The patients recruited into the e-STAR study are representative of the general population of patients with schizophrenia or schizoaffective disorder in Australia, although we possibly included a higher proportion of patients with schizoaffective disorder (22% cf 15% in previous reports [7
]). However, they were similar in age, sex and duration of illness to those reported in the SOHO study [12
]. They were also similar in age, sex, duration of illness and disease severity to those reported in the Spanish report of the e-STAR study [7
]. One of the difficulties of research in this area is that a proportion of eligible participants refuse to provide informed consent. As we did not keep a screening log, we are unable to determine what proportion of eligible participants chose not to participate.
One of the important findings of this study is its support of recent findings by Viner and colleagues [13
] in that many patients with chronic schizophrenia or schizoaffective disorder may benefit from an up-titration from 25 mg to 37.5 or 50 mg. Viner and colleagues [13
] suggest that although 25 mg is frequently the initial RLAI dose many patients require at least 37.5 mg, if not 50 mg, for symptom improvement. To achieve maximal clinical efficacy we found the most common number of titrations was 2 with an increasing proportion of patients on 37.5 and 50 mg dosages during the time-course of the study.
Patients receiving RLAI demonstrated improvements in CGI-S over the duration of the study - with a change in mean category from 4 - 'moderately ill' to 3 - 'mildly ill'. This correlates with a change in BPRS score from 40-45 to 32-36, or a reduction of approximately 10 points [14
], indicating a clinically significant change. Considering that reductions in CGI-S scores for more severely ill patients are potentially more important, this finding is clinically notable. This sub-group of ill patients are likely to experience a greater number of symptoms, and reductions are likely to correlate with more substantial symptom improvement, especially given the possibility of ceiling effects [14
]. The improvement observed is similar to previously reported reductions in CGI-S scores at 3-months of between 0.5 and 0.9 following initiation of RLAI in patients with schizophrenia [15
], and is consistent with the findings of the Spanish e-STAR investigators who reported a reduction in CGI-S score of 1.14 points [7
Recently, the GAF scale has been validated on the domains of psychological, social and occupational functioning in patients with schizophrenia [16
]. We observed improvements in GAF scores of approximately 15 points - a significant improvement in patient functioning. This is consistent with the findings of the Spanish e-STAR investigators who reported an increase in GAF score of 17.3 points [7
The mechanisms responsible for improvements in disease severity and functioning were not assessed in our study, however, we hypothesize that improvements were due to improved adherence with antipsychotic medication, as has been reported by others [17
Although initiation of RLAI resulted in an overall decrease in the percentage of patients using other psychiatric medications, the changes in concomitant medication use reported in this study are complicated by the collection technique we used to gather these data (a simple tick box of whether the medication had been used in the previous 3-months). As such, we are unable to separate medications taken during an acute admission, such as benzodiazepines, from those that were prescribed on a long-term basis. We know that patients are prescribed benzodiazepines as an alternative to neuroleptic treatment in acute psychosis [20
]. Lambert and colleagues [20
] report that benzodiazepines are prescribed for 17% of patients prior to admission, peaking at 42% on the first day of admission and reducing to 28% at the time of discharge.
Initiation of RLAI significantly reduced the number of hospitalisations for patients who remained on treatment for 12 and 24 months. This again reflects the findings of the Spanish e-STAR investigators [7
]. This finding has potential implications for health care costs in the long-term management of schizophrenia. Additionally, it suggests there may be considerable cost savings over a 24-month period through reduced hospitalisation [21
The treatment discontinuation rate in this study is high compared to that observed in the RLAI Spanish cohort of the e-STAR study at 24-months: 66.7% vs18.2% [7
]. It is not clear why there is this difference in discontinuation between the two countries: baseline demographics were similar in the two cohorts. It may reflect different mental health policies between the two countries, or the itinerant nature of the Australian population. The seemingly poor RLAI retention rate observed in this study, although improved for patients who completed the full 24-month period, may be explained by the population being more treatment resistant, as shown by the choice of post-RLAI antipsychotic treatment. Oral risperidone, olanzapine, clozapine, and zuclopenthixol, alone or in combination, were the most frequently prescribed medications post-RLAI. Furthermore, it is well known patients participating in antipsychotic treatment studies tend to have high dropout rates [22
]. There was little difference between baseline characteristics of those who completed the study compared to the overall study population (with the exception that the duration of diagnosis was longer in the completer population). Clozapine, the treatment of choice for treatment-resistant patients, was frequently prescribed post-discontinuation of RLAI (9.1%). However, the proportion of patients receiving combinations of antipsychotic therapies suggests that some were resistant to treatment, and therefore likely to be non-adherent.
The adverse event profile was as to be expected in this patient population [9
A prominent limitation of this study is the lack of a control arm. The data in this paper are from Australia only, and differences in culture and health care systems may mean our results are not generalisable to other countries. However, our results do support those reported by the Spanish e-STAR group [7
]. That said, the population observed is consistent with that seen in Australian practice and is therefore relevant to clinicians in Australia. Furthermore, it should be emphasised that this study was naturalistic (observational), containing both retrospective and prospective elements, however, as it was not blinded, there is the possibility of observational bias.