We spend a lot of time in researching and discussing the differences between the various antipsychotic drugs, but much less time in addressing the much more relevant problem, arguably the greatest in our everyday practice, of the management of non-adherence in our patients. Between 20 and 40% of our patients are disengaged from services within 12 months, more than 40% stop medication immediately after first hospitalization [1], nearly 20% of first-episode psychosis patients persistently refuse medications and another 50% are non-adherent at least once within 18 months.

Non-adherence is indeed difficult to assess and to manage, due to the numerous factors influencing our patients' attitude and willingness to follow our recommendations: the efficacy and tolerability of the drug, insight (with the need to differentiate between cognitive dysfunction and denial), the experience of the first contact with psychiatry, the influence of partners and caregivers, and many others [2].

Our hope that oral second-generation antipsychotics with less extrapyramidal side effects would lead to markedly increased adherence has not been fulfilled; most data show no clear advantage for these medications with respect to non-adherence rates and time to discontinuation [3]. One reason might be that the heterogeneity of these drugs is not fully exploited. The marked differences in their receptor binding and side effect profile would allow a much better individualization of treatment, addressing patients' complaints and problems (which side effects should be avoided by all means, which could be tolerated). An effort to involve the patient in these decisions certainly improves the therapeutic relationship, probably one of the most important factors affecting adherence [2]. Another element which may improve the therapeutic alliance is the frequency of contacts, even if needed “only” for safety reasons. The periodic laboratory tests required by clozapine treatment might be one reason for the surprisingly high patients' adherence to treatment with that drug [4]. The regular contact with the therapeutic team might also be one major advantage of using a long-acting antipsychotic, in addition to the straightforward identification of non-adherence, if the patient does not come for the injection. The resistance against the use of these preparations seems to be more in the mind of psychiatrists than in their patients [5].

Moreover, questions or evaluations concerning patients' quality of life during treatment with antipsychotic drugs would make explicit our willingness to not only reduce symptoms but also achieve more ambitious therapeutic goals. Not surprisingly, numerous studies indicate a relationship between patients' subjective wellbeing and their willingness to continue antipsychotic treatment [6].

Most randomized controlled trials do not show a superiority of long-acting antipsychotics over oral preparations. However, that is not surprising, since the major advantages of depot treatment cannot be detected in a double blind or similar design, but become obvious only in naturalistic trials [2, 7].

Finally, the complexity of the factors influencing adherence, their interaction and their continuing changes over time underline the need of integrated care treatment systems, targeting people with severe and persistent mental illness and those with the highest risk for service disengagement or medication non-adherence [8]. Such systems commonly include intensive care outpatient models such as intensive case management or assertive community treatment [9]. Compared to standard care, most such systems have shown lower rates of service disengagement and medication non-adherence [8, 10], better multidimensional outcomes [8, 10] and lower service costs [8].


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  2. References
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    Tiihonen J, Haukka J, Taylor M et al. A nationwide cohort study of oral and depot antipsychotics after first hospitalization for schizophrenia. Am J Psychiatry 2011;168:603-9.
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    Day JC, Bentall RP, Roberts C et al. Attitudes toward antipsychotic medication: the impact of clinical variables and relationships with health professionals. Arch Gen Psychiatry 2005;62:717-24.
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    Kreyenbuhl J, Slade EP, Medoff DR et al. Time to discontinuation of first- and second-generation antipsychotic medications in the treatment of schizophrenia. Schizophr Res 2011;131:127-32.
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    Mortimer AM, Singh P, Shepherd CJ et al. Clozapine for treatment-resistant schizophrenia: National Institute of Clinical Excellence (NICE) guidance in the real world. Clin Schizophr Relat Psychoses 2010;4:49-55.
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    Grimaldi-Bensouda L, Rouillon F, Astruc B et al. Does long acting injectable risperidone make a difference to the real-life treatment of schizophrenia? Results of the cohort study for the general study of schizophrenia. Schizophr Res 2012;134:187-94.
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    Schöttle D, Karow A, Schimmelmann BG et al. Integrated care in patients with schizophrenia: results of trials published between 2011 and 2013 focusing on effectiveness and efficiency. Curr Opin Psychiatry 2013;26:384-408.
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    Nordén T, Malm U, Norlander T. Resource group assertive community treatment (RACT) as a tool of empowerment for clients with severe mental illness: a meta-analysis. Clin Pract Epidemiol Ment Health 2012;8:144-51.
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    Lambert M, Bock T, Schöttle D et al. Assertive community treatment (ACT) as part of integrated care versus standard care: a 12-month trial in patients with first- and negatively selected multiple-episode schizophrenia-spectrum disorders treated with quetiapine IR. J Clin Psychiatry 2010;71:1313-23.