Olanzapine/fluoxetine: a Review of Its Use in Patients with Treatment-resistant Major Depressive Disorder

Overview

Journal CNS Drugs

Specialties Neurology
Pharmacology

Date 2010 Feb 17

PMID 20155998

Citations 8

Authors

Jamie D Croxtall

Lesley J Scott

Affiliations

Soon will be listed here.

Abstract

Olanzapine/fluoxetine (Symbyax) is an oral, once-daily, fixed-dose combination of the atypical antipsychotic olanzapine and the selective serotonin reuptake inhibitor (SSRI) fluoxetine. It is indicated, in adult patients, for the acute treatment of depressive episodes associated with bipolar I disorder and treatment-resistant major depressive disorder. In adult patients with treatment-resistant depression (major depressive disorder in adults who do not respond to two separate trials of different antidepressants of adequate dose and duration in the current episode), olanzapine plus fluoxetine combination therapy was generally more effective than either drug as monotherapy based on an integrated analysis of clinical trials of 8-12 weeks' duration. More limited data also indicate that longer-term treatment for 76 weeks with olanzapine plus fluoxetine was efficacious in this patient group. Combination therapy was generally well tolerated, with a tolerability profile similar to that of olanzapine monotherapy, although fluoxetine monotherapy was generally better tolerated than olanzapine plus fluoxetine. The combination of olanzapine plus fluoxetine, as a fixed-dose formulation, offers a useful treatment option in this difficult-to-treat patient group.

Citing Articles

A Scientometrics Analysis and Visualization of Depressive Disorder.

Xu D, Wang Y, Wang K, Wang Y, Dong X, Tang J Curr Neuropharmacol. 2020; 19(6):766-786.

PMID: 32888272 PMC: 8686305. DOI: 10.2174/1570159X18666200905151333.

Melatonin Augments the Effects of Fluoxetine on Depression-Like Behavior and Hippocampal BDNF-TrkB Signaling.

Li K, Shen S, Ji Y, Li X, Zhang L, Wang X Neurosci Bull. 2017; 34(2):303-311.

PMID: 29086908 PMC: 5856716. DOI: 10.1007/s12264-017-0189-z.

Aripiprazole: from pharmacological profile to clinical use.

Di Sciascio G, Riva M Neuropsychiatr Dis Treat. 2015; 11:2635-47.

PMID: 26508859 PMC: 4610784. DOI: 10.2147/NDT.S88117.

Effects of chronic electroacupuncture on depression- and anxiety-like behaviors in rats with chronic neuropathic pain.

Li Q, Yue N, Liu S, Wang Z, Mi W, Jiang J Evid Based Complement Alternat Med. 2014; 2014:158987.

PMID: 24795763 PMC: 3984799. DOI: 10.1155/2014/158987.

Clinical issues in use of atypical antipsychotics for depressed patients.

Pae C, Patkar A CNS Drugs. 2013; 27 Suppl 1:S39-45.

PMID: 23709360 DOI: 10.1007/s40263-012-0032-z.

References

Ordway G, Szebeni K . Effect of repeated treatment with olanzapine or olanzapine plus fluoxetine on tyrosine hydroxylase in the rat locus coeruleus. Int J Neuropsychopharmacol. 2004; 7(3):321-7. DOI: 10.1017/S1461145704004468. View

Callaghan J, Bergstrom R, Ptak L, Beasley C . Olanzapine. Pharmacokinetic and pharmacodynamic profile. Clin Pharmacokinet. 1999; 37(3):177-93. DOI: 10.2165/00003088-199937030-00001. View

Cheer S, Goa K . Fluoxetine: a review of its therapeutic potential in the treatment of depression associated with physical illness. Drugs. 2001; 61(1):81-110. DOI: 10.2165/00003495-200161010-00010. View

Corya S, Williamson D, Sanger T, Briggs S, Case M, Tollefson G . A randomized, double-blind comparison of olanzapine/fluoxetine combination, olanzapine, fluoxetine, and venlafaxine in treatment-resistant depression. Depress Anxiety. 2006; 23(6):364-72. DOI: 10.1002/da.20130. View

Schenker S, Bergstrom R, Wolen R, Lemberger L . Fluoxetine disposition and elimination in cirrhosis. Clin Pharmacol Ther. 1988; 44(3):353-9. DOI: 10.1038/clpt.1988.161. View

Gossen D, Vandenhende F, Onkelinx C, Gangji D . Influence of fluoxetine on olanzapine pharmacokinetics. AAPS PharmSci. 2002; 4(2):E11. PMC: 2751291. DOI: 10.1208/ps040211. View

Melkersson K, Dahl M . Adverse metabolic effects associated with atypical antipsychotics: literature review and clinical implications. Drugs. 2004; 64(7):701-23. DOI: 10.2165/00003495-200464070-00003. View

Bergemann N, Frick A, Parzer P, Kopitz J . Olanzapine plasma concentration, average daily dose, and interaction with co-medication in schizophrenic patients. Pharmacopsychiatry. 2004; 37(2):63-8. DOI: 10.1055/s-2004-815527. View

Maragnoli M, Fumagalli F, Gennarelli M, Racagni G, Riva M . Fluoxetine and olanzapine have synergistic effects in the modulation of fibroblast growth factor 2 expression within the rat brain. Biol Psychiatry. 2004; 55(11):1095-102. DOI: 10.1016/j.biopsych.2004.02.003. View

10.

Rush A, Trivedi M, Wisniewski S, Nierenberg A, Stewart J, Warden D . Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006; 163(11):1905-17. DOI: 10.1176/ajp.2006.163.11.1905. View

11.

Harvey A, Preskorn S . Fluoxetine pharmacokinetics and effect on CYP2C19 in young and elderly volunteers. J Clin Psychopharmacol. 2001; 21(2):161-6. DOI: 10.1097/00004714-200104000-00007. View

12.

Bobo W, Shelton R . Fluoxetine and olanzapine combination therapy in treatment-resistant major depression: review of efficacy and safety data. Expert Opin Pharmacother. 2009; 10(13):2145-59. DOI: 10.1517/14656560903130609. View

13.

Kassahun K, Mattiuz E, Nyhart Jr E, Obermeyer B, Gillespie T, Murphy A . Disposition and biotransformation of the antipsychotic agent olanzapine in humans. Drug Metab Dispos. 1997; 25(1):81-93. View

14.

Dodd S, Berk M . Olanzapine/fluoxetine combination for treatment-resistant depression: efficacy and clinical utility. Expert Rev Neurother. 2008; 8(9):1299-306. DOI: 10.1586/14737175.8.9.1299. View

15.

Corya S, Andersen S, Detke H, Kelly L, Van Campen L, Sanger T . Long-term antidepressant efficacy and safety of olanzapine/fluoxetine combination: a 76-week open-label study. J Clin Psychiatry. 2003; 64(11):1349-56. DOI: 10.4088/jcp.v64n1111. View

16.

Shelton R, Williamson D, Corya S, Sanger T, Van Campen L, Case M . Olanzapine/fluoxetine combination for treatment-resistant depression: a controlled study of SSRI and nortriptyline resistance. J Clin Psychiatry. 2005; 66(10):1289-97. DOI: 10.4088/jcp.v66n1012. View

17.

DeBattista C, Hawkins J . Utility of atypical antipsychotics in the treatment of resistant unipolar depression. CNS Drugs. 2009; 23(5):369-77. DOI: 10.2165/00023210-200923050-00002. View

18.

Thase M, Corya S, Osuntokun O, Case M, Henley D, Sanger T . A randomized, double-blind comparison of olanzapine/fluoxetine combination, olanzapine, and fluoxetine in treatment-resistant major depressive disorder. J Clin Psychiatry. 2007; 68(2):224-36. DOI: 10.4088/jcp.v68n0207. View

19.

Thase M . What role do atypical antipsychotic drugs have in treatment-resistant depression?. J Clin Psychiatry. 2002; 63(2):95-103. DOI: 10.4088/jcp.v63n0202. View

20.

Shelton R, Tollefson G, Tohen M, Stahl S, Gannon K, Jacobs T . A novel augmentation strategy for treating resistant major depression. Am J Psychiatry. 2001; 158(1):131-4. DOI: 10.1176/appi.ajp.158.1.131. View