International Journal of Psychiatry in Clinical Practice, 2009; 13: 253258
ORIGINAL ARTICLE
The use of prn medication in a child and adolescent mental health inpatient service in France
URSULA WINTERFELD1,2, MARIE-FRANCE LE HEUZEY2, ERIC ACQUAVIVA2, MARIE-CHRISTINE MOUREN2, FRANC ¸ OISE BRION1 & OLIVIER BOURDON1 1
Department of Pharmacy, AP-HP, Hoˆpital Robert Debre´, Paris, France and Universite´ Paris Descartes, Paris, France, and Department of Child and Adolescent Psychiatry, AP-HP, Hoˆpital Robert Debre´, Paris, France and Universite´ Paris Diderot, Paris, France
2
Abstract Objective. The aim of this study was to investigate the use of ‘‘as needed’’ (pro re nata or prn) psychotropic medication in a child and adolescent psychiatric inpatient population. The study was carried out on the psychiatry ward of a paediatric teaching hospital in Paris, France. Methods. A prospective analysis of prn psychotropic drug prescriptions and administrations was conducted for all patients hospitalised over a period of 4 months. The study group consisted of 187 patients. Results. In total, 93 prn prescriptions were written, for 27% of the patients (51) but only 14% (26) received a total of 76 administrations. Antipsychotic drugs accounted for 54% of the prescriptions, anxiolytics for 33%, antiepileptic drugs for 8%, antiparkinsonian drugs for 4% and hypnotic drugs for 1%. Anxiety was the reason given for 67% of the prn administrations, with hydroxyzine used in 69% of these cases. Disruptive behaviour accounted for 22% of prn administrations, with antipsychotic drugs accounting for 88% of these administrations. Insomnia accounted for 8% of prn administrations, and antipsychotic drug-induced dystonia accounted for 3% of such administrations. Conclusion. Controlled studies are required to assess the efficacy and safety of prn medication and the conditions in which its use is indicated.
Key Words: prn medication, psychiatry, child, adolescent, inpatient
Introduction Psychotropic drugs are widely used to treat children and adolescents with mental illnesses. Pro re nata (prn) or ‘‘as required’’ medication is a commonly used adjunct to routine prescribed medication. Between 50 and 100% of patients within paediatric inpatient mental health settings studied, received prn psychotropic medication on one or more occasions [1]. The use of prn medications in European child and adolescent psychiatry has not been studied extensively. Most existing research focused on US services. Evans and Di Scipio [2] investigated the use and mode of action of prn medication in 47 adolescents over a period of 1 year in an adolescent psychiatric inpatient unit in New York. During the study period,
they recorded 1459 prn drug administrations. Vitiello et al. [1] investigated the use of prn medication in 49 long-stay adolescent inpatients during a 12month period in Pennsylvania; 1263 doses of prn medication were administered. Garrison et al. [3] assessed the use of prn medication in an investigation of aggressive incidents and counter-aggressive strategies in a child and adolescent psychiatric inpatient unit in Massachusetts. Prn medication was administered in just under one-third of the 887 incidents recorded during the 12-month study. Kaplan and Busner [4] examined the use of prn psychotropic medication administered to 150 child and adolescent inpatients in three hospitals in the New York City area. They found significant differences between the three hospitals in terms of the use of prn medication and the classes of drugs administered. Bernard and
Correspondence: Olivier Bourdon, Pharmacie de l’Hoˆpital Robert Debre´, 48 Bd Se´rurier, 75019 Paris, France. Tel: 33 1 4003 5741. Fax: 33 1 4003 2481. E-mail: [email protected]
(Received 15 December 2008; accepted 20 February 2009) ISSN 1365-1501 print/ISSN 1471-1788 online # 2009 Informa UK Ltd. DOI: 10.3109/13651500902849987
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Littlejohn [5] studied the use of prn psychotropic medication in an inpatient unit for younger adolescents in England. Prn medication was administered to 60% of the 500 patients admitted. Dean et al. [6] studied the patterns of sedative prescription and administration on an ‘‘as needed’’ basis in a child and adolescent mental health inpatient service in Australia. In this sample, 71.3% of the patients were prescribed sedatives prn and 50.8% received at least one dose of prn sedation. Guidelines on the prescription and administration of prn psychotropic medication in child and adolescent inpatients are lacking. Furthermore, the clinical effectiveness of psychotropic prn medication in child and adolescent mental health settings has yet to be established. Therefore, information about the frequency and patterns of use of psychotropic drugs in children and adolescents hospitalised in psychiatric wards is valuable, as it allows clinicians to compare their practices. As part of a larger study of prescribing practices of psychopharmacotherapy in children and adolescents hospitalised in the psychiatry ward of a French paediatric teaching hospital [7], we analysed the use of prn psychotropic drugs in this population. This survey also investigates the factors influencing prn prescription and administration practices.
Any change in the drug given, its dose or dose schedule was treated as a new prescription. Treatment data were obtained from the computerised files with Patient Care System software (PCS† , IBM† , New York City, NY). Drug classes were analysed using the Anatomical Therapeutic Chemical Classification (ATC). The ATC system classifies therapeutic drugs. Its purpose is to serve as a tool for drug utilization research. The following ATC codes were considered to refer to psychotropic drugs: N03 (antiepileptic drugs), N04 (antiparkinsonian drugs), N05 (psycholeptic drugs: antipsychotic drugs, anxiolytics, hypnotic drugs), N06 (psychoanaleptic drugs: antidepressants, stimulants) and N07 (other nervous system drugs). The most prevalent DSM-IV-TR diagnoses were grouped into several broad categories: learning disorders, attention-deficit and disruptive behaviour disorders, anxiety disorders, eating disorders, depressive disorders and schizophrenia. Pervasive development disorders and mental retardation were grouped together. The diagnostic category ‘‘other disorders’’ comprised the following diagnoses: narcolepsy, conversion disorder, personality disorder, chronic motor or vocal tic disorder and Tourette’s disorder. Analysis
Methods Setting and design This prospective survey was carried out on the psychiatry ward of a paediatric teaching hospital in Paris, France. Data were collected in two acute psychiatric hospitalisation units consisting of 24 inpatient beds and partial hospitalisation facilities for nine patients, respectively. During partial hospitalisation, patients continue to live at home, but commute to the hospital up to 5 days per week. All patients newly admitted to these units between 13 March and 13 July, 2006 inclusive, were included in the study. Data were collected throughout the stay in hospital of each patient. The details recorded included demographic data (age, sex, weight, date of admission, date of discharge and admission unit), the clinical characteristics of the patients (Diagnostic and Statistical Manual for Mental Disorders (DSM-IV-TR) discharge diagnosis, symptoms and prior psychiatric hospitalisation), prn orders for psychotropic drugs (name of the drug concerned, dose, administration route, indication, time and date given and reasons for administration) and discharge medication (prn orders continued or discontinued) [8].
Data were analysed with StatView 5.0 (SAS Institute Inc, Cary, NC). Groups were compared using chi-squared and Fisher’s tests for categorical variables and Student’s t-tests and MannWhitney tests for continuous variables, depending on the characteristics of the variable considered.
Results Patient characteristics We included a total of 187 patients in our study. Half (93) the patients were hospitalised in the partial hospitalisation facility and the other half (94) were inpatients. Demographic and diagnostic data for patients with and without prn medication are presented in Table I. prn medication: prescription In total, 93 prescriptions were written for 27% of the patients (51). No prn psychotropic drugs were prescribed to 73% (136) of the patients. Antipsychotic drugs accounted for 54% (50) of prescriptions, anxiolytics for 33% (31), antiepileptic drugs for 8% (7), antiparkinsonian drugs for
Use of prn medication in children and adolescents
255
Table I. Demographic and diagnostic data for patients with and without prn medication.
Number of male patients (%) Age Mean9SD [minimum-maximum] (years) Length of stay Mean9SD (days) Number of patients with prior psychiatric hospitalisation (%) Number of inpatients (%) Diagnosis-number of patients (%) Learning disorders ADHD/disruptive behaviour disorders Pervasive development disorders/mental retardation Anxiety disorders Eating disorders Schizophrenia Depressive disorders Other Two diagnosesa
Patients with prn medication (n 51)
Patients without prn medication (n 136)
P
25 (49) 13.092.4 35929 18 (35)
107 (79) 9.793.1 1298 34 (25)
B0.0001b B0.0001c B0.0001d NS
46 (90)
48 (35)
B0.0001e
0 7 3 12 7 4 3 10 8
64 25 15 3 5 1 2 4 14
B0.0001b NS NS B0.0001b B0.05b B0.05b NS B0.05b NS
(0) (14) (6) (24) (14) (8) (6) (20) (16)
(47) (18) (11) (2) (4) (1) (1) (3) (10)
Md, median value; SD, standard deviation; ADHD, attention-deficit/hyperactivity disorder; Others, narcolepsy, conversion disorder, personality disorder, chronic motor or vocal tic disorder, Tourette’s disorder. a Eleven patients were diagnosed with ADHD/disruptive behaviour disorder and learning disorder; three were diagnosed with ADHD/ disruptive behaviour disorder and pervasive development disorders/mental retardation; two were diagnosed with ADHD/disruptive behaviour disorder and tic disorder; two were diagnosed with ADHD/disruptive behaviour disorder and anxiety disorder; two were diagnosed with learning and anxiety disorder; one was diagnosed with pervasive development disorder/mental retardation and tic disorder; one was diagnosed with mood and personality disorder. b Fisher’s exact test, cStudent’s t-test, dMannWhitney test, eChi-squared test.
4% (4) and hypnotic drugs for 1% (1). Antiepiepileptic drugs were mainly prescribed for anxiety or disruptive behaviour. Age and sex significantly differentiated patients with prn prescriptions from those without (Table I). Forty-nine percent (25/51) of the patients with prn prescriptions were male, versus 79% (107/136) of those without such prescriptions. The two groups were similar in terms of previous hospitalisation history. Patients with prn prescriptions had significantly longer stays than patients without such prescriptions. Finally, 90% (46/51) of the patients with prn prescriptions were inpatients, versus only 35% (48/136) of those without such prescriptions. The distribution of clinical diagnoses differed significantly between the two groups (Table I). The prn prescription group contained a larger proportion of patients with anxiety disorders, other disorders, eating disorders and schizophrenia. The proportion of patients with learning disorders was higher for the group without prn prescriptions than for those with such prescriptions. The prescriptions for prn medication concerned, in 67% (34/51) of cases, patients already receiving psychotropic medication on a regular basis. Overall, 62% (18) of prn antipsychotic drugs were prescribed for patients already regularly taking antipsychotic drugs, and 39% (9) of prn anxiolytics were prescribed to patients already taking anxiolytics
regularly. However, antiparkinsonian drugs were not simultaneously prescribed on a prn and regular basis in the same patient. At discharge, all prn prescriptions were discontinued. prn medication: administration The number of prn administrations did not differ significantly as a function of sex or age. Furthermore, the number of prn administrations was not correlated with length of stay, prior hospitalisation or diagnostic category. The ratio of prn doses prescribed to prn doses administered was analysed, taking medication class and diagnostic category into account (Table II). Twenty-six (14%) of the 51 patients for whom prn medication was prescribed received a total of 76 administrations. The mean number of prn administrations per patient was 2.992.9 (minimum 1; maximum 15). Anxiolytics accounted for 50% (38) of prn administrations, antipsychotic drugs for 37% (28), antiepileptic drugs for 9% (7), antiparkinsonian drugs for 3% (2) and hypnotic drugs for 1% (one). Thirty-four percent (26) of prn administrations concerned patients with other disorders, 17% (13) concerned patients with anxiety disorders, 13% (10) concerned patients with eating disorders, 11% (8) concerned patients with attention-deficit
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Table II. Prn drug prescription and administration by diagnosis (as number of doses prescribed/number of doses received (%)).
Medication
ADHD/ disruptive PDD/ behaviour Mental disorders retardation
Antipsychotic drugs Cyamemazine 75/0 Propericiazine 37/3 Loxapine 11/0 Anxiolytics Hydroxyzine 89/4 Clobazam Clorazepate Antiepileptic drugs Clonazepam Diazepam Antiparkinsonian drugs Tropatepine 10/1 Hypnotic drugs Zolpidem Total 222/8
(0) (8) (0)
18/1 (6) 8/2 (25)
Anxiety disorders
Eating disorders
125/1 (1)
237/3 (1)
Schizophrenia
517/4 (1)
Depressive disorders
Others
Two diagnoses
Total
55/0 (0)
278/11(4)
52/0 (0) 27 /1 (4) 9/0 (0)
1357/20 (1) 72/6 (8) 22/2 (9)
32/1 (3)
238/14 (6)
209/6 (3)
1077/38 (3) 130/0 (0) 65/0 (0)
2/2 (100)
(4)
299/6 (2)
210/7 (3)
130/0 (0) 65/0 (0) 106/5 (5)
13/2 (15)
119/7 (6) 65/0 (0)
65/0 (0) (10)
(4)
122/1 (1)
286/3 (1)
652/13 (2)
447/10 (2)
532/8 (1)
87/1 (1)
2 9/1 (3) 545/26 (5)
9/0 (0)
141/2 (1)
306/7 (2)
29/1 (3) 3077/76 (2)
ADHD, attention-deficit/hyperactivity disorder; PDD, pervasive development disorder; Others, narcolepsy, conversion disorder, personality disorder, chronic motor or vocal tic disorder, Tourette’s disorder.
and disruptive behaviour disorders, 11% (8) concerned patients with schizophrenia, 9% (7) concerned patients with two diagnoses, 4% (3) concerned patients with pervasive development disorders/mental retardation and 1% (1) concerned patients with depressive disorders. Drugs were administered orally in 94% (71) of cases, intramuscularly in 5% (4) of cases and sublingually in 1% (1) of cases. Prn medication was frequently administered in the evening, especially at bedtime, with a peak at 23:00 h (Figure 1). Several symptoms led to the 76 prn administrations (Table III). Anxiety accounted for 67% (51) of prn administrations, disruption on the ward for 22% (17), insomnia for 8% (6) and drug-induced dystonia for 3% (2). All prn drug administrations were consistent with the indication specified by the physician. Discussion In this study, we investigated the use of prn medication in child and adolescent psychiatric inpatient treatment. In our sample 27% (51) of the patients were prescribed a prn medication but only 14% (26) actually received a total of 76 administrations. The observed administration rates are lower than those reported in other studies (50100%) [1,2,46]. A large proportion of the patients in our study had learning disorders and almost half of the patients were treated in a partial hospitalisation facility. These
patients rarely receive psychotropic medication on a prn basis (9% (5) of prn prescriptions and 0% of prn administrations). This difference may also relate to the shorter duration of admissions in our facility. Unlike Dean et al. [6] (agitation and aggression accounting for 53% of the prn administrations), Kaplan and Busner [4] (agitation accounting for 91100% of prn administrations) and Vitiello et al. [1] (disruption on the ward accounting for 70% of the prn administrations), we found that agitation was not the predominant indication for prn medication in our study. Disruptive behaviour accounted for 22% of administrations. Intramuscular administration was used only for aggressive patients. US prevalence exceeds Western European prevalence for overall psychotropic use [9]. The variability in USEuropean psychotropic medication practice patterns reflects many differences such as diagnostic systems, practice guidelines, drug regulations, decentralized private versus centralized national health service delivery systems, availability and financing of services as well as cultural beliefs [10]. Most prn drugs were administered for anxiety. Sedation was usually the aim, as the drugs used on a prn basis were powerful sedatives. Few outcome data are available to determine which drugs are most appropriate for use in prn sedation. Indeed, the only controlled trial carried out to date on this issue reported that diphenhydramine was not superior to placebo [11]. No study has investigated the safety and efficacy of other agents, such as antipsychotic drugs or benzodiazepines, in this setting. There is limited evidence of the effectiveness of prn medication in adult psychiatric inpatients. Chakrabarti et al.
Use of prn medication in children and adolescents
Table III. Symptoms for which prn drugs were administered (n 76).
25
Number of administrations
257
20
Symptom
Number of administrations n (%)
15
Anxiety Disruptiona Insomnia Antipsychotic induced dystonia
10
51 17 6 2
(67) (22) (8) (3)
5 a
Includes self-harm behaviour and physical aggression directed against the staff.
0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23
Time
Figure 1. Distribution of the 76 prn administrations as a function of time of day.
published a Cochrane systematic review of prn psychotropic medications in acute mental health settings [12]. They concluded that there is no evidence about the risks and benefits of prn medication regimens as compared to regular regimens. However, several randomised and double-blind studies compared two prn regimens. In treating children, medication dosages and frequency of administration often are selected based on adult data. However, development can affect pharmacokinetics and drug disposition. Therefore, extrapolating adult dosages to children can have negative effects on both efficacy and safety [13]. Because of developmental differences, safety of medications must also be specifically studied in young children because they cannot be inferred from data collected in older children or adults. Sedative antihistamines were the most frequently administered prn drugs in our study, although antipsychotic drugs were the most frequently prescribed. Antihistamines are particularly popular as they have been shown to be safe and have no severe side effects. Demographic and clinical variables (age, sex, length of stay, prior hospitalisation history and diagnosis) were poor predictors of prn administration. However, variables not considered in our study may have had a significant effect. The interaction between patient and staff and staff variables (sex, age and training) may have had a significant effect and could have been considered together with patient variables. Our findings concerning the timing of prn drug administration are similar to those of other studies [1,2,5,6]. Prn medication was frequently administered in the evening when patients are likely to suffer from anxiety and often refuse to comply with bedtime rules. Some of the diurnal pattern is likely to be explained by institutional factors such as there being
fewer staff and a greater proportion of relatively unstructured time in the evenings. Sixty-seven percent of the prn drug prescriptions were for patients already receiving psychotropic medication on a regular basis. Thus, prn medication seemed to be used as a way of adding to regular psychotropic treatment, rather than replacing it. This pattern of use has been described in previous studies [6,14]. However, the combination of prn and regular medication may increase the risk of drug interactions or adverse effects. Too little information is currently available for the development of guidelines concerning the influence of existing regular medication on the selection and prescription of prn medication. This study was subject to several limitations, which must be borne in mind when interpreting the results. We included hospitalised children from only one clinical setting in our study. As we did not include outpatients, the results cannot easily be generalised to patients with less severe psychiatric problems or patients seen in other settings, such as outpatient clinics and other hospitals. Patients were diagnosed in routine clinical practice, with no diagnostic interviews carried out specifically for this study. Guidelines specifically addressing the processes associated with the prescription and administration of prn psychotropic medication in children and adolescents are lacking. Therefore, hospitals with child and adolescent inpatient units should consider periodically monitoring prn psychotropic drugs use, exploring the reasons for it and the way in which prn drugs are administered. Our prn medication practices can be benchmarked based on those of other paediatric university hospitals. Key points . Prn medication is used in the inpatient management of children and adolescents with mental health problems . Hospitals with child and adolescent inpatient units should consider periodically monitoring
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prn psychotropic drugs use, exploring the reasons for it and the way in which prn drugs are administered . Our prn medication practices can be benchmarked based on those of other paediatric university hospitals Acknowledgements None. Statement of Interest The authors declare that they have no conflict of interest.
[5] Bernard P, Littlejohn R. The use of as required medication on an adolescent psychiatric unit. Clin Child Psychol Psychiatry 2000;5:266. [6] Dean AJ, McDermott BM, Marshall RT. PRN sedationpatterns of prescribing and administration in a child and adolescent mental health inpatient service. Eur Child Adolesc Psychiatry 2006;15:27781. [7] Winterfeld U, Le Heuzey MF, Acquaviva E, Mouren MF, Brion F, Bourdon O. Psychotropic medication use in the child and adolescent psychiatry wards of a French hospital. Pharmacy World Sci 2008; accepted for publication. [8] American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Text revision ed. 2000. Washington, DC: American Psychiatric Association. [9] Zito JM, Safer DJ, Berg LT, Jahnsen K, Fegert JM, Gardner JF, et al. A three-country comparison of psychotropic medication prevalence in youth. Child Adolesc Psychiatry Ment Health 2008;2:26. [10] Vitiello B. An international perspective on pediatric psychopharmacology. Int Rev Psychiatry 2008;20:1216. [11] Vitiello B, Hill JL, Elia J, Cunningham E, McLeer SV, Behar D. P.r.n. medications in child psychiatric patients: a pilot placebo-controlled study. J Clin Psychiatry 1991;52: 499501. [12] Chakrabati A, Whicher E, Morrison M, Douglas-Hall P. As required medication regimens for seriously mentally ill people in hospital. Cochrane Database Syst Rev 2007;18: CD003441. [13] Vitiello B, Jensen PS. Medication development and testing in children and adolescents. Arch Gen Psychiatry 1997;54: 8716. [14] Mason AS, Nerviano V, DeBurger RA. Patterns of antipsychotic drug use in four Southeastern state hospitals. Dis Nerv Syst 1977;38:5415. /
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/
/
References [1] Vitiello B, Ricciuti AJ, Behar D. P.R.N. medications in child state hospital inpatients. J Clin Psychiatry 1987;48:3514. [2] Evans R, Di Scipio W. Nonpharmacologic factors in the administration of p.r.n. psychotropic medication on an adolescent unit. Am J Psychiatry 1980;137:1234. [3] Garrison WT, Ecker B, Friedman M, Davidoff R, Haeberle K, Wagner M. Aggression and counteraggression during child psychiatric hospitalization. J Am Acad Child Adolesc Psychiatry 1990;29:24250. [4] Kaplan SL, Busner J. The use of prn and stat medication in three child psychiatric inpatient settings. Psychopharmacol Bull 1997;33:1614. /
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/
/
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/
/
/
/
/
/
/
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ORIGINAL ARTICLE
The use of prn medication in a child and adolescent mental health inpatient service in France
URSULA WINTERFELD1,2, MARIE-FRANCE LE HEUZEY2, ERIC ACQUAVIVA2, MARIE-CHRISTINE MOUREN2, FRANC ¸ OISE BRION1 & OLIVIER BOURDON1 1
Department of Pharmacy, AP-HP, Hoˆpital Robert Debre´, Paris, France and Universite´ Paris Descartes, Paris, France, and Department of Child and Adolescent Psychiatry, AP-HP, Hoˆpital Robert Debre´, Paris, France and Universite´ Paris Diderot, Paris, France
2
Abstract Objective. The aim of this study was to investigate the use of ‘‘as needed’’ (pro re nata or prn) psychotropic medication in a child and adolescent psychiatric inpatient population. The study was carried out on the psychiatry ward of a paediatric teaching hospital in Paris, France. Methods. A prospective analysis of prn psychotropic drug prescriptions and administrations was conducted for all patients hospitalised over a period of 4 months. The study group consisted of 187 patients. Results. In total, 93 prn prescriptions were written, for 27% of the patients (51) but only 14% (26) received a total of 76 administrations. Antipsychotic drugs accounted for 54% of the prescriptions, anxiolytics for 33%, antiepileptic drugs for 8%, antiparkinsonian drugs for 4% and hypnotic drugs for 1%. Anxiety was the reason given for 67% of the prn administrations, with hydroxyzine used in 69% of these cases. Disruptive behaviour accounted for 22% of prn administrations, with antipsychotic drugs accounting for 88% of these administrations. Insomnia accounted for 8% of prn administrations, and antipsychotic drug-induced dystonia accounted for 3% of such administrations. Conclusion. Controlled studies are required to assess the efficacy and safety of prn medication and the conditions in which its use is indicated.
Key Words: prn medication, psychiatry, child, adolescent, inpatient
Introduction Psychotropic drugs are widely used to treat children and adolescents with mental illnesses. Pro re nata (prn) or ‘‘as required’’ medication is a commonly used adjunct to routine prescribed medication. Between 50 and 100% of patients within paediatric inpatient mental health settings studied, received prn psychotropic medication on one or more occasions [1]. The use of prn medications in European child and adolescent psychiatry has not been studied extensively. Most existing research focused on US services. Evans and Di Scipio [2] investigated the use and mode of action of prn medication in 47 adolescents over a period of 1 year in an adolescent psychiatric inpatient unit in New York. During the study period,
they recorded 1459 prn drug administrations. Vitiello et al. [1] investigated the use of prn medication in 49 long-stay adolescent inpatients during a 12month period in Pennsylvania; 1263 doses of prn medication were administered. Garrison et al. [3] assessed the use of prn medication in an investigation of aggressive incidents and counter-aggressive strategies in a child and adolescent psychiatric inpatient unit in Massachusetts. Prn medication was administered in just under one-third of the 887 incidents recorded during the 12-month study. Kaplan and Busner [4] examined the use of prn psychotropic medication administered to 150 child and adolescent inpatients in three hospitals in the New York City area. They found significant differences between the three hospitals in terms of the use of prn medication and the classes of drugs administered. Bernard and
Correspondence: Olivier Bourdon, Pharmacie de l’Hoˆpital Robert Debre´, 48 Bd Se´rurier, 75019 Paris, France. Tel: 33 1 4003 5741. Fax: 33 1 4003 2481. E-mail: [email protected]
(Received 15 December 2008; accepted 20 February 2009) ISSN 1365-1501 print/ISSN 1471-1788 online # 2009 Informa UK Ltd. DOI: 10.3109/13651500902849987
254
U. Winterfeld et al.
Littlejohn [5] studied the use of prn psychotropic medication in an inpatient unit for younger adolescents in England. Prn medication was administered to 60% of the 500 patients admitted. Dean et al. [6] studied the patterns of sedative prescription and administration on an ‘‘as needed’’ basis in a child and adolescent mental health inpatient service in Australia. In this sample, 71.3% of the patients were prescribed sedatives prn and 50.8% received at least one dose of prn sedation. Guidelines on the prescription and administration of prn psychotropic medication in child and adolescent inpatients are lacking. Furthermore, the clinical effectiveness of psychotropic prn medication in child and adolescent mental health settings has yet to be established. Therefore, information about the frequency and patterns of use of psychotropic drugs in children and adolescents hospitalised in psychiatric wards is valuable, as it allows clinicians to compare their practices. As part of a larger study of prescribing practices of psychopharmacotherapy in children and adolescents hospitalised in the psychiatry ward of a French paediatric teaching hospital [7], we analysed the use of prn psychotropic drugs in this population. This survey also investigates the factors influencing prn prescription and administration practices.
Any change in the drug given, its dose or dose schedule was treated as a new prescription. Treatment data were obtained from the computerised files with Patient Care System software (PCS† , IBM† , New York City, NY). Drug classes were analysed using the Anatomical Therapeutic Chemical Classification (ATC). The ATC system classifies therapeutic drugs. Its purpose is to serve as a tool for drug utilization research. The following ATC codes were considered to refer to psychotropic drugs: N03 (antiepileptic drugs), N04 (antiparkinsonian drugs), N05 (psycholeptic drugs: antipsychotic drugs, anxiolytics, hypnotic drugs), N06 (psychoanaleptic drugs: antidepressants, stimulants) and N07 (other nervous system drugs). The most prevalent DSM-IV-TR diagnoses were grouped into several broad categories: learning disorders, attention-deficit and disruptive behaviour disorders, anxiety disorders, eating disorders, depressive disorders and schizophrenia. Pervasive development disorders and mental retardation were grouped together. The diagnostic category ‘‘other disorders’’ comprised the following diagnoses: narcolepsy, conversion disorder, personality disorder, chronic motor or vocal tic disorder and Tourette’s disorder. Analysis
Methods Setting and design This prospective survey was carried out on the psychiatry ward of a paediatric teaching hospital in Paris, France. Data were collected in two acute psychiatric hospitalisation units consisting of 24 inpatient beds and partial hospitalisation facilities for nine patients, respectively. During partial hospitalisation, patients continue to live at home, but commute to the hospital up to 5 days per week. All patients newly admitted to these units between 13 March and 13 July, 2006 inclusive, were included in the study. Data were collected throughout the stay in hospital of each patient. The details recorded included demographic data (age, sex, weight, date of admission, date of discharge and admission unit), the clinical characteristics of the patients (Diagnostic and Statistical Manual for Mental Disorders (DSM-IV-TR) discharge diagnosis, symptoms and prior psychiatric hospitalisation), prn orders for psychotropic drugs (name of the drug concerned, dose, administration route, indication, time and date given and reasons for administration) and discharge medication (prn orders continued or discontinued) [8].
Data were analysed with StatView 5.0 (SAS Institute Inc, Cary, NC). Groups were compared using chi-squared and Fisher’s tests for categorical variables and Student’s t-tests and MannWhitney tests for continuous variables, depending on the characteristics of the variable considered.
Results Patient characteristics We included a total of 187 patients in our study. Half (93) the patients were hospitalised in the partial hospitalisation facility and the other half (94) were inpatients. Demographic and diagnostic data for patients with and without prn medication are presented in Table I. prn medication: prescription In total, 93 prescriptions were written for 27% of the patients (51). No prn psychotropic drugs were prescribed to 73% (136) of the patients. Antipsychotic drugs accounted for 54% (50) of prescriptions, anxiolytics for 33% (31), antiepileptic drugs for 8% (7), antiparkinsonian drugs for
Use of prn medication in children and adolescents
255
Table I. Demographic and diagnostic data for patients with and without prn medication.
Number of male patients (%) Age Mean9SD [minimum-maximum] (years) Length of stay Mean9SD (days) Number of patients with prior psychiatric hospitalisation (%) Number of inpatients (%) Diagnosis-number of patients (%) Learning disorders ADHD/disruptive behaviour disorders Pervasive development disorders/mental retardation Anxiety disorders Eating disorders Schizophrenia Depressive disorders Other Two diagnosesa
Patients with prn medication (n 51)
Patients without prn medication (n 136)
P
25 (49) 13.092.4 35929 18 (35)
107 (79) 9.793.1 1298 34 (25)
B0.0001b B0.0001c B0.0001d NS
46 (90)
48 (35)
B0.0001e
0 7 3 12 7 4 3 10 8
64 25 15 3 5 1 2 4 14
B0.0001b NS NS B0.0001b B0.05b B0.05b NS B0.05b NS
(0) (14) (6) (24) (14) (8) (6) (20) (16)
(47) (18) (11) (2) (4) (1) (1) (3) (10)
Md, median value; SD, standard deviation; ADHD, attention-deficit/hyperactivity disorder; Others, narcolepsy, conversion disorder, personality disorder, chronic motor or vocal tic disorder, Tourette’s disorder. a Eleven patients were diagnosed with ADHD/disruptive behaviour disorder and learning disorder; three were diagnosed with ADHD/ disruptive behaviour disorder and pervasive development disorders/mental retardation; two were diagnosed with ADHD/disruptive behaviour disorder and tic disorder; two were diagnosed with ADHD/disruptive behaviour disorder and anxiety disorder; two were diagnosed with learning and anxiety disorder; one was diagnosed with pervasive development disorder/mental retardation and tic disorder; one was diagnosed with mood and personality disorder. b Fisher’s exact test, cStudent’s t-test, dMannWhitney test, eChi-squared test.
4% (4) and hypnotic drugs for 1% (1). Antiepiepileptic drugs were mainly prescribed for anxiety or disruptive behaviour. Age and sex significantly differentiated patients with prn prescriptions from those without (Table I). Forty-nine percent (25/51) of the patients with prn prescriptions were male, versus 79% (107/136) of those without such prescriptions. The two groups were similar in terms of previous hospitalisation history. Patients with prn prescriptions had significantly longer stays than patients without such prescriptions. Finally, 90% (46/51) of the patients with prn prescriptions were inpatients, versus only 35% (48/136) of those without such prescriptions. The distribution of clinical diagnoses differed significantly between the two groups (Table I). The prn prescription group contained a larger proportion of patients with anxiety disorders, other disorders, eating disorders and schizophrenia. The proportion of patients with learning disorders was higher for the group without prn prescriptions than for those with such prescriptions. The prescriptions for prn medication concerned, in 67% (34/51) of cases, patients already receiving psychotropic medication on a regular basis. Overall, 62% (18) of prn antipsychotic drugs were prescribed for patients already regularly taking antipsychotic drugs, and 39% (9) of prn anxiolytics were prescribed to patients already taking anxiolytics
regularly. However, antiparkinsonian drugs were not simultaneously prescribed on a prn and regular basis in the same patient. At discharge, all prn prescriptions were discontinued. prn medication: administration The number of prn administrations did not differ significantly as a function of sex or age. Furthermore, the number of prn administrations was not correlated with length of stay, prior hospitalisation or diagnostic category. The ratio of prn doses prescribed to prn doses administered was analysed, taking medication class and diagnostic category into account (Table II). Twenty-six (14%) of the 51 patients for whom prn medication was prescribed received a total of 76 administrations. The mean number of prn administrations per patient was 2.992.9 (minimum 1; maximum 15). Anxiolytics accounted for 50% (38) of prn administrations, antipsychotic drugs for 37% (28), antiepileptic drugs for 9% (7), antiparkinsonian drugs for 3% (2) and hypnotic drugs for 1% (one). Thirty-four percent (26) of prn administrations concerned patients with other disorders, 17% (13) concerned patients with anxiety disorders, 13% (10) concerned patients with eating disorders, 11% (8) concerned patients with attention-deficit
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Table II. Prn drug prescription and administration by diagnosis (as number of doses prescribed/number of doses received (%)).
Medication
ADHD/ disruptive PDD/ behaviour Mental disorders retardation
Antipsychotic drugs Cyamemazine 75/0 Propericiazine 37/3 Loxapine 11/0 Anxiolytics Hydroxyzine 89/4 Clobazam Clorazepate Antiepileptic drugs Clonazepam Diazepam Antiparkinsonian drugs Tropatepine 10/1 Hypnotic drugs Zolpidem Total 222/8
(0) (8) (0)
18/1 (6) 8/2 (25)
Anxiety disorders
Eating disorders
125/1 (1)
237/3 (1)
Schizophrenia
517/4 (1)
Depressive disorders
Others
Two diagnoses
Total
55/0 (0)
278/11(4)
52/0 (0) 27 /1 (4) 9/0 (0)
1357/20 (1) 72/6 (8) 22/2 (9)
32/1 (3)
238/14 (6)
209/6 (3)
1077/38 (3) 130/0 (0) 65/0 (0)
2/2 (100)
(4)
299/6 (2)
210/7 (3)
130/0 (0) 65/0 (0) 106/5 (5)
13/2 (15)
119/7 (6) 65/0 (0)
65/0 (0) (10)
(4)
122/1 (1)
286/3 (1)
652/13 (2)
447/10 (2)
532/8 (1)
87/1 (1)
2 9/1 (3) 545/26 (5)
9/0 (0)
141/2 (1)
306/7 (2)
29/1 (3) 3077/76 (2)
ADHD, attention-deficit/hyperactivity disorder; PDD, pervasive development disorder; Others, narcolepsy, conversion disorder, personality disorder, chronic motor or vocal tic disorder, Tourette’s disorder.
and disruptive behaviour disorders, 11% (8) concerned patients with schizophrenia, 9% (7) concerned patients with two diagnoses, 4% (3) concerned patients with pervasive development disorders/mental retardation and 1% (1) concerned patients with depressive disorders. Drugs were administered orally in 94% (71) of cases, intramuscularly in 5% (4) of cases and sublingually in 1% (1) of cases. Prn medication was frequently administered in the evening, especially at bedtime, with a peak at 23:00 h (Figure 1). Several symptoms led to the 76 prn administrations (Table III). Anxiety accounted for 67% (51) of prn administrations, disruption on the ward for 22% (17), insomnia for 8% (6) and drug-induced dystonia for 3% (2). All prn drug administrations were consistent with the indication specified by the physician. Discussion In this study, we investigated the use of prn medication in child and adolescent psychiatric inpatient treatment. In our sample 27% (51) of the patients were prescribed a prn medication but only 14% (26) actually received a total of 76 administrations. The observed administration rates are lower than those reported in other studies (50100%) [1,2,46]. A large proportion of the patients in our study had learning disorders and almost half of the patients were treated in a partial hospitalisation facility. These
patients rarely receive psychotropic medication on a prn basis (9% (5) of prn prescriptions and 0% of prn administrations). This difference may also relate to the shorter duration of admissions in our facility. Unlike Dean et al. [6] (agitation and aggression accounting for 53% of the prn administrations), Kaplan and Busner [4] (agitation accounting for 91100% of prn administrations) and Vitiello et al. [1] (disruption on the ward accounting for 70% of the prn administrations), we found that agitation was not the predominant indication for prn medication in our study. Disruptive behaviour accounted for 22% of administrations. Intramuscular administration was used only for aggressive patients. US prevalence exceeds Western European prevalence for overall psychotropic use [9]. The variability in USEuropean psychotropic medication practice patterns reflects many differences such as diagnostic systems, practice guidelines, drug regulations, decentralized private versus centralized national health service delivery systems, availability and financing of services as well as cultural beliefs [10]. Most prn drugs were administered for anxiety. Sedation was usually the aim, as the drugs used on a prn basis were powerful sedatives. Few outcome data are available to determine which drugs are most appropriate for use in prn sedation. Indeed, the only controlled trial carried out to date on this issue reported that diphenhydramine was not superior to placebo [11]. No study has investigated the safety and efficacy of other agents, such as antipsychotic drugs or benzodiazepines, in this setting. There is limited evidence of the effectiveness of prn medication in adult psychiatric inpatients. Chakrabarti et al.
Use of prn medication in children and adolescents
Table III. Symptoms for which prn drugs were administered (n 76).
25
Number of administrations
257
20
Symptom
Number of administrations n (%)
15
Anxiety Disruptiona Insomnia Antipsychotic induced dystonia
10
51 17 6 2
(67) (22) (8) (3)
5 a
Includes self-harm behaviour and physical aggression directed against the staff.
0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23
Time
Figure 1. Distribution of the 76 prn administrations as a function of time of day.
published a Cochrane systematic review of prn psychotropic medications in acute mental health settings [12]. They concluded that there is no evidence about the risks and benefits of prn medication regimens as compared to regular regimens. However, several randomised and double-blind studies compared two prn regimens. In treating children, medication dosages and frequency of administration often are selected based on adult data. However, development can affect pharmacokinetics and drug disposition. Therefore, extrapolating adult dosages to children can have negative effects on both efficacy and safety [13]. Because of developmental differences, safety of medications must also be specifically studied in young children because they cannot be inferred from data collected in older children or adults. Sedative antihistamines were the most frequently administered prn drugs in our study, although antipsychotic drugs were the most frequently prescribed. Antihistamines are particularly popular as they have been shown to be safe and have no severe side effects. Demographic and clinical variables (age, sex, length of stay, prior hospitalisation history and diagnosis) were poor predictors of prn administration. However, variables not considered in our study may have had a significant effect. The interaction between patient and staff and staff variables (sex, age and training) may have had a significant effect and could have been considered together with patient variables. Our findings concerning the timing of prn drug administration are similar to those of other studies [1,2,5,6]. Prn medication was frequently administered in the evening when patients are likely to suffer from anxiety and often refuse to comply with bedtime rules. Some of the diurnal pattern is likely to be explained by institutional factors such as there being
fewer staff and a greater proportion of relatively unstructured time in the evenings. Sixty-seven percent of the prn drug prescriptions were for patients already receiving psychotropic medication on a regular basis. Thus, prn medication seemed to be used as a way of adding to regular psychotropic treatment, rather than replacing it. This pattern of use has been described in previous studies [6,14]. However, the combination of prn and regular medication may increase the risk of drug interactions or adverse effects. Too little information is currently available for the development of guidelines concerning the influence of existing regular medication on the selection and prescription of prn medication. This study was subject to several limitations, which must be borne in mind when interpreting the results. We included hospitalised children from only one clinical setting in our study. As we did not include outpatients, the results cannot easily be generalised to patients with less severe psychiatric problems or patients seen in other settings, such as outpatient clinics and other hospitals. Patients were diagnosed in routine clinical practice, with no diagnostic interviews carried out specifically for this study. Guidelines specifically addressing the processes associated with the prescription and administration of prn psychotropic medication in children and adolescents are lacking. Therefore, hospitals with child and adolescent inpatient units should consider periodically monitoring prn psychotropic drugs use, exploring the reasons for it and the way in which prn drugs are administered. Our prn medication practices can be benchmarked based on those of other paediatric university hospitals. Key points . Prn medication is used in the inpatient management of children and adolescents with mental health problems . Hospitals with child and adolescent inpatient units should consider periodically monitoring
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prn psychotropic drugs use, exploring the reasons for it and the way in which prn drugs are administered . Our prn medication practices can be benchmarked based on those of other paediatric university hospitals Acknowledgements None. Statement of Interest The authors declare that they have no conflict of interest.
[5] Bernard P, Littlejohn R. The use of as required medication on an adolescent psychiatric unit. Clin Child Psychol Psychiatry 2000;5:266. [6] Dean AJ, McDermott BM, Marshall RT. PRN sedationpatterns of prescribing and administration in a child and adolescent mental health inpatient service. Eur Child Adolesc Psychiatry 2006;15:27781. [7] Winterfeld U, Le Heuzey MF, Acquaviva E, Mouren MF, Brion F, Bourdon O. Psychotropic medication use in the child and adolescent psychiatry wards of a French hospital. Pharmacy World Sci 2008; accepted for publication. [8] American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Text revision ed. 2000. Washington, DC: American Psychiatric Association. [9] Zito JM, Safer DJ, Berg LT, Jahnsen K, Fegert JM, Gardner JF, et al. A three-country comparison of psychotropic medication prevalence in youth. Child Adolesc Psychiatry Ment Health 2008;2:26. [10] Vitiello B. An international perspective on pediatric psychopharmacology. Int Rev Psychiatry 2008;20:1216. [11] Vitiello B, Hill JL, Elia J, Cunningham E, McLeer SV, Behar D. P.r.n. medications in child psychiatric patients: a pilot placebo-controlled study. J Clin Psychiatry 1991;52: 499501. [12] Chakrabati A, Whicher E, Morrison M, Douglas-Hall P. As required medication regimens for seriously mentally ill people in hospital. Cochrane Database Syst Rev 2007;18: CD003441. [13] Vitiello B, Jensen PS. Medication development and testing in children and adolescents. Arch Gen Psychiatry 1997;54: 8716. [14] Mason AS, Nerviano V, DeBurger RA. Patterns of antipsychotic drug use in four Southeastern state hospitals. Dis Nerv Syst 1977;38:5415. /
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References [1] Vitiello B, Ricciuti AJ, Behar D. P.R.N. medications in child state hospital inpatients. J Clin Psychiatry 1987;48:3514. [2] Evans R, Di Scipio W. Nonpharmacologic factors in the administration of p.r.n. psychotropic medication on an adolescent unit. Am J Psychiatry 1980;137:1234. [3] Garrison WT, Ecker B, Friedman M, Davidoff R, Haeberle K, Wagner M. Aggression and counteraggression during child psychiatric hospitalization. J Am Acad Child Adolesc Psychiatry 1990;29:24250. [4] Kaplan SL, Busner J. The use of prn and stat medication in three child psychiatric inpatient settings. Psychopharmacol Bull 1997;33:1614. /
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