antipsychotic medication is the primary treatment modality for acute episodes as well as for relapse prevention in schizophrenia . however , the full benefits of medication as demonstrated by clinical research trials have failed to become implemented in routine clinical care . poor adherence to medication is thought to be a significant obstacle in achieving this goal [ 2 , 3 ] . up to 75% of patients with schizophrenia non - adherence to treatment is associated with poorer clinical and functional outcomes , increased use of emergency psychiatric services , and an increased number of hospitalizations . many intervention strategies have been used to improve medication adherence in patients with schizophrenia . in a recently published randomized , controlled , four - month study , an intervention based on a telephone call provided by a mental health nurse once monthly proved effective in enhancing oral antipsychotic adherence among patients with schizophrenia . non - adherence may be determined by many factors that could contribute to maintain patients in this situation even after intervention for improving adherence . identifying risk factors associated with failure after a specific intervention for enhancing adherence in patients with schizophrenia would allow improvement of the intervention . on the other hand , the identification of factors related to the success of a specific intervention would offer clinicians the opportunity to more adequately select patients who are eligible for such intervention . the aim was to identify factors associated with success following a 4-month telephone - based nursing strategy for improving adherence to maintenance antipsychotic treatment in patients with schizophrenia . after complete description of the study to the participants , written informed consent was obtained . the sample population for analysis comprised a total of 865 clinically stable outpatients having a dsm - iv - tr diagnosis of schizophrenia , being at least 18 years old , and taking a single oral antipsychotic drug . their mean age was 40.08 years ( sd 11.6 ) , and 65.3% were males . the mean baseline clinical global impression - severity score was 3.2 ( sd 1.2 ) . the patients randomized to the intervention group ( n=424 ) received a standardized telephone call made by a nurse at weeks 4 , 8 , and 12 . patients assigned to the control group ( n=441 ) were scheduled for the final visit four months after inclusion , without telephone calls , and emulating the usual period of clinical care among stable outpatients with schizophrenia in spain . each telephone call consisted of a brief semi - structured assessment of medication adherence ( a series of questions inquired about knowledge of the medication regimen and episodes of missed doses or incomplete adherence ) . in addition , the interview included the drug attitude inventory in its 10-item version ( dai-10 ) . nurses received specific training for the study from investigators before the first patient contact . adherence to antipsychotic treatment was evaluated by the treating psychiatrist and the nurse according to the register of adherence to treatment scale ( rat ) : high ( adherence with 80% of doses ) , moderate ( adherence with 60 - 79% of doses ) , low ( adherence with 20 - 59% of doses ) , and nil ( adherence with < 20% of doses ) . for the analysis , an improvement in adherence to treatment was considered when a patient was at least in an immediately higher level of adherence according to the rat at the end of the study compared to baseline ( e.g. , moderate adherence at the end of study vs. low adherence at baseline ) . a significantly higher percentage of patients in the intervention group ( 25.7% , n=109 ) improved adherence to treatment at the end of the study compared with the control group ( 16.8% , n=74 ) ( p=0.0013 ) .   to explore factors which could be related to improvement in adherence after the intervention , socio - demographic and clinical characteristics of the patients who improved their adherence status were compared with those who did not . no significant differences were observed in terms of age , gender , living status , education , marital and occupational status , schizophrenia subtypes , number of hospitalizations , class of antipsychotic drug ( typical vs. atypical ) or previous psychoeducation received . on the other hand , a significantly shorter duration of illness ( 11.6 vs. 13.5 years ; p=0.0196 ) , a greater number of previous acute episodes ( 2.3 vs. 1.6 ; p<0.0001 ) , and shorter periods of time from the last acute episode ( 1.9 vs. 3.5 years ; p<0.0001 ) or from last hospitalization ( 2.9 vs. 4.9 years ; p<0.0001 ) were observed in those patients who improved their adherence status at the end of the study compared to those patients who did not experience improvement . taking into account the bivariate analysis described above , a multivariate analysis ( logistic regression ) was performed to more adequately identify outcome predictors for improvement in adherence . socio - demographic and clinical variables were introduced in the model as independent variables , with improved adherence as the dependent variable . after backward stepwise elimination of the non - significant variables ( p>0.05 ) , the following variables remained in the model : group of study ( intervention vs. control , or= 1.86 , 95% ci=1.31 - 2.65 , p=0.0006 ) and baseline dai-10 score ( negative [ score < 0 ] vs. positive attitude towards medication [ score > 0 ] , or= 5.57 , 95% ci=3.83 - 8.11 , p<0.0001 ) . the odds ratio for improvement in adherence with the intervention was calculated in those patients with baseline negative and positive attitudes towards medication . the telephone - based nursing intervention was significantly associated with improved adherence in those patients with a previous negative perception of treatment ( or=4.7 , ci 95 % = 2.4 - 9.0 , p<0.0001 ) , but there was no significant association in those patients with a previous positive perception ( or=1.2 , 95% ci = 0.8 - 1.9 , p=0.3628 ) ( fig . a kappa index was obtained to assess the concordance between the improvement in adherence after the intervention and improvement in patient perceptions of treatment . a slight concordance was observed between these two variables ( k=0.21 ; 95% ci=0.15 - 0.27 ) . the principal findings from these analyses demonstrate that the intervention was significantly more effective in those patients with a previous negative perception of treatment compared to those with a good perception . the critical importance of optimal adherence to prescribed antipsychotic treatments has been convincingly demonstrated in patients with schizophrenia . positive attitude towards medication , as measured by the dai-10 , is associated with significantly higher adherence rates . this study suggests that adherence can be improved with an intervention even in those patients with a risk factor consistently associated to non - adherence , such as a negative attitude towards medication . furthermore , when a bad perception of antipsychotic treatment is detected in a patient , this telephone intervention could be applied in order to enhance adherence and , subsequently , to improve the outcome . improvement in adherence after the intervention in those patients with a baseline negative perception of treatment could be partially explained by improvement in their attitude towards medication . a slight concordance was observed between these two variables , suggesting that in some patients the telephone call improved the perception of antipsychotic treatment . alternatively , in those patients who enhanced adherence without improving their attitude towards medication , the intervention could be acting as a reminder , increasing the number of days patients are taking the medication as prescribed . we can hypothesize that patients increasing adherence will improve their attitude towards medication over the long term , as a consequence of their psychopathological improvement . a limitation of this analysis was the lack of assessment of some factors consistently related to non - adherence . a measure for insight was lacking in the study and factors related to medication , with the exception of the class of antipsychotic drug , were not systematically assessed . in addition , other environmental factors that are emerging as being predictive of non - adherence , including a poor alliance with the therapist or clinician , or less outpatient contact , were not assessed . consequently , the benefit of the intervention in non - adherent patients presenting these risk factors may not be established .   in summary , the results of this analysis reveal that a telephone call made by a mental health nurse is a successful intervention for enhancing adherence in stable patients with schizophrenia . this intervention could be especially useful for improving adherence in those patients with a negative attitude towards antipsychotic treatment .
a post hoc analysis was made to identify factors associated with success following a 4-month telephone - based strategy for enhancing adherence to antipsychotic treatment in schizophrenia . 
 a total of 928 stable outpatients were randomized to receive a monthly telephone call provided by a nurse or routine clinical care . 
 logistic regression with a backward stepwise procedure was used . a higher percentage of patients in the intervention group ( 25.7% , n=109 ) improved adherence at the end of the study compared with the control group ( 16.8% , n=74 ) ( p=0.0013 ) . 
 the intervention was significantly associated with adherence improvement in those patients with a previous negative attitude towards medication ( or=4.7 , 95% ci = 2.4 - 9.0 , p<0.0001 ) . 
 a slight concordance was obtained between adherence improvement and improvement in patient perception of treatment ( kappa=0.21 ; 95% ci=0.15 - 0.27 ) . 
 the identification of factors related to the effectiveness of a specific intervention would offer clinicians the opportunity to more adequately select patients who are eligible for such intervention .