Skip to main content
SpringerLink
Log in

Olanzapine/Fluoxetine

A Review of its Use in the Treatment of Acute Bipolar Depression

  • Adis Drug Evaluation
  • Published:
Drugs Aims and scope Submit manuscript

Summary

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 that is approved in the US for the treatment of depressive episodes associated with bipolar disorder in adults. Combination therapy with olanzapine plus fluoxetine is effective in the treatment of patients with acute bipolar depression. The combination improves depressive symptoms and symptom severity in this patient population, with an efficacy greater than that of olanzapine alone or lamotrigine. Furthermore, olanzapine plus fluoxetine is generally well tolerated. Although associated with weight gain and potential elevations in glucose, lipid and prolactin levels, the combination does not increase the risk of treatment-emergent mania. Additional placebo- and active comparator-controlled studies are required in order to confirm the efficacy of olanzapine/ fluoxetine in the treatment of bipolar depression and to definitively position olanzapine/fluoxetine with respect to other agents. In the meantime, fixed-dose olanzapine/fluoxetine offers an effective and generally well tolerated first-line option for the treatment of acute bipolar depression.

Pharmacological Properties

Olanzapine is an atypical antipsychotic agent that binds to a variety of neurotransmitter receptors, including serotonin and dopamine receptors. It has been suggested that the antidepressant activity of the drug may be linked to antagonism and down-regulation of serotonin 5-HT2A receptors. Fluoxetine is a potent SSRI that inhibits dopamine and noradrenaline (norepinephrine) transporters only weakly. The drug enhances serotonergic neurotransmission, which may, in part, mediate its antidepressant effects. However, the exact mechanism(s) of action responsible for the clinical benefits of olanzapine plus fluoxetine combination therapy in patients with bipolar depression is unclear at present, although it has been proposed to involve the activation of serotonin, dopamine and noradrenaline neural systems. In addition, preclinical data suggest the agents in combination may be more effective than the individual agents in upregulating dopamine and noradrenaline levels and fibroblast growth factor-2 expression in the brain.

Coadministration of olanzapine and fluoxetine has no clinically relevant effects on the pharmacokinetic profile of olanzapine. Both olanzapine and fluoxetine are well absorbed following oral administration, reaching maximum plasma concentrations approximately 4 and 6 hours after a fixed oral dose of olanzapine/ fluoxetine 12 mg/50 mg. The agents are extensively metabolized in the liver; olanzapine predominantly via cytochrome P450 (CYP) 1A2 and the flavincontaining mono-oxygenase system, and fluoxetine via CYP2D6 and CYP2C. Olanzapine/fluoxetine dosage adjustments are recommended in patients with hepatic impairment and in those who have a combination of factors that may affect olanzapine or fluoxetine metabolism; caution is advised in elderly patients. Several pharmacokinetic drug interactions have been shown to occur between both olanzapine and fluoxetine and some drugs that are either substrates and/or inducers/inhibitors of CYP isoenzymes; dosage adjustments may be required in some cases. Furthermore, the concomitant use of olanzapine/fluoxetine with certain drugs is contraindicated (e.g. monoamine oxidase inhibitors or pimozide), not recommended (e.g. some other serotonergic drugs, such as SSRIs) or requires caution owing to several potential pharmacodynamic interactions.

Therapeutic Efficacy

The efficacy of olanzapine plus fluoxetine combination therapy in adult patients with bipolar I depression has been demonstrated in two randomized, double-blind, multicentre, flexible-dose trials of 7 or 8 weeks’ duration.

In the 8-week study, olanzapine used in combination with fluoxetine improved symptoms of depression (Montgomery-Åsberg Depression Rating Scale [MADRS] total score) and symptom severity (Clinical Global Impressions [CGI] Bipolar Version-Severity of Depression [CGI-BP-S] scale score) to a significantly greater extent than placebo, with rates of response and remission also being significantly higher with the combination therapy. Moreover, olanzapine plus fluoxetine produced significantly greater improvements than placebo in measures of both mania (Young Mania Rating Scale [YMRS]) and anxiety (Hamilton Anxiety Rating scale [HAM-A]).

Furthermore, data from the 7- and 8-week studies demonstrated that olanzapine plus fluoxetine was more effective than olanzapine alone or lamotrigine in improving depressive symptoms (MADRS total score) or symptom severity (CGI-Severity of Illness scale score or CGI-BP-S score) in patients with bipolar depression. Recipients of olanzapine plus fluoxetine also had rates of response and remission that were significantly higher than olanzapine monotherapy recipients and similar to those seen in lamotrigine recipients. There was no significant difference between olanzapine plus fluoxetine and olanzapine alone with regard to improvements on the YMRS or HAM-A scale, although improvements on the YMRS were significantly greater with the combination therapy than with lamotrigine. Olanzapine plus fluoxetine also appeared to be more effective than lamotrigine in reducing suicidal thoughts (MADRS item 10) in the 7-week trial.

In addition, olanzapine in combination with fluoxetine improved certain aspects of health-related quality of life (Medical Outcomes Study 36-Item Short-Form Health Survey and Quality of Life in Depression Scale) to a significantly greater extent than olanzapine alone and was superior to lamotrigine in improving functioning (Global Assessment of Functioning score) in patients with bipolar depression in these short-term trials.

Tolerability

Olanzapine plus fluoxetine was generally well tolerated in adult patients with bipolar I depression in clinical trials of up to 8 weeks’ duration. Compared with placebo, olanzapine plus fluoxetine was associated with a significantly higher incidence of weight gain, increased appetite, dry mouth, asthenia and diarrhoea. The tolerability profile of the combination was broadly similar to that of olanzapine monotherapy, although was less favourable than lamotrigine in terms of adverse events such as somnolence, increased appetite, dry mouth, weight gain, sedation and tremor. However, limited data suggest olanzapine plus fluoxetine may be associated with a lower incidence of suicidal and self-injurious behaviour than lamotrigine.

Olanzapine used in combination with fluoxetine was not associated with an increase in treatment-emergent mania compared with placebo, olanzapine alone or lamotrigine in these trials, and had a low incidence of extrapyramidal symptoms generally similar to that with placebo or olanzapine monotherapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Table I
Table II
Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Notes

  1. The use of trade names is for product identification purposes only and does not imply endorsement.

References

  1. World Health Organization. The world health report 2001 [online]. Available from URL: http://www.who.int/whr/2001/en/ whr01_en.pdf [Accessed 2007 Oct 16]

  2. Kessler RC, Berglund P, Dernier O, et al. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the national comorbidity survey replication [published erratum appears in Arch Gen Psychiatry 2005; 62 (7): 768]. Arch Gen Psychiatry 2005 Jun; 62(6): 593–602

    Article  PubMed  Google Scholar 

  3. Post RM. The impact of bipolar depression. J Clin Psychiatry 2005; 66 Suppl. 5: 5–10

    CAS  Google Scholar 

  4. Malhi GS, Mitchell PB, Salim S. Bipolar depression: management options. CNS Drugs 2003; 17(1): 9–25

    Article  PubMed  CAS  Google Scholar 

  5. Ketter TA, Nasrallah HA, Fagiolini A. Mood stabilizers and atypical antipsychotics: bimodal treatments for bipolar disorder. Psychopharmacol Bull 2006; 39(1): 120–46

    PubMed  Google Scholar 

  6. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed, text revision. Washington, DC: American Psychiatric Association, 2000: 345–428

    Google Scholar 

  7. McIntyre R, Katzman M. The role of atypical antipsychotics in bipolar depression and anxiety disorders. Bipolar Disord 2003; 5 Suppl. 2: 20–35

    Article  Google Scholar 

  8. Simpson SG, Jamison KR. The risk of suicide in patients with bipolar disorders. J Clin Psychiatry 1999; 60 Suppl. 2: 53–6

    Google Scholar 

  9. Calabrese JR, Hirschfeld RMA, Reed M, et al. Impact of bipolar disorder on a U.S. community sample. J Clin Psychiatry 2003 Apr; 64(4): 425–32

    Article  Google Scholar 

  10. Calabrese JR, Hirschfeld RMA, Frye MA, et al. Impact of depressive symptoms compared with manic symptoms in bipolar disorder: results of a U.S. community-based sample. J Clin Psychiatry 2004 Nov; 65(11): 1499–504

    Google Scholar 

  11. Judd LL, Akiskal HS, Schettler PJ, et al. A prospective investigation of the natural history of the long-term weekly symptomatic status of bipolar II disorder. Arch Gen Psychiatry 2003 Mar; 60: 261–9

    Article  PubMed  Google Scholar 

  12. Judd LL, Akiskal HS, Schettler PJ, et al. The long-term natural history of the weekly symptomatic status of bipolar I disorder. Arch Gen Psychiatry 2002 Jun; 59: 530–7

    Article  PubMed  Google Scholar 

  13. Thase ME. Pharmacotherapy of bipolar depression: an update. Curr Psychiatry Rep 2006 Dec; 8(6): 478–88

    Article  PubMed  Google Scholar 

  14. Möller HJ, Grunze H. Have some guidelines for the treatment of acute bipolar depression gone too far in the restriction of antidepressants? Eur Arch Psychiatry Clin Neurosci 2000; 250(2): 57–68

    Article  PubMed  Google Scholar 

  15. Fountoulakis KN, Grunze H, Panagiotidis P, et al. Treatment of bipolar depression: an update. J Affect Disord. Epub 2007 Nov

  16. Eli Lilly and Company. Symbyax® (olanzapine and fluoxetine HCL capsules): US prescribing information [online]. Available from URL: http://pi.lilly.com/us/symbyax-pi.pdf [Accessed 2007 Oct 17]

  17. FDA. Zyprexa® (olanzapine tablets): US prescribing information [online]. Available from URL: http://www.fda.gov/cder/ foi/label/2007/020592s042s043,021086s022s023,s026lbl021 253.pdf [Accessed 2007 Sep 27]

  18. Food and Drug Administration. Prozac® (fluoxetine capsules, USP; fluoxetine oral solution, USP; fluoxetine delayed-release capsules, USP): US prescribing information [online]. Available from URL: http://www.fda.gov/cder/foi/label/2008/0189 36s084,020101s039,021235s0111bl.pdf [Accessed 2008 Mar 31]

  19. Hurst M, Lamb HM. Fluoxetine: a review of its use in anxiety disorders and mixed anxiety and depression. CNS Drugs 2000; 14(1): 51–80

    Article  CAS  Google Scholar 

  20. Benfield P, Heel RC, Lewis SP. Fluoxetine: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in depressive illness. Drugs 1986; 32: 481–508

    Article  PubMed  CAS  Google Scholar 

  21. McCormack PL, Wiseman LR. Olanzapine: a review of its use in the management of bipolar I disorder. Drugs 2004; 64(23): 2709–26

    Article  PubMed  CAS  Google Scholar 

  22. Bhana N, Perry CM. Olanzapine: a review of its use in the treatment of bipolar I disorder. CNS Drugs 2001; 15(11): 871–904

    Article  PubMed  CAS  Google Scholar 

  23. Callaghan JT, Bergstrom RF, Ptak LR, et al. Olanzapine: pharmacokinetic and pharmacodynamic profile. Clin Pharmacokinet 1999 Sep; 37(3): 177–93

    Article  PubMed  CAS  Google Scholar 

  24. Tohen M, Vieta E, Calabrese J, et al. Efficacy of olanzapine and olanzapine-fluoxetine combination in the treatment of bipolar I depression. Arch Gen Psychiatry 2003 Nov; 60(11): 1079–88

    Article  PubMed  CAS  Google Scholar 

  25. Brown EB, McElroy SL, Keck Jr PE, et al. A 7-week, randomized, double-blind trial of olanzapine/fluoxetine combination versus lamotrigine in the treatment of bipolar I depression. J Clin Psychiatry 2006 Jul; 67(7): 1025–33

    Article  PubMed  CAS  Google Scholar 

  26. Richelson E. Receptor pharmacology of neuroleptics: relation to clinical effects. J Clin Psychiatry 1999; 60 Suppl. 10: 5–14

    Google Scholar 

  27. Kapur S, Zipursky RB, Remington G, et al. 5-HT2 and D2 receptor occupancy of olanzapine in schizophrenia: a PET investigation. Am J Psychiatry 1998 Jul; 155(7): 921–8

    PubMed  CAS  Google Scholar 

  28. Yatham LN, Goldstein JM, Vieta E, et al. Atypical antipsychotics in bipolar depression: potential mechanisms of action. J Clin Psychiatry 2005; 66 Suppl. 5: 40–8

    Google Scholar 

  29. Koch S, Perry KW, Bymaster FP. Brain region and dose effects of an olanzapine/fluoxetine combination on extracellular monoamine concentrations in the rat. Neuropharmacology 2004 Feb; 46(2): 232–42

    Article  PubMed  CAS  Google Scholar 

  30. Zhang W, Perry KW, Wong DT, et al. Synergistic effects of olanzapine and other antipsychotic agents in combination with fluoxetine on norepinephrine and dopamine release in rat prefrontal cortex. Neuropsychopharmacology 2000 Sep; 23(3): 250–62

    Article  PubMed  CAS  Google Scholar 

  31. Maragnoli ME, Fumagalli F, Gennarelli M, et al. Fluoxetine and olanzapine have synergistic effects in the modulation of fibroblast growth factor 2 expression within the rat brain. Biol Psychiatry 2004 Jun 1; 55(11): 1095–102

    Article  PubMed  CAS  Google Scholar 

  32. Charney DS. Monoamine dysfunction and the pathophysiology and treatment of depression. J Clin Psychiatry 1998; 59 Suppl. 14: 11–4

    Google Scholar 

  33. Nutt DJ. The role of dopamine and norepinephrine in depression and antidepressant treatment. J Clin Psychiatry 2006; 67 Suppl. 6: 3–8

    Google Scholar 

  34. Evans SJ, Choudary PV, Neal CR, et al. Dysregulation of the fibroblast growth factor system in major depression. Proc Natl Acad Sci U S A 2004 Oct 26; 101(43): 15506–11

    Article  PubMed  CAS  Google Scholar 

  35. Ordway GA, Szebeni K. Effect of repeated treatment with olanzapine or olanzapine plus fluoxetine on tyrosine hydroxylase in the rat locus coeruleus. Int J Neuropsychopharmacol 2004 Sep; 7(3): 321–7

    Article  PubMed  CAS  Google Scholar 

  36. Nestler EJ, McMahon A, Sabban EL, et al. Chronic antidepressant administration decreases the expression of tyrosine hydroxylase in the rat locus coeruleus. Proc Natl Acad Sci U S A 1990 Oct; 87: 7522–6

    Article  PubMed  CAS  Google Scholar 

  37. Vaidya VA, Duman RS. Depression: emerging insights from neurobiology. Br Med Bull 2001; 57: 61–79

    Article  PubMed  CAS  Google Scholar 

  38. Malberg JE. Implications of adult hippocampal neurogenesis in antidepressant action. J Psychiatry Neurosci 2004 May; 29(3): 196–205

    PubMed  Google Scholar 

  39. Kodama M, Fujioka T, Duman RS. Chronic olanzapine or fluoxetine administration increases cell proliferation in hippocampus and prefrontal cortex of adult rat. Biol Psychiatry 2004 Oct 15; 56(8): 570–80

    Article  PubMed  CAS  Google Scholar 

  40. Marx CE, Shampine LJ, Khisti RT, et al. Olanzapine and fluoxetine administration and coadministration increase rat hippocampal pregnenolone, allopregnanolone and peripheral deoxycorticosterone: implications for therapeutic actions. Pharmacol Biochem Behav 2006 Aug; 84(4): 609–17

    Article  PubMed  CAS  Google Scholar 

  41. Horowitz JM, Goyal A, Ramdeen N, et al. Characterization of fluoxetine plus olanzapine treatment in rats: a behavior, endocrine, and immediate-early gene expression analysis. Synapse 2003 Dec 15; 50(4): 353–64

    Article  PubMed  CAS  Google Scholar 

  42. Gronier BS, Rasmussen K. Electrophysiological effects of acute and chronic olanzapine and fluoxetine in the rat prefrontal cortex. Neurosci Lett 2003 Oct 9; 349(3): 196–200

    Article  PubMed  CAS  Google Scholar 

  43. Seager MA, Huff KD, Barth VN, et al. Fluoxetine administration potentiates the effect of olanzapine on locus coeruleus neuronal activity. Biol Psychiatry 2004 Jun 1; 55(11): 1103–9

    Article  PubMed  CAS  Google Scholar 

  44. Seager MA, Barth VN, Phebus LA, et al. Chronic coadministration of olanzapine and fluoxetine activates locus coeruleus neurons in rats: implications for bipolar disorder. Psychopharmacology 2005 Aug; 181(1): 126–33

    Article  PubMed  CAS  Google Scholar 

  45. Melkersson K, Dahl M-L. Adverse metabolic effects associated with atypical antipsychotics: literature review and clinical implications. Drugs 2004; 64(7): 701–23

    Article  PubMed  CAS  Google Scholar 

  46. Data on file, Eli Lilly and Company, 2008

  47. Haddad PM, Wieck A. Antipsychotic-induced hyperprolactinaemia: mechanisms, clinical features and management. Drugs 2004; 64(20): 2291–314

    Article  PubMed  CAS  Google Scholar 

  48. Altamura AC, Moro AR, Percudani M. Clinical pharmacokinetics of fluoxetine. Clin Pharmacokinet 1994 Mar; 26(3): 201–14

    Article  PubMed  CAS  Google Scholar 

  49. Gossen D, de Suray J-M, Vandenhende F, et al. Influence of fluoxetine on olanzapine pharmacokinetics. AAPS PharmSci 2002; 4(2): E11

    Article  PubMed  Google Scholar 

  50. Kassahun K, Mattiuz E, Nyhart E, et al. Disposition and biotransformation of the antipsychotic agent olanzapine in humans. Drug Metab Dispos 1997 Mar; 25(1): 81–93

    PubMed  CAS  Google Scholar 

  51. Harvey AT, Preskorn SH. Fluoxetine pharmacokinetics and effect on CYP2C19 in young and elderly volunteers. J Clin Psychopharmacol 2001 Apr; 21(2): 161–6

    Article  PubMed  CAS  Google Scholar 

  52. Schenker S, Bergstrom RF, Wolen RL, et al. Fluoxetine disposition and elimination in cirrhosis. Clin Pharmacol Ther 1988 Sep; 44(3): 353–9

    Article  PubMed  CAS  Google Scholar 

  53. Bergemann N, Frick A, Parzer P, et al. Olanzapine plasma concentration, average daily dose, and interaction with comedication in schizophrenic patients. Pharmacopsychiatry 2004 Mar; 37(2): 63–8

    Article  PubMed  CAS  Google Scholar 

  54. Tohen M, Calabrese J, Vieta E, et al. Effect of comorbid anxiety on treatment response in bipolar depression. J Affect Disord 2007 Dec; 104(1–3): 137–46

    Article  PubMed  Google Scholar 

  55. Keck Jr PE, Calabrese JR, Corya SA, et al. Olanzapine/fluoxetine combination for rapid-cycling bipolar depression [abstract no. P29]. Acta Psychiatr Scand Suppl 2004; 110(423): 22–3

    Google Scholar 

  56. Tollefson DS, Thase ME, Briggs SD, et al. Onset of antidepressant effect of olanzapine and olanzapine/fluoxetine combination in bipolar depression. Bipolar Disord 2007 Sep; 9(6): 618–27

    Article  PubMed  Google Scholar 

  57. Amsterdam JD, Shults J. Comparison of fluoxetine, olanzapine, and combined fluoxetine plus olanzapine initial therapy of bipolar type I and type II major depression: lack of manic induction. J Affect Disord 2005 Jul; 87(1): 121–30

    Article  PubMed  CAS  Google Scholar 

  58. Shi L, Namjoshi MA, Swindle R, et al. Effects of olanzapine alone and olanzapine/fluoxetine combination on health-related quality of life in patients with bipolar depression: secondary analyses of a double-blind, placebo-controlled, randomized clinical trial. Clin Ther 2004 Jan; 26(1): 125–34

    Article  PubMed  CAS  Google Scholar 

  59. American Psychiatric Association. Practice guideline for the treatment of patients with bipolar disorder (revision). Am J Psychiatry 2002 Apr; 159 (4 Suppl.): 1–50

    Google Scholar 

  60. Suppes T, Kelly DI, Perla JM. Challenges in the management of bipolar depression. J Clin Psychiatry 2005; 66 Suppl. 5: 11–6

    Google Scholar 

  61. Grunze H. Reevaluating therapies for bipolar depression. J Clin Psychiatry 2005; 66 Suppl. 5: 17–25

    Google Scholar 

  62. Goodwin GM, for the Consensus Group of the British Association for Psychopharmacology. Evidence-based guidelines for treating bipolar disorder: recommendations from the British Association of Psychopharmacology. J Psychopharmacol 2003; 17(2): 149–73

    Article  PubMed  CAS  Google Scholar 

  63. Yatham LN, Kennedy SH, O’Donovan C, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines for the management of patients with bipolar disorder: update 2007. Bipolar Disord 2006 Dec; 8(6): 721–39

    Article  PubMed  CAS  Google Scholar 

  64. Grunze H, Kasper S, Goodwin G, et al. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of bipolar disorders. Part I: treatment of bipolar depression. World J Biol Psychiatry 2002 Jul; 3(3): 115–24

    Google Scholar 

  65. Suppes T, Dennehy EB, Swann AC, et al. Report of the Texas consensus conference panel on medication treatment of bipolar disorder 2000. J Clin Psychiatry 2002 Apr; 63(4): 288–99

    Article  PubMed  Google Scholar 

  66. GlaxoSmithKline. GlaxoSmithKline Clinical Trials Registry: lamotrigine studies [online]. Available from URL: http:// ctr.gsk.co.uk/Summary/lamotrigine/studylist.asp [Accessed 2008 Mar 14]

  67. Tondo L, Isacsson G, Baldessarini RJ. Suicidal behaviour in bipolar disorder: risk and prevention. CNS Drugs 2003; 17(7): 491–511

    Article  PubMed  CAS  Google Scholar 

  68. Keating GM, Robinson DM. Quetiapine: a review of its use in the treatment of bipolar depression. Drugs 2007; 67(7): 1077–95

    Article  PubMed  CAS  Google Scholar 

  69. AstraZeneca. Seroquel® (quetiapine fumarate) tablets: US prescribing information [online]. Available from URL: http:// www1.astrazeneca-us.com/pi/Seroquel.pdf [Accessed 2008 Mar 31]

  70. Corya SA, Perlis RH, Keck Jr PE, et al. A 24-week open-label extension study of olanzapine-fluoxetine combination and olanzapine monotherapy in the treatment of bipolar depression. J Clin Psychiatry 2006 May; 67(5): 798–806

    Article  PubMed  CAS  Google Scholar 

  71. Brown EB, Dunner DL, Adams D, et al. Olanzapine/fluoxetine combination versus lamotrigine in the long-term treatment of bipolar I depression [abstract no. NR189]. 159th Annual Meeting of the American Psychiatric Association; 2006 May 20–25; Toronto (ON): 78–9

  72. Food and Drug Administration. Lamictal® (lamotrigine) tablets: Lamictal® (lamotrigine) chewable dispersible tablets [online]. Available from URL: http://www.fda.gov/cder/foi/label/2006/ 020241s10s21s25s26s27,020764s3s14s18s19s20lbl.pdf [Accessed 2007 Oct 11]

  73. Lin D, Mok H, Yatham LN. Polytherapy in bipolar depression. CNS Drugs 2006; 20(1): 29–42

    Article  PubMed  CAS  Google Scholar 

  74. Haddad PM, Sharma SG. Adverse effects of atypical antipsychotics: differential risk and clinical implications. CNS Drugs 2007; 21(11): 911–36

    Article  PubMed  CAS  Google Scholar 

  75. European Medicines Agency. Zyprexa®: summary of product characteristics [online]. Available from URL: http://www.emea.europa.eu/humandocs/PDFs/EPAR/Zyprexa/H-115-PI-en.pdf [Accessed 2007 Oct 31]

  76. Revicki DA, Matza LS, Flood E, et al. Bipolar disorder and health-related quality of life: review of burden of disease and clinical trials. Pharmacoeconomics 2005; 23(6): 583–94

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Wolters Kluwer Health ¦ Adis, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, North Shore 0754, Auckland, New Zealand

    Emma D. Deeks & Gillian M. Keating

  2. Wolters Kluwer Health, Conshocken, Pennsylvania, USA

    Emma D. Deeks & Gillian M. Keating

Authors
  1. Emma D. Deeks
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gillian M. Keating
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Emma D. Deeks.

Additional information

Various sections of the manuscript reviewed by: R. Bottlender, Newham Centre for Mental Health, Queen Mary University of London, London, UK; J. Cookson, The Royal London Hospital, London, UK; T. Denko, Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA; H.C.R. Grunze, School of Neurology, Neurobiology and Psychiatry, University of Newcastle, Newcastle upon Tyne, UK; S. Kasper, Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.

Data Selection

Sources: Medical literature published in any language since 1980 on ‘olanzapine/fluoxetine’, identified using MEDLINE and EMBASE, supplemented by AdisBase (a proprietary database of Wolters Kluwer Health | Adis). Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from the company developing the drug.

Search strategy: MEDLINE, EMBASE and AdisBase search terms were ‘olanzapine/fluoxetine’ and ‘bipolar depression’. Searches were last updated 5 May 2008.

Selection: Studies in patients with bipolar depression who received olanzapine in combination with fluoxetine. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data are also included.

Index terms: Olanzapine, fluoxetine, bipolar depression, pharmacodynamics, pharmacokinetics, therapeutic use, tolerability.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Deeks, E.D., Keating, G.M. Olanzapine/Fluoxetine. Drugs 68, 1115–1137 (2008). https://doi.org/10.2165/00003495-200868080-00008

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-200868080-00008

Keywords

Search

Navigation