THERE IS NO evidence that a combination of antipsychotics is more effective than a single antipsychotic. In addition, combining antipsychotics is a major cause of excessive dosing, and evidence shows that excessive dosing of antipsychotics increases side-effects[1, 3] and mortality. Guidelines and algorithms have recommended that antipsychotic medications for patients with schizophrenia be prescribed simply, using an optimal dose.[5, 6] However, there are discrepancies between these guidelines or algorithms and actual prescription patterns, as excessive dosing and polypharmacy of antipsychotics are prevalent in East Asia.[7, 8]
Within mental health care units, patients are often administered unscheduled medications. The unscheduled medications fall into two categories: stat medication and p.r.n. medication. Although these categories are not clearly differentiated in previous studies, stat medication usually refers to medication prescribed and administered on the basis of doctors' decisions in addition to regularly prescribed medications, whereas p.r.n. medication refers to medication prescribed by doctors in advance, and administration on an as-needed basis according to nurses' clinical judgment under doctors' instructions. The use of p.r.n. psychotropic medication is a widespread but not fully proven interim method of treating acute psychotic symptoms or behavioral disturbances thought to be secondary to psychotic illness. Antipsychotics are one class of drug used as a p.r.n. psychotropic medication.[11, 12] A previous study showed that most psychotic patients are administered at least one dose of p.r.n. antipsychotic during their hospital stay. Furthermore, patients with schizophrenia in acute mental health-care settings may be given p.r.n. psychotropic medications frequently and at high doses. The main disadvantage of this practice is the misuse of medication, that is, the administration of too much medication or the administration of medication too quickly. This misuse may be caused by variations in nurses' opinions regarding the need for p.r.n. psychotics, punitive indications, or over-reliance on medication.
Recent studies revealed that cultural factors and the practice of adding p.r.n. psychotropic medication to regular medicine might increase the risk for excessive dosing and polypharmacy of antipsychotics.[17, 18] There are no published reports of prescription surveys assessing the use of p.r.n. psychotropic medication, excessive dosing, or polypharmacy of antipsychotics in East Asia. Previous studies have indicated that more Japanese patients with schizophrenia are prescribed antipsychotics at high doses than patients in other East Asian countries.[7, 8] It is thus important to investigate the risk of excessive dosing and polypharmacy of antipsychotics caused by p.r.n. psychotropic medication in Japan.
Aims of the study
Agitation is commonly cited as the rationale for both the prescription and administration of p.r.n. psychotropic medication. Patients with schizophrenia or related disorders who are admitted to acute psychiatric units may urgently require the reduction of agitation, and thus p.r.n. psychotropic medication is often prescribed and administered before regular antipsychotic medications have had a chance to take effect. In the present multi-center study, we investigated whether the prescription and administration of p.r.n. antipsychotics to agitated patients with schizophrenia increased the risk of excessive dosing and polypharmacy of antipsychotics in acute care settings.
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In the present study, at least one p.r.n. psychotropic medication for agitation was prescribed to three-quarters of patients with schizophrenia. Of those p.r.n. medications, nine-tenths were antipsychotics. Of these antipsychotics, 70% were SGA. Among the 281 patients who were prescribed p.r.n. antipsychotics for ‘agitation,’ the numbers of patients with excessive dosing and polypharmacy increased significantly after p.r.n. antipsychotics were added to the patients' regular medications, and the mean dosage and total daily doses of antipsychotics increased by 20%. Actually, 4% of patients who were prescribed p.r.n. antipsychotics for ‘agitation,’ were administered at least one p.r.n. psychotropic medication on only one survey day, and all the patients received excessive dosing or polypharmacy of antipsychotics as a result. These patients stayed longer than patients who were not actually administered p.r.n. antipsychotics on the survey day.
The present study suggests that the prescription of p.r.n. psychotropic medication may lead to the administration of antipsychotics outside of recommended prescription guidelines. In particular, there are serious problems related to the prescription of p.r.n. psychotropic medications for agitated patients with schizophrenia who are vulnerable to repeated dosing.[9, 14, 22] In the present study, patients who were administered p.r.n. antipsychotics on the survey day stayed longer in acute psychiatric wards and received more excessive dosing and polypharmacy of antipsychotic medication than other patients. The previous study showed that p.r.n. psychotropic medications are likely to be administered to patients in the first 4 days of admission, or to those who remain in hospital for longer periods of time. The patients who remain in hospital for longer periods may be refractory cases, and may be more vulnerable to repeated doses of p.r.n. psychotropic medication. In those cases in which p.r.n. antipsychotics were prescribed and administered repeatedly and over a long term, p.r.n. antipsychotics were shown to cause hidden excessive dosing and polypharmacy of antipsychotic medication.[17, 18] The p.r.n. process in psychiatric wards is complicated and potentially allows nurses to use their clinical judgment regarding the administration of p.r.n. medications prescribed by doctors. The proper use of p.r.n. antipsychotics by nurses depends on several factors, including clinical settings, preference for medication, relationship with doctors,[17, 25] nursing experience, nursing technique, and working environment.
The problems of hidden excessive dosing and polypharmacy of antipsychotics cannot be solved without optimization of the practice of prescribing and administering p.r.n. psychotropic medication. Currently, regarding stat psychotropic medication that is mainly the responsibility of doctors, we can refer to the guidelines for standard pharmacotherapy for patients with schizophrenia[5, 6] and to the guidelines for standard management of violence or agitation. These guidelines suggest that rapid tranquillization as an intervention for the short-term management of agitation with benzodiazepines or antipsychotics is both reasonably effective and safe. However, regarding p.r.n. psychotropic medication with which nurses' clinical decisions are closely involved, the guidelines suggest that the use of p.r.n. medication for the short-term management of agitation in psychiatric in-patient settings is inconsistent and the medication may not be appropriately administered or monitored. There is no high-quality evidence regarding the risks and benefits of p.r.n. psychotropic medication.[10, 26]
In many circumstances, there are no clear-cut clinical guidelines regarding p.r.n. psychotropic medication. It is possible that a non-pharmacological approach or a benzodiazepine may be a better initial approach than p.r.n. antipsychotics in agitated patients with schizophrenia who do not require rapid tranquilization. However, a previous study found that barriers to the acute use of benzodiazepines include doubts about their efficacy and concerns about drug dependence, despite evidence showing the safety and effectiveness of these drugs. It is possible that the present findings reflect the belief among Japanese psychiatrists and nurses that antipsychotics are more effective than benzodiazepines for agitated patients with schizophrenia.
In general, although SGA have fewer side-effects than FGA,[29, 30] SGA should be prescribed carefully in terms of their additional use as p.r.n. psychotropic medications. Evidence suggests that these drugs can cause adverse effects, such as Parkinson's-like syndrome, sexual dysfunction, and metabolic syndrome, which may affect treatment adherence.[31, 32] All three types of polypharmacy of antipsychotics as described in the present study can alter the predicted efficacy and adverse effects of medications through complex pharmacokinetics.[33-35] The risk-to-benefit ratio for the use of SGA on a p.r.n. basis may not be acceptable. It is recommended that one antipsychotic should be added to another antipsychotic only with careful consideration. However, the present study suggests that the use of SGA as p.r.n. psychotropic medications is common, and this practice may induce a high percentage of combination therapies, such as type 2 polypharmacy or type 3 polypharmacy.
Some studies and expert-consensus statements recommend that both doctors and nurses should carefully examine the necessity for the prescription and administration of p.r.n. antipsychotics, and that psychiatric services should provide educational programs for mental health professionals and reach consensus about the proper way to use p.r.n. medications.[25, 37] Doctors and nurses should attempt various approaches to minimize the unnecessary use of unscheduled psychotropic medication. These approaches might be reviewing clinical indications, frequency of administration, therapeutic benefits and side-effects each week, for instance. Results in this study suggest that p.r.n. medication practice be listed as a quality indicator in psychiatric inpatient care. The careful monitoring of p.r.n. medication practice could improve the quality and safety of psychiatric care.
This study contains the limitation that few patients were administered p.r.n. due to the short-term study period. We could not identify the potential for the risk of excessive dosing and polypharmacy in patients who were actually administered p.r.n. antipsychotics. As this study was intended as a prescription survey, not as a survey of patients in an interventional manner, we could not gather complete profiles of patients, including the clinical characteristics of symptoms and co-morbidities.
In conclusion, p.r.n. antipsychotics may cause hidden excessive dosing and polypharmacy of antipsychotics. Our results indicate the importance of monitoring the prescription and administration of p.r.n. antipsychotic medication to patients with schizophrenia.
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This study was conducted with the aid of Sponsored Research on Psychiatric and Neurological Diseases and Mental Health Research 2008, supported by the Ministry of Health, Labor and Welfare, Japan (Grant No; 20-8). The opinions expressed in this article are those of the authors and do not represent the official views of the Ministry. We are especially grateful to the members of the Japan Psychiatric Nurses Association, Keiko Matsumoto PhD, Mr Tamio Sueyasu MNSc, and Ms Sakae Nakano for data collection. The researchers would also like to thank the hospital staff who assisted with the survey.
No author reports that there is any conflict of interests to declare.