National Institute of Mental Health, Tokyo, Japan
Department of Mental Health, University of Tokyo, Japan
National Centre of Neurology and Psychiatry, Musashi Hospital, Tokyo, Japan
Correspondence: Dr Hiroto Ito, National Institute of Mental Health, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan. E-mail: Hiroto0405{at}aol.com
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ABSTRACT |
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Aims To identify the factors associated with the polypharmacy and excessive dosing phenomena.
Method We studied 139 patients with schizophrenia, in 19 acute psychiatric units in Japanese hospitals, who were due to be discharged between October and December 2003. We examined patient characteristics, nurses requests, and psychiatrists characteristics and perceptions of prescribing practice and algorithms.
Results Polypharmacy and excessive dosing were observed in 96 cases. Logistic regression analysis revealed that the use of multiple medications and excessive dosing were influenced by the psychiatrists scepticism towards the use of algorithms, nurses requests for more drugs and the patients clinical condition.
Conclusions Educational interventions are necessary for psychiatrists and nurses to follow evidence-based guidelines or algorithms.
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INTRODUCTION |
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METHOD |
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All the patients with schizophrenia discharged from the participating units between 1 October and 25 December 2003 were invited to take part in the study. Of 251 patients, 179 (71.3%) agreed to participate and provided written informed consent, a sample size considered to be sufficient to give an overview of the prescribing patterns during the study period. Thirty-four patients were eliminated from the analysis because of missing data, and a further six patients were eliminated because they had not been prescribed antipsychotics. Thus, we used data from 139 patients for our analysis. There was no significant difference in the age and gender of the patients selected for inclusion and exclusion.
The study was approved by the institutional review board of the Japanese National Centre of Neurology and Psychiatry and also by the institutional review board or board of directors of each participating hospital. Research coordinators collected patient information from the participating hospitals without identifying the patients.
Patient characteristics
We defined a standard dosage group comprising patients who were receiving
one antipsychotic drug with a dosage of less than 1000 mg chlorpromazine
equivalent. The remaining patients constituted the non-standard dosage group.
We asked psychiatrists about the clinical variables of the patients, including
psychiatric diagnosis and length of illness. All the patients had a clinical
diagnosis of schizophrenia based on DSMIV criteria
(American Psychiatric Association,
1994). Psychiatrists also rated the patients on the Global
Assessment of Functioning (GAF; American
Psychiatric Association, 1994) scale both at admission and at
discharge. Lower GAF scores indicate greater disability. Nurses provided
patient demographic variables and reported the use of seclusion and physical
restraint during in-patient care.
Psychiatrist characteristics and prescribing perceptions
We asked the 78 psychiatrists treating the 139 patients to provide
information on their demographic variables (age and gender), medical
qualifications, length of clinical experience, and perceptions of prescribing
practice and dosing algorithms.
The psychiatrists were asked to describe their perceptions of prescribing practice and algorithms before the patients were recruited. Questions on prescribing practice included cost considerations, familiarity with the research literature and the importance of experience-based prescribing. Perceptions of algorithms were elicited by questions such as I understand the contents of an algorithm, An algorithm disregards individual patient characteristics, I doubt the validity and evidence of an algorithm and I think that an algorithm is necessary for clinical practice. Each item was rated using a four-point Likert scale (1, strongly disagree; 2, disagree; 3, agree; 4, strongly agree). Japanese translations of algorithms and guidelines used in the UK (Taylor et al, 2001) and the USA (American Psychiatric Association, 1997) were available to these psychiatrists in addition to algorithms developed in Japan.
Nurses requests for drugs
The nurses completed a questionnaire survey. The questionnaire asked
whether they believed that it was necessary to increase the current dosage of
medication or add another drug; to decrease the current dosage or number of
drugs; or to change the current drug. We also asked the nurses to indicate the
reason why they believed a change was necessary in each case.
Statistical analysis
All dosages of antipsychotic drugs were converted into chlorpromazine
equivalents to facilitate comparisons
(Bezchlibnyk-Butler & Jeffries,
1998; Inagaki et al,
1999). We used t-tests to compare mean scores and
chi-squared tests to compare categorical data. The MannWhitney test was
used to compare the rank data between the standard and non-standard dosage
groups. Multiple logistic regression analysis was used to assess the
independent and interactive effects of the multiple factors that could
contribute to prescribing practice. After we examined the relationship of each
variable in the two prescribing practice groups, we included only the
significant variables when comparing the two groups in the logistic regression
analysis. All tests were two-tailed. Analyses were performed using the
Statistical Package for the Social Sciences, version 11.0.
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RESULTS |
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The psychiatrists mean age was 41.3 years (s.d.=10.7), with 12.9 years (s.d.=10.8) experience in psychiatric services. Of the 78 psychiatrists, 50 (64%) were designated psychiatrists with extra training; these individuals were qualified to make the decision for compulsory admission under the Mental Health and Welfare Law of Japan 1995. Regarding the psychiatrists demographic variables, medical qualifications, length of clinical experience and perceptions of prescribing practice, no significant difference was observed between the standard and non-standard dosage groups. There were, however, significant differences in the psychiatrists perceptions of algorithms. Psychiatrists caring for patients in the non-standard dosage group were significantly more likely to agree with the statement I doubt the validity and evidence of an algorithm (z=2.95, P=0.003) and more likely to disagree with the statement I think that an algorithm is necessary for clinical practice (z=2.49, P=0.013) compared with those in the standard dosage group.
Patient characteristics are shown in Table 2. There was no significant difference in age or gender between the standard and non-standard dosage groups. The non-standard dosage group had a significantly longer duration of illness than the standard dosage group. There was no significant difference in involuntary admission or the use of physical restraint during in-patient care. The GAF scores at admission did not differ significantly, whereas the GAF score of the non-standard dosage group at discharge was significantly lower than that of the standard dosage group.
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Forty-nine (59%) of the 83 nurses caring for our 139 patients were men. The nurses mean age was 35.3 years (s.d.=9.3), and they had an average of 9.4 years (s.d.=7.3) experience in psychiatric services. Nurses endorsed the statement that I would like to ask a psychiatrist to increase the current dosage or add another drug for 39 patients. The proportion of nurses agreeing with this statement was significantly greater in the non-standard dosage group than in the standard dosage group. The reasons nurses requested a change in treatment included no improvement in symptoms (24 patients; 62%), deterioration in symptoms (9 patients; 23%), beyond nursing care (4 patients; 10%) and other (2 patients, 5%). There was no significant difference between the standard and non-standard dosage groups with regard to the reasons for the desired alteration in drug treatment.
Logistic regression analysis revealed that the non-standard dosage group was significantly more likely to have both a longer duration of illness and a lower level of functioning as evaluated by the GAF scale (Table 3). The analysis also showed that the psychiatrists perceptions of algorithms were associated with polypharmacy and excessive dosing. Nurses in the non-standard dosage group were more likely to believe that their patients needed more drugs than those in the standard dosage group.
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DISCUSSION |
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Methodological considerations
We examined the factors influencing the patterns of prescription of
antipsychotics using three explanatory variables: patient characteristics,
nurses requests for drugs and psychiatrists perceptions of best
prescribing practice and algorithms. The psychiatrists perceptions were
subjective measures and we did not conduct an objective assessment of this
variable. Also, we were not able to examine subjective patient outcomes, such
as satisfaction with medication and quality of life, although the
psychiatrists rated the patients level of functioning using the GAF
score. Ideally, one should examine the relationship between prescribing
patterns and the long-term outcomes of patients.
Every acute psychiatric care unit had the same staffing ratio of patients to nurses. The size and ownership of the hospitals did not differ between the standard and non-standard dosage groups; however, we did not examine additional institutional characteristics and staffing, owing to substantial missing and inappropriate data for analysis. This study was not a retrospective review of patient records; rather, we obtained prospective data at the point when discharge was planned. Furthermore, the patient, nurse and psychiatrist data were collected separately and matched later. Thus, we were able to analyse prescribing patterns for individual patients rather than using a group analysis.
The number of participating hospitals was small because we used strict recruitment criteria. In Japan, there are still many psychiatric care units that are similar to rehabilitation units in Western countries. As Japan is now in a transitional period from long-term to acute hospital care, various measures are employed to shorten the patients length of stay. One such measure is that an acute psychiatric care unit is strictly defined in the reimbursement system. We used this criterion to select our hospital sample; however, only a limited number of hospitals have been officially designated as acute psychiatric care units. Therefore, our sample might not be nationally representative of all hospitals in Japan with acute psychiatric care units. To reduce the burden on participating hospitals the study period was only 2 months, and because of this the number of patients who met the diagnostic criteria during that period was limited.
Benefits and risks of combination therapy
It is not appropriate that polypharmacy and high-dosage prescribing should
always be viewed as a poor prescribing pattern, because using more than one
antipsychotic drug can be effective in some patients, and different
antipsychotics have different effects on different symptoms of psychosis
(Taylor, 2002). The Royal
College of Psychiatrists consensus statement in the UK
(Royal College of Psychiatrists,
1993) suggests that there are some justifiable cases of temporary
polypharmacy, including making a gradual change from one drug to another
(Thompson, 1994). Although
sulpiride augmentation of clozapine is suggested to be of benefit by a
randomised controlled trial (Shiloh et
al, 1997), evidence for the efficacy of combining
antipsychotics is limited (Freudenreich
& Goff, 2002). There are potential adverse effects, some of
which are even life-threatening (Centorrino
et al, 2004). Polypharmacy is associated with early death
(Waddington et al,
1998). Reilly et al
(2000) reported that use of
thioridazine was a predictor of QTc prolongation, and Ray et
al (2001) suggested that
even moderate doses of antipsychotics would increase the risk of sudden
cardiac death. Asian patients are more vulnerable to side-effects and might
require less antipsychotic medication than European patients
(Ungvari et al, 1996;
Chong et al,
2004).
Despite these known risks, polypharmacy and excessive dosing with antipsychotics persist in Japan. An inadequate knowledge of pharmacology may underlie this phenomenon (Kingsbury et al, 2001; Procyshyn et al, 2001). Based on a questionnaire regarding the use of depot formulations, Patel et al (2003) suggested that psychiatrists knowledge about maintenance medication was positively associated with attitudes toward the medication.
Concurrent prescription of atypical and typical antipsychotics is not recommended in principle by the National Institute for Clinical Excellence in the UK (National Institute for Clinical Excellence, 2002). It rarely improved outcomes, while it increased use of anticholinergic medication (Taylor et al, 2000). In our study, we found the combination of typical and atypical antipsychotics to be a popular prescribing pattern. Four atypical antipsychotics are available in Japan, including risperidone (since 1996), perospirone, quetiapine and olanzapine (since 2001), but clozapine has not been approved yet. The results suggest that many psychiatrists do not fully understand the mechanisms and advantages of atypical antipsychotics, and do not want to change their prescribing patterns.
Implications
There is much speculation about the factors associated with polypharmacy
and excessive dosing. Previous studies suggest that these might include
treatment setting; patient factors, such as age, severity of illness and
length of illness (Benson,
1983; Remington et
al, 2001; Bitter et
al, 2003; Sohler et
al, 2003; Centorrino
et al, 2004); and the providers knowledge of
pharmacology, the local prescribing culture, personal experience and
familiarity with the research literature
(Benson, 1983; Kingsbury et al,
2001; Procyshyn et
al, 2001). However, few of these factors have been proved to
be associated with patient treatment. These results are consistent with other
observations with regard to the severity
(Sohler et al, 2003)
and chronicity (Benson, 1983;
Diaz & de Leon, 2002) of
patients illness.
As in the investigation by Harrington et al (2002) of the issue of medication given at the discretion of nurses, most nurses requested higher doses of medication for the reason of patient symptoms in our study (85%). The process of psychiatrists agreement is unknown; however, there are two possibilities: one is that a patient still has a psychosis, and the other is that they wish to control patient behaviour. Scepticism towards algorithms and scientific evidence still exists among psychiatrists, which leads to their relying solely on clinical experience when prescribing antipsychotic medication. Consequently, psychiatrists who are sceptical about algorithms are potential targets for educational intervention. Also, educational programmes detailing scientific advances can be effective for healthcare providers, including psychiatrists and nurses.
Future interventions
Education, guidelines and algorithms are mentioned in the research
literature as ways to avoid irrational polypharmacy and high doses for the
purpose of unnecessary sedation (Ungvari
et al, 1997; Lehman
& Steinwachs, 1998; Covell
et al, 2002). In fact, the introduction of educational
programmes and guidelines is reportedly effective
(Avorn et al, 1992;
Grimshaw & Russell, 1993), but it also was reported that the degree of performance improvement varied
(Grimshaw & Russell, 1993)
and that systematic practice-based interventions and outreach visits were
necessary (Davis et al,
1995). McCue et al
(2003) suggested that a
rational strategy for prescribing can lead to a decrease in adverse drug
reactions and an improvement in patient outcomes, even when using more than
one antipsychotic drug.
We did not examine the effects of educational intervention in this study. An intervention study is necessary to assess the feasibility and impact of implementing an evidence-based medication algorithm; we plan to include this in our next research protocol.
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Clinical Implications and Limitations |
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LIMITATIONS
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ACKNOWLEDGMENTS |
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REFERENCES |
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American Psychiatric Association (1997) Practice guidelines for the treatment of patients with schizophrenia. American Journal of Psychiatry, 154 (suppl.), 1 -63.
Avorn, J., Soumerai, S. B., Everitt, D. E., et al (1992) A randomized trial of a program to reduce the use of psychoactive drugs in nursing homes. New England Journal of Medicine, 327, 168 -173.[Abstract]
Benson, P. R. (1983) Factors associated with antipsychotic drug prescribing by southern psychiatrists. Medical Care, 21, 639 -654.[Medline]
Bezchlibnyk-Butler, K. Z. & Jeffries, J. J. (1998) Clinical Handbook of Psychotropic Drugs (8th edn). Seattle, WA: Hogrefe & Huber.
Bitter, I., Chou, J. C., Ungvari, G. S., et al (2003) Prescribing for inpatients with schizophrenia: an international multi-center comparative study. Pharmacopsychiatry, 36, 143 -149.[CrossRef][Medline]
Centorrino, F., Goren, J. L., Hennen, J., et al
(2004) Multiple versus single antipsychotic agents for
hospitalized psychiatric patients: case control study of risks versus
benefits. American Journal of Psychiatry,
161, 700
-706.
Chong, M.Y., Tan, C. H., Fujii, S., et al (2004) Antipsychotic drug prescription for schizophrenia in East Asia: rationale for change. Psychiatry and Clinical Neurosciences, 58, 61 -67.[CrossRef][Medline]
Covell, N. H., Jackson, C.T., Evans, A. C., et al (2002) Antipsychotic prescribing practice in Connecticuts pubic mental health system: rates of changing medications and prescribing styles. Schizophrenia Bulletin, 28, 17-29.[Medline]
Davis, D. A., Thomson, M. A., Oxman, A. D., et al (1995) Changing physician performance: a systematic review of the effect of continuing medical education strategies. JAMA, 274, 700 -705.[Abstract]
Diaz, F. J. & de Leon, J. (2002) Excessive antipsychotic dosing in two US state hospitals. Journal of Clinical Psychiatry, 63, 998 -1003.[Medline]
Freudenreich, O. & Goff, D. C. (2002) Antipsychotic combination therapy in schizophrenia: a review of efficacy and risks of current combinations. Acta Psychiatrica Scandinavica, 106, 323 -330.[CrossRef][Medline]
Grimshaw, J. M. & Russell, I. T. (1993) Effect of clinical guidelines on medical practice: a systematic review of rigorous evaluations. Lancet, 342, 1317 -1322.[CrossRef][Medline]
Harrington, M., Lelliott, P., Paton, C., et al
(2002) The results of a multi-centre audit of the prescribing
of antipsychotic drugs for in-patients in the UK. Psychiatric
Bulletin, 26, 414
-418.
Inagaki, A., Inada, T., Fujii, Y., et al (1999) Equivalent Dose of Psychotropics (in Japanese). Tokyo: Seiwa Shoten.
Kingsbury, S. J., Yi, D. & Simpson, G. M.
(2001) Rational and irrational polypharmacy.
Psychiatric Services,
52, 1033
-1036.
Lehman, A. F. & Steinwachs, D. M. (1998) Translating research into practice: the Schizophrenia Patients Outcomes Research Team (PORT) treatment recommendations. Schizophrenia Bulletin, 24, 1 -10.[Medline]
Lelliott, P., Paton, C., Harrington, M., et al
(2002) The influence of patient variables on polypharmacy and
combined high dose of antipsychotic drugs prescribed for in-patients.
Psychiatric Bulletin,
26, 411
-414.
McCue, R. E., Waheed, R. & Urcuyo, L. (2003) Polypharmacy in patients with schizophrenia. Journal of Clinical Psychiatry, 64, 984 -989.[Medline]
National Institute for Clinical Excellence (2002) Guidance on the Use of Newer (Atypical) Antipsychotic Drugs for The treatment of Schizophrenia. Technology Appraisal Guidance No. 43. London: NICE.
Patel, M. X., Nikolaou, V. & David, A. S. (2003) Psychiatrists attitudes to maintenance medication for patients with schizophrenia. Psychological Medicine, 33, 83 -89.[CrossRef][Medline]
Procyshyn, R. M., Kennedy, N. B., Tse, G., et al (2001) Antipsychotic polypharmacy: a survey of discharge prescriptions from a tertiary care psychiatry institution. Canadian Journal of Psychiatry, 46, 334 -339.[Medline]
Ray, W. A., Meredith, S., Thapa, P. B., et al
(2001) Antipsychotics and the risk of sudden cardiac death.
Archives of General Psychiatry,
58, 1161
-1167.
Reilly, J. G., Avis, S. A., Ferrier, I. N., et al (2000) QTc-interval abnormalities and psychotropic drug therapy in psychiatric patients. Lancet, 355, 1048 -1052.[CrossRef][Medline]
Remington, G., Shammi, C. M., Sethna, R., et al
(2001) Antipsychotic dosing patterns for schizophrenia in
three treatment settings. Psychiatric Services,
52, 96-98.
Royal College of Psychiatrists (1993) Consensus Statement on the Use of High Dose Antipsychotic Medication. Council Report CR26. London: Royal College of Psychiatrists.
Shiloh, R., Zemishlany, Z., Aizenberg, D., et al (1997) Sulpiride augmentation in people with schizophrenia partially responsive to clozapine. A double-blind, placebo-controlled study. British Journal of Psychiatry, 171, 569 -573.[Abstract]
Sohler, N. L., Walkup, J., McAlpine, D., et al
(2003) Antipsychotic dosage at hospital discharge and
outcomes among persons with schizophrenia. Psychiatric
Services, 54, 1258
-1263.
Taylor, D. (2002) Antipsychotic prescribing
time to review practice. Psychiatric Bulletin,
26, 401
-402.
Taylor, D., Mace, S., Mir, S., et al (2000) A prescription survey of the use of atypical antipsychotics for hospital inpatients in the United Kingdom. International Journal of Psychiatry in Clinical Practice, 4, 41 -46.[CrossRef]
Taylor, D., McConnell, D., McConnell, H., et al (2001) The Maudsley 2001 Prescribing Guidelines (6th edn). London: Taylor & Francis.
Taylor, D., Mir, S., Mace, S., et al
(2002) Co-prescribing of atypical and typical antipsychotics
prescribing sequence and documented outcome. Psychiatric
Bulletin, 26, 170
-172.
Thompson, C. (1994) The use of high-dose antipsychotic medication. British Journal of Psychiatry, 164, 448 -458.[Medline]
Ungvari, G. S., Pang, A. H. T., Chiu, H. F. K., et al (1996) Psychotropic drug prescription in rehabilitation: a survey in Hong Kong. Social Psychiatry and Psychiatric Epidemiology, 31, 288 -291.[Medline]
Ungvari, G. S., Chow, L. Y., Chiu, H. F., et al (1997) Modifying psychotropic drug prescription patterns: a follow-up survey. Psychiatry and Clinical Neurosciences, 51, 309 -314.[Medline]
Waddington, J. L., Youssef, H. A. & Kinsella, A. (1998) Mortality in schizophrenia. Antipsychotic polypharmacy and absence of adjunctive anticholinergics over the course of a 10-year prospective study. British Journal of Psychiatry, 173, 325 -329.[Abstract]
Received for publication June 16, 2004. Revision received November 16, 2004. Accepted for publication November 20, 2004.