As expected, there was no increase in the utilisation of risperidone compared with the other atypical antipsychotic drugs after the introduction of generic risperidone in either Belgium, Ireland, Scotland or Sweden (Figure 1), or in Bury PCT (Figure 3). In fact, if anything the reverse was seen, with increased prescribing of patented atypical antipsychotics in the four countries (Figure 1). A similar picture was also seen in Austria and Spain (Table 3; Figure 2) with generic extended release (ER) quetiapine not being available in Spain until near the end of the study. However, there were significant differences in the rate of decline in risperidone utilisation between the four countries before generic risperidone was launched (Table 1). However, there was less variation in the rate of decline after generic risperidone became available (Figure 1; Table 1), with the combined decline in risperidone utilisation falling to −0.00548% per month from −0.144% per month (Table 1). The rate of decline was greater in Sweden than Scotland (Table 2). However, there was overall a reasonable consistency between the four countries, irrespective of their characteristics [39, 68], reflected by the lack of a statistically significant change in slope after month 0 (Table 1). This was also no statistically significant difference in the rate of risperidone utilisation after generic risperidone became available in the separate analyses conducted in Belgium, Scotland and Sweden [46, 48, 56].
The consistent findings between the seven European countries and regions, including Austria (Table 3), Spain (Figure 2) and Bury PCT (Figure 3), regarding risperidone utilisation following the introduction of generics would suggest that following generic availability, there was no increased prescribing of oral risperidone for new patients, for whom risperidone could be one of the treatment options. However, we cannot say this with certainty without analysing patient-specific data. No increased prescribing of risperidone following introduction of generics (Figures 1, 2 and 3; Tables 1 and 3) may reflect the advice from organisations such as the National Institute for Health and Care Excellence in the UK and from various published studies that treatment of patients with schizophrenia should be individualised to maximise patient outcomes [17–19, 69, 70]. The growing utilisation of the other atypical antipsychotics, especially quetiapine and aripiprazole, in the various countries following the introduction of generic risperidone (Figures 1 and 2; Table 3) may reflect the marketing activities of the manufacturers of patented atypical antipsychotic drugs including ER quetiapine in Spain, influencing the choice of antipsychotic drug prescribed [46, 48, 71–73]. However, it is more likely to reflect the recognised weight neutrality with aripiprazole versus olanzapine and risperidone, as well as the effectiveness of aripiprazole and quetiapine ER in treating patients with major depressive disorders who have had an incomplete response to antidepressants, and of quetiapine ER in treating patients with bipolar depression [74–76], given the limited utilisation of patented paliperidone in recent years (Table 4). However, this remains to be elucidated in further research. There was also no substantial increase in the utilisation of long-acting risperidone in the four principal countries following the introduction of oral generic risperidone. If anything, the reverse was seen in Belgium in recent years, as reimbursement is denied if the medical adviser appointed by the patient’s insurer is not satisfied with the rationale provided by the physician .
The findings also potentially suggest there is no ‘spillover’ or cross-transfer of learning in practice from one disease area to another to produce changes in physician prescribing habits, that is, no crossover of learning to increase the prescribing of generics when available as seen with the PPIs, renin-angiotensin inhibitor drugs and statins [1, 38–41, 43–45, 59, 77]. We believe this is an important finding from this research. However, this finding is tempered by the recognised need to tailor pharmacological treatment for patients with schizophrenia or bipolar disease, especially with regard to issues such as weight gain and effectiveness in different patient populations, as well as reluctance among physicians to switch treatments when patients are stable on a particular atypical antipsychotic drug.
We believe a second important finding is that in some disease areas it is difficult for health authorities to encourage the preferential prescribing of multiple sourced versus patented drugs, apart from introducing measures such as prescribing restrictions for different formulations of a molecule . This illustrated by limited initiatives in any of the seven countries and regions to enhance the prescribing of oral risperidone following the introduction of generics. This is unlike the situation for the PPIs, renin-angiotensin inhibitor drugs and the statins [1, 38, 40, 42, 77]. We believe, based on our findings (especially those from Bury PCT following its activities (Figure 3) when recently it was very successful in significantly enhancing the prescribing of generic losartan versus patented ARBs (angiotensin receptor blocker) for treating hypertension with multiple demand-side measures ), that the influence of measures such as prescribing guidance or guidelines highlighting the preferential prescribing of generic atypical antipsychotic drugs as first line treatments may be limited. This is especially the case if there is a good clinical rationale for prescribing a patented product including concerns with weight gain. Additional measures could include instigating reimbursement restrictions for oral patented atypical antipsychotics, which is similar to the situation for long-acting risperidone injections in Austria and Belgium [47, 48]. However, such measures may again be difficult to implement, given the subjective nature of choosing pharmacological treatment options to maximise patient outcomes in these complex disease areas, and may even be counterproductive.
The considerable variation between European countries in the prescribing of oral generic risperidone versus originators (Table 5) reflects the different policies in these countries to encourage use of generics. The high rates seen in Scotland and Sweden suggest that there are no problems with generic risperidone in clinical practice. This is no doubt enhanced by the strict regulations for granting marketing authorisation for generics in Europe, with authorities removing generic products where concerns exist [63, 64, 78]. Consequently, the differences are down to different demand-side measures between the four countries. The high utilisation of oral generic risperidone in Scotland reflects generally high voluntary INN (International Non-proprietary Name) prescribing rates across classes. This starts with extensive physician education in medical school to prescribe by INN, which is followed up in ambulatory care through pharmacists working for the Health Boards monitoring the prescribing of drugs [40, 46, 49]. The high rates in Sweden reflect the instigation of compulsory generic substitution, including risperidone, apart from in a limited number of cases [39, 40, 56, 77, 79, 80]. We believe the high voluntary INN prescribing rates in the UK provides guidance to other countries. This is because such activities reduce patient confusion once multiple sources become available, especially if patients are dispensed different branded generics with different names on each occasion, without adequate explanation. This can happen in Sweden with compulsory generic substitution, apart from a limited number of situations authorised by the Medicine Product Agency , and more recently with monthly auctions as the cheapest branded generic secures an appreciable proportion of prescriptions for the molecule the following month [1, 38]. The dispensing of different branded generics on each occasion can possibly cause confusion and concern if patients do not receive adequate information about their medicines . This can potentially result in either duplication of medicines, or alternatively, in patients not taking their prescribed treatments as directed, which could be problematic [82, 83]. INN prescribing, apart from a limited number of well-known situations, is one way to address this [49, 80, 84, 85].
There were also appreciable differences between countries concerning the price of generic risperidone (Table 4). This reflects the different policies between the four countries with regard to enhancing the utilisation of generics, as well as their different pricing policies. The considerable price reduction for generic risperidone in Scotland, which is similar to those for other generics, follows recent reforms in the UK to enhance transparency in the cost of producing generics, as well as discounts offered by manufacturers to wholesalers and pharmacists to preferentially dispense their generic [41, 49]. The price reduction in Sweden, which is also similar to those for other generics, is a result of the introduction of compulsory generic substitution with the lowest priced molecule [1, 38, 80]. Generic prices are likely to fall further in Sweden with the recent introduction of monthly auctions, with the manufacturer who wins the auction being guaranteed a considerable proportion of dispensed generics the following month [1, 38]. The more modest price reduction for generic risperidone in Belgium reflects the current situation, where generic companies only have to lower their prices to the reference price level to be reimbursed. This was only 16% versus pre-patent loss prices until 2002, 20% until 2003, 26% until 2005, and is currently 31% [48, 68, 85]. The high prices for generics in Ireland reflect the limited measures to date to reduce these, although this is now changing [39, 86]. These findings are consistent with other research showing that the lowest prices for generics in Europe are seen in countries with the greatest market share [62, 63, 67]. Consequently, measures to increase the attractiveness of the generic market, as well as enhance the transparency in their pricing, as seen in Sweden and the UK, provide guidance to countries seeking ways to achieve further savings from the use of generics. This is especially the case where it is difficult to encourage the preferential prescribing of generics versus patented products, for example, atypical antipsychotic drugs.
We are aware there are a number of limitations with this study. This includes no access to patient data to assess whether there has been an increase in the prescribing of risperidone as first line treatment since the introduction of generics. In addition, there is no knowledge of the prescribed indications, especially with risperidone being the only atypical antipsychotic drug currently licensed for asymptomatic treatment in patients with dementia. However, the consistent continued decline in the utilisation of risperidone following the introduction of generics, coupled with increased utilisation of patented atypical antipsychotic drugs (Figures 1 and 2; Table 3), suggests there has been no increase in the prescribing of risperidone following generics. This may be enhanced by increased awareness of the lack of effect on weight with aripiprazole, and the effectiveness of aripiprazole and quetiapine ER in major depressive disorders. We have also not assessed whether there are any differences in outcomes between oral generic and originator risperidone. Previous research findings and the continued high utilisation of generic risperidone in Scotland and Sweden (Table 5) suggest there are no problems with generic atypical antipsychotic drugs in clinical practice [6, 46, 49, 50, 87]. However, again, we cannot say this with certainty without specific patient research. Finally, we are unable to determine or comment on the extent of any polypharmacy with atypical antipsychotic drugs.