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Pharmacopsychiatry 2019; 52(03): 142-146
DOI: 10.1055/a-0606-5240
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

Response to Agomelatine Treatment is Independent of Smoking Status and Dosage: Results From the AGOPSYCH Study

Susanne Englisch
1   Central Institute of Mental Health, Department of Psychiatry and Psychotherapy, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
2   University Medical Center Mainz, Department of Psychiatry and Psychotherapy, Mainz, Germany
,
Hanna Sophie Jung
3   Municipal Hospital Karlsruhe, Department of Psychiatry and Psychotherapy, Karlsruhe, Germany
,
Antje Lewien
4   Department of Psychosomatic Medicine and Psychotherapy, University of Göttingen, Göttingen, Germany
,
Anna Becker
1   Central Institute of Mental Health, Department of Psychiatry and Psychotherapy, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
,
Ulrike Nowak
5   Institute of Psychology, Clinical Psychology and Psychotherapy, University of Hamburg, Hamburg, Germany
,
Hanna Braun
1   Central Institute of Mental Health, Department of Psychiatry and Psychotherapy, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
,
Sarah Eisenacher
1   Central Institute of Mental Health, Department of Psychiatry and Psychotherapy, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
,
Jascha Thiem
1   Central Institute of Mental Health, Department of Psychiatry and Psychotherapy, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
,
Andreas Meyer-Lindenberg
1   Central Institute of Mental Health, Department of Psychiatry and Psychotherapy, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
,
Mathias Zink
1   Central Institute of Mental Health, Department of Psychiatry and Psychotherapy, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
6   District Hospital Ansbach, Department of Psychiatry, Psychotherapy and Psychosomatic Medicine, Ansbach, Germany
› Author Affiliations
Further Information

Publication History

received 17 December 2017
revised 12 March 2018

accepted 10 April 2018

Publication Date:
07 May 2018 (online)

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Abstract

Introduction Cigarette smoking influences response to antidepressant treatment. It accelerates the metabolism of several cytochrome P450 (CYP) subtypes, including CYP1A2, and therefore bears the risk of pharmacokinetic interactions with psychotropic drugs using that pathway. Agomelatine is a substrate of CYP1A2; the association between nicotine use and agomelatine dosage, however, has never been studied before.

Methods Smoking habits were correlated with agomelatine doses and treatment outcomes in a sample of 27 patients with lifetime diagnoses within the schizophrenia spectrum who received agomelatine treatment in addition to their stable antipsychotic treatment regimen because of depressive symptoms.

Results No interactions were found between smoking status and agomelatine dosage, and treatment outcomes did not differ between smokers and nonsmokers.

Discussion Agomelatine efficacy appears to be independent of dosage and smoking status, pointing toward mechanisms beyond mere dose-response relationships. Further research will be necessary to validate these findings.

Key words

agomelatine - nicotine - smoking - interaction - pharmacokinetics - CYP1A2 - schizophrenia - depression
 

  • References

  • 1 Kalman D, Morissette SB, George TP. Co-morbidity of smoking in patients with psychiatric and substance use disorders. Am J Addict 2005; 14: 106-123
    CrossrefPubMedGoogle Scholar
  • 2 Oliveira P, Ribeiro J, Donato H. et al. Smoking and antidepressants pharmacokinetics: A systematic review. Ann Gen Psychiatry 2017; 16: 17-24
    CrossrefPubMedGoogle Scholar
  • 3 Pelkonen O, Turpeinen M, Hakkola J. et al. Inhibition and induction of human cytochrome P450 enzymes: Current status. Arch Toxicol 2008; 82: 667-715
    CrossrefPubMedGoogle Scholar
  • 4 Zhou SF, Wang B, Yang LP. et al. Structure, function, regulation and polymorphism and the clinical significance of human cytochrome P450 1A2. Drug Metab Rev 2010; 42: 268-354
    CrossrefPubMedGoogle Scholar
  • 5 Zevin S, Benowitz NL. Drug interactions with tobacco smoking. An update. Clin Pharmacokinet 1999; 36: 425-438
    CrossrefPubMedGoogle Scholar
  • 6 Hukkanen J, Jacob 3rd P, Peng M. et al. Effect of nicotine on cytochrome P450 1A2 activity. Br J Clin Pharmacol 2011; 72: 836-838
    CrossrefPubMedGoogle Scholar
  • 7 Lundmark J, Reis M, Bengtsson F. Serum concentrations of fluoxetine in the clinical treatment setting. Ther Drug Monit 2001; 23: 139-147
    CrossrefPubMedGoogle Scholar
  • 8 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
    CrossrefPubMedGoogle Scholar
  • 9 Unterecker S, Hiemke C, Greiner C. et al. The effect of age, sex, smoking and co-medication on serum levels of venlafaxine and O-desmethylvenlafaxine under naturalistic conditions. Pharmacopsychiatry 2012; 45: 229-235
    Article in Thieme ConnectPubMedGoogle Scholar
  • 10 Fric M, Pfuhlmann B, Laux G. et al. The influence of smoking on the serum level of duloxetine. Pharmacopsychiatry 2008; 41: 151-155
    Article in Thieme ConnectPubMedGoogle Scholar
  • 11 Jaquenoud Sirot E, Harenberg S, Vandel P. et al. Multicenter study on the clinical effectiveness, pharmacokinetics, and pharmacogenetics of mirtazapine in depression. J Clin Psychopharmacol 2012; 32: 622-629
    CrossrefPubMedGoogle Scholar
  • 12 Hsyu PH, Singh A, Giargiari TD. et al. Pharmacokinetics of bupropion and its metabolites in cigarette smokers versus nonsmokers. J Clin Pharmacol 1997; 37: 737-743
    CrossrefPubMedGoogle Scholar
  • 13 Tsuda Y, Saruwatari J, Yasui-Furukori N. Meta-analysis: The effects of smoking on the disposition of two commonly used antipsychotic agents, olanzapine and clozapine. BMJ Open 2014; 4: e004216
    CrossrefPubMedGoogle Scholar
  • 14 Racagni G, Riva M, Molteni R. et al. Mode of action of agomelatine: Synergy between melatonergic and 5-HT2C receptors. World J Biol Psychiatry 2011; 12: 574-587
    CrossrefPubMedGoogle Scholar
  • 15 Owen RT. Agomelatine: A novel pharmacological approach to treating depression. Drugs Today (Barc) 2009; 45: 599-608
    CrossrefPubMedGoogle Scholar
  • 16 Englisch S, Jung HS, Lewien A. et al. Agomelatine for the treatment of major depressive episodes in schizophrenia-spectrum disorders: An open-prospective proof-of-concept study. J Clin Psychopharmacol 2016; 36: 597-607
    CrossrefPubMedGoogle Scholar
  • 17 Addington D, Addington J, Schissel B. A depression rating scale for schizophrenics. Schizophr Res 1990; 3: 247-251
    CrossrefPubMedGoogle Scholar
  • 18 Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry 1960; 23: 56-62
    CrossrefPubMedGoogle Scholar
  • 19 Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 1987; 13: 261-276
    CrossrefPubMedGoogle Scholar
  • 20 Gahr M, Freudenmann RW, Connemann BJ. et al. Agomelatine and hepatotoxicity: Implications of cumulated data derived from spontaneous reports of adverse drug reactions. Pharmacopsychiatry 2013; 46: 214-220
    Article in Thieme ConnectPubMedGoogle Scholar
  • 21 Gahr M, Kratzer W, Fuchs M. et al. Safety and tolerability of agomelatine: Focus on hepatotoxicity. Curr Drug Metab 2014; 15: 694-702
    PubMedGoogle Scholar
  • 22 Landi MT, Sinha R, Lang NP. et al. Human cytochrome P4501A2. IARC Sci Publ 1999; 148: 173-195
    PubMedGoogle Scholar
  • 23 Kennedy SH, Eisfeld BS. Agomelatine and its therapeutic potential in the depressed patient. Neuropsychiatr Dis Treat 2007; 3: 423-428
    PubMedGoogle Scholar
  • 24 Bogaards J, Hissink EM, Briggs M. et al. Prediction of interindividual variation in drug plasma levels in vivo from individual enzyme kinetic data and physiologically based pharmacokinetic modeling. Eur J Pharm Sci 2000; 12: 117-124
    CrossrefPubMedGoogle Scholar
  • 25 www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/00915/WC500046227pdf
    PubMed
  • 26 Eser D, Baghai TC, Möller HJ. Agomelatine: The evidence for its place in the treatment of depression. Core Evid 2010; 4: 171-179
    PubMedGoogle Scholar
  • 27 Ostad Haji E, Hiemke C, Pfuhlmann B. Therapeutic drug monitoring for antidepressant drug treatment. Curr Pharm Des 2012; 18: 5818-5827
    CrossrefPubMedGoogle Scholar
  • 28 Lobo ED, Quinlan T, O’Brien L. et al. Population pharmacokinetics of orally administered duloxetine in patients: Implications for dosing recommendation. Clin Pharmacokinet 2009; 48: 189-197
    CrossrefPubMedGoogle Scholar
  • 29 Buoli M, Mauri MC, Altamura AC. Pharmacokinetic evaluation of agomelatine for the treatment of generalised anxiety disorder. Expert Opin Drug Metab Toxicol 2014; 10: 885-892
    CrossrefPubMedGoogle Scholar
  • 30 De Berardis D, Fornaro M, Serroni N. et al. Agomelatine beyond borders: Current evidences of its efficacy in disorders other than major depression. Int J Mol Sci 2015; 16: 1111-1130
    CrossrefPubMedGoogle Scholar
  • 31 Gillette MU, Tischkau SA. Suprachiasmatic nucleus: The brain's circadian clock. Recent Prog Horm Res 1999; 54: 33-58
    PubMedGoogle Scholar
  • 32 Vazquez-Palacios G, Bonilla-Jaime H, Velazquez-Moctezuma J. Antidepressant effects of nicotine and fluoxetine in an animal model of depression induced by neonatal treatment with clomipramine. Prog Neuropsychopharmacol Biol Psychiatry 2005; 29: 39-46
    CrossrefPubMedGoogle Scholar
  • 33 Covey LS, Glassman AH, Stetner F. Cigarette smoking and major depression. J Addict Dis 1998; 17: 35-46
    PubMedGoogle Scholar
  • 34 Leucht S, Corves C, Arbter D. et al. Second-generation versus first-generation antipsychotic drugs for schizophrenia: A meta-analysis. Lancet 2009; 373: 31-41
    CrossrefPubMedGoogle Scholar
  • 35 Hasan A, Falkai P, Wobrock T. et al. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of schizophrenia, part 2: Update 2012 on the long-term treatment of schizophrenia and management of antipsychotic-induced side effects. World J Biol Psychiatr 2013; 14: 2-44
    CrossrefPubMedGoogle Scholar
  • 36 Hieronymus F, Nilsson S, Eriksson E. A mega-analysis of fixed-dose trials reveals dose-dependency and a rapid onset of action for the antidepressant effect of three selective serotonin reuptake inhibitors. Transl Psychiatry 2016; 6: e834
    CrossrefPubMedGoogle Scholar