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Pharmacopsychiatry 2007; 40(3): 121-127
DOI: 10.1055/s-2007-977712
Original Paper

© Georg Thieme Verlag KG Stuttgart · New York

Value and Actuality of the Prescription Information for Therapeutic Drug Monitoring of Psychopharmaceuticals: A Comparison with the Medico-Scientific Evidence

S. Ulrich 1 , C. Hiemke 2 , G. Laux 3 , B. Müller-Oerlinghausen 4 , U. Havemann-Reinecke 5 , P. Riederer 6 , G. Zernig 7 , P. Baumann 8 , TDM group of the Arbeitsgemeinschaft Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP)[*]
  • 1esparma GmbH Osterweddingen, Germany
  • 2Psychiatric Clinic University Hospital Mainz, Mainz, Germany
  • 3Psychiatric Clinic Gabersee, Wasserburg/Inn, Germany
  • 4Drug Commission of the German Medical Association Berlin, Germany
  • 5Psychiatric Clinic University Hospital Göttingen, Göttingen, Germany
  • 6Psychiatric Clinic University Hospital Würzburg, Würzburg, Germany
  • 7Experimental Psychiatry Unit, Department of Psychiatry, Medical University Innsbruck, Austria
  • 8Psychiatric Clinic University Hospital Prilly-Lausanne, Switzerland
Further Information

Publication History

received 29. 3. 2007 revised 2. 4. 2007

accepted 4. 4. 2007

Publication Date:
01 June 2007 (online)

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Abstract

Therapeutic drug monitoring (TDM) of psychopharmaceuticals, i.e., the assay of plasma concentrations, is a practical therapeutic application of pharmacokinetic principles in psychiatry. The prescription information (summary of product characteristics, SPC) is provided by pharmaceutical companies according to the requirements of regulatory authorities. The present study investigated the degree of agreement of German SPCs for 48 psychopharmaceuticals with the existing medico-scientific evidence in the area of TDM. For this aim, an empirical summary score of SPC content related to TDM (SPCCTDM) was calculated and compared with the level of recommendation of TDM (LOR) of the AGNP-TDM expert group consensus guidelines. Considerable disagreement was found between the information on TDM in SPCs and existing medico-scientific evidence, e.g., in the case of antidepressant and antipsychotic drugs. Even for well studied compounds, such as amitriptyline and clozapine, insufficient information on TDM is included in German SPCs. Small differences existed in the TDM-related information in SPCs of generic drugs with, however, much variance between Germany, Austria and Switzerland. Generally, it must be concluded that deficits exist in the preparation of German SPCs for psychopharmaceutical drugs with respect to empirical pharmacokinetic data, i.e., TDM-relevant information. It is recommended that SPCs of psychopharmaceuticals should be improved in terms of TDM-related information and that target plasma concentrations be adjusted according to the guidelines of the AGNP-TDM expert group. A higher level of good pharmacokinetic practice may be thus achieved.

Key words

therapeutic drug monitoring - prescription information - pharmacovigilance - amitriptyline - haloperidol

References

  • 1 Bauer M, Whybrow PC, Angst J, Versiani M, Möller HJ. World Federation of Societies of Biological Psychiatry: Task Force on Treatment Guidelines for Unipolar Depressive Disorders . World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of unipolar depressive disorders, Part 1: Acute and continuation treatment of major depressive disorder.  World J Biol Psychiat. 2002;  3 5-43
    CrossrefPubMedSearch in Google Scholar
  • 2 Baumann P, Hiemke C, Ulrich S, Eckermann G, Gaertner I, Gerlach M, Kuss HJ, Laux G, Müller-Oerlinghausen B, Rao ML, Riederer P, Zernig G. AGNP-TDM expert group consensus guidelines: therapeutic drug monitoring in psychiatry.  Pharmacopsychiatry. 2004;  37 243-265
    Thieme ConnectPubMedSearch in Google Scholar
  • 3 Baumann P, Hiemke C, Ulrich S, Eckermann G, Kuss HJ, Laux G, Müller-Oerlinghausen BM, Rao ML, Riederer P, Zernig G. Le dosage plasmatique des médicaments psychotropes à des fins thérapeutiques: recommandations du groupe d’experts AGNP-TDM.  Rev Med Suisse. 2006;  2 1413-1426
    PubMedSearch in Google Scholar
  • 4 Baumann P, Hiemke C, Ulrich S, Gaertner I, Rao ML, Eckermann G, Gerlach M, Kuss HJ, Laux G, Müller-Oerlinghausen B, Riederer P, Zernig G. Therapeutic drug monitoring of psychotropic drugs: An outline of the AGNP-TDM expert group consensus guideline.  Ther Drug Monit. 2004;  26 167-170
    PubMedSearch in Google Scholar
  • 5 BfArM . 2006;  http://www.bfarm.de/cln_043/nn_424574/DE/Arzneimittel/mufag/ mufagDb/mufagdb-node.html_nnn=true
  • 6 Bergk V, Haefeli WE, Gasse C, Brenner H, Martin-Facklam M. Information deficits in the summary of product characteristics preclude an optimal management of drug interactions: a comparison with evidence from the literature.  Eur J Clin Pharmacol. 2005;  61 327-235
    CrossrefPubMedSearch in Google Scholar
  • 7 European Commission (EC) . Notice to Applicants: A guideline on summary of product characteristics.  http://ec.europa.eu/enterprise/pharmaceuticals/ eudralex/vol-2/c/spcguidrev1-oct2005.pdf , Sept 2006; 
    Search in Google Scholar
  • 8 European Medicines Agency (EMEA) . Note for guidance on dose response information to support drug registration (CPMP/ICH/378/95).  http://www.emea.europa.eu/pdfs/human/ich/037895en.pdf , Sept 2006; 
    Search in Google Scholar
  • 9 Falkai P, Wobrock T, Lieberman J, Glenthoj B, Gattaz WF, Moller HJ. WFSBP Task Force on Treatment Guidelines for Schizophrenia . World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of schizophrenia, part 2: long-term treatment of schizophrenia.  World J Biol Psychiat. 2006;  7 5-40
    CrossrefPubMedSearch in Google Scholar
  • 10 Gebran N, Al Haidari K. Assessment of prescribing information for generic drugs manufactured in the Middle East and marketed in Saudi Arabia.  Ann Saudi Med. 2006;  26 192-199
    PubMedSearch in Google Scholar
  • 11 Gex-Fabry M, Balant-Gorgia AE, Balant LP. Therapeutic drug monitoring databases for postmarketing surveillance of drug-drug interactions.  Drug Saf. 2001;  24 947-959
    CrossrefPubMedSearch in Google Scholar
  • 12 Gilles M, Deuschle M, Kellner S, Shams M, Krumm B, Härtter S, Heuser I, Hiemke C. Paroxetine serum concentrations in depressed patients and response to treatment.  Pharmacopsychiatry. 2005;  38 118-121
    Thieme ConnectPubMedSearch in Google Scholar
  • 13 Gräfe KA. Fachinformation: veraltet, ungenau oder fehlerhaft.  Pharmazeutische Zeitung. 2006;  3 222
    PubMedSearch in Google Scholar
  • 14 Grasmäder K, Verwohlt PL, Kuhn KU, Frahnert C, Hiemke C, Dragicevic A, von Widdern O, Zobel A, Maier W, Rao ML. Relationship between mirtazapine dose, plasma concentration, response, and side effects in clinical practice.  Pharmacopsychiatry. 2005;  38 113-117
    Thieme ConnectPubMedSearch in Google Scholar
  • 15 Hiemke C, Baumann P, Laux G, Kuss HJ. Therapeutisches Drug Monitoring in der Psychiatrie.  Psychopharmakotherapie. 2005;  12 166-182
    Search in Google Scholar
  • 16 Leinonen E, Lillsunde P, Laukkanen V, Ylitalo P. Effects of carbamazepine on serum antidepressant concentrations in psychiatric patients.  J Clin Psychopharmacol. 1991;  11 313-318
    PubMedSearch in Google Scholar
  • 17 Müller MJ, Regenbogen B, Sachse J, Eich FX, Härtter S, Hiemke C. Gender aspects in the clinical treatment of schizophrenic inpatients with amisulpride: a therapeutic drug monitoring study.  Pharmacopsychiat. 2006;  39 41-46
    PubMedSearch in Google Scholar
  • 18 Perry PJ, 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
    PubMedSearch in Google Scholar
  • 19 Perry PJ, Lund BC, 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
    CrossrefPubMedSearch in Google Scholar
  • 20 Reggi V, Balocco-Mattavelli R, Bonati M, Breton I, Figueras A. et al . Prescribing information in 26 countries: a comparative study.  Eur J Clin Pharmacol. 2003;  59 263-270
    CrossrefPubMedSearch in Google Scholar
  • 21 Riederer P, Laux G. Therapeutic drug monitoring of psychotropics: report of a consensus conference.  Pharmacopsychiat. 1992;  25 271-272
    PubMedSearch in Google Scholar
  • 22 SRZ 2006: FachInfo . , Fachinformationsverzeichnis Deutschland, Ausgabe 2006/1-CD-Version, Satz-Rechen-Zentrum Berlin, Bessemerstraße 83-91, D-12103 Berlin
  • 23 Steinmetz KL, Coley KC, Pollock BG. Assessment of geriatric information on the drug label for commonly prescribed drugs in older people.  J Am Geriatr Soc. 2005;  53 891-894
    CrossrefPubMedSearch in Google Scholar
  • 24 Ulrich S, Läuter J. A comprehensive survey of the relationship between serum concentration and therapeutic effect of amitriptyline in depression.  Clin Pharmacokin. 2002;  41 853-876
    CrossrefPubMedSearch in Google Scholar
  • 25 Ulrich S, Schroeder I, Partscht G, Baumann P. Therapeutisches Drug Monitoring von psychotropen Pharmaka: Eine allgemeine Einführung.  Psychopharmakotherapie. 2000;  7 2-14
    PubMedSearch in Google Scholar
  • 26 Ulrich S, Wolf R, Staedt J. Serum level of clozapine and relapse.  Ther Drug Monit. 2003;  25 252-255
    CrossrefPubMedSearch in Google Scholar
  • 27 Ulrich S, Wurthmann C, Brosz M, Meyer FP. The relationship between serum concentration and therapeutic effect of haloperidol in patients with acute schizophrenia: A review.  Clin Pharmacokin. 1998;  34 227-263
    PubMedSearch in Google Scholar
  • 28 Van der Zwaag C, McGee M, McEvoy JP, Freudenreich O, Wilson WH, Cooper TB. Response of patients with treatment refractory schizophrenia to clozapine within three serum level ranges.  Am J Psychiat. 1996;  153 1579-1584
    PubMedSearch in Google Scholar
  • 29 Van Putten T, Marder SR, Wirshing WC, Aravagiri M, Chabert N. Neuroleptic plasma levels.  Schizophr Bull. 1991;  17 197-216
    PubMedSearch in Google Scholar
  • 30 Zineh I, Pebanco GD, Aquilante CL, Gerhard T, Beitelshees AL, Beasley BN, Hartzema AG. Discordance between availability of pharmacogenetics studies and pharmacogenetics-based prescribing information for the top 200 drugs.  Ann Pharmacother. 2006;  40 639-644
    PubMedSearch in Google Scholar

1 Other members of the AGNP-TDM expert group N. Bergemann, Heidelberg; M. Dobmeier, Cham; G. Eckermann, Kaufbeuren; M. Gerlach, Würzburg; E. Haen, Regensburg; E. Jaquenoud-Sirot, Königsfelden; M. Köhnke, Rostock; H. J. Kuss, München; T. Messer, Augsburg; B. Pfuhlmann, Würzburg; M. L. Rao, Bonn; B. Schoppek, Haar, M. Schwarz, München

Correspondence

PD Dr. S. Ulrich

Lange Göhren 3

39 171 Osterweddingen

Germany

Phone: 039/205/422 143

Fax: 039/205/422 222

Email: s.ulrich@esparma.de