Skip to main content

The characteristics of discharge prescriptions including pro re nata psychotropic medications for patients with schizophrenia and major depressive disorder from the survey of the “Effectiveness of guidelines for dissemination and education in psychiatric treatment (EGUIDE)” project

Abstract

Background

Several guidelines recommend monotherapy in pharmacotherapy for schizophrenia and major depressive disorder. The content of regular prescriptions has been reported in several studies, but not enough research has been conducted on the content of pharmacotherapy, including pro re nata (PRN) medications. The purpose of this study was to evaluate the content of pharmacotherapy, including PRN medications, and to clarify the relationship with regular prescriptions.

Methods

We used data from the “Effectiveness of Guidelines for Dissemination And Education in psychiatric treatment” (EGUIDE) project to investigate the presence or absence of PRN psychotropic medications at discharge for each drug category. We compared the PRN psychotropic prescription ratio at discharge by diagnosis for each drug category. The antipsychotic monotherapy ratio and no prescription ratio of other psychotropics for schizophrenia at discharge and the antidepressant monotherapy ratio and no prescription ratio of other psychotropics for major depressive disorder at discharge were calculated for each regular prescription, including PRN psychotropic medications, as quality indicators (QIs). Spearman's rank correlation test was performed for QI values of regular prescriptions and the QI ratio between regular prescriptions and prescriptions including PRN medications for each diagnosis.

Results

The PRN psychotropic prescription ratio at discharge was 28.7% for schizophrenia and 30.4% for major depressive disorder, with no significant differences by diagnosis. The prescription ratios of PRN antipsychotic medications and PRN antiparkinsonian medications were significantly higher for schizophrenia. The prescription ratios of PRN anxiolytic and hypnotic and PRN antidepressant medications were significantly higher for patients with major depressive disorder. For both schizophrenia and major depressive disorder, the QI was lower for discharge prescriptions, including PRN medications, than for regular prescriptions. QI values for regular prescriptions and the QI ratio were positively correlated.

Conclusions

Considering PRN psychotropic medications, the monotherapy ratio and no prescription ratio of other psychotropics at discharge decreased in pharmacotherapy for schizophrenia and major depressive disorder. A higher ratio of monotherapy and no prescription of other psychotropics on regular prescriptions may result in less concomitant use of PRN psychotropic medications. Further studies are needed to optimize PRN psychotropic prescriptions.

Background

Schizophrenia and major depressive disorder are serious chronic disorders that cause impaired social functioning [1, 2], and pharmacotherapy is an important part of their treatment. Several guidelines recommend monotherapy with antipsychotics for schizophrenia [3, 4] and monotherapy with antidepressants for major depressive disorder [5,6,7,8]. The “Effectiveness of Guidelines for Dissemination and Education in psychiatric treatment” (EGUIDE) project is a nationwide multicenter study launched in Japan in 2016 [9]. The EGUIDE project is an educational program for psychiatrists on guidelines for schizophrenia and major depressive disorder, and the content of inpatient treatment is quantified as a quality indicator (QI) and evaluated over time [10,11,12,13,14,15,16,17,18,19]. A QI is an indicator for quality of care by assessing the structure, process, and result of medical care and helps to assess whether a patient's care is consistent with the evidence-based standard of care [20]. The results from the EGUIDE project show monotherapy rates at discharge and concomitant rates of other psychotropic medications as QIs of treatment [10, 11]. For example, the antipsychotic monotherapy ratio in the inpatient treatment of schizophrenia in Japan is approximately 60%, and the antidepressant monotherapy ratio in the inpatient treatment of major depressive disorder in Japan is approximately 60%. However, these QIs were calculated for regular prescriptions that are taken daily on a regular basis.

In the psychiatric field, pro re nata (PRN) psychotropic medications are often used “as needed” for psychiatric symptoms such as agitation and insomnia, in addition to regular pharmacotherapy. It has been reported that PRN psychotropic medications are prescribed to 70–90% of patients hospitalized for psychiatric disorders [21, 22]. Moreover, the study from the EGUIDE project reported that the PRN psychotropic prescription ratio was approximately 30% for inpatients with schizophrenia and major depressive disorder, even for discharge prescriptions [15]. Previous studies on the frequency of PRN psychotropic medication use have been limited to local settings, at a single or a few facilities, and to a wide range of psychiatric diagnoses. A study in an adolescent acute psychiatric ward reported that the average use of PRN psychotropic drugs was 0.35 times/day (standard deviation (SD) = 0.60) [23]. In addition, a single-center study on 205 patients admitted for the treatment of schizophrenia reported that the use of PRN psychotropic drugs was 0–4.18 times/day, with a mean of 0.48 times/day (SD = 0.73) [24]. These reports suggest that PRN psychotropic medication is a frequently used treatment. Therefore, QIs, such as the monotherapy ratio, should be evaluated not only for regular prescriptions but also for pharmacotherapies, including PRN psychotropic medications. There is no high-quality evidence on the effectiveness of PRN psychotropic medications, and PRN psychotropic drug use is based on clinical experience and habits [25]. Furthermore, it has been suggested that PRN psychotropic drug prescriptions are at risk of leading to polypharmacy and high-dose prescribing [15, 26, 27]. It has also been suggested that the use of PRN psychotropic medications may in fact prolong hospital stay and increase readmission rate [24]. Thus, PRN psychotropic medications are widely used without sufficient evidence to recommend their use, and factors related to their prescription need to be clarified.

In this study, we aimed to reevaluate the pharmacotherapy of inpatients with schizophrenia and major depressive disorder at discharge in Japan, including the use of PRN psychotropic drugs. The data from the EGUIDE project were used to examine the content of prescriptions that included PRN psychotropic drugs for each drug category.

Methods

This study was a continuous, nationwide, cross-sectional study. This study was approved by the ethics committees of the National Center for Neuropsychiatry and Neurology (approval number B2022-004) and the participating EGUIDE sites. This study was conducted in compliance with the Declaration of Helsinki and its amendments. The study protocol was registered in the University Hospital Medical Information Network Registry (UMIN000022645). We created a dataset of the treatment at discharge between April and September of each year from 2016 to 2020 from the 240 hospitals that participated in the EGUIDE project. Using this dataset, a pharmacotherapy survey was conducted, including PRN psychotropic prescriptions, on patients with diagnoses of schizophrenia and major depressive disorder discharged from each facility between April and September of the first year of participation in the EGUIDE project. Patients were able to opt out of the purpose and procedures of the study and refuse study participation. We gathered the medical record information of patients at each institution with opt-out consent. Diagnoses of schizophrenia and major depressive disorder were made according to the Diagnostic and Statistical Manual of Mental Disorders 5th edition [28]. For patients who were hospitalized multiple times, only the treatment of the first hospitalization was included. Patients whose discharge prescriptions were unknown were excluded from the study. In addition, we excluded patients with schizophrenia who did not have regular prescriptions of antipsychotics at discharge and patients with major depressive disorder who did not have regular prescriptions of antidepressants at discharge. Prescription data of 2498 patients who were diagnosed with schizophrenia and 1022 patients who were diagnosed with major depressive disorder (MDD) were gathered from 97 institutions.

We investigated the age at discharge and sex of the patients and the presence or absence of PRN psychotropic prescriptions at discharge for each psychotropic drug category. We performed t-test and χ2 tests on the association between each diagnosis and age; and sex. We then performed χ2 tests on the association between each diagnosis and PRN psychotropic prescription ratio at discharge for each psychotropic drug category.

In addition, QI values for regular prescriptions at discharge and for prescriptions including PRN psychotropic drugs at discharge were calculated. Additional file 1: Tables S1 and S2 show the specifics of QIs in this study. Furthermore, the ratio of QI values for prescriptions, including PRN medications, to QI values for regular prescriptions was calculated. Spearman's rank correlation test was performed on QI values for regular prescriptions and the QI ratio between regular prescriptions and prescriptions including PRN medications for each diagnosis. Because we performed the analysis 7 times throughout this study, the significance level of 5% was set at 5.5 × 10–3 (0.05/9) with Bonferroni correction due to multiple testing. All statistical analyses were performed using IBM SPSS Statistics 26.0 (IBM Co., Armonk, NY, USA) and Excel (Microsoft, Redmond, WA, USA).

Results

The PRN psychotropic prescription ratio at discharge for each drug category and demographic data for the patients are shown in Table 1. There was no difference in the PRN psychotropic prescription ratio between schizophrenia and MDD. For each psychotropic category, the PRN antipsychotic prescription ratio was significantly higher for schizophrenia than for MDD (p = 4.9 × 10–9, df (1) = 34.22). The PRN anxiolytic and hypnotic prescription ratio was significantly higher for MDD than for schizophrenia (p = 2.0 × 10–3, df (1) = 9.51). The PRN antidepressant prescription ratio was significantly higher for MDD than for schizophrenia (p = 9.4 × 10–6, df (1) = 19.63). The PRN antiparkinsonian prescription ratio was significantly higher for schizophrenia than for MDD (p = 1.5 × 10–4, df (1) = 14.42).

Table 1 Demographic and clinical data

The PRN prescription ratios by drug category for patients with PRN psychotropic prescriptions at discharge are shown in Additional file 1: Table S3. Among patients with schizophrenia, more than half had PRN antipsychotic prescriptions and PRN anxiolytic and hypnotic prescriptions, whereas less than 10% had PRN antidepressant prescriptions and PRN antiparkinsonian prescriptions. Among patients with MDD, more than half had PRN anxiolytic and hypnotic prescriptions, whereas less than 10% had PRN antidepressant prescriptions and PRN antiparkinsonian prescriptions.

In addition, Tables 2 and 3 show the QI values for regular prescriptions, prescriptions including PRN medications, and the QI ratio between regular prescriptions and prescriptions including PRN medications.

Table 2 QI values for patients with schizophrenia
Table 3 QI values for patients with major depressive disorder

A positive correlation was found between QI values for regular prescriptions and the QI ratio for schizophrenia [rs = 0.965, p = 1.8 × 10–3] (Fig. 1A). A positive correlation was also found between QI values for regular prescriptions and the QI ratio for MDD [rs = 0.963, p = 2.0 × 10–3)] (Fig. 1B).

Fig. 1
figure 1

Relations between quality indicator (QI) for regular prescriptions and QI ratio in schizophrenia in Figure A (left-hand) and in major depressive disorder in Figure B (right-hand)

Discussion

This is the first study to investigate PRN psychotropic prescriptions at discharge in inpatient treatment of schizophrenia and MDD by drug category. PRN psychotropic medications were prescribed at discharge to 28.7% of patients with schizophrenia and 30.4% of patients with MDD. There were no significant differences in the PRN psychotropic prescription ratio by diagnosis. On the other hand, the PRN antipsychotic prescription ratio and PRN antiparkinsonian prescription ratio were significantly higher for patients with schizophrenia than for those with MDD. The PRN anxiolytic and hypnotic prescription ratio and PRN antidepressant prescription ratio were significantly higher for patients with MDD than for patients with schizophrenia. This difference suggests that PRN psychotropic medications in certain drug categories are more likely to be prescribed depending on the diagnosis. Generally, antipsychotics are prescribed for SZ and antidepressants for MDD [3,4,5,6,7,8]. Therefore, it is obvious that the kind of prescribed medication depends on the diagnosis. It has been reported that PRN antipsychotic medications aimed at calming acute agitation are more common for patients with schizophrenia [26]. For this reason, PRN antipsychotic prescriptions might be more common for patients with schizophrenia than for those with MDD. PRN antidepressant medications were prescribed at low rates for both schizophrenia and MDD, possibly because antidepressants have fewer sedative effects [29, 30] and take time to develop their effects [31]. In addition, the guidelines for patients with SZ do not recommend prescribing antidepressants for SZ [3, 4]. Nevertheless, PRN antidepressants were prescribed to some SZ patients in this study. Therefore, education and dissemination of guideline-based treatment is required for PRNs as well. Since anticholinergics are widely used for the treatment and prevention of extrapyramidal symptoms produced by antipsychotics, especially acute dystonia [32], the PRN antiparkinsonian prescription ratio may have been higher for schizophrenia than for MDD. Insomnia is a frequent symptom in both schizophrenia and MDD [33,34,35] and may be one reason for the high PRN anxiolytic and hypnotic prescription ratio for both disorders.

In this study, the QI values decreased with the inclusion of PRN prescriptions for all QIs except no prescription ratio of mood stabilizers and antiepileptics. A previous study suggested that the polypharmacy ratio increases when PRN prescriptions are included [36], and a similar trend might be observed in this study. Furthermore, a positive correlation was found between QI values for regular prescriptions and the QI ratio for both schizophrenia and MDD. This means that higher QI values for regular prescriptions indicate a smaller reduction in QI values for prescriptions including PRN medications. Higher QI values for regular prescriptions indicate that there are fewer concomitant medications in that drug category on regular prescriptions, and a smaller reduction in QI values for prescriptions including PRN medications indicates fewer PRN prescriptions in that drug category. In other words, these results suggest that drug categories that are less likely to be used in combination on regular prescriptions are less likely to be prescribed as PRN medications. Despite several guidelines [3,4,5,6,7,8] recommending monotherapy for the treatment of schizophrenia and MDD, in clinical practice, both schizophrenia and MDD are treated with multiple psychotropics [37,38,39]. PRN psychotropic prescriptions are habitually practiced without sufficient evidence [25], and the need for guidelines on the proper use of PRN medications has been pointed out [24, 40, 41]. The results of this study suggest that promoting monotherapy as recommended in the guidelines, taking PRN medications into consideration, may lead to a reduction in PRN psychotropic prescriptions, which in turn may lead to an improvement in the QI value of each drug category. It has also been noted that PRN psychotropic medications for hospitalized patients may continue to be prescribed without regular monitoring of their use, and the need for education of health care providers regarding PRN psychotropic medications has been noted [24]. The EGUIDE project reported that educational programs on guidelines improved the clinical knowledge of participants [9], and there is a need to accumulate evidence on PRN psychotropic medications and provide appropriate education regarding PRN medications in the future.

Limitations

There are several limitations in this study. First, this study did not assess the severity of psychiatric symptoms using a rating scale such as the Positive and Negative Syndrome Scale or the Hamilton Depression Rating Scale. Since treatment for patients with SZ and MDD may be influenced by the severity of the patients [3,4,5,6,7,8], further studies are needed taking into account the severity of illness. Second, this study examined only the presence or absence of PRN psychotropic prescriptions at discharge and did not assess the frequency of PRN medication use during hospitalization or the amount used per visit. Therefore, further studies are needed taking into account the frequency of PRN use during hospitalization and the amount of PRN used per visit. Third, the data in this study were collected from medical institutions that voluntarily participated in the survey, approximately half of which were university hospitals, which limits the generalizability of the results.

Conclusion

Regarding PRN psychotropic medications, the monotherapy ratio and no prescription of other psychotropic medications ratio at discharge decreased in the pharmacotherapy for schizophrenia and MDD. A higher ratio of monotherapy and no prescription of other psychotropics on regular prescriptions may result in less concomitant use of PRN psychotropic medications. Further studies are needed to optimize PRN psychotropic prescriptions.

Availability of data and materials

The datasets generated and/or analyzed during the current study are not publicly available due to privacy and ethical restrictions (i.e., we did not obtain informed consent on the public availability of raw data) but are available from the corresponding author on reasonable request.

Abbreviations

df:

Degrees of freedom

EGUIDE:

The effectiveness of guidelines for dissemination and education in psychiatric treatment

MDD:

Major depressive disorder

PRN:

Pro re nata

QI:

Quality indicator

References

  1. Onitsuka T, Hirano Y, Nakazawa T, Ichihashi K, Miura K, Inada K, et al. Toward recovery in schizophrenia: current concepts, findings, and future research directions. Psychiatry Clin Neurosci. 2022;76(7):282–91. https://doi.org/10.1111/pcn.13342.

    Article  CAS  Google Scholar 

  2. Vuorilehto MS, Melartin TK, Isometsä ET. Course and outcome of depressive disorders in primary care: a prospective 18-month study. Psychol Med. 2009;39(10):1697–707. https://doi.org/10.1017/S0033291709005182.

    Article  CAS  Google Scholar 

  3. American Psychiatric Association. The American Psychiatric Association Practice Guideline for the treatment of patients with Schizophrenia. 3rd ed. Washington D.C: American Psychiatric Association; 2021.

    Google Scholar 

  4. Japanese Society of Neuropsychopharmacology. Guideline for pharmacological therapy of Schizophrenia. Neuropsychopharmacol Rep. 2021;41:266–324. https://doi.org/10.1002/npr2.12193.

    Article  Google Scholar 

  5. American Psychiatric Association. Practice guideline for the treatment of patients with major depressive disorder. 3rd ed. Washington D.C: American Psychiatric Association; 2010.

    Google Scholar 

  6. Ogasawara K. Ozaki N [Review of the new treatment guideline for major depressive disorder by the Japanese Society of Mood Disorders]. Brain Nerve. 2012;64:1159–65.

    Google Scholar 

  7. Higuchi T. Major depressive disorder treatment guidelines in Japan. J Clin Psychiatry. 2010. https://doi.org/10.4088/JCP.9058se1c.05gry.

    Article  Google Scholar 

  8. Baba H, Kito S, Nukariya K, Takeshima M, Fujise N, Iga J, Oshibuchi H, Kawano M, Kimura M, Mizukami K, Mimura M. Committee for treatment guidelines of mood disorders, Japanese society of mood disorders. Guidelines for diagnosis and treatment of depression in older adults: a report from the Japanese Society of mood disorders. Psychiatry Clin Neurosci. 2022;76(6):222–34.

    Article  Google Scholar 

  9. Takaesu Y, Watanabe K, Numata S, Iwata M, Kudo N, Oishi S, et al. Improvement of psychiatrists’ clinical knowledge of the treatment guidelines for schizophrenia and major depressive disorders using the “Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE)” project: a nationwide dissemination, education, and evaluation study. Psychiatry Clin Neurosci. 2019;73(10):642–8. https://doi.org/10.1111/pcn.12911.

    Article  Google Scholar 

  10. Ichihashi K, Hori H, Hasegawa N, Yasuda Y, Yamamoto T, Tsuboi T, et al. Prescription patterns in patients with schizophrenia in Japan: first-quality indicator data from the survey of “Effectiveness of Guidelines for Dissemination and Education in psychiatric treatment (EGUIDE)” project. Neuropsychopharmacol Rep. 2020;40(3):281–6. https://doi.org/10.1002/npr2.12122.

    Article  Google Scholar 

  11. Iida H, Iga J, Hasegawa N, Yasuda Y, Yamamoto T, Miura K, et al. Unmet needs of patients with major depressive disorder—findings from the “Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE)” project: a nationwide dissemination, education, and evaluation study. Psychiatry Clin Neurosci. 2020;74(12):667–9. https://doi.org/10.1111/pcn.13143.

    Article  Google Scholar 

  12. Numata S, Nakataki M, Hasegawa N, Takaesu Y, Takeshima M, Onitsuka T, et al. Improvements in the degree of understanding the treatment guidelines for schizophrenia and major depressive disorder in a nationwide dissemination and implementation study. Neuropsychopharmacol Rep. 2021;41(2):199–206. https://doi.org/10.1002/npr2.12173.

    Article  Google Scholar 

  13. Hashimoto N, Yasui-Furukori N, Hasegawa N, Ishikawa S, Numata S, Hori H, et al. Characteristics of discharge prescriptions for patients with schizophrenia or major depressive disorder: Real-world evidence from the Effectiveness of Guidelines for Dissemination and Education (EGUIDE) psychiatric treatment project. Asian J Psychiatr. 2021;63: 102744. https://doi.org/10.1016/j.ajp.2021.102744.

    Article  Google Scholar 

  14. Furihata R, Otsuki R, Hasegawa N, Tsuboi T, Numata S, Yasui-Furukori N, et al. Hypnotic medication use among inpatients with schizophrenia and major depressive disorder: results of a nationwide study. Sleep Med. 2022;89:23–30. https://doi.org/10.1016/j.sleep.2021.11.005.

    Article  Google Scholar 

  15. Ichihashi K, Kyou Y, Hasegawa N, Yasui-Furukori N, Shimizu Y, Hori H, et al. The characteristics of patients receiving psychotropic pro re nata medication at discharge for the treatment of schizophrenia and major depressive disorder: a nationwide survey from the EGUIDE project. Asian J Psychiatr. 2022;69: 103007. https://doi.org/10.1016/j.ajp.2022.103007.

    Article  Google Scholar 

  16. Yamada H, Motoyama M, Hasegawa N, Miura K, Matsumoto J, Ohi K, et al. A dissemination and education programme to improve the clinical behaviours of psychiatrists in accordance with treatment guidelines for schizophrenia and major depressive disorders: the Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE) project. BJPsych Open. 2022;8(3): e83. https://doi.org/10.1192/bjo.2022.44.

    Article  Google Scholar 

  17. Muraoka H, Kodaka F, Hasegawa N, Yasui-Furukori N, Fukumoto K, Kashiwagi H, et al. Characteristics of the treatments for each severity of major depressive disorder: a real-world multi-site study. Asian J Psychiatr. 2022;18(74): 103174. https://doi.org/10.1016/j.ajp.2022.103174.

    Article  Google Scholar 

  18. Ogasawara K, Numata S, Hasegawa N, Nakataki M, Makinodan M, Ohi K, et al. Subjective assessment of participants in education programs on clinical practice guidelines in the field of psychiatry. Neuropsychopharmacol Rep. 2022;42(2):221–5. https://doi.org/10.1002/npr2.12245.

    Article  Google Scholar 

  19. Ochi S, Tagata H, Hasegawa N, Yasui-Furukori N, Iga JI, Kashiwagi H, et al. Clozapine treatment is associated with higher prescription rate of antipsychotic monotherapy and lower prescription rate of other concomitant psychotropics: a real-world nationwide study. Int J Neuropsychopharmacol. 2022. https://doi.org/10.1093/ijnp/pyac036.

    Article  Google Scholar 

  20. Mainz J. Defining and classifying clinical indicators for quality improvement. Int J Qual Health Care. 2003;15(6):523–30. https://doi.org/10.1093/intqhc/mzg081.

    Article  Google Scholar 

  21. John AB, Karina L, Neil H. A best-evidence synthesis review of the administration of psychotropic pro re nata (PRN) medication in in-patient mental health settings. J Clin Nurs. 2008;17:1122–31. https://doi.org/10.1111/j.1365-2702.2007.02236.x.

    Article  Google Scholar 

  22. Krystle M, Vinita A, Ilan F, Renee T. Descriptive analysis of pro re nata medication use at a Canadian psychiatric hospital. Int J Ment Health Nurs. 2017;226:402–8. https://doi.org/10.1111/inm.12265.

    Article  Google Scholar 

  23. Saito E, Eng S, Grosso C, Ozinci Z, Van Meter A. Pro Re Nata medication use in acute care adolescent psychiatric unit. J Child Adolesc Psychopharmacol. 2020;30(4):250–60. https://doi.org/10.1089/cap.2019.0131.

    Article  Google Scholar 

  24. Kyou Y, Oishi S, Takizawa T, Yoshimura Y, Hashimoto I, Suzuki R, et al. Influence of psychotropic pro re nata drug use on outcomes in hospitalized patients with schizophrenia. Clin Psychopharmacol Neurosci. Papers in press available online. https://www.cpn.or.kr/submission/Source/Search.html?tmp_tr_num=2357

  25. Douglas-Hall P, Whicher E. “As required” medication regimens for seriously mentally ill people in hospital. Cochrane Database Syst Rev. 2015;7:CD003441.

    Google Scholar 

  26. Fujita J, Nishida A, Sakata M, Noda T, Ito H. Excessive dosing and polypharmacy of antipsychotics caused by pro re nata in agitated patients with schizophrenia. Psychiatry Clin Neurosci. 2013;67:345–51. https://doi.org/10.1111/pcn.12056.

    Article  CAS  Google Scholar 

  27. Paton C, Barnes TRE, Cavanagh M-R, Taylor D, Lelliott P, Team PUP. High-dose and combination antipsychotic prescribing in acute adult wards in the UK: the challenges posed by p.r.n. prescribing. Br J Psychiatry. 2008;192:435–9.

    Article  Google Scholar 

  28. American Psychiatric Publishing. DSM-5 diagnostic and statistical manual of mental health disorders. 5th ed. Arlington, VA: American Psychiatric Publishing; 2013.

    Book  Google Scholar 

  29. Jindal RD. Insomnia in patients with depression: some pathophysiological and treatment considerations. CNS Drugs. 2009;23(4):309–29. https://doi.org/10.2165/00023210-200923040-00004.

    Article  CAS  Google Scholar 

  30. Wichniak A, Wierzbicka A, Walęcka M, Jernajczyk W. Effects of antidepressants on sleep. Curr Psychiatry Rep. 2017;19(9):63. https://doi.org/10.1007/s11920-017-0816-4.

    Article  Google Scholar 

  31. Malhi GS, Bell E, Morris G, Hamilton A. The delay in response to antidepressant therapy: a window of opportunity? Aust N Z J Psychiatry. 2020;54(2):127–9. https://doi.org/10.1177/0004867419900313.

    Article  Google Scholar 

  32. Bezchlibnyk-Butler KZ, Remington GJ. Antiparkinsonian drugs in the treatment of neuroleptic-induced extrapyramidal symptoms. Can J Psychiatry. 1994;39(2):74–84. https://doi.org/10.1177/070674379403900203.

    Article  CAS  Google Scholar 

  33. Liu X, Buysse DJ, Gentzler AL, Kiss E, Mayer L, Kapornai K, et al. Insomnia and hypersomnia associated with depressive phenomenology and comorbidity in childhood depression. Sleep. 2007;30(1):83–90. https://doi.org/10.1093/sleep/30.1.83.

    Article  Google Scholar 

  34. Sunderajan P, Gaynes BN, Wisniewski SR, Miyahara S, Fava M, Akingbala F, et al. Insomnia in patients with depression: a STAR*D report. CNS Spectr. 2010;15(6):394–404. https://doi.org/10.1017/s1092852900029266.

    Article  Google Scholar 

  35. Robertson I, Cheung A, Fan X. Insomnia in patients with schizophrenia: current understanding and treatment options. Prog Neuropsychopharmacol Biol Psychiatry. 2019;8(92):235–42. https://doi.org/10.1016/j.pnpbp.2019.01.016.

    Article  Google Scholar 

  36. Kaikoushi K, Karanikola M, Middleton N, Bella E, Chatzittofis A. Prescription patterns in psychiatric compulsory care: polypharmacy and high-dose antipsychotics. BJPsych Open. 2021;7(5): e149. https://doi.org/10.1192/bjo.2021.982.

    Article  Google Scholar 

  37. McIntyre RS, Jerrell JM. Polypharmacy in children and adolescents treated for major depressive disorder: a claims database study. J Clin Psychiatry. 2009;70(2):240–6. https://doi.org/10.4088/jcp.08m04212.

    Article  Google Scholar 

  38. Mojtabai R, Olfson M. National trends in psychotropic medication polypharmacy in office-based psychiatry. Arch Gen Psychiatry. 2010;67(1):26–36. https://doi.org/10.1001/archgenpsychiatry.2009.175.

    Article  Google Scholar 

  39. Yang SY, Chen LY, Najoan E, Kallivayalil RA, Viboonma K, Jamaluddin R, et al. Polypharmacy and psychotropic drug loading in patients with schizophrenia in Asian countries: fourth survey of Research on Asian Prescription Patterns on antipsychotics. Psychiatry Clin Neurosci. 2018;72(8):572–9. https://doi.org/10.1111/pcn.12676.

    Article  CAS  Google Scholar 

  40. Hilton MF, Whiteford HA. Pro re nata medication for psychiatric inpatients: time to act. Aust N Z J Psychiatry. 2008;42(7):555–64. https://doi.org/10.1080/00048670802119804.

    Article  Google Scholar 

  41. Baker JA, Lovell K, Harris N. The impact of a good practice manual on professional practice associated with psychotropic PRN in acute mental health wards: an exploratory study. Int J Nurs Stud. 2008;45(10):1403–10. https://doi.org/10.1016/j.ijnurstu.2008.01.004.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors thank the following psychiatrists belonging EGUIDE members.

Funding

This work was supported by the Japan Agency for Medical Research and Development (AMED) under Grant Number JP16dk0307060, JP19dk0307083, and JP22dk0307112, JSPS KAKENHI Grant Number JP21K17261, the Health and Labor Sciences Research Grants (H29‐Seishin‐Ippan‐001, 19GC1201), the Japanese Society of Neuropsychopharmacology, the Japanese Society of Mood Disorders, the Japanese Society of Clinical Neuropsychopharmacology, and the Japanese Society of Psychiatry and Neurology. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Author information

Authors and Affiliations

Authors

Contributions

YK and NY-F were critically involved in collecting and analyzing the data, and wrote the first draft of the manuscript. KIn and KW were critically involved in the design of the study and contributed to the interpretation of the data and writing of the manuscript. NHase, KId, KIc, NHash, HH, YS, YI, and HM, were involved in analyzing the data and contributed to the interpretation of the data and the writing of the manuscript. HYamad, HI, KOh, YY, KOg, SN, JI, TT, SO, FK, RF, TO, MM, HK, MT, CK, AH, KA, HYamag, MK, TN, MU, TK, SK, JM, and KM, were involved in and contributed to the participant recruitment process and data collection, and the data interpretation. RH supervised the entire project, and was critically involved in data collection, design, analysis and interpretation of the data. All authors approved the final version of the manuscript and agree to be accountable for all aspects of this work. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Norio Yasui-Furukori.

Ethics declarations

Ethics approval and consent to participate

This study was approved by the ethics committees of the National Center for Neuropsychiatry (approval number B2022-004) and Neurology and at the participating EGUIDE sites.

Consent for publication

Not applicable.

Competing interests

The authors declare no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Additional file 1: Table S1.

Definition of Quality Indicators for patients with schizophrenia in this study. Table S2. Definition of Quality Indicators for patients with major depressive disorder in this study. Table S3. PRN prescription ratio at discharge by drug category.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kyou, Y., Yasui-Furukori, N., Hasegawa, N. et al. The characteristics of discharge prescriptions including pro re nata psychotropic medications for patients with schizophrenia and major depressive disorder from the survey of the “Effectiveness of guidelines for dissemination and education in psychiatric treatment (EGUIDE)” project. Ann Gen Psychiatry 21, 52 (2022). https://doi.org/10.1186/s12991-022-00429-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12991-022-00429-8

Keywords