a novel antidepressant with multimodal activity: review of preclinical and clinical data. Pharmacol Ther 145:43–57

    Article  CAS  PubMed  Google Scholar 

  164. Traynelis SF, Wollmuth LP, McBain CJ et al (2010) Glutamate receptor ion channels: structure, regulation, and function. Pharmacol Rev 62(3):405–496

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. Li N, Lee B, Liu RJ et al (2010) mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science 329(5994):959–964

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. Price RB, Iosifescu DV, Murrough JW et al (2014) Effects of ketamine on explicit and implicit suicidal cognition: a randomized controlled trial in treatment-resistant depression. Depress Anxiety 31(4):335–343

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Xu AJ, Niciu MJ, Lundin NB et al (2015) Lithium and valproate levels do not correlate with Ketamine’s antidepressant efficacy in treatment-resistant bipolar depression. Neural Plast 2015:858251

    PubMed  PubMed Central  Google Scholar 

  168. Zarate CA Jr, Singh JB, Carlson PJ et al (2006) A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry 63(8):856–864

    Article  CAS  PubMed  Google Scholar 

  169. Murrough JW, Perez AM, Pillemer S et al (2013) Rapid and longer-term antidepressant effects of repeated ketamine infusions in treatment-resistant major depression. Biol Psychiatry 74(4):250–256

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Meyer JH, Wilson AA, Sagrati S et al (2004) Serotonin transporter occupancy of five selective serotonin reuptake inhibitors at different doses: an [11C]DASB positron emission tomography study. Am J Psychiatry 161(5):826–835

    Article  PubMed  Google Scholar 

  171. Nogami T, Takano H, Arakawa R et al (2013) Occupancy of serotonin and norepinephrine transporter by milnacipran in patients with major depressive disorder: a positron emission tomography study with [(11)C]DASB and (S, S)-[(18)F]FMeNER-D(2). Int J Neuropsychopharmacol 16(5):937–943

    Article  CAS  PubMed  Google Scholar 

  172. Laib AK, Brunen S, Pfeifer P, Vincent P, Hiemke C (2014) Serum concentrations of hydroxybupropion for dose optimization of depressed patients treated with bupropion. Ther Drug Monit 36(4):473–479

    Article  CAS  PubMed  Google Scholar 

  173. Baumann P, Hiemke C, Ulrich S et al (2004) The AGNP-TDM expert group consensus guidelines: therapeutic drug monitoring in psychiatry. Pharmacopsychiatry 37(6):243–265

    Article  CAS  PubMed  Google Scholar 

  174. Muller MJ, Dragicevic A, Fric M et al (2003) Therapeutic drug monitoring of tricyclic antidepressants: how does it work under clinical conditions? Pharmacopsychiatry 36(3):98–104

    Article  CAS  PubMed  Google Scholar 

  175. Preskorn SH, Fast GA (1991) Therapeutic drug monitoring for antidepressants: efficacy, safety, and cost effectiveness. J Clin Psychiatry 52(Suppl):23–33

    PubMed  Google Scholar 

  176. Ulrich S, Lauter J (2002) Comprehensive survey of the relationship between serum concentration and therapeutic effect of amitriptyline in depression. Clin Pharmacokinet 41(11):853–876

    Article  CAS  PubMed  Google Scholar 

  177. Glotzbach RK, Preskorn SH (1982) Brain concentrations of tricyclic antidepressants: single-dose kinetics and relationship to plasma concentrations in chronically dosed rats. Psychopharmacology (Berl) 78(1):25–27

    Article  CAS  Google Scholar 

  178. Asberg M, Cronholm B, Sjoqvist F, Tuck D (1971) Relationship between plasma level and therapeutic effect of nortriptyline. Br Med J 3(5770):331–334

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Perry PJ, Browne JL, Alexander B et al (1985) Relationship of free nortriptyline levels to therapeutic response. Acta Psychiatr Scand 72(2):120–125

    Article  CAS  PubMed  Google Scholar 

  180. Bruijn JA, Moleman P, Mulder PG et al (1996) A double-blind, fixed blood-level study comparing mirtazapine with imipramine in depressed in-patients. Psychopharmacology (Berl) 127(3):231–237

    Article  CAS  Google Scholar 

  181. Jaquenoud Sirot E, van der Velden JW, Rentsch K, Eap CB, Baumann P (2006) Therapeutic drug monitoring and pharmacogenetic tests as tools in pharmacovigilance. Drug Saf 29(9):735–768

    Article  PubMed  Google Scholar 

  182. Dawling S (1982) Monitoring of tricyclic antidepressant therapy. Clin Biochem 15(1):56–61

    Article  CAS  PubMed  Google Scholar 

  183. Gupta SK, Shah JC, Hwang SS (1999) Pharmacokinetic and pharmacodynamic characterization of OROS and immediate-release amitriptyline. Br J Clin Pharmacol 48(1):71–78

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  184. Vuille F, Amey M, Baumann P (1991) Use of plasma level monitoring of antidepressants in clinical practice. Towards an analysis of clinical utility. Pharmacopsychiatry 24(6):190–195

    Article  CAS  PubMed  Google Scholar 

  185. Riant P, Urien S, Albengres E, Renouard A, Tillement JP (1988) Effects of the binding of imipramine to erythrocytes and plasma proteins on its transport through the rat blood-brain barrier. J Neurochem 51(2):421–425

    Article  CAS  PubMed  Google Scholar 

  186. Pfuhlmann B, Gerlach M, Burger R et al (2007) Therapeutic drug monitoring of tricyclic antidepressants in everyday clinical practice. J Neural Transm Suppl 72:287–296

    Article  CAS  PubMed  Google Scholar 

  187. Baumann P, Ulrich S, Eckermann G et al (2005) The AGNP-TDM Expert Group Consensus Guidelines: focus on therapeutic monitoring of antidepressants. Dialogues Clin Neurosci 7(3):231–247

    PubMed  PubMed Central  Google Scholar 

  188. Berm EJ, Paardekooper J, Brummel-Mulder E, Hak E, Wilffert B, Maring JG (2015) A simple dried blood spot method for therapeutic drug monitoring of the tricyclic antidepressants amitriptyline, nortriptyline, imipramine, clomipramine, and their active metabolites using LC-MS/MS. Talanta 134:165–172

    Article  CAS  PubMed  Google Scholar 

  189. Finley PR (2005) Antidepressants. In: Murphy JE (ed) Clinical pharmacokinetics, 5th edn. American Society of Health-System Pharmacists, Inc., Baltimore, pp 119–134

    Google Scholar 

  190. Meineke I, Kress I, Poser W, Ruther E, Brockmoller J (2004) Therapeutic drug monitoring of mirtazapine and its metabolite desmethylmirtazapine by HPLC with fluorescence detection. Ther Drug Monit 26(3):277–283

    Article  CAS  PubMed  Google Scholar 

  191. Reis M, Prochazka J, Sitsen A, Ahlner J, Bengtsson F (2005) Inter- and intraindividual pharmacokinetic variations of mirtazapine and its N-demethyl metabolite in patients treated for major depressive disorder: a 6-month therapeutic drug monitoring study. Ther Drug Monit 27(4):469–477

    Article  CAS  PubMed  Google Scholar 

  192. Shams M, Hiemke C, Hartter S (2004) Therapeutic drug monitoring of the antidepressant mirtazapine and its N-demethylated metabolite in human serum. Ther Drug Monit 26(1):78–84

    Article  CAS  PubMed  Google Scholar 

  193. Rush AJ, Trivedi MH, Wisniewski SR et al (2006) Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry 163(11):1905–1917

    Article  PubMed  Google Scholar 

  194. Trivedi MH, Rush AJ, Wisniewski SR et al (2006) Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. Am J Psychiatry 163(1):28–40

    Article  PubMed  Google Scholar 

  195. Kirchheiner J, Seeringer A, Viviani R (2010) Pharmacogenetics in psychiatry–a useful clinical tool or wishful thinking for the future? Curr Pharm Des 16(2):136–144

    Article  CAS  PubMed  Google Scholar 

  196. Lee KC, Ma JD, Kuo GM (2010) Pharmacogenomics: bridging the gap between science and practice. J Am Pharm Assoc (2003) 50(1):e1–e14; quiz e5–7

    Article  Google Scholar 

  197. Tansey KE, Guipponi M, Hu X et al (2013) Contribution of common genetic variants to antidepressant response. Biol Psychiatry 73(7):679–682

    Article  CAS  PubMed  Google Scholar 

  198. Porcelli S, Fabbri C, Serretti A (2012) Meta-analysis of serotonin transporter gene promoter polymorphism (5-HTTLPR) association with antidepressant efficacy. Eur Neuropsychopharmacol 22(4):239–258

    Article  CAS  PubMed  Google Scholar 

  199. Risch N, Herrell R, Lehner T et al (2009) Interaction between the serotonin transporter gene (5-HTTLPR), stressful life events, and risk of depression: a meta-analysis. JAMA 301(23):2462–2471

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  200. Yoshida K, Ito K, Sato K et al (2002) Influence of the serotonin transporter gene-linked polymorphic region on the antidepressant response to fluvoxamine in Japanese depressed patients. Prog Neuropsychopharmacol Biol Psychiatry 26(2):383–386

    Article  CAS  PubMed  Google Scholar 

  201. Houston JP, Kohler J, Ostbye KM, Heinloth A, Perlis RH (2011) Association of catechol-O-methyltransferase variants with duloxetine response in major depressive disorder. Psychiatry Res 189(3):475–477

    Article  CAS  PubMed  Google Scholar 

  202. Shi Y, Yuan Y, Xu Z et al (2012) Genetic variation in the calcium/calmodulin-dependent protein kinase (CaMK) pathway is associated with antidepressant response in females. J Affect Disord 136(3):558–566

    Article  CAS  PubMed  Google Scholar 

  203. Montminy M (1997) Transcriptional regulation by cyclic AMP. Annu Rev Biochem 66:807–822

    Article  CAS  PubMed  Google Scholar 

  204. Pilar-Cuellar F, Vidal R, Diaz A et al (2013) Neural plasticity and proliferation in the generation of antidepressant effects: hippocampal implication. Neural Plast 2013:537265

    PubMed  PubMed Central  Google Scholar 

  205. Niitsu T, Fabbri C, Bentini F, Serretti A (2013) Pharmacogenetics in major depression: a comprehensive meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry 45:183–194

    Article  CAS  PubMed  Google Scholar 

  206. Maddox JC, Levi M, Thompson C (1994) The compliance with antidepressants in general practice. J Psychopharmacol 8(1):48–52

    Article  CAS  PubMed  Google Scholar 

  207. Ereshefsky L, Riesenman C, Lam YW (1996) Serotonin selective reuptake inhibitor drug interactions and the cytochrome P450 system. J Clin Psychiatry 57(Suppl 8):17–24; discussion 5

    CAS  PubMed  Google Scholar 

  208. Kirchheiner J, Schmidt H, Tzvetkov M et al (2007) Pharmacokinetics of codeine and its metabolite morphine in ultra-rapid metabolizers due to CYP2D6 duplication. Pharmacogenomics J 7(4):257–265

    Article  CAS  PubMed  Google Scholar 

  209. Gaedigk A, Gotschall RR, Forbes NS, Simon SD, Kearns GL, Leeder JS (1999) Optimization of cytochrome P4502D6 (CYP2D6) phenotype assignment using a genotyping algorithm based on allele frequency data. Pharmacogenetics 9(6):669–682

    Article  CAS  PubMed  Google Scholar 

  210. Gaedigk A, Simon SD, Pearce RE, Bradford LD, Kennedy MJ, Leeder JS (2008) The CYP2D6 activity score: translating genotype information into a qualitative measure of phenotype. Clin Pharmacol Ther 83(2):234–242

    Article  CAS  PubMed  Google Scholar 

  211. Laika B, Leucht S, Heres S, Steimer W (2009) Intermediate metabolizer: increased side effects in psychoactive drug therapy. The key to cost-effectiveness of pretreatment CYP2D6 screening? Pharmacogenomics J 9(6):395–403

    Article  CAS  PubMed  Google Scholar 

  212. Ruano G, Szarek BL, Villagra D et al (2013) Length of psychiatric hospitalization is correlated with CYP2D6 functional status in inpatients with major depressive disorder. Biomark Med 7(3):429–439

    Article  CAS  PubMed  Google Scholar 

  213. Hodgson K, Tansey K, Dernovsek MZ et al (2014) Genetic differences in cytochrome P450 enzymes and antidepressant treatment response. J Psychopharmacol 28(2):133–141

    Article  PubMed  CAS  Google Scholar 

  214. Hicks JK, Swen JJ, Thorn CF et al (2013) Clinical Pharmacogenetics Implementation Consortium guideline for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants. Clin Pharmacol Ther 93(5):402–408

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  215. Leckband SG, Kelsoe JR, Dunnenberger HM et al (2013) Clinical Pharmacogenetics Implementation Consortium guidelines for HLA-B genotype and carbamazepine dosing. Clin Pharmacol Ther 94(3):324–328

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  216. Rickels K, Athanasiou M, Robinson DS, Gibertini M, Whalen H, Reed CR (2009) Evidence for efficacy and tolerability of vilazodone in the treatment of major depressive disorder: a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry 70(3):326–333

    Article  CAS  PubMed  Google Scholar 

  217. Musil R, Zill P, Seemuller F et al (2013) Genetics of emergent suicidality during antidepressive treatment–data from a naturalistic study on a large sample of inpatients with a major depressive episode. Eur Neuropsychopharmacol 23(7):663–674

    Article  CAS  PubMed  Google Scholar 

  218. Hall-Flavin DK, Winner JG, Allen JD et al (2013) Utility of integrated pharmacogenomic testing to support the treatment of major depressive disorder in a psychiatric outpatient setting. Pharmacogenet Genomics 23(10):535–548

    Article  CAS  PubMed  Google Scholar 

  219. Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group (2007) Recommendations from the EGAPP Working Group: testing for cytochrome P450 polymorphisms in adults with nonpsychotic depression treated with selective serotonin reuptake inhibitors. Genet Med 9(12):819–825

    Google Scholar 

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Authors and Affiliations

  1. Department of Clinical Pharmacy, School of Pharmacy, University of California, San Francisco, CA, USA

    Patrick R. Finley PharmD

  2. Department of Clinical Pharmacy, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, San Diego, CA, USA

    Jennifer Le PharmD, MAS & Kelly C. Lee PharmD

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    Michael W. Jann

  2. Department of Pharmacotherapy, Univ. North Texas Sys, Col Pharm, FORT WORTH, Texas, USA

    Scott R. Penzak

  3. Department of Pharmacotherapy, Univ. North Texas Sys, Col Pharm., FORT WORTH, Texas, USA

    Lawrence J. Cohen

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Finley, P.R., Le, J., Lee, K.C. (2016). Antidepressants. In: Jann, M., Penzak, S., Cohen, L. (eds) Applied Clinical Pharmacokinetics and Pharmacodynamics of Psychopharmacological Agents. Adis, Cham. https://doi.org/10.1007/978-3-319-27883-4_9

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