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Pharmacopsychiatry 2012; 45(02): 72-76
DOI: 10.1055/s-0031-1291294
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

Therapeutic Drug Monitoring of Children and Adolescents Treated with Fluoxetine

M. Koelch
1   Department of Child and Adolescent Psychiatry and Psychotherapy, University of Ulm, Ulm, Germany
,
A.-K. Pfalzer
1   Department of Child and Adolescent Psychiatry and Psychotherapy, University of Ulm, Ulm, Germany
,
K. Kliegl
1   Department of Child and Adolescent Psychiatry and Psychotherapy, University of Ulm, Ulm, Germany
,
S. Rothenhöfer
2   Hospitals of Cologne City GmbH, Child and Adolescent Psychiatry and Psychotherapy, Cologne, Germany
,
A. G. Ludolph
1   Department of Child and Adolescent Psychiatry and Psychotherapy, University of Ulm, Ulm, Germany
,
J. M. Fegert
1   Department of Child and Adolescent Psychiatry and Psychotherapy, University of Ulm, Ulm, Germany
,
R. Burger
3   Laboratory for Therapeutic Drug Monitoring, Clinics for Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany
,
C. Mehler-Wex
1   Department of Child and Adolescent Psychiatry and Psychotherapy, University of Ulm, Ulm, Germany
,
J. Stingl
4   Institute of Pharmacology of Natural Products and Clinical Pharmacology, University Ulm, Ulm, Germany
,
R. Taurines
5   Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany
,
K. Egberts
5   Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany
,
M. Gerlach
5   Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany
› Author Affiliations
Further Information

Publication History

received 30 June 2011
revised 09 September 2011

accepted 26 September 2011

Publication Date:
15 November 2011 (online)

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Abstract

Introduction:

Information about therapeutic serum levels of fluoxetine (FLX) and its major metabolite norfluoxetine (NORFLX) in children and adolescents is scarce.

Methods:

Therapeutic drug monitoring (TDM) of FLX was routinely performed in 71 subjects treated for a major depressive disorder (MDD) (10–60 mg/d FLX, median: 20 mg/d). Correlations between serum concentration and dosage, age, gender, smoking habits and adverse events were analysed.

Results:

Serum concentrations of the active moiety (FLX + NORFLX) ranged from 21 to 613 ng/mL (mean concentration of 213±118 ng/mL, median: 185 ng/mL). High inter-individual variability in serum concentrations of the active moiety of FLX at each dosage level was observed and no relationship between serum concentration and clinical outcome was found. Apart from smoking, none of the factors tested had a significant effect on the serum concentration.

Discussion:

It was shown that serum concentrations of the active moiety of FLX in children and adolescents seem to be similar to those in adults, with a high level of inter-individual variation. The proportion of patients who showed benefits from treatment with a dose of 20 mg/d FLX was high.

Key words

antidepressants - pharmacokinetics - therapeutic drug monitoring - children - adolescents
 

  • References

  • 1 Goodyer I, Dubicka B, Wilkinson P et al. Selective serotonin reuptake inhibitors (SSRIs) and routine specialist care with and without cognitive behaviour therapy in adolescents with major depression: randomised controlled trial. BMJ 2007; 335 (7611) 142
    CrossrefPubMedGoogle Scholar
  • 2 March J, Silva S, Petrycki S et al. Fluoxetine, cognitive-behavioral therapy, and their combination for adolescents with depression: Treatment for adolescents with depression study (TADS) randomized controlled trial. JAMA 2004; 292: 807-820
    CrossrefPubMedGoogle Scholar
  • 3 Altamura AC, Moro AR, Percudani M. Clinical pharmacokinetics of fluoxetine. Clin Pharmacokinet 1994; 26: 201-214
    CrossrefPubMedGoogle Scholar
  • 4 Bergstrom RF, Lemberger L, Farid NA et al. Clinical pharmacology and pharmacokinetics of fluoxetine: a review. Br J Psychiatry Suppl 1988; 3: 47-50
    PubMedGoogle Scholar
  • 5 Baumann P, Hiemke C, Ulrich S et al. The AGNP-TDM expert group consensus guidelines: therapeutic drug monitoring in psychiatry. Pharmacopsychiatry 2004; 37: 243-265
    Article in Thieme ConnectPubMedGoogle Scholar
  • 6 Wilens TE, Cohen L, Biederman J et al. Fluoxetine pharmacokinetics in pediatric patients. J Clin Psychopharmacol 2002; 22: 568-575
    CrossrefPubMedGoogle Scholar
  • 7 Cherma MD, Ahlner J, Bengtsson F et al. Antidepressant drugs in children and adolescents, analytical and demographic data in a naturalistic, clinical study. J Clin Psychopharmacol 2011; 31: 98-102
    CrossrefPubMedGoogle Scholar
  • 8 Reis M, Aamo T, Spigset O et al. Serum concentrations of antidepressant drugs in a naturalistic setting: compilation based on a large therapeutic drug monitoring database. Ther Drug Monit 2009; 31: 42-56
    CrossrefPubMedGoogle Scholar
  • 9 Hammad TA, Laughren T, Racoosin J. Suicidality in pediatric patients treated with antidepressant drugs. Arch Gen Psychiatry 2006; 63: 332-339
    CrossrefPubMedGoogle Scholar
  • 10 Safer DJ, Zito JM. Treatment-emergent adverse events from selective serotonin reuptake inhibitors by age group: children versus adolescents. J Child Adolesc Psychopharmacol 2006; M; 16: 159-169
    CrossrefPubMedGoogle Scholar
  • 11 Mehler-Wex C, Kölch M, Kirchheiner J et al. Drug monitoring in child and adolescent psychiatry for improved efficacy and safety of psychopharmacotherapy. Child Adolesc Psychiatry Ment Health 2009; 3: 14
    CrossrefPubMedGoogle Scholar
  • 12 Guy W. ECDEU assessment manual. Rockville, National Institute of Mental Health 1976;
    PubMedGoogle Scholar
  • 13 Lingjaerde O, Ahlfors UG, Bech P et al. The UKU side effect rating scale. A new comprehensive rating scale for psychotropic drugs and a cross-sectional study of side effects in neuroleptic-treated patients. Acta Psychiatr Scand Suppl 1987; 334: 1-100
    PubMedGoogle Scholar
  • 14 Scordo MG, Spina E, Dahl M-L et al. Influence of CYP2C9, 2C19 and 2D6 genetic polymorphisms on the steady-state plasma concentrations of the enantiomers of fluoxetine and norfluoxetine. Basic Clin Pharmacol Toxicol 2005; 97: 296-301
    CrossrefPubMedGoogle Scholar
  • 15 Miksys S, Tyndale RF. Nicotine induces brain CYP enzymes: relevance to Parkinson’s disease. J Neural Transm Suppl 2006; 70: 177-180
    PubMedGoogle Scholar
  • 16 Aklillu E, Persson I, Bertilsson L et al. Frequent distribution of ultrarapid metabolizers of debrisoquine in an ethiopian population carrying duplicated and multiduplicated functional CYP2D6 alleles. J Pharmacol Exp Ther 1996; 278: 441-446
    PubMedGoogle Scholar
  • 17 Holtkamp K, Konrad K, Kaiser N et al. A retrospective study of SSRI treatment in adolescent anorexia nervosa: insufficient evidence for efficacy. J Psychiatr Res 2005; 39: 303-310
    CrossrefPubMedGoogle Scholar