The importance of cooperation in the treatment of schizophrenia-related psychoses. A review of research
DOI:
https://doi.org/10.12923/2353-8627/2025-0021Keywords:
schizophrenia, treatment compliance, research reviewAbstract
Objective: To conduct a comprehensive review of the literature on factors determining cooperation in pharmacological treatment in people with schizophrenia.
Method: A systematic review of the MEDLINE and PsycINFO databases for papers published from 1969 to 2024 was performed. Prospective, cross-sectional and retrospective studies as well as meta-analyses meeting methodological quality criteria were included in the analysis.
Results: The percentage of non-cooperative patients ranges from approximately 20% to 56% in the literature, with an average level close to 41%. The most commonly identified predictors of non-cooperation are poorer insight into the illness, younger age, psychoactive substance use, and greater severity of positive and negative symptoms. Non-cooperation is associated with a significantly higher risk of relapse and rehospitalisation, as well as poorer social and occupational functioning. Positive attitudes towards pharmacotherapy, a good therapeutic relationship, and family support improve cooperation regardless of the level of insight, which justifies combining psychoeducational, relational, and environmental interventions with the optimization of pharmacological treatment.
Conclusions: Cooperation in pharmacological treatment is a key, modifiable factor in the course of schizophrenia. Effective strategies require a multidimensional approach that includes psychoeducation, psychosocial support, improvement of the therapeutic alliance, minimisation of adverse effects, and the introduction of simpler and more convenient treatment plans. Further well-designed, prospective studies evaluating the long-term effectiveness of interventions that increase cooperation are needed.
References
1. Lally J., Ajnakina O., Stubbs B. et al. Remission and recovery from first-episode psychosis in adults: systematic review and meta-analysis of long-term outcome studies. British Journal of Psychiatry, 2017;211(6):350-358. doi:10.1192/bjp. bp.117.201475
2. Lieberman J.A., Drake R.E., Sederer L.I. et al. Science and Recovery in Schizophrenia. Psychiatric Services, 2008;59(5):487-496. doi:10.1176/ps.2008.59.5.487
3. Charlson F.J., Ferrari A.J., Santomauro D.F., Diminic S., Stockings E., Scott J.G. et al. Global Epidemiology and Burden of Schizophrenia: Findings From the Global Burden of Disease Study 2016. Schizophr Bull, 2018;17;44(6):1195-1203. doi: 10.1093/schbul/sby058. PMID: 29762765; PMCID: PMC6192504.
4. Haynes R.B., McDonald H.P., Garg A.X., Helping Patients Follow Prescribed Treatment: Clinical Applications. JAMA, 2002;288(22):2880–3.
5. Lacro J.P., Dunn L.B., Dolder C.R., Leckband S.G., Jeste D.V. Prevalence of and risk factors for medication nonadherence in patients with schizophrenia: a comprehensive review of recent literature. J Clin Psychiatry, 2002;63(10):892-909. doi: 10.4088/ jcp.v63n1007. PMID: 12416599.
6. Kim J., Ozzoude M., Nakajima S., Shah P., Caravaggio F., Iwata Y. et al. Insight and medication adherence in schizophrenia: An analysis of the CATIE trial. Neuropharmacology, 2020; 15;168:107634. doi: 10.1016/j.neuropharm.2019.05.011. Epub 2019 May 9. PMID: 31077729.
7. Ascher-Svanum H., Faries D. E., Zhu B., Ernst F. R., Swartz M. S., Swanson J. W. Medication adherence and long-term functional outcomes in the treatment of schizophrenia in usual care. The Journal of Clinical Psychiatry, 2006;67(3), 453-460.
8. Ascher-Svanum H., Zhu B., Faries D. E., Furiak N. M., Montgomery, W. Medication adherence levels and differential use of mentalhealth services in the treatment of schizophrenia. BMC Research Notes, 2009;2(1), 6. doi:10.1186/1756-0500-2-6.
9. Valenstein M., Ganoczy D., McCarthy JF., Myra K., Lee T.A., Blow F.C. Antipsychotic adherence over time among patients receiving treatment for schizophrenia: a retrospective review. The Journal of Clinical Psychiatry, 2006;67(10), 1542-1550
10. Błądziński P. Związek wglądu pacjenta i jego współpracy w leczeniu farmakologicznym z odległymi wynikami leczenia schizofrenii. Niepublikowany maszynopis pracy doktorskiej, 2015.
11. Thara R. Twenty‑Year Course of Schizophrenia: The Madras Longitudinal Study. Can J Psychiatry. 2004;49(8):564-569.
12. Higashi K., Medic G., Littlewood K.J., Diez T., Granström O., De Hert M. Medication adherence in schizophrenia: factors influencing adherence and consequences of nonadherence, a systematic literature review. Ther Adv Psychopharmacol, 2013;3(4):200-18. doi: 10.1177/2045125312474019. PMID: 24167693; PMCID: PMC3805432.
13. Perkins D.O., Johnson J.L., Hamer R.M., Zipursky R.B., Keefe R.S., Centorrino F. et al. Predictors of antipsychotic medication adherence in patients recovering from a first psychotic episode. Schizophrenia Research, 2006;83(1), 53-63
14. McCabe R., Bullenkamp J., Hansson L., Lauber C., Martinez‑Leal R., Rössler W. et al. The therapeutic relationship and adherence to medication in schizophrenia. PLoS One, 2012;7(4):e36080
15. Linden M., Godemann F., Gaebel W., Köpke W., Müller P., Müller- Spahn F., et al. A prospective study of factors influencing adherence to a continuous neuroleptic treatment program in schizophrenia patients during 2 years. Schizophr Bull, 2001;27(4):585-96. doi: 10.1093/oxfordjournals.schbul. a006898. PMID: 11824485.
16. Stentzel U., van den Berg N., Schulze L.N., Schwaneberg T., Radicke F., Langosch J.M. et al. Predictors of antipsychotic medication adherence: results from the Tecla trial. Patient Prefer Adherence, 2018;12:2291–300.
17. Chandra I.S., Kumar K.L., Reddy M.P., Reddy C.M. Attitudes toward Medication and Reasons for Non-Compliance in Patients with Schizophrenia. Indian J Psychol Med, 2014;36(3):294- 8. doi: 10.4103/0253-7176.135383. PMID: 25035554; PMCID: PMC4100416.
18. Tsang H.W., Fung K.M., Chung R.C. Self-stigma and stages of change as predictors of treatment adherence of individuals with schizophrenia. Psychiatry Research, 2010;180(1), 10-15.
19. Hudson T.J., Owen R.R., Thrush C.R., Han X., Pyne J.M., Thapa P. et al. A pilot study of barriers to medication adherence in schizophrenia. J Clin Psychiatry, 2004;65(2):211–6.
20. Baloush-Kleinman, V., Levine, S. Z., Roe, D., Shnitt, D., Weizman, A., Poyurovsky, M. Adherence to antipsychotic drug treatment in early-episode schizophrenia: a six-month naturalistic followup study. Schizophrenia Research, 2011;130(1), 176-181.
21. Johnson S., Sathyaseelan M., Charles H., Jeyaseelan V., Jacob K.S. Insight, psychopathology, explanatory models and outcome of schizophrenia in India: a prospective 5-year cohort study. BMC Psychiatry, 2012 27;12:159. doi: 10.1186/1471-244X-12-159. PMID: 23013057; PMCID: PMC3514157.
22. Lindenmayer J.P., Liu‑Seifert H., Kulkarni P.M., Kinon B.J., Stauffer V., Edwards S.E. et al. Medication nonadherence and treatment outcome in patients with schizophrenia or schizoaffective disorder with suboptimal prior response. J Clin Psychiatry, 2009;70(7):990-6. doi: 10.4088/JCP.08m04221. PMID: 19497244.
23. Jónsdóttir H., Opjordsmoen S., Birkenaes A.B., Simonsen C., Engh J.A., Ringen P.A. et al. Predictors of medication adherence in patients with schizophrenia and bipolar disorder. Acta 244 P. Błądziński, A. Cechnicki, P. Stankiewicz, D. Lech, I. Plencler-Turakiewicz, M. Żwirska, A. Kalisz Curr Probl Psychiatry, Vol. 26 (2025) Psychiatr Scand, 2013;127(1):23–33.
24. Schwartz R.C., Cohen B.N., Grubaugh A. Does insight affect longterm inpatient treatment outcome in chronic schizophrenia? Comprehensive Psychiatry, 1997;38(5), 283-288.
25. Rzewuska M. Drug maintenance treatment compliance and its correlation with the clinical picture and course of schizophrenia. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2002;26(4), 811-814.
26. Weiden P.J., Kozma C., Grogg A., Locklear J. Partial compliance and risk of rehospitalization among California Medicaid patients with schizophrenia. Psychiatr Serv, 2004;55(8):886–91.
27. Drake R.J., Dunn G., Tarrier N., Bentall R.P., Haddock G., Lewis S.W. Insight as a predictor of the outcome of first-episode nonaffective psychosis in a prospective cohort study in England. J Clin Psychiatry, 2007;68(1):81–86.
28. Acosta F. J., Ramallo-Fariña Y., Siris S. G. Should full adherence be a necessary goal in schizophrenia? Full versus non-full adherence to antipsychotic treatment. Comprehensive Psychiatry, 2014;55(1), 33-39.
29. Bressington D., Mui J., Gray R. Factors associated with antipsychotic medication adherence in community-based patients with schizophrenia in Hong Kong: a cross sectional study. Int J Ment Health Nurs, 2013;22(1):35-46. doi: 10.1111/j.1447-0349.2012.00830.x. PMID: 22738372.
30. Beck E. M., Cavelti M., Wirtz M., Kossowsky J., Vauth R. How do socio-demographic and clinical factors interact with adherence attitude profiles in schizophrenia? A cluster-analytical approach. Psychiatry Research, 2011;187(1), 55-61.
31. Yang J., Ko Y.H., Paik J.W., Lee M.S., Han C., Joe S.H. et al. Symptom severity and attitudes toward medication: impacts on adherence in outpatients with schizophrenia. Schizophrenia Research, 2012;134(2), 226-231.
32. Mohamed S., Rosenheck R., McEvoy J., Swartz M., Stroup S., Lieberman J.A. Cross-sectional and longitudinal relationships between insight and attitudes toward medication and clinical outcomes in chronic schizophrenia. Schizophrenia Bulletin, 2009;35(2), 336-346.
33. Kamali M., Kelly B.D., Clarke M., Browne S., Gervin M., Kinsella A. et al. A prospective evaluation of adherence to medication in first‑episode schizophrenia. Eur Psychiatry. 2006;21(1):29–33.
34. Dassa D., Boyer L., Benoit M., Bourcet S., Raymondet P., Bottai T. Factors associated with medication non-adherence in patients suffering from schizophrenia: a cross-sectional study in a universal coverage health-care system. Australian and New Zealand Journal of Psychiatry, 2010;44(10), 921-928.
35. Löffler W., Kilian R., Toumi M., Angermeyer M.C. Schizophrenic patients' subjective reasons for compliance and noncompliance with neuroleptic treatment. Pharmacopsychiatry, 2003;36(3):105-12. doi: 10.1055/s-2003-39985. PMID: 12806568.
36. Lang K., Meyers J., Korn J., Lee S., Sikirica M., Crivera C. et al. Medication adherence and hospitalization among patients with schizophrenia treated with antipsychotics. Psychiatr Serv, 2010;61(12):1239-47. doi: 10.1176/ps.2010.61.12.1239. PMID: 21123409.
37. Janssen B., Gaebel W., Haerter M., Komaharadi F., Lindel B., Weinmann S. Evaluation of factors influencing medication compliance in inpatient treatment of psychotic disorders. Psychopharmacology (Berl). 2006;187(2):229–36.
38. Acosta F. J., Bosch E., Sarmiento G., Juanes, N., Caballero-Hidalgo A., et al. Evaluation of noncompliance in schizophrenia patients using electronic monitoring (MEMS®) and its relationship to sociodemographic, clinical and psychopathological variables. Schizophrenia Research, 2009;107(2), 213-217.
39. Liu-Seifert H., Osuntokun O. O., Feldman P. D. Factors associated with adherence to treatment with olanzapine and other atypical antipsychotic medications in patients with schizophrenia. Comprehensive Psychiatry, 2012;53(1), 107-115.
40. Lieberman J.A., Stroup T.S., McEvoy J.P., Swartz M.S., Rosenheck R.A., Perkins D.O. et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med, 2005;353(12):1209–1223. doi:10.1056/NEJMoa051688.
41. McCann T.V., Clark E., Lu S. Subjective side effects of antipsychotics and medication adherence in people with schizophrenia. Journal of Advanced Nursing, 2009;65(3), 534- 543.
42. Novick D, Haro JM, Suarez D, Perez V, Dittmann RW, Haddad PM. Predictors and clinical consequences of non-adherence with antipsychotic medication in the outpatient treatment of schizophrenia. Psychiatry Res, 2010;176(2–3):109–13.
43. Leucht S., Heres S. Epidemiology, clinical consequences, and psychosocial treatment of nonadherence in schizophrenia. J Clin Psychiatry, 2006;67(Suppl 5):3–8.
44. De Haan L., van Amelsvoort T., Dingemans P., Linszen D. Risk factors for medication non‑adherence in patients with first episode schizophrenia and related disorders: a prospective five‑year follow‑up. Pharmacopsychiatry, 2007;40(6):264–8.
45. Bodén R., Brandt L., Kieler H., Andersen M., Reutfors J. Early non-adherence to medication and other risk factors for rehospitalization in schizophrenia and schizoaffective disorder. Schizophr Res, 2011;133(1-3):36-41. doi: 10.1016/j. schres.2011.08.024. Epub 2011 Oct 5. PMID: 21982098.
46. Panish J., Karve S., Candrilli S.D., Dirani R. Association between adherence to and persistence with atypical antipsychotics and psychiatric relapse among US Medicaid‐enrolled patients with schizophrenia. J Pharm Health Serv Res, 2013;4(1):29–39.
47. Shao W.C., Chen H., Chang Y.F., Lin W.C., Lin E.C. The Relationship Between Medication Adherence and Rehospitalization: A Prospective Study of Schizophrenia Patients Discharged From Psychiatric Acute Wards. Hu li za zhi The Journal of Nursing, 2013;60(5), 31-40.
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Piotr Błądziński, Andrzej Cechnicki, Przemysław Stankiewicz, Dominik Lech, Iga Plencler-Turakiewicz, Monika Żwirska, Aneta Kalisz (Author)

This work is licensed under a Creative Commons Attribution 4.0 International License.