Pharmacopsychiatry 2004; 37(6): 243-265
DOI: 10.1055/s-2004-832687
Review
© Georg Thieme Verlag KG Stuttgart · New York

The AGNP-TDM Expert Group Consensus Guidelines: Therapeutic Drug Monitoring in Psychiatry

P. Baumann1 , C. Hiemke2 , S. Ulrich3 , G. Eckermann4 , I. Gaertner5 , M. Gerlach6 , H.-J. Kuss7 , G. Laux8 , B. Müller-Oerlinghausen9 , M. L. Rao10 , P. Riederer11 , G. Zernig12
  • 1Department of Psychiatry, University of Lausanne, Prilly-Lausanne, Switzerland
  • 2Department of Psychiatry, University of Mainz, Germany
  • 3Department of Clinical Pharmacology, University of Magdeburg, Magdeburg, Germany
  • 4Bezirkskrankenhaus Kaufbeuren, Kaufbeuren, Germany
  • 5Department of Psychiatry, University of Tübingen, Tübingen, Germany
  • 6Department of Child and Adolescent Psychiatry, University of Würzburg, Würzburg, Germany
  • 7Department of Psychiatry, University of Munich, Munich, Germany
  • 8Bezirksklinikum Gabersee, Wasserburg/Inn, Germany
  • 9Drug Commission of the German Medical Association, Berlin and Cologne, Germany
  • 10Department of Psychiatry, University of Bonn
  • 11Department of Psychiatry, University of Wuerzburg, Würzburg, Germany
  • 12Department of Psychiatry, University of Innsbruck, Innsbruck, Austria
Further Information

Publication History

Received: 4.4.2004

Accepted: 12.5.2004

Publication Date:
19 November 2004 (online)

Therapeutic Drug Monitoring (TDM) is a valid tool to optimise pharmacotherapy. It enables the clinician to adjust the dosage of drugs according to the characteristics of the individual patient. In psychiatry, TDM is an established procedure for lithium, some antidepressants and antipsychotics. In spite of its obvious advantages, however, the use of TDM in everyday clinical practice is far from optimal. The interdisciplinary TDM group of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) has therefore worked out consensus guidelines to assist psychiatrists and laboratories involved in psychotropic drug analysis to optimise the use of TDM of psychotropic drugs. Five research-based levels of recommendation were defined with regard to routine monitoring of plasma concentrations for dose titration of 65 psychoactive drugs: (1) strongly recommended, (2) recommended, (3) useful, (4) probably useful and (5) not recommended. A second approach defined indications to use TDM, e. g. control of compliance, lack of clinical response or adverse effects at recommended doses, drug interactions, pharmacovigilance programs, presence of a genetic particularity concerning the drug metabolism, children, adolescents and elderly patients. Indications for TDM are relevant for all drugs either with or without validated therapeutic ranges. When studies on therapeutic ranges are lacking, target ranges should be plasma concentrations that are normally observed at therapeutic doses of the drug. Therapeutic ranges of plasma concentrations that are considered to be optimal for treatment are proposed for those drugs, for which the evaluation of the literature demonstrated strong evidence. Moreover, situations are defined when pharmacogenetic (phenotyping or genotyping) tests are informative in addition to TDM. Finally, practical instructions are given how to use TDM. They consider preparation of TDM, analytical procedures, reporting and interpretation of results and the use of information for patient treatment. Using the consensus guideline will help to ensure optimal clinical benefit of TDM in psychiatry.

References

  • 1 Adler L, Hajak G, Lehmann K, Kunert H -J, Hoffmann G, Issinger J. et al . On the problems of switching from intravenous to oral administration in drug treatment of endogenous depression - A placebo-controlled double-blind trial with Doxepin.  Pharmacopsychiatry. 1997;  30 62-69
  • 2 Alexanderson B H, Evans D A, Sjöqvist S. Steady-state plasma levels of nortriptyline in twins: influence of genetic factors and drug therapy.  Br Med J. 1969;  686 764-768
  • 3 Altamura A C, Mauri M C, Guercetti G. Age, therapeutic ”milieu” and clinical outcome in depressive patients treated with viloxazine. Prog Neuropsychopharmacol Biol Psychiatry 1986
  • 4 American Academy of Pediatrics. Use of psychoactive medication during pregnancy and possible effects on the fetus and newborn. Pediatrics 2000 105: 880-887
  • 5 American Psychiatric Association Practice Guidelines. Practice guideline for the treatment of patients with major depressive disorder (revision). Am J Psychiatry 2000 157 Supplement(4)
  • 6 Amsterdam J D, Brunswick D J, Winokur A, Rickels K. Desipramine and 2-hydroxydesipramine plasma levels in endogenous depressed patients.  Arch Gen Psychiatry. 1985;  42 361-364
  • 7 Amsterdam J D, Fawcett J, Quitkin F M, Reimherr F W, Rosenbaum J F, Michelson D. et al . Fluoxetine and norfluoxetine plasma concentrations in major depression: a multicenter study.  Am J Psychiatry. 1997;  154 963-969
  • 8 Aravagiri M, Marder S R, Wirshing D, Wirshing W C. Plasma concentrations of risperidone and its 9-hydroxy metabolite and their relationship to dose in schizophrenic patients: simultaneous determination by a high performance liquid chromatography with electrochemical detection.  Pharmacopsychiatry. 1998;  31 102-109
  • 9 Åsberg M, Cronholm B, Sjoqvist F, Tuck D. Correlation of subjective side effects with plasma concentrations of nortriptyline.  Br Med J. 1970;  4(726) 18-21
  • 10 Åsberg M, Cronholm B, Sjöqvist F, Tuck D. Relationship between plasma level and therapeutic effect of nortriptyline.  Br Med J. 1971;  3 331-334
  • 11 Åsberg M, Sjöqvist F. On the role of plasma level monitoring of tricyclic antidepressants in clinical practice.  Comm Psychopharmacol. 1978;  2 381-391
  • 12 Axelson D A, Perel J M, Birmaher B, Rudolph G R, Nuss S, Bridge J. et al . Sertraline pharmacokinetics and dynamics in adolescents.  J Am Acad Child Adolesc Psychiatry. 2002;  41(9) 1037-1044
  • 13 Bailey B, McGuigan M. Lithium poisoning from a poison control center perspective.  Ther Drug Monit. 2000;  22(6) 650-655
  • 14 Balant-Gorgia A E, Balant L. Antipsychotic drugs. Clinical pharmacokinetics of potential candidates for plasma concentration monitoring.  Clin Pharmacokinet. 1987;  13 65-90
  • 15 Balant-Gorgia A E, Eisele R, Aeschlimann J M, Balant L P, Garrone G. Plasma flupentixol concentrations and clinical response in acute schizophrenia.  Ther Drug Monit. 1985;  7(4) 411-414
  • 16 Balant-Gorgia E A, Balant L P. Therapeutic drug monitoring - Relevance during the drug treatment of psychiatric disorders.  CNS Drugs. 1995;  4 432-453
  • 17 Baldessarini R J, Cohen B M, Teicher M H. Significance of neuroleptic dose and plasma level in the pharmacological treatment of psychoses.  Arch Gen Psychiatry. 1988;  45 79-91
  • 18 Banger M, Hermes B, Härtter S, Hiemke C. Monitoring serum concentrations of clomipramine and metabolites: fluorescence polarization immunoassay versus high performance liquid chromatography.  Pharmacopsychiatry. 1997;  30 128-132
  • 19 Baptista T, Teneud L, Contreras Q, Alastre T, Burguera J L, de Burguera M. et al . Lithium and body weight gain.  Pharmacopsychiatry. 1995;  28 35-44
  • 20 Bauer M, Whybrow P C, Angst J, Versiani M, Möller H J. 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 Journal of Biological Psychiatry. 2002;  3 5-43
  • 21 Baumann P. Pharmacokinetic-pharmacodynamic relationship of the selective serotonin reuptake inhibitors.  Clin Pharmacokinet. 1996;  31 444-469
  • 22 Baumann P, Eap C B. Pharmacogenetics of chiral psychotropic drugs. In: Lerer B, editor Pharmacogenetics of Psychotropic Drugs. Cambridge; Cambridge university press 2002: 181-214
  • 23 Baumann P, Hiemke C, Ulrich S, Gaertner I, Rao M L, Eckermann G. et al . Therapeutic monitoring of psychotropic drugs - An outline of the AGNP-TDM expert group consensus guideline.  Ther Drug Monit. 2004;  26(2) 167-170
  • 24 Baumann P, Jonzier-Perey M, Koeb L, Le P K, Tinguely D, Schöpf J. Amitriptyline pharmacokinetics and clinical response: I. Free and total plasma amitriptyline and nortriptyline.  Int Clin Psychopharmacol. 1986;  1 89-101
  • 25 Baumann P, Kahn J M. Les médicaments génériques: quels sont les problèmes et d’où viennent-ils?.  Med Hyg. 2003;  61(2434) 879-884
  • 26 Baumann P, Meyer J W, Amey M, Baettig D, Bryois C, Jonzier-Perey M. et al . Dextromethorphan and mephenytoin phenotyping of patients treated with thioridazine or amitriptyline.  Ther Drug Monit. 1992;  14 1-8
  • 27 Baumann P, Nil R, Bertschy G, Jecker A, Brändli H, Morand J. et al . A double-blind double-dummy study of citalopram comparing infusion versus oral administration.  J Affect Disord. 1998;  49 203-210
  • 28 Baumann P, Nil R, Souche A, Montaldi S, Baettig D, Lambert S. et al . A double-blind, placebo-controlled study of citalopram with and without lithium in the treatment of therapy-resistant depressive patients: a clinical, pharmacokinetic, and pharmacogenetic investigation.  J Clin Psychopharmacol. 1996;  16 307-314
  • 29 Baumann P, Zullino D F, Eap C B. Enantiomers’ potential in psychopharmacology - a critical analysis with special emphasis on the antidepressant escitalopram.  Eur Neuropsychopharmacol. 2002;  12 433-444
  • 30 Beauclair L, Fontaine R, Annable L, Holobow N, Chouinard G. Clonazepam in the treatment of panic disorder: a double-blind, placebo-controlled trial investigating the correlation between clonazepam concentrations in plasma and clinical response.  J Clin Psychopharmacol. 1994;  14(2) 111-118
  • 31 Beedham C, Miceli J J, Obach R S. Ziprasidone metabolism, aldehyde oxidase, and clinical implications.  J Clin Psychopharmacol. 2003;  23(3) 229-232
  • 32 Beelen A P, Yeo K T, Lewis L D. Asymptomatic QTc prolongation associated with quetiapine fumarate overdose in a patient being treated with risperidone.  Hum Exp Toxicol. 2001;  20(4) 215-219
  • 33 Benet L Z, Kroetz D L, Sheiner L B. Pharmacokinetics the dynamics of drug absorption, distribution, and elimination. In: Hardman JG, Limbird LE, editors Goodman & Gilman’s The pharmacological basis of therapeutics. New York; McGraw-Hill Companies 1996: 3-27
  • 34 Bengtsson F. Therapeutic drug monitoring of psychotropic drugs TDM ”nouveau”.  Ther Drug Monit. 2004;  26(2) 145-151
  • 35 Bergemann N, Kopitz J, Kress K R, Frick A. Plasma amisulpride levels in schizophrenia or schizoaffective disorder.  European Neuropsychopharmacology. 2004;  14 245-250
  • 36 Bertilsson L, Dahl M L. Polymorphic drug oxidation - Relevance to the treatment of psychiatric disorders.  CNS Drugs. 1996;  5 200-223
  • 37 Bertilsson L, Mellström B, Sjöqvist F, Mårtensson B, Åsberg M. Slow hydroxylation of nortriptyline and concomitant poor debrisoquine hydroxylation: clinical implications.  Lancet. 1981;  i 560-561
  • 38 Bjerkenstedt L, Flyckt L, Overø K F, Lingjaerde O. Relationship between clinical effects, serum drug concentration and serotonin uptake inhibition in depressed patients treated with citalopram. A double-blind comparison of three dose levels.  Eur J Clin Pharmacol. 1985;  28 553-557
  • 39 Bjorndal N, Bjerre M, Gerlach J, Kristjansen P, Magelund G, Oestrich I H. et al . High dosage haloperidol therapy in chronic schizophrenic patients: a double-blind study of clinical response, side effects, serum haloperidol, and serum prolactin.  Psychopharmacology. 1980;  67(1) 17-23
  • 40 Bondolfi G, Chautems C, Rochat B, Bertschy G, Baumann P. Non-response to citalopram in depressive patients: pharmacokinetic and clinical consequences of a fluvoxamine augmentation.  Psychopharmacology. 1996;  128 421-425
  • 41 Bondolfi G, Eap C B, Bertschy G, Zullino D, Vermeulen A, Baumann P. The effect of fluoxetine on the pharmacokinetics and safety of risperidone in psychotic patients.  Pharmacopsychiatry. 2002;  35 50-56
  • 42 Bondolfi G, Lissner C, Kosel M, Eap C B, Baumann P. Fluoxetine augmentation in citalopram non-responders: pharmacokinetic and clinical consequences.  Int J Neuropsychopharmacol. 2000;  3 55-60
  • 43 Bork J A, Rogers T, Wedlund P J, De Leon J. A pilot study on risperidone metabolism: the role of cytochromes P450 2D6 and 3A.  J Clin Psychiatry. 1999;  60 469-476
  • 44 Bowden C L, Janicak P G, Orsulak P, Swann A C, Davis J M, Calabrese J R. et al . Relation of serum valproate concentration to response in mania.  Am J Psychiatry. 1996;  153 765-770
  • 45 Breyer-Pfaff U, Brinkschulte M, Rein W, Schied H W, Straube E. Prediction and evaluation criteria in perazine therapy of acute schizophrenics pharmacokinetic data.  Pharmacopsychiatry. 1983;  16 160-165
  • 46 Breyer-Pfaff U, Gaertner H J. Antidepressiva pharmakologie, therapeutischer Einsatz und Klinik der Depression. Wissenschaftliche Verlagsgesellschaft GmbH Stuttgart; 1987
  • 47 Breyer-Pfaff U, Gaertner H J, Giedke H. Plasma levels, psychophysiological variables, and clinical response to amitriptyline.  Psychiatry Res. 1982;  6(2) 223-234
  • 48 Breyer-Pfaff U, Gaertner H J, Kreuter F, Scharek G, Brinkschulte M, Wiatr R. Antidepressive effect and pharmacokinetics of amitriptyline with consideration of unbound drug and 10-hydroxynortriptyline plasma levels.  Psychopharmacology. 1982;  76(3) 240-244
  • 49 Brinkmann U, Eichelbaum M. Polymorphisms in the ABC drug transporter gene MDR1.  Pharmacogenomics. 2001;  1 59-64
  • 50 Brockmöller J, Kirchheiner J, Schmider J, Walter S, Sachse C, Müller-Oerlinghausen B. et al . The impact of the CYP2D6 polymorphism on haloperidol pharmacokinetics and on the outcome of haloperidol treatment.  Clin Pharmacol Ther. 2002;  72(4) 438-452
  • 51 Broich K, Heinrich S, Marneros A. Acute clozapine overdose: plasma concentration and outcome.  Pharmacopsychiatry. 1998;  31 149-151
  • 52 Brøsen K. Drug-metabolizing enzymes and therapeutic drug monitoring in psychiatry.  Ther Drug Monit. 1996;  18 93-396
  • 53 Buick A R, Doig M V, Jeal S C, Land G S, Mcdowall R D. Method validation in the bioanalytical laboratory.  J Pharm Biomed Anal. 1990;  8 629-637
  • 54 Burch J E, Raddats M A. Time course of plasma drug levels during once-daily oral administration of clomipramine.  Psychopharmacology. 1982;  77 344-347
  • 55 Burchell B. Transformation reactions: glucuronidation. In: Woolf TF, editor Handbook of drug metabolism. New York - Basel; Marcel Dekker, Inc 1999: 153-173
  • 56 Burke M J, Preskorn S H. Therapeutic drug monitoring of antidepressants - Cost implications and relevance to clinical practice.  Clin Pharmacokinet. 1999;  37 147-165
  • 57 Burt V K, Suri R, Altshuler L, Stowe Z, Hendrick V C, Muntean E. The use of psychotropic medications during breast-feeding.  Am J Psychiatry. 2001;  158(7) 1001-1009
  • 58 Caccia S, Garattini S. Formation of active metabolites of psychotropic drugs: an updated review of their significance.  Clin Pharmacokinet. 1990;  18 434-459
  • 59 Callaghan J T, Bergstrom R F, Ptak L R, Beasley C M. Olanzapine - pharmacokinetic and pharmacodynamic profile.  Clin Pharmacokinet. 1999;  37 177-193
  • 60 Causon R. Validation of chromatographic methods in biomedical analysis viewpoint and discussion.  Journal of Chromatography B. 1997;  689 175-180
  • 61 Chaudron L H, Jefferson J W. Mood stabilizers during breastfeeding. A review.  J Clin Psychiatry. 2001;  61 79-90
  • 62 Chen S, Chou W H, Blouin R A, Mao Z, Humphries L L, Meek C. et al . The cytochrome P450 2D6 (CYP2D6) enzyme polymorphism: screening costs and influence on clinical outcomes in psychiatry.  Clin Pharmacol Ther. 1996;  60 522-534
  • 63 Chou W H, Yan F- X, Barnhill J, Rogers T, Cronin M, Pho M. et al . Extension of a pilot study: impact from the cytochrome P450 2D6 polymorphism on outcome and costs associated with severe mental illness.  J Clin Psychopharmacol. 2000;  20 246-251
  • 64 Comer S D, Collins E D, Kleber H D, Nuwayser E S, Kerrigan J H, Fischman M W. Depot naltrexone: long-lasting antagonism of the effects of heroin in humans.  Psychopharmacology. 2002;  159(4) 351-360
  • 65 Cournoyer G, De Montigny C, Ouellette J, Langlois R, Elie R, Caille G. et al . A comparative double-blind controlled study of trimipramine and amitriptyline in major depression: lack of correlation with 5-hydroxytryptamine reuptake blockade.  J Clin Psychopharmacol. 1987;  7 385-393
  • 66 Coutts R T, Urichuk L J. Polymorphic cytochromes P450 and drugs used in psychiatry.  Cell Mol Neurobiol. 1999;  19 325-354
  • 67 Creese I, Snyder S H. A simple and sensitive radioreceptor assay for antischizophrenic drugs in blood.  Nature. 1977;  270 80-182
  • 68 Dahl M L. Cytochrome P450 phenotyping/genotyping in patients receiving antipsychotics: useful aid to prescribing?.  Clin Pharmacokinet. 2002;  41(7) 453-470
  • 69 Dahl M L, Sjöqvist F. Pharmacogenetic methods as a complement to therapeutic monitoring of antidepressants and neuroleptics.  Ther Drug Monit. 2000;  22 114-117
  • 70 Danish University Antidepressant G roup. Clomipramine dose-effect study in patients with depression: clinical end points and pharmacokinetics.  Clin Pharmacol Ther. 1999;  66 152-165
  • 71 Dasberg H H, van der K E, Guelen J P, Van Praag H M. Plasma concentrations of diazepam and of its metabolite N-desmethyldiazepam in relation to anxiolytic effect.  Clin Pharmacol Ther. 1974;  15(5) 473-483
  • 72 De la Torre R, Ortuño J, Pascual J A, Gonzalez S, Ballesta J. Quantitative determination of tricyclic antidepressants and their metabolites in plasma by solid-phase extraction (bond-elut TCA) and separation by capillary gas chromatography with nitrogen-phosphorous detection.  Ther Drug Monit. 1998;  20 340-346
  • 73 De Leon J. Glucuronidation enzymes, genes and psychiatry.  Int J Neuropsychopharmacol. 2003;  6 57-72
  • 74 De Oliveira I R, Dardennes R M, Amorim E S, Diquet B, de Sena E P, Moreira E C. et al . Is there a relationship between antipsychotic blood levels and their clinical efficacy? An analysis of studies design and methodology.  Fundam Clin Pharmacol. 1995;  9 488-502
  • 75 Deuschle M, Härtter S, Hiemke C, Standhardt H, Heuser I. Doxepin and its metabolites in plasma and cerebrospinal fluid in depressed patients.  Psychopharmacology. 1997;  131(1) 19-22
  • 76 DeVane C L. Pharmacogenetics and drug metabolism of newer antidepressant agents.  J Clin Psychiat. 1994;  55(suppl 12) 38-45
  • 77 Divoll M, Greenblatt D J, Lacasse Y, Shader R I. Benzodiazepine overdosage: plasma concentrations and clinical outcome.  Psychopharmacology. 1981;  73(4) 381-383
  • 78 Doherty M M, Charman W N. The mucosa of the small intestine - How clinically relevant as an organ of drug metabolism?.  Clin Pharmacokinet. 2002;  41(4) 235-253
  • 79 Donoghue J, Taylor D M. Suboptimal use of antidepressants in the treatment of depression.  CNS Drugs. 2000;  13 365-383
  • 80 Dyson E H, Simpson D, Prescott L F, Proudfoot A T. Self-poisoning and therapeutic intoxication with lithium.  Hum Toxicol. 1987;  6(4) 325-329
  • 81 Eadie M J. Formation of active metabolites of anticonvulsant drugs - A review of their pharmacokinetic and therapeutic significance.  Clin Pharmacokinet. 1991;  21 27-41
  • 82 Eap C B, Bender S, Gastpar M, Fischer W, Haarmann C, Powell K. et al . Steady state plasma levels of the enantiomers of trimipramine and of its metabolites in CYP2D6-, CYP2C19- and CYP3A4/5-phenotyped patients.  Ther Drug Monit. 2000;  22 209-214
  • 83 Eap C B, Bender S, Jaquenoud Sirot E, Cucchia G, Jonzier-Perey M, Baumann P, Allorge D, Broly F. Nonresponse to clozapine and ultrarapid CYP1A2 activity clinical data and analysis of CYP1A2 gene.  J Clin Psychopharmacol. 2004;  24 214-219
  • 84 Eap C B, Bourquin M, Martin J -L, Spagnoli J, Livoti S, Powell K. et al . Plasma concentrations of the enantiomers of methadone and therapeutic response in methadone maintenance treatment.  Drug Alcohol Depend. 2000;  61 47-54
  • 85 Eap C B, Buclin T, Baumann P. Interindividual variability of the clinical pharmacokinetics of methadone: implications for the treatment of opioid dependence.  Clin Pharmacokinet. 2002;  41(14) 1153-1193
  • 86 Eap C B, Guentert T W, Schäublin-Loidl M, Stabl M, Koeb L, Powell K. et al . Plasma levels of the enantiomers of thioridazine, thioridazine 2-sulfoxide, thioridazine 2-sulfone, and thioridazine 5-sulfoxide in poor and extensive metabolizers of dextromethorphan and mephenytoin.  Clin Pharmacol Ther. 1996;  59 322-331
  • 87 Eap C B, Yasui N, Kaneko S, Baumann P, Powell K, Otani K. Effects of carbamazepine coadministration on plasma concentrations of the enantiomers of mianserin and of its metabolites.  Ther Drug Monit. 1999;  21 166-170
  • 88 Eilers R. Therapeutic drug monitoring for the treatment of psychiatric disorders - Clinical use and cost effectiveness.  Clin Pharmacokinet. 1995;  29 442-450
  • 89 Ellinwood E H, Jr., Heatherly D G, Nikaido A M, Bjornsson T D, Kilts C, Heatherly D G, Nikaido A M, Bjornsson T D, Kilts C. Comparative pharmacokinetics and pharmacodynamics of lorazepam, alprazolam and diazepam.  Psychopharmacology. 1985;  86(4) 392-399
  • 90 Ensom M HH, Chang T KH, Patel P. Pharmacogenetics - The therapeutic drug monitoring of the future?.  Clin Pharmacokinet. 2001;  40(11) 783-802
  • 91 Ereshefsky L. Pharmacokinetics and drug interactions: update for new antipsychotics.  J Clin Psychiatry. 1996;  57 (suppl. 11) 12-25
  • 92 Ernst C L, Goldberg J F. The reproductive safety profile of mood stabilizers, atypical antipsychotics, and broad-spectrum psychotropics.  J Clin Psychiatry. 2002;  63 (suppl. 4) 42-55
  • 93 Falcy M, Riboulet-Delmas G, Efthymiou M L. [Acute poisoning by viloxazine chlorhydrate taken by itself].  Encephale. 1983;  9(2) 137-144
  • 94 Farde L, Nordström A L, Wiesel F A, Pauli S, Halldin C, Sedvall G. Positron emission tomographic analysis of central D1 and D2 dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine.  Arch Gen Psychiatry. 1992;  49 538-544
  • 95 Fawcett J, Stein D J, Jobson K O, . editors .Textbook of treatment algorithms in Psychopharmacology. Chichester (England), New York , Singapore, Ontario; John Wiley & Sons 1999: 1-205
  • 96 Fitzgerald P B, Kapur S, Remington G, Roy P, Zipursky R B. Predicting haloperidol occupancy of central dopamine D2 receptors from plasma levels.  Psychopharmacology. 2000;  149 1-5
  • 97 Ford J M, Truman C A, Wilcock G K, Roberts C JC. Serum concentrations of tacrine hydrochloride predict its adverse effects in Alzheimer’s disease.  Clin Pharmacol Ther. 1993;  53 691-695
  • 98 Friedel R O, Veith R C, Bloom V, Bielski R J. Desipramine plasma levels and clinical response in depressed outpatients.  Comunications in Pychopharmacology. 1979;  3 81-87
  • 99 Fritze J, Laux G, Sofic E, Koronakis P, Schoerlin M P, Riederer P. et al . Plasma moclobemide and metabolites: lack of correlation with clinical response and biogenic amines.  Psychopharmacology. 1989;  99(2) 252-256
  • 100 Furlanut M, Perosa A, Benetello P, Colombo G. Electrochemical detection of benperidol in serum for drug monitoring in humans.  Ther Drug Monit. 1987;  9(3) 343-346
  • 101 Gabris G, Baumann P, Jonzier-Perey M, Bosshart P, Woggon B, Küpfer A. N-methylation of maprotiline in debrisoquine/mephenitoin-phenotyped depressive patients.  Biochem Pharmacol. 1985;  34 409-410
  • 102 Garzone P D, Kroboth P D. Pharmacokinetics of the newer benzodiazepines.  Clin Pharmacokinet. 1989;  16(6) 337-364
  • 103 Gelenberg A J, Carroll J A, Baudhuin M G, Jefferson J W, Greist J H. The meaning of serum lithium levels in maintenance therapy of mood disorders: a review of the literature.  J Clin Psychiatry. 1989;  50 Suppl. 17-22
  • 104 Gerstenberg G, Aoshima T, Fukasawa T, Yoshida K, Takahashi H, Higuchi H. et al . Relationship between clinical effects of fluvoxamine and the steady-state plasma concentrations of fluvoxamine and its major metabolite fluvoxamino acid in Japanese depressed patients.  Psychopharmacology. 2003;  167(4) 443-448
  • 105 Gex-Fabry M, Balant-Gorgia A E, Balant L P. Potential of concentration monitoring data for a short half-life drug: Analysis of pharmacokinetic variability for moclobemide.  Ther Drug Monit. 1995;  17 39-46
  • 106 Gex-Fabry M, Balant-Gorgia A E, Balant L P. Clomipramine concentration as a predictor of delayed response: a naturalistic study.  Eur J Clin Pharmacol. 1999;  54 895-902
  • 107 Gex-Fabry M, Balant-Gorgia A E, Balant L P. Therapeutic drug monitoring of olanzapine: the combined effect of age, gender, smoking, and comedication.  Ther Drug Monit. 2003;  25 46-53
  • 108 Glassmann A H, Schildkraut J J, Orsulak P J,. et al . Tricyclic antidepressants, blood level measurements and clinical outcome: an APA task force report.  Am J Psychiat. 1985;  142 155-162
  • 109 Goeringer K E, Raymon L, Christian G D, Logan B K. Postmortem forensic toxicology of selective serotonin reuptake inhibitors: a review of pharmacology and report of 168 cases.  J Forensic Sci. 2000;  45(3) 633-648
  • 110 Goodnick P J. Pharmacokinetic optimisation of therapy with newer antidepressants.  Clin Pharmacokinet. 1994;  27 307-330
  • 111 Gram L F. Plasma level monitoring of tricyclic antidepressants: methodological and pharmacokinetic considerations.  Commun Psychopharmacol. 1978;  2 373-380
  • 112 Green M. A practical guide to analytical method validation. Analytical Chemistry News and Features 1996: 305-309
  • 113 Greenblatt D J. Clinical pharmacokinetics of oxazepam and lorazepam.  Clin Pharmacokinet. 1981;  6 89-105
  • 114 Greenblatt D J. Basic pharmacokinetic principles and their application to psychotropic drugs.  J Clin Psychiatry. 1993;  54 8-13
  • 115 Greenblatt D J, Von Moltke L L, Harmatz J S, Ciraulo D A, Shader R I. Alprazolam pharmacokinetics, metabolism, and plasma levels: clinical implications.  J Clin Psychiatry. 1993;  54 4-14
  • 116 Greenblatt D J, Von Moltke L L, Harmatz J S, Shader R I. Human cytochromes and some newer antidepressants: Kinetics, metabolism, and drug interactions.  J Clin Psychopharmacol. 1999;  19(Suppl. 1)(5) 23S-35
  • 117 Hammer W M, Brodie B B. Application of isotope derivative technique to assay of secondary amines: estimation of desipramine by acetylation with H3-Acetic anhydride.  J Pharmacol Exp Ther. 1967;  157 503-508
  • 118 Hansen L B, Larsen N L. Therapeutic advantages of monitoring plasma concentrations of perphenazine in clinical practice.  Psychopharmacol. 1985;  87 16-19
  • 119 Härtter S, Hermes B, Hiemke C. Automated determination of trimipramine and N-desmethyl-trimipramine in human plasma or serum by HPLC with on-line solid phase extraction.  J Liq Chromatogr. 1995;  18 3495-3505
  • 120 Härtter S, Wetzel H, Hammes E, Torkzadeh M, Hiemke C. Nonlinear pharmacokinetics of fluvoxamine and gender differences.  Ther Drug Monit. 1998;  20 446-449
  • 121 Hasegawa M, Gutierrez-Esteinou R, Way L, Meltzer H Y. Relationship between clinical efficacy and clozapine concentrations in plasma in schizophrenia: effect of smoking.  J Clin Psychopharmacol. 1993;  13 383-390
  • 122 Heller S, Hiemke C, Stroba G, Rieger-Gies A, Daum-Kreysch E, Sachse J, Hartter S. Assessment of Storage and Transport Stability of New Antidepressant and Antipsychotic Drugs for a Nationwide TDM Service (Letter).  Therapeutic Drug Monitoring. 2004;  26(4) 459-461
  • 123 Hiemke C, Dragicevic A, Gründer G, Härtter S, Sachse J, Vernaleken I. et al . Therapeutic monitoring of new antipsychotic drugs.  Ther Drug Monit. 2004;  26(2) 156-160
  • 124 Hiemke C, Härtter S. Pharmacokinetics of selective serotonin reuptake inhibitors.  Pharmacol Ther. 2000;  85 11-28
  • 125 Houghton G W, Dennis M J, Templeton R, Martin B K. A repeated dose pharmacokinetic study of a new hypnotic agent, zopiclone (Imovane).  Int J Clin Pharmacol Ther Toxicol. 1985;  23(2) 97-100
  • 126 Ilett K F, Blythe T H, Hackett L P, Ong R TT, Tannenbaum D A, Clarke T MF. Plasma concentrations of dothiepin and its metabolites are not correlated with clinical efficacy in major depressive illness.  Ther Drug Monit. 1993;  15 351-357
  • 127 Ingels M, Beauchamp J, Clark R F, Williams S R. Delayed valproic acid toxicity: a retrospective case series.  Ann Emerg Med. 2002;  39(6) 616-621
  • 128 Isacsson G, Holmgren P, Druid H, Bergman U. The utilization of antidepressants - a key issue in the prevention of suicide: an analysis of 5281 suicides in Sweden during the period 1992 - 1994.  Acta Psychiatr Scand. 1997;  96 94-100
  • 129 Iwersen S, Schmoldt A. One fatal and one nonfatal intoxication with tranylcypromine. Absence of amphetamines as metabolites.  J Anal Toxicol. 1996;  20(5) 301-304
  • 130 Johansson B. A review of the pharmacokinetics and pharmacodynamics of disulfiram and its metabolites.  Acta Psychiatr Scand Suppl. 1992;  369 15-26
  • 131 Jonasson B, Saldeen T. Citalopram in fatal poisoning cases.  Forensic Sci Int. 2002;  126(1) 1-6
  • 132 Jungkunz G, Kuss H J. On the relationship of nortriptyline: amitriptyline ratio to clinical improvement of amitriptyline treated depressive patients.  Pharmakopsychiatr Neuropsychopharmakol. 1980;  13(3) 111-116
  • 133 Kaferstein H, Sticht G, Pluisch F. [Poisoning by perazine-organ distribution and interpretation].  Arch Kriminol. 2000;  206(3 - 4) 82-87
  • 134 Kapur S, Zipursky R, Jones C, Shammi C S, Remington G, Seeman P. A positron emission tomography study of quetiapine in Schizophrenia - A preliminary finding of an antipsychotic effect with only transiently high dopamine D2 receptor occupancy.  Arch Gen Psychiatry. 2000;  57 553-559
  • 135 Kapur S, Zipursky R B, Remington G, Jones C, DaSilva J, Wilson A A. et al . 5-HT2 and D2 receptor occupancy of olanzapine in schizophrenia: a PET investigation.  Am J Psychiatry. 1998;  155 921-928
  • 136 Kasper S, Dötsch M, Kick H, Vieira A, Möller H J. Plasma concentrations of fluvoxamine and maprotiline in major depression: implications on therapeutic efficacy and side effects.  Eur Neuropsychopharmacol. 1993;  3 13-21
  • 137 Kaye C M, Haddock R E, Langley P F, Mellows G, Tasker T CG, Zussman B D. et al . A review of the metabolism and pharmacokinetics of paroxetine in man.  Acta Psychiatr Scand. 1989;  80 (suppl. 350) 60-75
  • 138 Keck P E, Jr., McElroy S L. Clinical pharmacodynamics and pharmacokinetics of antimanic and mood-stabilizing medications.  J Clin Psychiatry. 2002;  63 Suppl 4 3-11
  • 139 Kirchheiner J, Brøsen K, Dahl M L, Gram L F, Kasper S, Roots I. et al . CYP2D6 and CYP2C19 genotype-based dose recommendations for antidepressants: a first step towards subpopulation-specific dosages.  Acta Psychiatr Scand. 2001;  104(3) 73-192
  • 140 Kjolbye M, Thomsen K, Rogne T, Rehfelt E, Olesen O V. Search for a therapeutic range for serum zuclopenthixol concentrations in schizophrenic patients.  Ther Drug Monit. 1994;  16(6) 541-547
  • 141 Kollroser M, Schober C. Simultaneous determination of seven tricyclic antidepressant drugs in human plasma by direct-injection HPLC-APCI-MS-MS with an ion trap detector.  Ther Drug Monit. 2002;  24 537-544
  • 142 Kondo T, Otani K, Ishida M, Tanaka O, Kaneko S, Fukushima Y. Adverse effects of zotepine and their relationship to serum concentrations of the drug and prolactin.  Ther Drug Monit. 1994;  16 120-124
  • 143 Kornhuber J, Quack G, Danysz W, Jellinger K, Danielczyk W, Gsell W. et al . Therapeutic brain concentration of the NMDA receptor antagonist amantadine.  Neuropharmacology. 1995;  34 713-721
  • 144 Kramer Nielsen K, Brøsen K, Gram L F, Bech P, Bolwig T G, Sørensen P K. et al . Steady-state plasma levels of clomipramine and its metabolites: impact of the sparteine/debrisoquine oxidation polymorphism.  Eur J Clin Pharmacol. 1992;  43 405-411
  • 145 Kratzsch C, Frank T P, Kraemer T, Armin A W, Maurer H H. Screening, library-assisted identification and validated quantification of fifteen neuroleptics and three of their metabolites in plasma by liquid chromatography/mass spectrometry with atmospheric pressure chemical ionization.  J Mass Spectrom. 2003;  38 283-295
  • 146 Kuehl P, Zhang J, Lin Y, Lamba J, Assem M, Schuetz J. et al . Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expression.  Nat Genet. 2001;  27(4) 383-391
  • 147 Kupfer D J, Hanin I, Spiker D G, Grau T, Coble P. Amitriptyline plasma levels and clinical response in primary depression.  Clin Pharmacol Ther. 1977;  22(6) 904-911
  • 148 Lane H Y, Chiu W -C, Chou J CY, Wu S -T, Su M H, Chang W H. Risperidone in acutely exacerbated schizophrenia: dosing strategies and plasma levels.  J Clin Psychiatry. 2000;  61 209-214
  • 149 Laux G, Riederer P, . editors .Plasmaspiegelbestimmung von Psychopharmaka: Therapeutisches Drug - Monitoring, Versuch einer ersten Standortbestimmung. Stuttgart (Germany); Wissenschaftliche Verlagsgesellschaft mbH Stuttgart 1992: 7-128
  • 150 Leinonen E, Lepola U, Koponen H, Kinnunen I. The effect of age and concomitant treatment with other psychoactive drugs on serum concentrations of citalopram measured with a nonenantioselective method.  Ther Drug Monit. 1996;  18 111-117
  • 151 Lerer B, Macciardi F. Pharmacogenetics of antidepressant and moodstabilizing drugs: a review of candidate-gene studies and future research directions.  Int J Neuropsychopharmacol. 2002;  5 255-275
  • 152 Leucht S, Steimer W, Kreuz S, Abraham D, Orsulak P J, Kissling W. Doxepin plasma concentrations: is there really a therapeutic range?.  J Clin Psychopharmacol. 2001;  21(4) 432-439
  • 153 Levine B, Jenkins A J, Queen M, Jufer R, Smialek J E. Distribution of venlafaxine in three postmortem cases.  J Anal Toxicol. 1996;  20 502-505
  • 154 Lin J H, Yamazaki M. Role of P-glycoprotein in pharmacokinetics - Clinical implications.  Clin Pharmacokinet. 2003;  42(1) 59-98
  • 155 Linder M W, Keck P E, Jr. Standards of laboratory practice: antidepressant drug monitoring.  Clin Chem. 1998;  44 1073-1084
  • 156 Liston H L, Markowitz J S, DeVane C L. Drug glucuronidation in clinical psychopharmacology.  J Clin Psychopharmacol. 2001;  21 500-515
  • 157 Llewellyn A, Stowe Z N. Psychotropic medications in lactation.  J Clin Psychiatry. 1998;  59(suppl. 2) 41-52
  • 158 Lovell R W, Bunker W W. Lithium assay errors.  Am J Psychiatry. 1997;  154(10) 1477
  • 159 Lundmark J, Bengtsson F, Nordin C, Reis M, Walinder J. Therapeutic drug monitoring of selective serotonin reuptake inhibitors influences clinical dosing strategies and reduces drug costs in depressed elderly patients.  Acta Psychiatr Scand. 2000;  101 354-359
  • 160 Lundmark J, Reis M, Bengtsson F. Therapeutic drug monitoring of sertraline: variability factors as displayed in a clinical setting.  Ther Drug Monit. 2000;  22 446-454
  • 161 Lundmark J, Reis M, Bengtsson F. Serum concentrations of fluoxetine in the clinical treatment setting.  Ther Drug Monit. 2001;  23 139-147
  • 162 Lundmark J, Thomsen I S, Fjord-Larsen T, Manniche P M, Mengel H, Møller-Nielsen E M. et al . Paroxetine: pharmacokinetic and antidepressant effect in the elderly.  Acta Psychiatr Scand. 1989;  80(suppl. 350) 76-80
  • 163 Madsen A L, Karle A, Rubin P, Cortsen M, Andersen H S, Hemmingsen R. Progressive atrophy of the frontal lobs in first-episode schizophrenia: interaction with clinical course and neuroleptic treatment.  Acta Psychiat Scand. 1999;  100 367-374
  • 164 Maguire K P, Norman T R, Burrows G D, Davies B. Blood and plasma concentrations of dothiepin and its major metabolites and clinical response.  J Affect Disord. 1982;  4 41-48
  • 165 Mancama D, Arranz M J, Kerwin R W. Genetic predictors of therapeutic response to clozapine - Current status of research.  CNS Drugs. 2002;  16(5) 317-324
  • 166 Mancama D, Kerwin R W. Role of pharmacogenomics in individualising treatment with SSRIs.  CNS Drugs. 2003;  17(3) 143-151
  • 167 Marder S R, Midha K K, van Putten T, Aravagiri M, Hawes E M, Hubbard J W. et al . Plasma levels of fluphenazine in patients receiving fluphenazine decanoate. Relationship to clinical response.  Br J Psychiatry. 1991;  158 658-665
  • 168 Mason B J, Goodman A M, Dixon R M, Hameed M H, Hulot T, Wesnes K. et al . A pharmacokinetic and pharmacodynamic drug interaction study of acamprosate and naltrexone.  Neuropsychopharmacology. 2002;  27(4) 596-606
  • 169 Mavissakalian M R, Jones B, Olson S, Perel J M. Clomipramine in obsessive-compulsive disorder: clinical response and plasma levels.  J Clin Psychopharmacol. 1990;  10(4) 261-268
  • 170 McEvoy J P, Scheifler P L, Frances A. The expert consensus guideline series - treatment of Schizophrenia 1999.  J Clin Psychiatry. 1999;  60(Suppl. 11) 12-18
  • 171 McIntyre I M, King C V, Cordner S M, Drummer O H. Postmortem clomipramine: therapeutic or toxic concentrations?.  J Forensic Sci. 1994;  39(2) 486-493
  • 172 McManus P, Mant A, Mitchell P, Birkett D, Dudley J. Co-prescribing of SSRIs and TCAs in Australia: how often does it occur and who is doing it?.  Br J Clin Pharmacol. 2001;  51(1) 93-98
  • 173 Meibohm B, Beierle I, Derendorf H. How important are gender differences in pharmacokinetics.  Clin Pharmacokinet. 2002;  41(5) 329-342
  • 174 Meredith P A. Generic drugs - Therapeutic equivalence.  Drug Safety. 1996;  15(4) 233-242
  • 175 Meyer U A. Pharmacogenetics and adverse drug reactions.  Lancet. 2000;  356 1667-1671
  • 176 Mihara K, Kondo T, Suzuki A, Yasui-Furukori N, Ono S, Otani K. et al . Effects of genetic polymorphism of CYP1A2 inducibility on the steady-state plasma concentrations of trazodone and its active metabolite m-chlorophenylpiperazine in depressed Japanese patients.  Pharmacol Toxicol. 2001;  88 267-270
  • 177 Mihara K, Otani K, Tybring G, Dahl M L, Bertilsson L, Kaneko S. The CYP2D6 genotype and plasma concentrations of mianserin enantiomers in relation to therapeutic response to mianserin in depressed Japanese patients.  J Clin Psychopharmacol. 1997;  17 467-471
  • 178 Milner D A, Hall M, Davis G G, Brissie R M, Robinson C A. Fatal multiple drug intoxication following acute sertraline use.  J Anal Toxicol. 1998;  22 545-548
  • 179 Molander L, Borgstrom L. Relationship between plasma concentration and arousal in normal subjects after single oral and parenteral doses of melperone, a butyrophenone neuroleptic.  Psychopharmacology. 1983;  79(2 - 3) 111-114
  • 180 Monteleone P, Gnocchi G, Delrio G. Plasma trazodone concentrations and clinical response in elderly depressed patients: a preliminary study.  J Clin Psychopharmacol. 1989;  9(4) 284-287
  • 181 Montgomery S A, Montgomery D B, McAuley R, Rani S J. Mianserin plasma levels and differential clinical response in endogenous and reactive depression.  Acta Psychiatr Belg. 1978;  78 798-812
  • 182 Moulin A, Truffer D, Rauch-Desanti C, Istin M, Grognet J M, Dufour A. Comparison of HPLC and RIA methods applied to the quantification of amisulpride in human plasma.  Eur J Drug Metab Pharmacokinet. 1991;  3 507-512
  • 183 Müller M J, Dragicevic A, Fric M, Gaertner I, Grasmader K, Härtter S. et al . Therapeutic drug monitoring of tricyclic antidepressants: how does it work under clinical conditions?.  Pharmacopsychiatry. 2003;  36(3) 98-104
  • 184 Müller M J, Härtter S, Köhler D, Hiemke C. Serum levels of sulpiride enantiomers after oral treatment with racemic sulpiride in psychiatric patients: a pilot study.  Pharmacopsychiatry. 2001;  34 27-32
  • 185 Müller-Oerlinghausen B, Fähndrich E. The relationship between pharmacokinetic data and the clinical response in patients treated with maprotiline or clomipramine by intravenous infusion.  Pharmacopsychiatry. 2002;  18 100-101
  • 186 Müller-Oerlinghausen B, Rüther E. Clinical profile and serum concentration of viloxazine as compared to amitriptyline.  Pharmakopsychiatr Neuropsychopharmakol. 1979;  12(4) 321-337
  • 187 Müller-Oerlinghausen B, Schley J. Serumspiegel von Perazin und seinen Metaboliten: Qualitätskontrolle, Kosten, Interpretation und praktische Bedeutung. In: Helmchen H, Hippius H, Tölle R, editors Therapie mit Neuroleptika - Perazin. New York; Georg Thieme Verlag Stuttgart; 1988: S27
  • 188 Murray M. P450 Enzymes. Inhibition mechanisms, genetic regulation and effects of liver disease.  Clin Pharmacokinet. 1992;  23 132-146
  • 189 Nakajima M, Yokoi T, Mizutani M, Kinoshita M, Funayama M, Kamataki T. Genetic polymorphism in the 5′-flanking region of human CYP1A2 gene: effect on the CYP1A2 inducibility in humans.  J Biochem. 1999;  125 803-808
  • 190 Nelson J C. Current status of tricyclic antidepressants in psychiatry: their pharmacology and clinical applications.  J Clin Psychiatry. 1991;  52 193-200
  • 191 Nelson J C, Jatlow P I, Mazure C. Desipramine plasma levels and response in elderly melancholic patients.  J Clin Psychopharmacol. 1985;  5 217-220
  • 192 Nishikage H, Nakanishi T, Takamitsu Y, Yamamoto J. Sequential changes in the plasma concentration of risperidone following intentional overdose.  Clin Neuropharmacol. 2002;  25(6) 307-309
  • 193 Norman T R, Burrows G D, Davies B M, Maguire K P, Wurm J M. Viloxazine plasma concentrations and clinical response.  J Affect Disord. 1980;  2(3) 157-164
  • 194 Ohman D, Norlander B, Peterson C, Bengtsson F. Bioanalysis of racemic reboxetine and its desethylated metabolite in a therapeutic drug monitoring setting using solid phase extraction and HPLC.  Ther Drug Monit. 2001;  23 27-34
  • 195 Olesen O V, Licht R W, Thomsen E, Bruun T, Viftrup J E, Linnet K. Serum concentrations and side effects in psychiatric patients during risperidone therapy.  Ther Drug Monit. 1998;  20 380-384
  • 196 Orsulak P J. Therapeutic monitoring of antidepressant drugs - Guidelines updated.  Ther Drug Monit. 1989;  11 497-507
  • 197 Otani K, Aoshima T. Pharmacogenetics of classical and new antipsychotic drugs.  Ther Drug Monit. 2000;  22 118-121
  • 198 Otani K, Kaneko S, Sasa H, Kondo T, Fukushima Y. Is there a therapeutic window for plasma concentration of mianserin plus desmethylmianserin.  Hum Psychopharmacol Clin Exp. 1991;  6 243-248
  • 199 Otani K, Tybring G, Mihara K, Yasui N, Kaneko S, Ohkubo T. et al . Correlation between steady-state plasma concentrations of mianserin and trazodone in depressed patients.  Eur J Clin Pharmacol. 1998;  53 347-349
  • 200 Özdemir V, Kalow W, Okey A B, Lam M S, Albers L J, Reist C. et al . Treatment-resistance to clozapine in association with ultrarapid CYP1A2 activity and the C->A polymorphism in intron 1 of the CYP1A2 gene: effect of grapefruit juice and low-dose fluvoxamine.  J Clin Psychopharmacol. 2001;  21(6) 603-607
  • 201 Pedersen O L, Gram L F, Kristensen C B, Moller M, Thayssen P, Bjerre M. et al . Overdosage of antidepressants: clinical and pharmacokinetic aspects.  Eur J Clin Pharmacol. 1982;  23 513-521
  • 202 Pellizzoni C, Poggesi I, Jørgensen N P, Edwards D MF, Paus E, Benedetti M S. Pharmacokinetics of reboxetine in healthy volunteers. Single against repeated oral doses and lack of enzymatic alterations.  Biopharm Drug Dispos. 1996;  17 623-633
  • 203 Perry P J. The relationship between antidepressant response and tricyclic antidepressant plasma concentrations: a retrospective analysis of the literature using logistic regression analysis lin.  Pharmacokinet. 1987;  13 381-392
  • 204 Perry P J, Lund B C, Sanger T, Beasley C. Olanzapine plasma concentrations and clinical response: acute phase results of the North American olanzapine trial.  J Clin Psychopharmacol. 2001;  21 14-20
  • 205 Perry P J, Miller D D, Arndt S V, Cadoret R J. Clozapine and norclozapine plasma concentrations and clinical response of treatment-refractory schizophrenic patients.  Am J Psychiatry. 1991;  148 231-235
  • 206 Perry P J, Sanger T, Beasley C. Olanzapine plasma concentrations and clinical response in acutely III schizophrenic patients.  J Clin Psychopharmacol. 1997;  17 472-477
  • 207 Perry P J, Zeilmann C, Arndt S. Tricyclic antidepressant concentrations in plasma: an estimate of their sensitivity and specificity as a predictor of response.  J Clin Psychopharmacol. 1994;  14 230-240
  • 208 Petit P, Lonjon R, Cociglio M, Sluzewska A, Blayac J P, Hue B. et al . Carbamazepine and its 10,11-epoxide metabolite in acute mania: clinical and pharmacokinetic correlates.  Eur J Clin Pharmacol. 1991;  41(6) 541-546
  • 209 Preskorn S, Jerkovich G S. Central nervous system toxicity of tricyclic antidepressants: phenomenology, course, risk factors, and role of therapeutic drug monitoring.  J Clin Psychopharmacol. 1990;  10 88-95
  • 210 Preskorn S H, Burke M J, Fast G A. Therapeutic drug monitoring: Principles and practice.  Ther Drug Monit. 1993;  16 611-641
  • 211 Preskorn S H, Fast G A. Therapeutic drug monitoring for antidepressants: efficacy, safety, and cost effectiveness.  J Clin Psychiat. 1991;  52(Suppl.) 23-33
  • 212 Preskorn S H, Fast G A. Tricyclic antidepressant-induced seizures and plasma drug concentration.  J Clin Psychiatry. 1992;  53 160-162
  • 213 Preskorn S H, Fleck R J, Schroeder D H. Therapeutic drug monitoring of bupropion.  Am J Psychiatry. 1990;  147 1690-1691
  • 214 Puech A, Fleurot O, Rein W. Amisulpride, an atypical antipsychotic, in the treatment of acute episodes of schizophrenia: a dose-ranging study vs. haloperidol.  Acta Psychiatr Scand. 1998;  98 65-72
  • 215 Rao M L. Modification of radioreceptor assay technique for the estimation of serum neuroleptic drug levels leads to improved precision and sensitivity.  Psychopharmacol. 1986;  90 48-553
  • 216 Rao M L, Staberock U, Baumann P, Hiemke C, Deister A, Cuendet C. et al . Monitoring tricyclic antidepressant concentrations in serum by fluorescence polarization immunoassay compared with gas chromatography an HPLC.  Clin Chem. 1994;  40 29-933
  • 217 Rasmussen B B, Brøsen K. Is therapeutic drug monitoring a case for optimizing clinical outcome and avoiding interactions of the selective serotonin reuptake inhibitors.  Ther Drug Monit. 2000;  22 43-154
  • 218 Regenthal R, Krueger M, Koeppel C, Preiss R. Drug levels: therapeutic and toxic serum/plasma concentrations of common drugs.  J Clin Monit Comput. 1999;  15(7 - 8) 529-544
  • 219 Reis M, Lundmark J, Bjork H, Bengtsson F. Therapeutic drug monitoring of racemic venlafaxine and its main metabolites in an everyday clinical setting.  Ther Drug Monit. 2002;  24(4) 545-553
  • 220 Reisby N, Gram L F, Bech P, Nagy A, Petersen G O, Ortmann J. et al . Imipramine: clinical effects and pharmacokinetic variability.  Psychopharmacology. 1977;  54(3) 263-272
  • 221 RiveraCalimlim L, Castaneda L, Lasagna L. Effects of mode of management on plasma chlorpromazine in psychiatric patients.  Clin Pharmacol Ther. 1973;  14(6) 978-986
  • 222 Roberts C J, Ford J M, Truman C A, Scott M, Makela P M, Wilcock G K. Assessment of the value of therapeutic monitoring of tacrine in Alzheimer’s disease.  Eur J Clin Pharmacol. 1998;  54(9 - 10) 721-724
  • 223 Roberts R L, Joyce P R, Mulder R T, Begg E J, Kennedy M A. A common P-glycoprotein polymorphism is associated with nortriptyline-induced postural hypotension in patients treated for major depression.  Pharmacogenomics Journal. 2002;  2(3) 191-196
  • 224 Rochat B, Kosel M, Boss G, Testa B, Gillet M, Baumann P. Stereoselective biotransformation of the selective serotonin reuptake inhibitor, citalopram, and its demethylated metabolites by monoamine oxidases in human liver.  Biochem Pharmacol. 1998;  56 15-23
  • 225 Rodriguez d lT, Dreher J, Malevany I, Bagli M, Kolbinger M, Omran H. et al . Serum levels and cardiovascular effects of tricyclic antidepressants and selective serotonin reuptake inhibitors in depressed patients.  Ther Drug Monit. 2001;  23(4) 435-440
  • 226 Rogers S L, Friedhoff L T. The efficacy and safety of donepezil in patients with Alzheimer’s disease: results of a US Multicentre, Randomized, Double-Blind, Placebo-Controlled Trial. The Donepezil Study Group.  Dementia. 1996;  7(6) 293-303
  • 227 Roh H K, Chung J Y, Oh D Y, Park C S, Svensson J O, Dahl M L. et al . Plasma concentrations of haloperidol are related to CYP2D6 genotype at low, but not high doses of haloperidol in Korean schizophrenic patients.  Br J Clin Pharmacol. 2001;  52 265-271
  • 228 Rudorfer M V, Potter W Z. The role of metabolites of antidepressants in the treatment of depression [review].  CNS Drugs. 1997;  7 273-312
  • 229 Sachse C, Brockmöller J, Bauer S, Roots I. Functional significance of a C ->A polymorphism in introm I of the cytochrome P450 CYP1A2 gene tested with caffeine.  Br J Clin Pharmacol. 1999;  47 445-449
  • 230 Sachse J, Härtter S, Müller M J, Dragicevic A, Hiemke C. Therapeutisches Drug Monitoring von Quetiapin.  Psychopharmakotherapie. 2003;  10 19-22
  • 231 Sajbel T A, Carter G W, Wiley R B. Converting patients from brand-name clozapine to generic clozapine.  Ann Pharmacother. 2001;  35(3) 281-284
  • 232 Salva P, Costa J. Clinical pharmacokinetics and pharmacodynamics of zolpidem. Therapeutic implications.  Clin Pharmacokinet. 1995;  29(3) 142-153
  • 233 Schoerlin M -P, Mayersohn M, Korn A, Eggers H. Disposition kinetics of moclobemide, a monoamine oxidase-A enzyme inhibitor: single and multiple dosing in normal subjects.  Clin Pharmacol Ther. 1987;  42 395-404
  • 234 Schou M. Forty years of lithium treatment.  Arch Gen Psychiatry. 1997;  54 9-13
  • 235 Schulz M, Schmoldt A. Therapeutic and toxic blood concentrations of more than 500 drugs.  Pharmazie. 1997;  52 895-911
  • 236 Scordo M G, Spina E. Cytochrome P450 polymorphisms and response to antipsychotic therapy.  Pharmacogenomics. 2002;  3(2) 201-218
  • 237 Seeman P, Van Tol H HM. Deriving the therapeutic concentrations for clozapine and haloperidol: the apparent dissociation constant of a neuroleptic at the dopamine D2 or D4 receptor varies with the affinity of the competing radioligand.  Eur J Pharm-Mol Pharmacol Section. 1995;  291 59-66
  • 238 Seiler W, Wetzel H, Hillert A, Schollnhammer G, Langer M, Barlage U. et al . Pharmacokinetics and bioavailability of benperidol in schizophrenic patients after intravenous and two different kinds of oral application.  Psychopharmacology (Berl). 1994;  116(4) 457-463
  • 239 Shah V P, Midha K K, Dighe S, McGilveray I J, Skelly J P, Yacobi A. et al . Analytical methods validation - bioavailability, bioeqivalence and pharmacokinetic studies.  Pharm Res. 1992;  9(4) 588-592
  • 240 Simmons S A, Perry P J, Rickert E D, Browne J L. Cost-benefit analysis of prospective pharmocokinetic dosing of nortriptyline in depressed.  J Affect Disord. 1985;  8 47-53
  • 241 Sindrup S H, Brøsen K, Gram L F, Hallas J, Skjelbo E, Allen A. et al . The relationship between paroxetine and the sparteine oxidation polymorphism.  Clin Pharmacol Ther. 1992;  51 278-287
  • 242 Small J G, Hirsch S R, Arvanitis L A, Miller B G, Link C GG, Seroquel Study G roup. Quetiapine in patients with Schizophrenia - A high- and low-dose double-blind comparison with placebo.  Arch Gen Psychiatry. 1997;  54 549-557
  • 243 Spector R. Drug transport in the mammalian central nervous system: multiple complex systems.  Pharmacology. 2000;  60 58-73
  • 244 Spina E, Avenoso A, Facciolà G, Salemi M, Scordo M G, Ancione M. et al . Relationship between plasma risperidone and 9-hydroxyrisperidone concentrations and clinical response in patients with schizophrenia.  Psychopharmacology. 2001;  153 238-243
  • 245 Steimer W, Potter J M. Pharmacogenetic screening and therapeutic drugs.  Clin Chim Acta. 2002;  315(1 - 2) 137-155
  • 246 Stein S, Schmoldt A, Schulz M. Fatal intoxication with melperone.  Forensic Sci Int. 2000;  113(1 - 3) 409-413
  • 247 Strakowski S M, Keck P E, Jr., Wong Y W, Thyrum P T, Yeh C. The effect of multiple doses of cimetidine on the steady-state pharmacokinetics of quetiapine in men with selected psychotic disorders.  J Clin Psychopharmacol. 2002;  22(2) 201-205
  • 248 Tasker T CG, Kaye C M, Zussman B D, Link C GG. Paroxetine plasma levels: lack of correlation with efficacy or adverse events.  Acta Psychiatr Scand. 1989;  80(suppl. 350) 152-155
  • 249 The Scottish Schizophrenia Research G roup. The Scottish first episode Schizophrenia study. II. Treatment: imozide versus flupenthixol .  Br J Psychiatry. 1987;  150 334-338
  • 250 Thürmann P A, Hompesch B C. Influence of gender on the pharmacokinetics and pharmacodynamics of drugs.  Int J Clin Pharmacol Ther. 1998;  36 586-590
  • 251 Tibballs J. Acute toxic reaction to carbamazepine: clinical effects and serum concentrations.  J Pediatr. 1992;  121(2) 295-299
  • 252 Timmer C J, Lohmann A AM, Mink C PA. Pharmacokinetic dose-proportionality study at steady state of mirtazapine from remeron tablets.  Hum Psychopharmacol. 1995;  10 S97-106
  • 253 Timmer C J, Sitsen J MA, Delbressine L P. Clinical pharmacokinetics of mirtazapine.  Clin Pharmacokinet. 2000;  38 461-474
  • 254 Tiseo P J, Rogers S L, Friedhoff L T. Pharmacokinetic and pharmacodynamic profile of donepezil HCl following evening administration.  Br J Clin Pharmacol. 1998;  46 Suppl 1 13-18
  • 255 Tokunaga H, Kudo K, Imamura T, Jitsufuchi N, Ohtsuka Y, Ikeda N. Plasma concentrations of antipsychotic drugs in psychiatric inpatients.  Nippon Hoigaku Zasshi. 1997;  51 417-422
  • 256 Torrens M, Castillo C, San L, del Moral E, Gonzalez M L, de laTorre R. Plasma methadone concentrations as an indicator of opioid withdrawal symptoms and heroin use in a methadone maintenance program.  Drug Alcohol Depend. 1998;  52(3) 193-200
  • 257 Troy S M, Parker V D, Fruncillo R J, Chiang S T. The pharmacokinetics of venlafaxine when given in a twice-daily regimen.  J Clin Pharmacol. 1995;  35 404-409
  • 258 Tse G, Thompson D, Procyshyn R M. Generic clozapine: a cost-saving alternative to brand name clozapine?.  PharmacoEconomics. 2003;  21(1) 1-11
  • 259 Uhr M, Steckler T, Yassouridis A, Holsboer F. Penetration of amitriptyline, but not of fluoxetine, into brain is enhanced in mice with blood-brain barrier deficiency due to Mdr1a P-glycoprotein gene disruption.  Neuropsychopharmacology. 2000;  22 380-387
  • 260 Ulrich S, Danos P, Baumann B, Müller D, Lehmann D, et al. Serum concentration of chlormethiazole and therapeutic effect in acute alcohol withdrawal syndrome - an open clinical trial.  Ther Drug Monit. 2002;  24 446-454
  • 261 Ulrich S, Neuhof S, Braun V, Meyer F P. Therapeutic window of serum haloperidol concentration in acute schizophrenia and schizoaffective disorder.  Pharmacopsychiat. 1998;  31 163-169
  • 262 Ulrich S, Neuhof S, Braun V, Meyer F P. Reduced haloperidol does not interfere with the antipsychotic activity of haloperidol in the treatment of acute schizophrenia.  Int Clin Psychopharmacol. 1999;  14 219-228
  • 263 Ulrich S, Wurthmann C, Brosz M, Meyer F P. The relationship between serum concentration and therapeutic effect of haloperidol in patients with acute schizophrenia.  Clin Pharmacokinet. 1998;  34 227-263
  • 264 Van der Weide J, Steijns L S, van Weelden M J. The effect of smoking and cytochrome P450 CYP1A2 genetic polymorphism on clozapine clearance and dose requirement.  Pharmacogenetics. 2003;  13(3) 169-172
  • 265 Van Putten T, Marder S R. Variable dose studies provide misleading therapeutic windows (Letter).  J Clin Psychoparmacol. 1986;  6 55-56
  • 266 van Putten T, Marder S R, Wirshing W C, Aravagiri M, Chabert N. Neuroleptic plasma levels.  Schizophr Bull. 1991;  17(2) 197-216
  • 267 VanderZwaag C, McGee M, McEvoy J P, Freudenreich O, Wilson W H, Cooper T B. Response of patients with treatment-refractory schizophrenia to clozapine within three serum level ranges.  Am J Psychiatry. 1996;  153(2) 1579-1584
  • 268 Vasudev K, Goswami U, Kohli K. Carbamazepine and valproate monotherapy: feasibility, relative safety and efficacy, and therapeutic drug monitoring in manic disorder.  Psychopharmacology. 2000;  150(1) 15-23
  • 269 Veefkind A H, Haffmans P MJ, Hoencamp E. Venlafaxine serum levels and CYP2D6 genotype.  Ther Drug Monit. 2000;  22 202-208
  • 270 Veenstra D L, Higashi M K. Assessing the cost-effectiveness of pharmacogenomics.  AAPS Pharmsci. 2000;  2(article 29)(3) 1-11
  • 271 Velazquez C, Carlson A, Stokes K A, Leikin J B. Relative safety of mirtazapine overdose.  Vet Hum Toxicol. 2001;  43(6) 342-344
  • 272 Veuthey J L, Souverain S, Rudaz S. Column-switching procedures for the analysis of drugs in biologic samples.  Ther Drug Monit. 2004;  26(2) 161-166
  • 273 Vuille F, Amey M, Baumann P. Use of plasma level monitoring of antidepressants in clinical practive - Towards an analysis of clinical utility.  Pharmacopsychiatry. 1991;  24 190-195
  • 274 Weigmann H, Gerek S, Zeisig A, Muller M, Härtter S, Hiemke C. Fluvoxamine but not sertraline inhibits the metabolism of olanzapine: evidence from a therapeutic drug monitoring service.  Ther Drug Monit. 2001;  23 410-413
  • 275 Wetzel H, Anghelescu I, Szegedi A, Wiesner J, Weigmann H, Härtter S. et al . Pharmacokinetic interactions of clozapine with selective serotonin reuptake inhibitors: differential effects of fluvoxamine and paroxetine in a prospective study.  J Clin Psychopharmacol. 1998;  18 2-9
  • 276 Wilner K D, Tensfeldt T G, Baris B, Smolarek T A, Turncliff R Z, Colburn W A. et al . Single- and multiple-dose pharmacokinetics of ziprasidone in healthy young and elderly volunteers.  Br J Clin Pharmacol. 2000;  49(Suppl. 1) 15S-20
  • 277 Wincor M Z, Munjack D J, Palmer R. Alprazolam levels and response in panic disorder: preliminary results.  J Clin Psychopharmacol. 1991;  11(1) 48-51
  • 278 Zullino D F, Delessert D, Eap C B, Preisig M, Baumann P. Tobacco and cannabis smoking cessation can lead to intoxication with clozapine.  Int Clin Psychopharmacol. 2002;  17 141-143

Pierre Baumann, Ph. D. Prof.

Unité de biochimie et psychopharmacologie clinique

Département universitaire de psychiatrie adulte

Centre de neurosciences psychiatriques

CH -1008 Prilly-Lausanne/Switzerland

Phone: 0041 21 643 64 34

Fax: 0041 21 643 64 44

Email: Pierre.Baumann@inst.hospvd.ch