The effect of variable cigarette consumption on the interaction with clozapine and olanzapine
Abstract
Objective Cigarette smoking has been shown in several studies to induce the metabolism of the cytochrome P4501A2 (CYP1A2) substrates clozapine and olanzapine. The aim of the present study was to investigate the dose-dependent effect of cigarette smoking on serum concentrations of these drugs in a naturalistic setting.Methods In 73 schizophrenic patients recruited from psychiatric nursing homes, patient characteristics, smoking habits, drug dosing and serum concentrations of clozapine (n=33) and olanzapine (n=40) were registered. Concentration to dose (C/D) ratios of clozapine and olanzapine in non-smokers and subgroups of smokers were compared.Results Fifty-nine patients (80%) were smokers and these were stratified into the following groups according to smoking habits: 1-6 (n=0), 7-12 (n=13), 13-19 (n=18) and >or=20 (n=28) cigarettes daily. While the mean ratio was twice as high in non-smokers compared to smokers for both drugs (p<0.01), the C/D ratios of clozapine and olanzapine were not significantly different between the subgroups of smokers (p >0.15). Absolute serum concentrations were also higher in non-smokers compared to smokers: 50% for clozapine (p=0.058) and 67% for olanzapine (p<0.01).Conclusion A daily consumption of 7-12 cigarettes is probably sufficient for maximum induction of clozapine and olanzapine metabolism. A 50% lower starting dose of both drugs in non-smokers seems rational to avoid side effects.
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For olanzapine and clozapine, a 50% higher dosage might be required in smokers with bipolar disorder.
“Dose adaption or even a change of medication might be indicated in smokers with BD, i.e., for olanzapine and clozapine a 50% higher dosage might be required (65).”
From The detrimental effects of smoking on the course and outcome in adults with bipolar disorder—A narrative review (2023) · cites this paper as [65]
Cites
Clozapine for the Treatment-Resistant Schizophrenic: A Double-blind Comparison With Chlorpromazine
Kane, J. (1988) · Archives of General Psychiatry · doi:10.1001/archpsyc.1988.01800330013001 · Cited by 4,156 · see citing works
de Leon, J., & Diaz, F. J. (2005) · Schizophrenia Research · doi:10.1016/j.schres.2005.02.010 · Cited by 1,276 · see citing works
Sex Differences in the Risk of Schizophrenia: Evidence From Meta-analysis
Aleman, A., Kahn, R. S., & Selten, J.-P. (2003) · Archives of General Psychiatry · doi:10.1001/archpsyc.60.6.565 · Cited by 818 · see citing works
Sachse, C., Brockmöller, J., Bauer, S., & Roots, I. (1999) · British Journal of Clinical Pharmacology · doi:10.1046/j.1365-2125.1999.00898.x · Cited by 751 · see citing works
Callaghan, J. T., Bergstrom, R. F., Ptak, L. R., & Beasley, C. M. (1999) · Clinical Pharmacokinetics · doi:10.2165/00003088-199937030-00001 · Cited by 544 · see citing works
Tohen, M. F., Greil, W., Calabrese, J. R., Sachs, G. S., Yatham, L. N., Müller-Oerlinghausen, B., Koukopoulos, A., Cassano, G. B., Grunze, H., Licht, R. W., et al. (2005) · American Journal of Psychiatry · doi:10.1176/appi.ajp.162.7.1281 · Cited by 365 · see citing works
Lohr, J. B., & FLYNN, K. (1992) · Schizophrenia Research · doi:10.1016/0920-9964(92)90024-y · Cited by 340 · see citing works
Rostami‐Hodjegan, A., Amin, A. M., Spencer, E. P., Lennard, M. S., Tucker, G. T., & Flanagan, R. J. (2004) · Journal of Clinical Psychopharmacology · doi:10.1097/01.jcp.0000106221.36344.4d · Cited by 279 · see citing works
Plasma clozapine concentrations predict clinical response in treatment-resistant schizophrenia.
Potkin, S. G., Bera, R., Gulasekaram, B., Costa, J., Hayes, S., Jin, Y., Richmond, G., Carreon, D., Sitanggan, K., & Gerber, B. (1994) · PubMed · Cited by 206 · see citing works
Carrillo, J. A., Herráiz, A. G., Ramos, S., Gervasini, G., Vizcaíno, S., & Benítez, J. (2003) · Journal of Clinical Psychopharmacology · doi:10.1097/00004714-200304000-00003 · Cited by 177 · see citing works
van der Weide, J., Steijns, L. S. W., & van Weelden, M. J. M. (2003) · Pharmacogenetics · doi:10.1097/00008571-200303000-00006 · Cited by 176 · see citing works
Gex‐Fabry, M., Balant-Gorgia, A. E., & Balant, L. P. (2003) · Therapeutic Drug Monitoring · doi:10.1097/00007691-200302000-00007 · Cited by 167 · see citing works
Olesen, O. V., & Línnet, K. (2001) · The Journal of Clinical Pharmacology · doi:10.1177/00912700122010717 · Cited by 158 · see citing works
Tobacco and cannabis smoking cessation can lead to intoxication with clozapine or olanzapine
ZULLINO, D. F., Delessert, D., Eap, C. B., Preisig, M., & Baumann, P. (2002) · International Clinical Psychopharmacology · doi:10.1097/00004850-200205000-00008 · Cited by 149 · see citing works
Individual Changes in Clozapine Levels After Smoking Cessation: Results and a Predictive Model
Meyer, J. M. (2001) · Journal of Clinical Psychopharmacology · doi:10.1097/00004714-200112000-00005 · Cited by 121 · see citing works
Skogh, E., Reis, M., Dahl, M., Lundmark, J., & Bengtsson, F. (2002) · Therapeutic Drug Monitoring · doi:10.1097/00007691-200208000-00010 · Cited by 114 · see citing works
Bondolfi, G., Morel, F., Crettol, S., Rachid, F., Baumann, P., & Eap, C. B. (2005) · Therapeutic Drug Monitoring · doi:10.1097/01.ftd.0000164609.14808.93 · Cited by 94 · see citing works
Clozapine Serum Concentrations are Lower in Smoking than in Non‐Smoking Schizophrenic Patients
Seppälä, N., Leinonen, E. V. J., Lehtonen, M., et al. (1999) · Pharmacology & Toxicology · doi:10.1111/j.1600-0773.1999.tb02016.x · Cited by 92 · see citing works
Examining Concentration-Dependent Toxicity of Clozapine: Role of Therapeutic Drug Monitoring
Khan, A. Y., & Preskorn, S. (2005) · Journal of Psychiatric Practice · doi:10.1097/00131746-200509000-00003 · Cited by 90 · see citing works
Relationship between patient variables and plasma clozapine concentrations: a dosing nomogram
Perry, P. J., Bever, K. A., Arndt, S. V., et al. (1998) · Biological Psychiatry · doi:10.1016/s0006-3223(97)00531-3 · Cited by 86 · see citing works
Effects of Age and Sex on Olanzapine Plasma Concentrations
Weiss, U., Marksteiner, J., Kemmler, G., Saria, A., & Aichhorn, W. (2005) · Journal of Clinical Psychopharmacology · doi:10.1097/01.jcp.0000185427.08268.db · Cited by 73 · see citing works
Raaska, K., Raitasuo, V., Laitila, J., & Neuvonen, P. J. (2004) · Pharmacology & Toxicology · doi:10.1111/j.1742-7843.2004.pto940104.x · Cited by 57 · see citing works
The Association of Weight Gain and Olanzapine Plasma Concentrations
Perry, P. J., Argo, T. R., Carnahan, R. M., Lund, B. C., Holman, T. L., Ellingrod, V. L., & Miller, D. D. (2005) · Journal of Clinical Psychopharmacology · doi:10.1097/01.jcp.0000162800.64378.82 · Cited by 55 · see citing works
Tyson, P. J., Roberts, K., & Mortimer, A. M. (2004) · International Journal of Neuroscience · doi:10.1080/00207450490430552 · Cited by 45 · see citing works
Therapeutic Monitoring of Psychotropic Drugs
Baumann, P., Hiemke, C., Ulrich, S., Gaertner, I., Rao, M. L., Eckermann, G., Gerlach, M., Kuss, H., Laux, G., Müller-Oerlinghausen, B., et al. (2004) · Therapeutic Drug Monitoring · doi:10.1097/00007691-200404000-00014 · Cited by 43 · see citing works
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Heffner, J. L., Strawn, J. R., DelBello, M. P., Strakowski, S. M., & Anthenelli, R. M. (2011) · Bipolar Disorders · doi:10.1111/j.1399-5618.2011.00943.x · Cited by 148 · see citing works
Rüther, T., Bobes, J., De Hert, M., Svensson, T. H., Mann, K., Batra, A., Gorwood, P., & Möller, H. J. (2014) · European Psychiatry · doi:10.1016/j.eurpsy.2013.11.002 · Cited by 149 · see citing works
Clinically Significant Drug Interactions with Atypical Antipsychotics
Kennedy, W. K., Jann, M. W., & Kutscher, E. C. (2013) · CNS Drugs · doi:10.1007/s40263-013-0114-6 · Cited by 95 · see citing works
Fornaro, M., Carvalho, A. F., De Prisco, M., Mondin, A. M., Billeci, M., Selby, P., Iasevoli, F., Berk, M., Castle, D. J., & de Bartolomeis, A. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.11.039 · Cited by 82 · see citing works
Tobacco use in bipolar disorder
Thomson, D., Berk, M., Dodd, S., Rapado-Castro, M., Quirk, S. E., Ellegaard, P. K., Berk, L., & Dean, O. M. (2015) · Clinical Psychopharmacology and Neuroscience · doi:10.9758/cpn.2015.13.1.1 · Cited by 63 · see citing works
Grunze, A., Mosolov, S., Grunze, H., & Born, C. (2023) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.1114432 · Cited by 11 · see citing works
- Authors
- Haslemo, T., Eikeseth, P. H., Tanum, L., Molden, E., & Refsum, H.
- Affiliations
- Diakonhjemmet Hospital (NO)
- Lovisenberg Diakonale Sykehus (NO)
- Corresponding author
- Haslemo, Tore
- Venue
- European Journal of Clinical Pharmacology
- Published
- 2006-11-07
- Volume
- 62
- Issue
- 12
- Pages
- 1049-1053
- ISSN
- 0031-6970 (ISSN-L)
- 1432-1041
- OpenAlex
- W1968322454
- Cited by
- 178
- References
- 25
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 8 · 2023: 15 · 2022: 7 · 2021: 13 · 2020: 15 · 2019: 10 · 2018: 4 · 2017: 5 · 2016: 9 · 2015: 10 · 2014: 8 · 2013: 10 · 2012: 10
- FWCI
- 7.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- European Journal of Clinical Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- cigarette smoking, clozapine, olanzapine, CYP1A2 induction, drug metabolism, dose-dependent effects, concentration-to-dose ratio, serum drug concentration, schizophrenia, antipsychotic dosing, psychiatric nursing homes
- MeSH terms
- Olanzapine, Adult, Aged, Benzodiazepines, Chromatography, High Pressure Liquid, Clozapine, Dose-Response Relationship, Drug, Drug Interactions, Female, Humans, Inpatients, Male, Metabolic Clearance Rate, Middle Aged, Nursing Homes, Schizophrenia, Smoking, Mass Spectrometry, Antipsychotic Agents, Drug Monitoring, Cytochrome P-450 CYP1A2
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