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Meta-Analysis
. 2014 Mar 4;4(3):e004216.
doi: 10.1136/bmjopen-2013-004216.

Meta-analysis: the effects of smoking on the disposition of two commonly used antipsychotic agents, olanzapine and clozapine

Yoshiyuki Tsuda  1 , Junji Saruwatari, Norio Yasui-Furukori
Affiliations
Meta-Analysis

Meta-analysis: the effects of smoking on the disposition of two commonly used antipsychotic agents, olanzapine and clozapine

Yoshiyuki Tsuda et al. BMJ Open. .

Abstract

Objective: To clarify the effects of smoking on the disposition of two commonly used antipsychotics, olanzapine and clozapine, and to create standards to adjust the doses of these drugs in clinical practice based on the smoking status.

Design: A meta-analysis was conducted by searching MEDLINE, Scopus and the Cochrane Library for relevant prospective and retrospective studies.

Included studies: We included the studies that investigated the effects of smoking on the concentration to dose (C/D) ratio of olanzapine or clozapine.

Primary outcome measure: The weighted mean difference was calculated using a DerSimonian-Laird random effects model, along with 95% CI.

Results: Seven association studies, comprising 1094 patients (652 smokers and 442 non-smokers) with schizophrenia or other psychiatric disorders, were included in the meta-analysis of olanzapine. The C/D ratio was significantly lower in smokers than in non-smokers (p<0.00001), and the mean difference was -0.75 (ng/mL)/(mg/day) (95% CI -0.89 to -0.61). Therefore, it was estimated that if 10 and 20 mg/day of olanzapine would be administered to smokers, about 7 and 14 mg/day, respectively, should be administered to non-smokers in order to obtain the equivalent olanzapine concentration. Four association studies of clozapine were included in the meta-analysis of clozapine, comprising 196 patients (120 smokers and 76 non-smokers) with schizophrenia or other psychiatric disorders. The C/D ratio was significantly lower in smokers than in non-smokers (p<0.00001), and the mean difference was -1.11 (ng/mL)/(mg/day) (95% CI -1.53 to -0.70). Therefore, it was estimated that if 200 and 400 mg/day of clozapine would be administered to smokers, about 100 and 200 mg/day, respectively, should be administered to non-smokers.

Conclusions: We suggest that the doses of olanzapine and clozapine should be reduced by 30% and 50%, respectively, in non-smokers compared with smokers in order to obtain an equivalent olanzapine or clozapine concentration.

Keywords: Mental Health.

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Figures

Figure 1
Figure 1
A flow chart of the study selection process. C/D, concentration to dose.
Figure 2
Figure 2
Forest plot olanzapine (n=8).
Figure 3
Figure 3
Forest plot (A) olanzapine study (n=7) (B) prospective olanzapine study (n=3) (C) retrospective olanzapine study (n=4).
Figure 4
Figure 4
Forest plot clozapine (n=4).
See this image and copyright information in PMC

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References

    1. Mauri MC, Volonteri LS, Colasanti A, et al. Clinical pharmacokinetics of atypical antipsychotics: a critical review of the relationship between plasma concentrations and clinical response. Clin Pharmacokinet 2007;46:359–88 - PubMed
    1. Bishara D, Olofinjana O, Sparshatt A, et al. Olanzapine: a systematic review and meta-regression of the relationships between dose, plasma concentration, receptor occupancy, and response. J Clin Psychopharmacol 2013;33:329–35 - PubMed
    1. Si TM, Zhang YS, Shu L, et al. Use of clozapine for the treatment of schizophrenia: findings of the 2006 research on the china psychotropic prescription studies. Clin Psychopharmacol Neurosci 2012;10:99–104 - PMC - PubMed
    1. Bersani FS, Capra E, Minichino A, et al. Factors affecting interindividual differences in clozapine response: a review and case report. Hum Psychopharmacol 2011;26:177–87 - PubMed
    1. Morisano D, Wing VC, Sacco KA, et al. Effects of tobacco smoking on neuropsychological function in schizophrenia in comparison to other psychiatric disorders and non-psychiatric controls. Am J Addict 2013;22:46–53 - PubMed

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