Skip to main content
SpringerLink
Log in

Factors Related to Early Clinical Effects of Quetiapine Extended-Release: A Multinational, Prospective, Observational Study

  • Short Communication
  • Published:
Clinical Drug Investigation Aims and scope Submit manuscript

Abstract

Background and Objectives

The first weeks of treatment with antipsychotics are important for the development of their long-term efficacy. The objective of this study was to identify factors related to early clinical effects and quality of life (QoL) improvements with quetiapine extended-release (XR).

Methods

Six hundred and sixty-five patients starting with quetiapine XR were followed up for 8 weeks (schizophrenia = 153, major depression = 200, bipolar depression = 252, other psychiatric conditions = 60). Clinical effects were assessed by the Clinical Global Impression of Change scale (CGI-C), QoL by the visual analog scale (VAS) of the EQ-5D (QoL-VAS), and adherence by the Moriksy scale. Adverse events were explored: movement disorders by the UKU and Simpson-Angus scales, weight gain by calibrated balances, and diurnal somnolence by the Epworth Somnolence Scale (ESS).

Results

The mean dose of quetiapine XR during follow-up was 195.6 ± 154.8 mg/day. CGI and QoL-VAS scores improved significantly at week 8 by 2.7 ± 0.1 points and 25.1 ± 0.9 points. Adverse events were observed in 34 and 26 % of patients at weeks 4 and 8, respectively. A significant reduction in ESS score was also observed at week 8. Factors independently associated with change in QoL-VAS ≥20 points (n = 292, 43 %) were female gender, more severe disease at baseline, higher antipsychotic dose during follow-up, and improvements in somnolence. Factors independently associated with clinically significant improvement (CGI-C ≥5, n = 610, 93 %) were greater change in QoL-VAS, less frequent movement disorders at baseline, and lack of adverse events during follow-up, especially somnolence.

Conclusions

Results from this real-setting, large observational study in Central America suggest that disease severity at baseline, gender, antipsychotic dose, and occurrence of adverse reactions has a significant impact on the early clinical effects of quetiapine XR.

Clinicaltrials.gov registration number NCT02409823.

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

Access this article

Log in via an institution

Price includes VAT (Finland)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

References

  1. Baldwin CM, Scott LJ. Quetiapine extended release: in schizophrenia. CNS Drugs. 2009;23:261–9.

    Article  CAS  PubMed  Google Scholar 

  2. Weisler R, McIntyre RS, Bauer M. Extended-release quetiapine fumarate in the treatment of patients with major depressive disorder: adjunct therapy. Expert Rev Neurother. 2013;13:1183–200.

    Article  CAS  PubMed  Google Scholar 

  3. Altamura AC, Moliterno D, Paletta S, et al. Effect of quetiapine and norquetiapine on anxiety and depression in major psychoses using a pharmacokinetic approach: a prospective observational study. Clin Drug Investig. 2012;32:213–9.

    Article  CAS  PubMed  Google Scholar 

  4. Selle V, Schalkwijk S, Vazquez GH, et al. Treatments for acute bipolar depression: meta-analyses of placebo-controlled, monotherapy trials of anticonvulsants, lithium and antipsychotics. Pharmacopsychiatry. 2014;47:43–52.

    Article  CAS  PubMed  Google Scholar 

  5. Hatta K, Ito H. Strategies for early non-response to antipsychotic drugs in the treatment of acute-phase schizophrenia. Clin Psychopharmacol Neurosci. 2014;12:1–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Hatta K, Otachi T, Fujita K, et al. Antipsychotic switching versus augmentation among early non-responders to risperidone or olanzapine in acute-phase schizophrenia. Schizophr Res. 2014;158:213–22.

    Article  PubMed  Google Scholar 

  7. Kinon BJ, Lieberman JA. Mechanisms of action of atypical antipsychotic drugs: a critical analysis. Psychopharmacology. 1996;124:2–34.

    Article  CAS  PubMed  Google Scholar 

  8. Nakajima S, Suzuki T, Watanabe K, et al. Accelerating response to antidepressant treatment in depression: a review and clinical suggestions. Prog Neuropsychopharmacol Biol Psychiatry. 2010;34:259–64.

    Article  CAS  PubMed  Google Scholar 

  9. Pae CU, Wang SM, Han C, et al. Aripiprazole augmentation for major depressive disorder: dosing patterns in a naturalistic treatment setting. Int Clin Psychopharmacol. 2014;29:116–9.

    Article  PubMed  Google Scholar 

  10. Gopal S, Liu Y, Alphs L, et al. Incidence and time course of extrapyramidal symptoms with oral and long-acting injectable paliperidone: a posthoc pooled analysis of seven randomized controlled studies. Neuropsychiatr Dis Treat. 2013;9:1381–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Datto C, Berggren L, Patel JB, et al. Self-reported sedation profile of immediate-release quetiapine fumarate compared with extended-release quetiapine fumarate during dose initiation: a randomized, double-blind, crossover study in healthy adult subjects. Clin Ther. 2009;31:492–502.

    Article  CAS  PubMed  Google Scholar 

  12. Mortimer AM. Symptom rating scales and outcome in schizophrenia. Br J Psychiatry Suppl. 2007;50:s7–14.

    Article  PubMed  Google Scholar 

  13. EuroQoL Group. EuroQol: a new facility for the measurement of health-related quality of life. Health Policy. 1990;16:199–208.

    Article  Google Scholar 

  14. Morisky DE, Ang A, Krousel-Wood M, et al. Predictive validity of a medication adherence measure in an outpatient setting. J Clin Hypertens (Greenwich). 2008;10:348–54.

    Article  Google Scholar 

  15. Pope A, Adams C, Paton C, et al. Assessment of adverse effects in clinical studies of antipsychotic medication: survey of methods used. Br J Psychiatry. 2010;197:67–72.

    Article  PubMed  Google Scholar 

  16. Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep. 1991;14:540–5.

    CAS  PubMed  Google Scholar 

  17. WHO Collaborating Centre for Drug Statistics Methodology. Guidelines for ATC classification and DDD assignment 2012. Oslo: World Health Organization; 2011.

    Google Scholar 

  18. Breum L, Fernstrom H. Drug-induced obesity. In: Bjorntorp P, editor. International textbook of obesity. New York: Wiley; 2001.

    Google Scholar 

  19. Ness-Abramof R, Apovian CM. Drug-induced weight gain. Drugs Today (Barc). 2005;41:547–55.

    Article  CAS  Google Scholar 

  20. Pagel JF. Excessive daytime sleepiness. Am Fam Physician. 2009;79:391–6.

    CAS  PubMed  Google Scholar 

  21. Perez-Lloret S, Merello M. Tardive dyskinesias and other drug-induced movement disorders. In: Gálvez-Jiménez N, Tuite PJ, editors. Uncommon causes of movement disorders. Cambdrige: Cambridge University Press; 2011.

    Google Scholar 

  22. Jung SH, Yoon JS, Ahn YM, et al. Influencing factors and predictors of early response in schizophrenia patients receiving the paliperidone extended-release tablets (paliperidone ER). Psychiatry Investig. 2013;10:407–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Kinon BJ, Chen L, Stauffer VL, et al. Early onset of antipsychotic action in schizophrenia: evaluating the possibility of shorter acute efficacy trials. J Clin Psychopharmacol. 2010;30:286–9.

    Article  CAS  PubMed  Google Scholar 

  24. Ruberg SJ, Chen L, Stauffer V, et al. Identification of early changes in specific symptoms that predict longer-term response to atypical antipsychotics in the treatment of patients with schizophrenia. BMC Psychiatry. 2011;11:23.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Pae CU, Chiesa A, Mandelli L, et al. Predictors of early worsening after switch to aripiprazole: a randomized, controlled, open-label study. Clin Drug Investig. 2010;30:187–93.

    Article  CAS  PubMed  Google Scholar 

  26. Katz MM, Tekell JL, Bowden CL, et al. Onset and early behavioral effects of pharmacologically different antidepressants and placebo in depression. Neuropsychopharmacology. 2004;29:566–79.

    Article  CAS  PubMed  Google Scholar 

  27. Fabbri C, Marsano A, Balestri M, et al. Clinical features and drug induced side effects in early versus late antidepressant responders. J Psychiatr Res. 2013;47:1309–18.

    Article  PubMed  Google Scholar 

  28. Crespo-Facorro B, de la Foz VO, Ayesa-Arriola R, et al. Prediction of acute clinical response following a first episode of non affective psychosis: results of a cohort of 375 patients from the Spanish PAFIP study. Prog Neuropsychopharmacol Biol Psychiatry. 2013;44:162–7.

    Article  PubMed  Google Scholar 

  29. Ascher-Svanum H, Zhu B, Faries DE, et al. Adherence and persistence to typical and atypical antipsychotics in the naturalistic treatment of patients with schizophrenia. Patient Prefer Adherence. 2008;2:67–77.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Berger A, Edelsberg J, Sanders KN, et al. Medication adherence and utilization in patients with schizophrenia or bipolar disorder receiving aripiprazole, quetiapine, or ziprasidone at hospital discharge: a retrospective cohort study. BMC Psychiatry. 2012;12:99.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Fenton WS, Blyler CR, Heinssen RK. Determinants of medication compliance in schizophrenia: empirical and clinical findings. Schizophr Bull. 1997;23:637–51.

    Article  CAS  PubMed  Google Scholar 

  32. Rascati KL, Richards KM, Ott CA, et al. Adherence, persistence of use, and costs associated with second-generation antipsychotics for bipolar disorder. Psychiatr Serv. 2011;62:1032–40.

    Article  PubMed  Google Scholar 

  33. Meulien D, Huizar K, Brecher M. Safety and tolerability of once-daily extended release quetiapine fumarate in acute schizophrenia: pooled data from randomised, double-blind, placebo-controlled studies. Hum Psychopharmacol. 2010;25:103–15.

    Article  CAS  PubMed  Google Scholar 

  34. Russell JM, Mackell JA. Bodyweight gain associated with atypical antipsychotics: epidemiology and therapeutic implications. CNS Drugs. 2001;15:537–51.

    Article  CAS  PubMed  Google Scholar 

  35. Attard A, Taylor DM. Comparative effectiveness of atypical antipsychotics in schizophrenia: what have real-world trials taught us? CNS Drugs. 2012;26:491–508.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

CA-APD Study Team: Guatemala: Recinos, Byron MD; Porras, Julio MD; Reyes, Cesar MD; Valdez, Gloria MD; Palomo, Edna MD; Ortiz, Alejandra MD; Hernandez Bocaletti, Luis MD; Sierra, Claudia MD; Santos, Mirna MD. El Salvador, San Salvador: Rodriguez Elias, Fanny Elizabeth MD; Alvayeros Azucena, Jorge Alberto MD; Mena de Cardenas, Carmen MD; Canales Peña, Laura Elizabeth MD; Hurtarte Vidal, Alejandro MD; Rivas Aguilar, Marina Esther MD; Galdamez Martinez, Tamesy Xucit MD; Trujillo Delgado, Carlos MD. Honduras, San Pedro: Paz, Bezner MD; Paredes, Yolany MD; Espinoza, Bizmark MD; Sosa, Alfredo MD; Orellana, Mauricio MD. Honduras, Tegucigalpa: Rovelo, Mauricio MD; Chirinos, Americo MD; Barahona, Ana MD; Cruz, Jose Luis MD; Murillo, Sara MD; Antanunez, Elia MD. Nicaragua, Managua: Molina, Luis MD; Garcia, Nelson MD; Chavez, Jairo MD; Morales, Zenelia MD; Sanchez, Clara MD; Sanchez, Mauricio MD; Trujillo, Heydi MD; Delgado, Petronio MD; Jiron, Elda MD; Mendoza, Martha Gioconda MD. Panamá: Calderón, Jose MD; Boyd, Yadira MD; Hazera, Maribel MD; Velazco, Publio MD; Gómez, Daisy MD; Gutierrez, María Eugenia MD; Amador, Amarilis MD.

Author information

Authors and Affiliations

  1. Clínica de Especialidades Altamira, Managua, Nicaragua

    Luis Molina

  2. Universidad San Carlos de Guatemala, Guatemala, Guatemala

    Byron Recinos

  3. Hospital Juan de Dios de San Pedro, San Pedro, Honduras

    Bezner Paz

  4. Instituto de Salud Mental, Tegucigalpa, Honduras

    Mauricio Rovelo

  5. Colonia Médica, San Salvador, El Salvador

    Fanny Elizabeth Elias Rodriguez

  6. Clínica de la Conducta, Panama, Panama

    José Calderón

  7. Drugtech, Corporación Farmacéutica Recalcine, San José de Costa Rica, Costa Rica

    Arturo Arellano & Santiago Pomata

  8. Pharmacoepidemiology Unit, Etymos Consulting Group, Buenos Aires, Argentina

    María Verónica Rey

  9. Institute of Cardiology Research (ININCA), University of Buenos Aires, Buenos Aires, Argentina

    Santiago Perez-Lloret

  10. National Research Council (CONICET), Marcelo T. de Alvear 2270, (C1122AAJ), Buenos Aires, Argentina

    Santiago Perez-Lloret

Authors
  1. Luis Molina
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Byron Recinos
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bezner Paz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mauricio Rovelo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Fanny Elizabeth Elias Rodriguez
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. José Calderón
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Arturo Arellano
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Santiago Pomata
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. María Verónica Rey
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Santiago Perez-Lloret
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Santiago Perez-Lloret.

Ethics declarations

Funding

This study was financed by a non-restrictive educational grant from Drugtech, Recalcine Pharmaceutical Corporation (San José de Costa Rica, Costa Rica).

Conflict of interest

Dr Molina has nothing to disclose. Dr Recinos has lectured for Pfizer, Asofarma, Lundbeck, and Roche. Dr Paz has nothing to disclose. Dr Rovelo has lectured for Bial, Astrazeneca, Asofarma, and Pfizer. Dr Elias Rodriguez has lectured for Asofarma and Abbott. Dr Calderon has nothing to disclose. Dr Arellano and Mr Pomata are employees of Drugtech. Dr Rey is CEO of Etymos Consulting Group. Dr Perez-Lloret has consulted for Aguettant and Servier Laboratories.

Ethical approval

This study was approved by the Independent Ethics Committee for Clinical Pharmacology Studies (Buenos Aires, Argentina). All procedures in this study were in accordance with the 1964 Declaration of Helsinki (and its amendments). All patients provided informed consent before entering the study.

Additional information

For the CA-APD Study Team. Members are listed in Acknowledgment section.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Molina, L., Recinos, B., Paz, B. et al. Factors Related to Early Clinical Effects of Quetiapine Extended-Release: A Multinational, Prospective, Observational Study. Clin Drug Investig 36, 491–497 (2016). https://doi.org/10.1007/s40261-016-0395-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40261-016-0395-x

Keywords

Search

Navigation