Evaluating Appropriateness of Prescribing of Long-Acting Risperidone: DISCUSSION

antipsychotic agents

This retrospective evaluation focused on patients newly started on long-acting risperidone for injection because the appropriateness of this agent during the initial months of therapy requires an understanding of its unique pharmaco- kinetic characteristics. Thus, we aimed to describe the prescribing patterns for this relatively new antipsychotic formulation and to identify any knowledge gaps. The results showed that for 40% of the patients for whom appropriateness could be assessed, one or more of the criteria for appropriate prescribing were not fulfilled. This indicates a significant opportunity within the Fraser Health Authority to improve the use of this agent and to optimize patient outcomes.
In this study we were unable to assess overall appropriate­ness of prescribing for 27 (33%) of the 82 patients newly started on long-acting risperidone, largely because of early discharge from hospital. If it is assumed that prescribing was appropriate for all of these patients, then the overall proportion of patients with appropriate initial therapy would have been 73% (60/82). Conversely, if it is assumed that prescribing was inappropriate for all of these patients, then the overall propor­tion would have been only 40% (33/82). The actual rate of appropriate prescribing probably lies between these 2 values.

At the time of this study’s design, in June 2008, the only indications for long-acting risperidone for injection approved by Health Canada were schizophrenia and related psychotic disorders. Two of the patients in this study, who had bipolar I disorder, did not meet the study criterion for indication, but the drug has since been approved in Canada for this condition. As such, no improvements in prescribing are required in this area. However, the inclusion of bipolar I disorder as an indication for special authority coverage of long- acting risperidone for injection should be reassessed by PharmaCare. buy female viagra

In this study, 5 (9%) patients received the drug at intervals other than every 2 weeks. Among those patients, orders for a single dose were common, with no specification that the dose should be repeated at 2-week intervals. As a result, subsequent doses were given either 1 week early or 1 week late. Unlike the situation for other long-acting drugs given by injection, the effect of the first dose of long-acting risperidone will not be evident at the time the second dose is due; therefore, there is no pharmacokinetic reason to wait to specify the frequency or dose for the second injection. It is also important that orders for long-acting risperidone be written as continuation orders, to be administered every 2 weeks, so that the medication will be included on the active medication list when the patient is transferred or discharged from the hospital.A majority of patients newly started on long-acting risperidone received an initial dose of 25 mg. This is consistent with current recommendations for dose initiation, based on a prospective fixed-dose study that showed no additional benefit of starting with dosages above 25 mg every 2 weeks. In a more recent prospective study, however, in which patients receiving long-acting risperidone by injection were followed for 3 years, the authors found that patients were more likely to continue with therapy if the dosage was higher than 25 mg every 2 weeks. Given that current evidence pertaining to the dose—response relation for long-acting risperidone by injection is unclear, the current study did not include the initial dose as a criterion for evaluating the appropriateness of prescribing.
Three patients in the current study started long-acting risperidone at a dose of 12.5 mg. Despite a lack of clinical trials evaluating this dose, the manufacturer suggests that a starting dose of 12.5 mg may be appropriate for patients with certain clinical factors, such as renal or hepatic impairment, drug interactions with inhibitors of the cytochrome P450 2D6 isoenzyme (which may increase plasma levels of risperidone), or a history of movement disorders with antipsychotics. Accord­ing to the results of serum creatinine and liver enzyme tests, none of the patients who were started on the 12.5-mg dose had clinically significant renal or hepatic dysfunction, nor were any of them taking other medications that would have interacted significantly with risperidone. In addition, all of these patients received 25 mg as their second dose. Therefore, the reasons for starting these 3 patients on a lower dose of long-acting risperidone were not apparent and were unlikely to have been clinically meaningful.

Dose escalations of long-acting risperidone should not be made more frequently than every 4 weeks, given that observ­able drug effects should not be anticipated before this time. In an academic detailing study carried out in the United Kingdom, Paton and others found that only 50% of prescribing psychiatrists understood that it takes at least 6 weeks to reach steady-state plasma concentrations at any given dose. In the present study, almost one-quarter of the patients received premature dose increases. Most of these patients received an initial 25-mg dose, followed by a 37.5-mg dose 2 weeks later. However, according to information available in the health records, there was no evidence to suggest that any of these patients were stabilized and that they had tolerated higher doses of long-acting risperidone in the past. The most common reason for increasing the dose of the second injection was lack of efficacy. Given the kinetics of long-acting risperidone for injection, whereby appreciable drug release does not occur until 3 weeks after the first injection, this practice would be questionable, because patients and clinicians would not have had an opportunity to assess any response at 2 weeks after the initial injection. Clinicians should also be aware that if the dose is increased too quickly, it becomes more difficult to manage possible extrapyramidal side effects, since the medication will remain in the patient’s system for a prolonged period. Additionally, if a higher dose is the ultimate target, then starting at 25 mg simply prolongs the time to achieve steady state. To see the effects of any specific dose, conservative practitioners should wait at least 6 weeks to assess patients at steady-state drug levels before making dose adjustments. This appears to represent a significant gap in prescribers’ knowledge about this drug formulation. canadian pharmacy viagra

Long-acting risperidone for injection is the only antipsychotic for depot injection currently available for which antipsychotic supplementation for at least 3 weeks is recommended for new users. Prescribers should be aware that the drug has a significantly slower onset of action than conven­tional antipsychotic depot drugs. In this study, 13% of patients did not receive 3 full weeks of antipsychotic supplementation. This is similar to the finding in a larger retrospective study that 16.5% of 1232 acute care patients did not receive oral supplementation during the first 3 weeks.

Category: Drug

Tags: antipsychotic agents, delayed-action preparations, long-acting medications, physicians' practice patterns, retrospective study, risperidone

Leave a Reply

Your email address will not be published. Required fields are marked *