Background. Numerous studies have been conducted with a view to developing strategies for improvement of medical compliance in patients with schizophrenia. All of the studies conducted so far have had an individual approach to compliance based on the assumption that noncompliance is determined individually due to inappropriate behavior in the patient. We conducted a pragmatic controlled trial with a system-oriented approach, to provide a new perspective on compliance and test the efficacy of a multifactorial intervention at the system level in a routine clinical setting, an approach that has not previously been used for the improvement of compliance. Methods. 30 patients were allocated to the system-oriented therapy and 40 patients were allocated to the reference intervention, which consisted of individually based compliance therapy. The follow-up period was six months. Primary endpoint was improvement in compliance, measured by improvement in a compliance scale specifically developed for the project. Results. When accounting for missing values with a multiple imputation approach, we found a tendency toward a difference in both the compliance scale and PANSS favoring the system-oriented therapy, although it did not reach statistical significance. A significant difference in incidence of adverse events and time to first readmission was found. Attrition rates were significantly higher in the reference group and nonsignificant among individuals with lower compliance, which may have diluted effect estimates. This was reflected by significant differences found in an analysis based on a last observation carried forward approach. Conclusion. This study suggests that compliance problems are better solved by a multifactorial intervention at the system level than at the individual level. 1. Background Schizophrenia is a severe mental illness [1], for which the cornerstone of treatment is antipsychotic medication [2]. Compliance with the medications is poor, as only approximately 50% of the prescribed medication is consumed [3], even though a compromised compliance has extensive clinical and economic consequences [4, 5]. Consequently, numerous studies have been conducted to develop strategies for the improvement of compliance in schizophrenia [6–18]. These studies have all had an individual approach to compliance based on the assumption that noncompliance is individually determined and due to inappropriate behavior of the patient. Alternatively noncompliance could be regarded as an “incident” caused by a “system failure” [19], that is, a product of failed
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