Reasons and Outcomes of Olanzapine Dose Adjustments in the Outpatient Treatment of Schizophrenia

Abstract

Introduction: Antipsychotic treatment dose adjustments may influence treatment outcomes in patients with schizophrenia.

Methods: We analysed data from 4 247 outpatients with schizophrenia who started olanzapine monotherapy in the 3-year, prospective, observational SOHO study to determine factors associated with olanzapine dose adjustments and how these impact on treatment effectiveness and tolerability.

Results: Regression analyses showed an association between changes in the Clinical Global Impression (CGI) and olanzapine dose changes: patients with a lack of effectiveness were more likely to have their dose increased, whereas patients with good treatment response were more likely to have a dose decrease. Improvement in tardive dyskinesia was associated with dose increase or no change (p=0.034) and worsening of sexual problems was associated with dose decrease (p=0.001). Conversely, an increase in olanzapine dose was associated with subsequent clinical improvement (CGI), but dose adjustment had no significant effects on tolerability outcomes.

Discussion: These results indicate that psychiatrists tend to modify olanzapine dose according to treatment response. Dose increases seem to be associated with a better response to treatment and not with a worsening of side-effects.

References

• 1 Albers LJ, Ozdemir V, Marder SR. et al . Low-dose fluvoxamine as an adjunct to reduce olanzapine therapeutic dose requirements: a prospective dose-adjusted drug interaction strategy.  J Clin Psychopharmacol. 2005;  25 170-174
• 2 American Psychiatric Association (APA) . Practice guidelines for the treatment of patients with schizophrenia. Washington, DC: APA 1997
• 3 Ascher-Svanum H, Stensland M, Kinon J. et al . Weight gain as a prognostic indicator of therapeutic improvement during acute treatment of schizophrenia with placebo or active antipsychotic.  J Psychopharmacol. 2005;  19 ((6 Suppl)) 110-117
• 4 Baker RW, Kinon BJ, Maguire GA. et al . Effectiveness of rapid initial dose escalation of up to forty milligrams per day of oral olanzapine in acute agitation.  J Clin Psychopharmacol. 2003;  23 342-348
• 5 Bergemann N, Frick A, Parzer P. et al . Olanzapine plasma concentration, average daily dose, and interaction with co-medication in schizophrenic patients.  Pharmacopsychiatry. 2004;  37 63-68
• 6 Breier A, Meehan K, Birkett M. et al . A double-blind, placebo-controlled dose-response comparison of intramuscular olanzapine and haloperidol in the treatment of acute agitation in schizophrenia.  Arch Gen Psychiatry. 2002;  59 441-448
• 7 Chakos M, Lieberman J, Hoffman E. et al . Effectiveness of second-generation anti-psychotics in patients with treatment-resistant schizophrenia: a review and meta-analysis of randomized trials.  Am J Psychiatry. 2001;  158 518-526
• 8 Chiu CC, Lane HY, Huang MC. et al . Dose-dependent alterations in the pharmacokinetics of olanzapine during co-administration of fluvoxamine in patients with schizophrenia.  J Clin Pharmacol. 2004;  44 1385-1390
• 9 Covell NH, Jackson CT, Evans AC. et al . Antipsychotic prescribing practices in Connecticut's Public Mental Health System: rates of changing medications and prescribing styles.  Schizophr Bull. 2002;  28 17-29
• 10 Czobor P, Volavka J, Sheitman B. et al . Antipsychotic-induced weight gain and therapeutic response: a differential association.  J Clin Psychopharmacol. 2002;  22 244-251
• 11 Gorwood P. Meeting everyday challenges: antipsychotic therapy in the real world.  Eur Neuropsychopharmacol. 2006;  16 ((Suppl. 3)) 156-162
• 12 Guy G. Clinical Global Impression. In ECDEU Assessment Manual for Psychopharmacology (Revised). Rockville, Maryland: National Institute of Mental Health 1976
• 13 Haan L, Nimwegen L, Amelsvoort T. et al . Improvement of subjective well-being and enduring symptomatic remission, a 5-year follow-up of first episode schizophrenia.  Pharmacopsychiatry. 2008;  41 125-128
• 14 Hanley JA, Negassa A, Edwardes MD. et al . Statistical analysis of correlated data using generalized estimating equations: an orientation.  Am J Epidemiol. 2003;  157 364-375
• 15 Haro JM, Edgell ET, Jones PB. et al . The European Schizophrenia Outpatient Health Outcomes (SOHO) study: rationale, methods and recruitment.  Acta Psychiatr Scand. 2003;  107 222-232
• 16 Haro JM, Edgell ET, Frewer P. et al . The European Schizophrenia Outpatient Health Outcomes Study: baseline findings across country and treatment.  Acta Psychiatr Scand. 2003;  107 ((Suppl. 416)) 7-15
• 17 Haro JM, Kamath SA, Ochoa S. et al . The Clinical Global Impression-Schizophrenia scale: a simple instrument to measure the diversity of symptoms present in schizophrenia.  Acta Psychiatr Scand. 2003;  107 ((Suppl. 416)) 16-23
• 18 Haro JM, Suarez D, Novick D. et al . Three-year antipsychotic effectiveness in the outpatient care of schizophrenia: observational versus randomized studies results.  Eur Neuropsychopharmacol. 2007;  17 235-244
• 19 Hofer A, Hummer M, Huber R. et al . Selection bias in clinical trials with antipsychotics.  J Clin Psychopharmacol. 2000;  20 699-702
• 20 Kasper S. Optimisation of long-term treatment in schizophrenia: treating the true spectrum of symptoms.  Eur Neuropsychopharmacol. 2006;  16 ((Suppl. 3)) 135-141
• 21 Kinon BJ, Basson BR, Gilmore JA. et al . Long-term olanzapine treatment: weight change and weight-related health factors in schizophrenia.  J Clin Psychiatry. 2001;  62 92-100
• 22 Kinon BJ, Volavka J, Stauffer V. et al . Standard and higher dose of olanzapine in patients with schizophrenia or schizoaffective disorder: a randomized, double-blind, fixed-dose study.  J Clin Psychopharmacol. 2008;  28 392-400
• 23 Lambert M, Haro JM, Novick D. et al . Olanzapine versus other antipsychotics in actual outpatient settings: 6-month safety results from the European Schizophrenia Outpatient Health Outcomes (SOHO) study.  Acta Psychiatr Scand. 2005;  111 232-243
• 24 Lipkovich I, Baron D, Houston J. et al . Flexible-dose clinical trials. Predictors and outcomes of antipsychotic dose adjustments.  J Clin Psychopharmacol. 2005;  25 381-386
• 25 Mauri M, Simoncini M, Castrogiovanni S. et al . A psychoeducational program for weight loss in patients who have experienced weight gain during antipsychotic treatment with olanzapine.  Pharmacopsychiatry. 2008;  41 17-23
• 26 Mauri MC, Colasanti A, Rossattini M. et al . A single-blind, randomized comparison of olanzapine at a starting dose of 5 mg versus 20 mg in acute schizophrenia.  Clin Neuropharmacol. 2006;  29 126-131
• 27 Mauri MC, Colasanti A, Rossattini M. et al . Ziprasidone outcome and tolerability: a practical clinical trial with plasma drug levels.  Pharmacopsychiatry. 2007;  40 89-92
• 28 Meltzer HY, Perry E, Jayathilake K. Clozapine-induced weight gain predicts improvement in psychopathology.  Schizophr Res. 2003;  59 19-27
• 29 Stroup TS, Alves WM, Hamer RM. et al . Clinical trials for antipsychotic drugs: design conventions, dilemmas and innovations.  Nat Rev Drug Discov. 2006;  5 133-146
• 30 Suarez D, Haro JM. Overview of the findings from the European SOHO study.  Expert Rev Neurother. 2008;  8 873-880
• 31 Thornley B, Adams C. Content and quality of 2000 controlled trials in schizophrenia over 50 years.  BMJ. 1998;  317 1181-1184
• 32 Westheide J, Cohen S, Bender S. et al . Sexual dysfunction in psychiatric inpatients the role of antipsychotic medication.  Pharmacopsychiatry. 2007;  40 140-145

Correspondence