Pharmacopsychiatry 2019; 52(02): 107
DOI: 10.1055/s-0039-1679178
P6 Therapeutic drug monitoring
Georg Thieme Verlag KG Stuttgart · New York

The clinical relevance of the pharmacological interaction between clozapine and sertraline

M Kuzin
1   Department of Psychiatry, Psychotherapy and Psychosomatics, JARA Translational Brain Medicine, RWTH Aachen University, Aachen, Germany
,
G Schoretsanitis
1   Department of Psychiatry, Psychotherapy and Psychosomatics, JARA Translational Brain Medicine, RWTH Aachen University, Aachen, Germany
,
E Haen
1   Department of Psychiatry, Psychotherapy and Psychosomatics, JARA Translational Brain Medicine, RWTH Aachen University, Aachen, Germany
,
C Hiemke
1   Department of Psychiatry, Psychotherapy and Psychosomatics, JARA Translational Brain Medicine, RWTH Aachen University, Aachen, Germany
,
G Gründer
1   Department of Psychiatry, Psychotherapy and Psychosomatics, JARA Translational Brain Medicine, RWTH Aachen University, Aachen, Germany
,
M Paulzen
1   Department of Psychiatry, Psychotherapy and Psychosomatics, JARA Translational Brain Medicine, RWTH Aachen University, Aachen, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
21 February 2019 (online)

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    Introduction:

    Clozapine (CLZ) is an atypical antipsychotic with particular indication for the treatment of treatment-resistant schizophrenia patients. Clozapine is often combined with other psychotropic agents in clinical routine. For example, for post-psychotic depression the prescription of antidepressants such as selective serotonin reuptake inhibitors including sertraline (SER) is recommended.

    Nevertheless, polypharmacy, i.e. combination of multiple medications, may increase the risk of the drug-drug interactions. In case of clozapine, pharmacokinetic interactions may be mediated by effects on the cytochrome P450 (CYP) 1A2, as well as 2C19, 3A4 and 2D6, which are predominantly involved in the oxidative metabolism of CLZ. The available data on the potential interaction between SER and CLZ is based on a few studies and case reports and shows a possible significant increase of CLZ and N-desmethylclozapine. The aim of this study was to evaluate pharmacokinetic interactions between SER and CLZ using therapeutic drug monitoring (TDM).

    Methods:

    A large TDM database with plasma concentrations of CLZ (n = 1644) was analyzed. The sample was divided into four groups: non-smokers (n = 250) and smokers (n = 326) under clozapine monotherapy, non-smokers (n = 18) and smokers (n = 17) co-medicated with sertraline. Due to non-normal distribution of data, a non-parametrical Mann Whitney U test (M-W-U) with a significance level of 0.05 was applied.

    Results:

    Smokers receiving co-medication had higher BMI values than monotherapy smokers (30.79 (SD = 5.49) vs. 27.83 (SD = 5.6), p = 0.044 for M-W-U). Regarding pharmacokinetic parameters, no significant differences were reported between study groups (p > 0.05 for M-W-U in all cases).

    Conclusion:

    Previously reported weak inhibiting effects of sertraline on CYP2D6 activity seem to be of minor clinical importance when clozapine is concomitantly applied. However, potentially inhibiting effects of sertraline on distinct cytochrome CYP P450 isoenzymes have to be taken into account, whenever combined treatment strategies are applied. Therapeutic drug monitoring helps to uncover pharmacokinetic interactions.


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