Background Background Studies investigating the Studies investigating the efficacy of clinical interventions for efficacy of clinical interventions for reducing treatment non-adherence have reducing treatment non-adherence have generated contrasting findings, and generated contrasting findings, and treatment non-adherence remains treatment non-adherence remains common in clinical practice. common in clinical practice. Aims Aims To systematically review whether To systematically review whether there are effective clinical interventions there are effective clinical interventions that community psychiatric services can that community psychiatric services can implement to reduce non-adherence. implement to reduce non-adherence. Method Method Systematic review and meta- Systematic review and meta- regression analysis of randomised regression analysis of randomised controlled trials (RCTs) and controlled controlled trials (RCTs) and controlled clinical trials (CCTs) were used to assess clinical trials (CCTs) were used to assess the efficacy of interventions to enhance the efficacy of interventions to enhance adherence. adherence. Results Results We reviewed 24 studies, more We reviewed 24 studies, more than half of which were RCTs. In 14 studies than half of which were RCTs. In 14 studies the experimental intervention was an the experimental intervention was an educational programme. Five studies educational programme. Five studies evaluated pre-discharge educational evaluated pre-discharge educational sessions, three studies explored the sessions, three studies explored the benefit of psychotherapeutic benefit of psychotherapeutic interventions and two studies looked at interventions and two studies looked at the effect of telephone prompts.The the effect of telephone prompts.The overall estimate of the efficacy of these overall estimate of the efficacy of these interventions produced an odds ratio of interventions produced an odds ratio of 2.59 (95% CI 2.21^3.03) for dichotomous 2.59 (95% CI 2.21^3.03) for dichotomous outcomes, and a standardised mean outcomes, and a standardised mean difference of 0.36 (95% CI 0.06^0.66) for difference of 0.36 (95% CI 0.06^0.66) for continuous outcomes. continuous outcomes. Conclusions Conclusions Community psychiatric Community psychiatric services can potentially use effective services can potentially use effective clinical interventions, backed by scientific clinical interventions, backed by scientific evidence, for reducing patient non- evidence, for reducing patient non- adherence. adherence. Declaration of interest Declaration of interest None. None. Treatment non-adherence remains one of the Treatment non-adherence remains one of the greatest challenges in psychiatry. It has been greatest challenges in psychiatry. It has been estimated that 20–50% of any patient popu- estimated that 20–50% of any patient popu- lation is at least partially non-compliant, and lation is at least partially non-compliant, and that in patients with schizophrenia and that in patients with schizophrenia and related psychotic disorders rates can run as related psychotic disorders rates can run as high as 70–80% (Breen & Thornhill, high as 70–80% (Breen & Thornhill, 1998). Adherence has been defined as the ex- 1998). Adherence has been defined as the ex- tent to which a person’s behaviour coincides tent to which a person’s behaviour coincides with the medical advice given (Sackett with the medical advice given (Sackett & Haynes, 1976). The definition of non- Haynes, 1976). The definition of non- adherence includes failure to enter a treat- adherence includes failure to enter a treat- ment programme, premature termination of ment programme, premature termination of therapy and incomplete implementation of therapy and incomplete implementation of instructions (including prescriptions). instructions (including prescriptions). Several randomised controlled trials Several randomised controlled trials (RCTs) and controlled clinical trials (CCTs) (RCTs) and controlled clinical trials (CCTs) have been conducted to assess the efficacy have been conducted to assess the efficacy of a wide range of clinical interventions to of a wide range of clinical interventions to reduce non-adherence in patients with psy- reduce non-adherence in patients with psy- chosis (Chen, 1991). The focus of most of chosis (Chen, 1991). The focus of most of these studies has been the reduction of non- these studies has been the reduction of non- adherence to psychotropic medication or to adherence to psychotropic medication or to scheduled appointments. Zygmunt and col- scheduled appointments. Zygmunt and col- leagues, who systematically reviewed RCTs leagues, who systematically reviewed RCTs and CCTs assessing psychosocial inter- and CCTs assessing psychosocial inter- ventions for improving medication adherence ventions for improving medication adherence in schizophrenia, showed that only a third of in schizophrenia, showed that only a third of included studies reported significant treat- included studies reported significant treat- ment effects (Zygmunt ment effects (Zygmunt et al et al, 2002). However, , 2002). However, this review did not employ meta-analytic this review did not employ meta-analytic techniques, excluded studies assessing inter- techniques, excluded studies assessing inter- ventions for improving adherence to sched- ventions for improving adherence to sched- uled appointments and included highly uled appointments and included highly selected populations of patients with selected populations of patients with schizophrenia. In this systematic review we schizophrenia. In this systematic review we adopted meta-analytic techniques to estab- adopted meta-analytic techniques to estab- lish whether there are effective clinical lish whether there are effective clinical interventions that community psychiatric ser- interventions that community psychiatric ser- vices can implement to reduce medication vices can implement to reduce medication and appointment non-adherence in patients and appointment non-adherence in patients with psychosis. with psychosis. METHOD METHOD Inclusion criteria Inclusion criteria The review included studies assessing the The review included studies assessing the efficacy of interventions aimed at reducing efficacy of interventions aimed at reducing patient non-adherence. Studies with a patient non-adherence. Studies with a random assignment design and studies with random assignment design and studies with a comparison of outcome between two or a comparison of outcome between two or more groups without a random assignment more groups without a random assignment design were considered for inclusion. Only design were considered for inclusion. Only studies of patients with schizophrenia and studies of patients with schizophrenia and related disorders or psychoses were related disorders or psychoses were selected. Studies, written in English, were selected. Studies, written in English, were included if adherence was one of the included if adherence was one of the primary outcome measures, if patients were primary outcome measures, if patients were recruited in a psychiatric setting and if the recruited in a psychiatric setting and if the control group received standard care. Studies control group received standard care. Studies of compulsory treatment and those assessing of compulsory treatment and those assessing adherence to initial appointments were adherence to initial appointments were excluded. However, studies focusing on excluded. However, studies focusing on adherence to after-care programmes (i.e. adherence to after-care programmes (i.e. appointments after hospital discharge) were appointments after hospital discharge) were included. included. Search strategy Search strategy Relevant studies were located by searching Relevant studies were located by searching Medline and PsycINFO from January Medline and PsycINFO from January 1980 onwards. The following keywords 1980 onwards. The following keywords were used: ADHERENCE were used: ADHERENCE or or COMPLI- COMPLI- ANCE ANCE or or DROPOUT DROPOUT or or ATTENDANCE ATTENDANCE or or CONCORDANCE CONCORDANCE or or TERMINATION TERMINATION or or CONTINUITY CONTINUITY and and SCHIZOPHRENIA SCHIZOPHRENIA or or PSYCHOSIS. Reference lists of relevant PSYCHOSIS. Reference lists of relevant papers and previous systematic reviews papers and previous systematic reviews were hand-searched for published reports were hand-searched for published reports and citations of unpublished research. and citations of unpublished research. Data extraction Data extraction An An ad hoc ad hoc data extraction form was data extraction form was developed. Two reviewers independently developed. Two reviewers independently extracted the following information: extracted the following information: country in which the study was conducted, country in which the study was conducted, study setting, design, length of follow-up, study setting, design, length of follow-up, main patient characteristics, description of main patient characteristics, description of experimental and control intervention, experimental and control intervention, and definition of non-adherence. Defini- and definition of non-adherence. Defini- tions were grouped into two categories: tions were grouped into two categories: (a) (a) not taking psychotropic drugs as not taking psychotropic drugs as prescribed prescribed (b) (b) not keeping appointments as scheduled. not keeping appointments as scheduled. Several methods have been reported to es- Several methods have been reported to es- tablish adherence; these were grouped into tablish adherence; these were grouped into four categories: four categories: (a) (a) patient interview patient interview (b) (b) case-note evaluation case-note evaluation (c) (c) rating scale rating scale (d) (d) urine test. urine test. Clinical interventions for improving patient Clinical interventions for improving patient adherence were grouped into the following adherence were grouped into the following categories: categories: (a) (a) educational strategies educational strategies 197 197 BRITISH JOURNAL OF PSYCHIATRY BRITISH JOURNAL OF PSYCHIATRY (2003), 183, 197^206 (2003), 183, 197^206 REVIEW ARTICLE REVIEW ARTICLE Clinical interventions for treatment non-adherence Clinical interventions for treatment non-adherence in psychosis: meta-analysis in psychosis: meta-analysis MICHELA NOSE, CORRADO BARBUI, RICHARD GRAY MICHELA NOSE ¤ , CORRADO BARBUI, RICHARD GRAY and MICHELE TANSELLA and MICHELE TANSELLA