Adherence and long-acting injectable antipsychotics in schizophrenia: An update

Adherence and long-acting injectable antipsychotics in schizophrenia: an update Nonadherence to antipsychotics poses a major problem in the long-term management of schizophrenia. Subjective measures of adherence (self-reports, provider reports) are unreliable, more objective methods (e.g., electronic monitoring, plasma levels) are neither available in clinical practice, nor are they infallible. Risk factors include history of nonadherence, substance use, limited insight, treatment with antidepressants, medication-induced cognitive impairment, hostility, and violent behavior. Nonadherence results in partial or no response to antipsychotic treatment with many adverse consequences, including higher mortality. A recent meta-analysis somewhat surprisingly failed to prove higher adherence to long-acting injectable antipsychotics (LAI) than to oral antipsychotics. However, unexpectedly high adherence in the reviewed trials suggests selection bias. This is further supported indirectly by the findings from two large observational studies from Finland. They showed that LAI, as compared to oral formulations of the same drugs, were associated with a significantly lower risk of rehospitalization and drug discontinuation. Prescription data from the Czech Republic indicate that LAI are underutilized. Contrary to traditional assumptions, patients with previous exposure to LAI appraised them favorably and frequently preferred them in the long-term treatment. LAI may be considered not only for nonadherent, relapsing or difficult-to-manage patients, but also for actively participating, well-informed patients with insight.

Kaynakça

1. Perkins DO. Predictors of noncompliance in patients with schizophrenia. J Clin Psychiatry 2002; 63:1121-1128.

2. Velligan DI, Weiden PJ, Sajatovic M, Scott J, Carpenter D, Ross R, Docherty JP. The expert consensus guideline series: adherence problems in patients with serious and persistent mental illness. J Clin Psychiatry 2009;70 (Suppl.4):1-46.

3. Mohr P, Volavka J. Adherence and depot formulations of antipsychotics in schizophrenia. Psychiatrie 2011; 15:105-113. [in Czech]

4. Cooper D, Moisan J, Gregoire JP. Adherence to atypical antipsychotic treatment among newly treated patients: a population-based study in schizophrenia. J Clin Psychiatry 2007; 68:818-825.

5. Fleischhacker WW, Keet IP, Kahn RS. The European First Episode Schizophrenia Trial (EUFEST): rationale and design of the trial. Schizophr Res 2005;78:147-156.

6. Lieberman JA, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DO, Keefe RS, Davis SM, Davis CE, Lebowitz BD, Severe J, Hsiao JK. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 2005; 353:1209-1223.

7. Kahn RS, Fleischhacker WW, Boter H, Davidson M, Vergouwe Y, Keet IP, Gheorghe MD, Rybakowski JK, Galderisi S, Libiger J, Hummer M, Dollfus S, Lopez-Ibor JJ, Hranov LG, Gaebel W, Peuskens J, Lindefors N, Riecher-Rossler A, Grobbee DE. Effectiveness of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: an open randomised clinical trial. Lancet 2008; 371:1085-1097.

8. Valenstein M, Copeland LA, Blow FC, McCarthy JF, Zeber JE, Gillon L, Bingham CR, Stavenger T. Pharmacy data identify poorly adherent patients with schizophrenia at increased risk for admission. Med Care 2002; 40:630-639.

9. Velligan DI, Lam YW, Glahn DC, Barrett JA, Maples NJ, Ereshefsky L, Miller AL. Defining and assessing adherence to oral antipsychotics: a review of the literature. Schizophr Bull 2006; 32:724-742.

10. Kemp R, Hayward P, Applewhaite G, Everitt B, David A. Compliance therapy in psychotic patients: randomised controlled trial. BMJ 1996; 312:345-349.

11. Jonsdottir H, Opjordsmoen S, Birkenaes AB, Engh JA, Ringen PA, Vaskinn A, Aamo TO, Friis S, Andreassen OA. Medication adherence in outpatients with severe mental disorders: relation between self-reports and serum level. J Clin Psychopharmacol 2010; 30:169-175.

12. Velligan DI, Wang M, Diamond P, Glahn DC, Castillo D, Bendle S, Lam YW, Ereshefsky L, Miller AL. Relationships among subjective and objective measures of adherence to oral antipsychotic medications. Psychiatr Serv 2007; 58:1187-1192.

13. Lindenmayer JP, Liu-Seifert H, Kulkarni PM, Kinon BJ, Stauffer V, Edwards SE, Chen L, Adams DH, Ascher-Svanum H, Buckley PF, Citrome L, Volavka J. Medication nonadherence and treatment outcome in patients with schizophrenia or schizoaffective disorder with suboptimal prior response. J Clin Psychiatry 2009; 70:990-996.

14. Czobor P, Volavka J, Derks EM, Bitter I, Libiger J, Kahn RS, Fleischhacker WW. Insight and hostility as predictors and correlates of non-adherence in the European First Episode Schizophrenia Trial (EUFEST). J Clin Psychopharmacol 2012 (in press).

15. Swartz MS, Wagner HR, Swanson JW, Stroup TS, McEvoy JP, Reimherr F, Miller DD, McGee M, Khan A, Canive JM, Davis SM, Hsiao JK, Lieberman JA. The effectiveness of antipsychotic medications in patients who use or avoid illicit substances: results from the CATIE study. Schizophr Res 2008; 100:39-52.

16. Ascher-Svanum H, Zhu B, Faries D, Lacro JP, Dolder CR. A prospective study of risk factors for nonadherence with antipsychotic medication in the treatment of schizophrenia. J Clin Psychiatry 2006; 67:1114-1123.

17. Jonsdottir H, Opjordsmoen S, Birkenaes AB, Simonsen C, Engh JA, Ringen PA, Vaskinn A, Friis S, Sundet K, Andreassen OA. Predictors of medication adherence in patients with schizophrenia and bipolar disorder. Acta Psychiatr Scand 2012;doi: 10.1111/j.1600-0447.2012.01911.x.

18. Lysaker P, Bell M. Work rehabilitation and improvements in insight in schizophrenia. J Nerv Ment Dis 1995; 183:103-106.

19. Byerly MJ, Fisher R, Carmody T, Rush AJ. A trial of compliance therapy in outpatients with schizophrenia or schizoaffective disorder. J Clin Psychiatry 2005; 66:997-1001.

20. Weiden PJ, Kozma C, Grogg A, Locklear J. Partial compliance and risk of rehospitalization among California Medicaid patients with schizophrenia. Psychiatr Serv 2004; 55:886-891.

21. Subotnik KL, Nuechterlein KH, Ventura J, Gitlin MJ, Marder S, Mintz J, Hellemann GS, Thornton LA, Singh IR. Risperidone Nonadherence and Return of Positive Symptoms in the Early Course of Schizophrenia. Am J Psychiatry 2011; 168:286-292.

22. Tiihonen J, Lonnqvist J, Wahlbeck K, Klaukka T, Niskanen L, Tanskanen A, Haukka J. 11-year follow-up of mortality in patients with schizophrenia: a population-based cohort study (FIN11 study). Lancet 2009; 374:620-627.

23. Tiihonen J, Haukka J, Taylor M, Haddad PM, Patel MX, Korhonen P. A Nationwide Cohort Study of Oral and Depot Antipsychotics After First Hospitalization for Schizophrenia. Am J Psychiatry 2011; 168:603-609.

24. Dolder CR, Lacro JP, Dunn LB, Jeste DV. Antipsychotic medication adherence: is there a difference between typical and atypical agents? Am J Psychiatry 2002; 159:103-108.

25. Valenstein M, Blow FC, Copeland LA, McCarthy JF, Zeber JE, Gillon L, Bingham CR, Stavenger T. Poor antipsychotic adherence among patients with schizophrenia: medication and patient factors. Schizophr Bull 2004; 30:255-264.

26. Nakonezny PA, Byerly MJ. Electronically monitored adherence in outpatients with schizophrenia or schizoaffective disorder: a comparison of first- vs. second-generation antipsychotics. Schizophr Res 2006; 82:107-114.

27. Tiihonen J, Walhbeck K, Lonnqvist J, KlaukkaT, Ioannidis JP, Volavka J, Haukka J. Effectiveness of antipsychotic treatments in a nationwide cohort of patients in community care after first hospitalisation due to schizophrenia and schizoaffective disorder: observational follow-up study. BMJ 2006; 333:224- 227.

28. Leucht C, Heres S, Kane JM, Kissling W, Davis JM, Leucht S. Oral versus depot antipsychotic drugs for schizophrenia-A critical systematic review and meta-analysis of randomised longterm trials. Schizophr Res 2001; 127:83-92.

29. Macfadden W, Ma YW, Thomas Haskins J, Bossie CA, Alphs L. A prospective study comparing the long-term effectiveness of injectable risperidone long-acting therapy and oral aripiprazole in patients with schizophrenia. Psychiatry (Edgmont) 2010; 7:23- 31.

30. Rosenheck RA, Krystal JH, Lew R, Barnett PG, Fiore L, Valley D, Thwin SS, Vertrees JE, Liang MH; CSP555 Research Group. Long-acting risperidone and oral antipsychotics in unstable schizophrenia. N Engl J Med 2011; 364:842-851.

31. Detke HC, Weiden PJ, Llorca P-M, Choukour M, Watson SB, Brunner E, McDonnell DP, Ascher-Svanum H. Open-Label Comparison of Olanzapine Long-Acting Injection and Oral Olanzapine: A 2-Year, Randomized Study in Outpatients With Schizophrenia. World Congress of Biological Psychiatry, 2011.

32. Weiden PJ, Schooler NR, Weedon JC, Elmouchtari A, Sunakawa- McMillan A. Maintenance treatment with long-acting injectable risperidone in first-episode schizophrenia: a randomized effectiveness study. J Clin Psychiatry 2012; 73:1224-1233.

33. Peuskens J, Olivares JM, Pecenak J, Tuma I, Bij de Weg H, Eriksson L, Resseler S, Akhras K, Jacobs A. Treatment retention with risperidone long-acting injection: 24-month results from the Electronic Schizophrenia Treatment Adherence Registry (e-STAR) in six countries. Curr Med Res Opin 2010; 26:501-509.

34. Ceskova E, Pecenak J, Tuma I, Anders M, Mohr P. Efficacy of risperidone long-term acting injections (Risperdal Consta) in the treatment of schizophrenia and schizoaffective disorders: 2-year results of the e-STAR in the Czech and Slovak Republics [in Czech]. Czech Slov Psychiatry 2011; 107:137-143.

35. Olivares JM, Rodriguez-Morales A, Diels J, Povey M, Jacobs A, Zhao Z, Lam A. Long-term outcomes in patients with schizophrenia treated with risperidone long-acting injection or oral antipsychotics in Spain: results from the electronic Schizophrenia Treatment Adherence Registry (e-STAR). Eur Psychiatry 2009; 24:287-296.

36. Novick,D, Haro JM, Bertsch J, Anand H, Jemiai N, Haddad PM. Comparison of treatment discontinuation and hospitalization among nonadherent patients initiating depot or oral typical antipsychotic medications. Int Clin Psychopharmacol 2012; 27:275-282.

37. Olfson M, Marcus SC, Doshi JA. Continuity of care after inpatient discharge of patients with schizophrenia in the Medicaid program: a retrospective longitudinal cohort analysis. J Clin Psychiatry 2010; 71:831-838.

38. Pereira S, Pinto R. A survey of the attitudes of chronic psychiatric patients living in the community toward their medication. Acta Psychiatr Scand 1997; 95:464-468.

39. Walburn J, Gray R, Gournay K, Quraishi S, David AS. Systematic review of patient and nurse attitudes to depot antipsychotic medication. Br J Psychiatry 2001; 179:300-307.

40. Desai NM, Huq Z, Martin SD, McDonald G. Switching from depot antipsychotics to risperidone: results of a study of chronic schizophrenia. The Schizophrenia Treatment & Assessment Group. Adv Ther 1999; 16:78-88.

41. Waddell L, Taylor M. Attitudes of patients and mental health staff to antipsychotic long-acting injections: systematic review. Br J Psychiatry Suppl 2009; 52:43-50.

42. Heres S, Schmitz FS, Leucht S, Pajonk FG. The attitude of patients towards antipsychotic depot treatment. Int Clin Psychopharmacol 2007; 22:275-282.

43. Svedberg B, Backenroth-Ohsako G, Lützén K. On the path to recovery: patients’ experiences of treatment with long-acting injections of antipsychotic medication. Int J Ment Health Nurs 2003; 12:110-118.

44. Jaeger M, Rossler W. Attitudes towards long-acting depot antipsychotics: a survey of patients, relatives and psychiatrists. Psychiatry Res 2010;175:58-62.

45. Besenius C, Clark-Carter D, Nolan P. Health professionals’ attitudes to depot injection antipsychotic medication: a systematic review. J Psychiatr Ment Health Nurs 2010; 17:452- 562.

46. Patel MX, Nikolaou V, David AS. Psychiatrists’ attitudes to maintenance medication for patients with schizophrenia. Psychol Med 2003; 33:83-89.

47. Patel MX, Haddad PM, Chaudhry IB, McLoughlin S, Husain N, David AS. Psychiatrists’ use, knowledge and attitudes to first- and second-generation antipsychotic long-acting injections: comparisons over 5 years. J Psychopharmacol 2010; 24:1473- 1482.

48. Heres S, Hamann J, Kissling W, Leucht S. Attitudes of psychiatrists toward antipsychotic depot medication. J Clin Psychiatry 2006; 67:1948-1953.

49. Hamann J, Mendel R, Heres S, Leucht S, Kissling W. How much more effective do depot antipsychotics have to be compared to oral antipsychotics before they are prescribed? Eur Neuropsychopharmacol 2010; 20:276-279.

50. Heres S, Reichhart T, Hamann J, Mendel R, Leucht S, Kissling W. Psychiatrists’ attitude to antipsychotic depot treatment in patients with first-episode schizophrenia. Eur Psychiatry 2011; 26:297-301.

51. Heres S, Hamann J, Mendel R, Wickelmaier F, Pajonk FG, Leucht S, Kissling W. Identifying the profile of optimal candidates for antipsychotic depot therapy A cluster analysis. Prog Neuropsychopharmacol Biol Psychiatry 2008; 32:1987-1993.

52. Lasser RA, Bossie CA, Zhu Y, Locklear JC, Kane JM. Longacting risperidone in young adults with early schizophrenia or schizoaffective illness. Ann Clin Psychiatry 2007; 19:65-71.

53. Emsley R, Medori R, Koen L, Oosthuizen PP, Niehaus DJ, Rabinowitz J. Long-acting injectable risperidone in the treatment of subjects with recent-onset psychosis: a preliminary study. J Clin Psychopharmacol 2008; 28:210-133. Erratum in: J Clin Psychopharmacol 2008; 28:624.

54. Emsley R, Oosthuizen P, Koen L, Niehaus D, Martinez L. A study of the clinical outcome following treatment discontinuation after remission in first-episode schizophrenia. Eur Neuropsychopharmacol 2009; 19 (Suppl.3):486-487.

Kaynak Göster