Skip to main content
Log in

Predictors of Early Worsening after Switch to Aripiprazole

A Randomized, Controlled, Open-Label Study

  • Original Research Article
  • Published:
Clinical Drug Investigation Aims and scope Submit manuscript

Abstract

Background: Despite the increasing evidence relating to strategies for switching between different antipsychotics, little evidence is available about predictors of improvement or worsening while switching. In a previous study, we compared different options for switching to aripiprazole and found that patients with schizophrenia switched to aripiprazole with immediate discontinuation of the previous antipsychotic showed an increase in symptom severity after 1 week.

Objective: To identify predictors of worsening in the first 4 weeks after the switch to aripiprazole in partial non-responders to previous treatments.

Methods: This was a 12-week randomized, controlled, open-label study that was carried out in the Department of Psychiatry of the Catholic University of Korea, Seoul, Korea. The study included 77 patients with schizophrenia whose symptoms were not optimally controlled and/or who did not tolerate their current antipsychotic medications well. Patients were randomly assigned to one of three different strategies for switching to aripiprazole 10 mg, i.e.: (i) simultaneous discontinuation of the current antipsychotic; (ii) tapering off the current antipsychotic over 4 weeks with half the dose after the first 2 weeks; or (iii) tapering off the current antipsychotic over 4 weeks after maintenance of the current dose for 2 weeks. The main outcome measure was the difference in Brief Psychiatric Rating Scale (BPRS) scores from baseline to weeks 1, 2 and 4.

Results: Baseline severity of disease, as measured by the Clinical Global Impression-Severity Scale, BPRS and Schedule for the Assessment of Negative Symptoms, significantly predicted worsening at weeks 1, 2 and 4. Specifically, lesser disease severity at baseline significantly predicted worsening after switching to aripiprazole.

Conclusion: Patients with relatively mild illness severity might be more susceptible to early worsening of symptoms when switched to aripiprazole. However, the limitations of the present study, including a small sample size, absence of a control group designed to control for nonspecific factors such as regression to the mean, and implementation of a switching strategy that included only aripiprazole, mean the present findings should be considered with caution and further research is needed.

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

Access this article

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

Instant access to the full article PDF.

Table I

Similar content being viewed by others

References

  1. National Institute for Clinical Excellence. Schizophrenia: core interventions in the treatment and management of schizophrenia in primary and secondary care. National Collaborating Centre for Mental Health (NCCMH). London: NICE, 2003 Mar 25

  2. Leslie DL, Rosenheck RA. From conventional to atypical antipsychotics and back: dynamic processes in the diffusion of new medications. Am J Psychiatry 2002; 159(9): 1534–40

    Article  PubMed  Google Scholar 

  3. 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. Schizophrenia Bull 2002; 28(1): 17–29

    Article  Google Scholar 

  4. Rothbard AB, Kuno E, Foley K. Trends in the rate and type of antipsychotic medications prescribed to persons with schizophrenia. Schizophrenia Bull 2003; 29(3): 531–40

    Article  Google Scholar 

  5. Kinon BJ, Basson BR, Gilmore JA, et al. Strategies for switching from conventional antipsychotic drugs or risperidone to olanzapine. J Clin Psychiatry 2000; 61(11): 833–40

    Article  PubMed  CAS  Google Scholar 

  6. Casey DE, Carson WH, Saha AR, et al. Switching patients to aripiprazole from other antipsychotic agents: a multicenter randomized study. Psychopharmacology (Berlin) 2003; 166(4): 391–9

    CAS  Google Scholar 

  7. Takeuchi H, Suzuki T, Uchida H, et al. A randomized, open-label comparison of 2 switching strategies to aripiprazole treatment in patients with schizophrenia: add-on, wait, and tapering of previous antipsychotics versus addon and simultaneous tapering. J Clin Psychopharmacol 2008; 28(5): 540–3

    Article  PubMed  CAS  Google Scholar 

  8. Pae CU, Serretti A, Chiesa A, et al. Immediate versus gradual suspension of previous treatments during switch to aripiprazole: results of a randomized, open label study. Eur Neuropsychopharmacol 2009; 19(8): 562–70

    Article  PubMed  CAS  Google Scholar 

  9. Henderson DC, Nasrallah RA, Goff DC. Switching from clozapine to olanzapine in treatment-refractory schizophrenia: safety, clinical efficacy, and predictors of response. J Clin Psychiatry 1998; 59(11): 585–8

    Article  PubMed  CAS  Google Scholar 

  10. Shajahan P, Macrae A, Bashir M, et al. Who responds to aripiprazole in clinical practice? An observational study of combination versus monotherapy. J Psychopharmacol 2008; 22(7): 778–83

    Article  PubMed  CAS  Google Scholar 

  11. El-Sayeh HG, Morganti C, Adams CE. Aripiprazole for schizophrenia: systematic review. Br J Psychiatry 2006; 189: 102–8

    Article  PubMed  CAS  Google Scholar 

  12. Bhattacharjee J, El-Sayeh HG. Aripiprazole versus typical antipsychotic drugs for schizophrenia. Cochrane Database Syst Rev 2008; (3): CD006617

  13. Mago R. Proposed strategies for successful clinical management with aripiprazole. Expert Opin Pharmacother 2008; 9(8): 1279–90

    Article  PubMed  CAS  Google Scholar 

  14. Casey D, Daniel D, Wassef A, et al. Effect of divalproex combined with olanzapine or risperidone in patients with an acute exacerbation of schizophrenia. Neuropsycho-pharmacology 2003; 28(1): 182–92

    Article  CAS  Google Scholar 

  15. Ramaswamy S, Vijay D, William M, et al. Aripiprazole possibly worsens psychosis. Int Clin Psychopharmacol 2004; 19(1): 45–8

    Article  PubMed  Google Scholar 

  16. Di Lorenzo R, Amoretti A, Forghieri M, et al. Aripiprazole: effectiveness and safety under naturalistic conditions. Exp Clin Psychopharmacol 2007; 15(6): 569–75

    Article  PubMed  Google Scholar 

  17. Kerwin R, Millet B, Herman E, et al. A multicentre, randomized, naturalistic, open-label study between aripiprazole and standard of care in the management of community-treated schizophrenic patients: Schizophrenia Trial of Aripiprazole (STAR) study. Eur Psychiatry 2007; 22(7): 433–43

    Article  PubMed  Google Scholar 

  18. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association, 1994

    Google Scholar 

  19. Guy W. Clinical Global Impression. In: Assessment manual for psychopharmacology. Washington, DC: Department of Health Education and Welfare, 1976: 217–22

  20. Flemenbaum A, Zimmermann RL. Inter- and intra-rater reliability of the Brief Psychiatric Rating Scale. Psychol Rep 1973; 32(3): 783–92

    Article  PubMed  CAS  Google Scholar 

  21. Andreasen N. Scale for the assessment of negative symptoms. Iowa City (IO): University of Iowa, 1983

    Google Scholar 

  22. Simpson GM, Angus JW. A rating scale for extrapyramidal side effects. Acta Psychiatr Scand Suppl 1970; 21: 211–9

    Google Scholar 

  23. Barnes TR. A rating scale for drug-induced akathisia. Br J Psychiatry 1989; 154: 672–6

    Article  PubMed  CAS  Google Scholar 

  24. Branch PR. Abnormal involuntary movement scale (AIMS). Early Clin Drug Eval Unit Intercom 1975; 4(1): 3–6

    Google Scholar 

  25. Rivas-Vasquez RA. Aripiprazole: a novel antipsychotic with dopamine-stabilising properties. Professional Psychol: Res Pract 2003; 34: 108–11

    Article  Google Scholar 

  26. Raja M. Improvement or worsening of psychotic symptoms after treatment with low doses of aripiprazole. Int J Neuropsychopharmacol 2007; 10: 107–10

    Article  PubMed  CAS  Google Scholar 

  27. Reeves RR, Mack JE. Worsening schizoaffective disorder with aripiprazole. Am J Psychiatry 2004; 161(7): 1308

    Article  PubMed  Google Scholar 

  28. Travis MJ, Burns T, Dursun S, et al. Aripiprazole in schizophrenia: consensus guidelines. Int J Clin Pract 2005; 59(4): 485–95

    Article  PubMed  CAS  Google Scholar 

  29. Takeuchi H, Uchida H, Suzuki T, et al. Predictors of clinical worsening after a switch to aripiprazole in patients with schizophrenia: a 1-year naturalistic follow-up study. J Clin Psychopharmacol 2009; 29(4): 394–5

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by a grant from the Medical Research Center, Korea Science and Engineering Foundation, Republic of Korea (R13-2002-005-04001-0). The authors have no conflicts of interest that are directly relevant to the content of the study.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Chi-Un Pae or Alessandro Serretti.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pae, CU., Chiesa, A., Mandelli, L. et al. Predictors of Early Worsening after Switch to Aripiprazole. Clin. Drug Investig. 30, 187–193 (2010). https://doi.org/10.2165/11533060-000000000-00000

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/11533060-000000000-00000

Keywords

Navigation