| Abstract|| |
Background: Published studies have not demonstrated the benefits of the practice of psychotropic PRN administration.
Aim: The goal of this study is to perform a systematic review on pro re nata (PRN) psychotropic medications administration in children and adolescents and examine the safety and effectiveness of this practice in child and adolescent psychiatric care units.
Settings and Design: This is a systematic review.
Materials and Methods: Several databases were searched till date. One hundred and sixty-five titles and abstracts were found and a total of 14 studies, for which most were retrospective, met the absolute criteria. The patients studied were children, adolescents and patients that presented to the emergency room or admitted as inpatient.
Results: Indications for admission included aggression and agitation for all the studies. Most the medications used include haloperidol, olanzapine, diazepam, and risperidone. Commonly reported adverse effects following the administration of the PRN medications were sleepiness, acute dystonia, and drowsiness. The effectiveness of PRN medications, which was reported in four of reviewed studies, ranged from 30% to 50%.
Conclusion: Different effectiveness/outcome measures were used for all the studies; therefore, we could not generalize effectiveness across all the studies. Findings of the reviewed articles show the imperativeness of more research to evaluate the safety and effectiveness of PRN medications among child and adolescent populations.
Keywords: Adolescent, children, effectiveness, pro re nata medications, psychotropic
|How to cite this article:|
Asogwa K, Okudo J, Idowu J. The use and effectiveness of pro re nata psychotropic medications in children and adolescents: A systematic review. Indian J Psychiatry 2017;59:264-74
|How to cite this URL:|
Asogwa K, Okudo J, Idowu J. The use and effectiveness of pro re nata psychotropic medications in children and adolescents: A systematic review. Indian J Psychiatry [serial online] 2017 [cited 2018 Sep 25];59:264-74. Available from: http://www.indianjpsychiatry.org/text.asp?2017/59/3/264/216189
| Introduction|| |
Pro re nata (PRN) psychotropic medications have been used in child and adolescent psychiatric care facilities for the purposes of managing aggression and quelling agitated patients.,,, Other reasons may include hallucinations and destructiveness, for which etiology would include attention-deficit hyperactivity disorder (ADHD), mood disorder, psychosis, intellectual disability, autism spectrum disorders, insomnia, and anxiety.,,,,,,,,,
Studies have shown that PRN psychotropic medications have been used more in males;,,, in addition, the median age of the patients for the studies is 11 years  although it varied in other studies., Patients in child and adolescent psychiatric centers have at least received PRN psychotropic medications on more than one encounter with boys receiving these medications more than girls in the preschool age., Some studies suggest that more than 90% of patients have received PRN psychotropic medications in their hospital encounters. Some studies have suggested a racial predilection in favor of African–American  and other studies have not determined any racial predilection.
Protocol for the administration and monitoring of these medications may not be readily available in the literature in this study population. Not much is known about the intricate details or protocol for administering these medications. Benzodiazepines are very popular in this category, in addition, antipsychotics are well known.,,,,, In some units, nurses are responsible for decision-making in the administration of PRN psychotropic medications; and in other situations, physicians are responsible.,,,,, PRN psychotropic medications have been used to reduce mechanical restraint and other forms of management for these patients.
The reasons for administering PRN psychotropic medications differ for the physicians and nurses; therefore, specific instructions with specific indications are imperative in this regard.,,,,,,,, Several factors can be opined for this, and they include lack of staff, limited knowledge and skills, and limited time and pressure from family on the hospital wards.,,, Many of these medications are more popularly administered at night. Despite these mentioned factors, PRN psychotropic medications are required by the nurses to control patients and maintain a haven in the inpatient setting without requiring the physician to be available or using physical restraint.,, Furthermore, it gives nurses judgmental leverage in unforeseen circumstances. In fact, nearly 80% of PRN psychotropic medications are the nurses' prerogative or initiative.,,,
As well described in the literature, aggressiveness and agitation may be underlying symptoms of certain psychiatric conditions in child and adolescent patients. For this, PRN psychotropic medications become the most useful medications; some authors have even opined that it is a considerably famous option for this age group of patients.
It is very important to consider the implications of PRN medications, especially as related to litigation, patient safety, professional ethics, and clinical efficacy, especially in the light of the target of human rights litigation as has been the case with the United States Department of Justice opposed to psychiatric facilities in the different states. Patients who are aggressive and agitated following phencyclidine/stimulants intoxication or due to delirium tremens are largely treated with benzodiazepines. PRN psychotropic medications administration raises concerns about efficacy, use, and safety. The goal of this study is to perform a systematic review on PRN psychotropic medications administration in children and adolescents and examine the use, safety, and effectiveness of this practice in child and adolescent psychiatric care units.
| Methodology|| |
A systematic literature search was conducted on articles containing studies on PRN psychotropic medications in children and adolescents. The systematic literature search also included studies conducted in psychiatric centers for children and adolescents in different parts of the world. Key words used include PRN medications, psychotropic medications, stat medications, as required medications, as usual medications, as needed medications, children, adolescent, psychiatric facility and psychiatric inpatients. The following databases were searched: PubMed (National Library of Medicine); MEDLINE (Ovid: 1950 to most current); PsycInfo, Cumulative Index of Nursing and Google Scholar, Embase and LILACS. Other relevant articles were hand searched in Scopus (Elsevier) to determine if they were cited by studies that previous searches had omitted. The inclusion criteria for each searched article were defined and all papers screened for inclusion in this review. Each selected article irrespective of the study design was also included; most articles selected were cross sectional. Included studies had determined usage of PRN medications in child and adolescent psychiatric facilities in any part of the world for time frames before 2017. These studies were all written in English. The titles and abstracts were reviewed to evaluate the relevance of the study, ensure eligibility criteria were met in answering the research question and these were given due consideration; this was also done to be sure that inclusion criteria were well defined and understood. To further ensure eligibility criteria, ten citations were randomly selected from the database of articles found.
Study quality assessment
In assessing the quality of the studies, we included the use of PRN psychotropic medications in children and adolescents in psychiatric facilities by specific questions, presence of a verifiable outcome measurement, clear statement of the research question/objectives, statistical analyses appropriate to the study design and limitations and how well they were addressed. High-quality studies were selected for data abstraction. Data abstraction was performed based on the study objective and variables of interest to summarize the findings of the studies to prepare an evidence table. The components of the table included the following: title of study, authors, location of study, sample characteristics, objectives, and study design and major findings. The synthesis of the findings of the evidence table was applied in the development of the overall conclusions. All the authors approved the proposal for this study. This study was not performed on human subjects therefore approval was not obtained from the local ethics committee. A total of fourteen studies met all the criteria and have been reviewed and included in this paper [Table 1].
| Results|| |
After initial search of EMBASE, PsycINFO, MEDLINE PubMed, Ovid MEDLINE, and Google Scholar, 165 articles were identified. Further review of the identified articles based on the relevance and full-text article assessment for eligibility; 14 articles were identified for inclusion in the systematic review of effectiveness/safety of PRN psychotropic medications. Studies were conducted in the United States, the United Kingdom, Canada, France, and Australia. The target group consisted children and adolescents in child and adolescent mental care facilities. Of the studies included for review, there was only one controlled study, nine retrospective studies,,,,,,,,, two cross-sectional studies,, and two prospective studies , were reviewed.
Frequently prescribed PRN psychotropic medications include antipsychotics, benzodiazepines, and antihistamines.,,,,,, Chlorpromazine and haloperidol being the most commonly prescribed typical antipsychotic medication, with increasing interest in atypical antipsychotics.,, Use of non–benzodiazepines sedatives, and anticholinergic as pro re nata medications were documented in six studies.,,,,, In two studies,, only one medication was used as PRN while intramuscular ziprasidone, lorazepam, and haloperidol were used to control agitation during the period of hospitalization.
Out of the 14 studies reviewed, 8 did not document any adverse effect.,,,,,,, Five of the studies assessed the adverse effects of PRN psychotropic medications. Sleepiness was noted in two studies., Acute dystonia/motor reactions were noted in two studies., Acute dystonia due to the effect of haloperidol was also reported. Out of the fourteen studies, drowsiness was reported in two studies,, and it accounted for 60% of the reported adverse effects in one of them. Confusion, increased seizure frequency, nosebleed, sore muscle, and general ache; each accounted for 1.3% of the reported adverse effect in the same study. Agitation and bizarre behavior were also noted. A decrease in pulse rate was the only reported adverse effect of the PRN psychotropic medication administered.
Indication of pro re nata psychotropic medications
Aggression and agitation were the most common documented reasons for administering PRN psychotropic medications. Agitation accounting for 100% of PRN psychotropic medication administered. Aggression was reported in seven of the articles reviewed, accounting for 25.5%–75.9%, of PRN psychotropic medication administered. Aggression toward staff accounted for frequent intramuscular PRN psychotropic medication administration. Only one of the studies did not report reasons for PRN psychotropic medication. Disruptive behavior as a reason for PRN psychotropic medication administration ranged from 22% to 70%. Insomnia accounted for 6%–9% to 15%. Losing control as the indication for the PRN psychotropic medication was reported in over 50%. Two of the reviewed articles reported self-injurious behavior., Other reported indications are neuroleptic-induced dystonia, anxiety, violent/paranoid thinking, and anger.
Schizophrenia, ADHD, depressive disorder, bipolar disorder, pervasive disorder, mental retardation, and conduct disorder were commonly reported diagnoses in all fourteen studies. The following is a breakdown in parenthesis to show how many studies reported each diagnosis. Schizophrenia (5), bipolar disorder (3), ADHD (6), pervasive disorder (4), depressive disorder (4), and conduct disorder (3) were reported.,,,,,,,,,,,,, Psychoactive substance disorder was reported as one of the diagnoses, two articles reported a diagnosis of personality disorder , while four articles did not report any diagnosis.,,, Other reported diagnoses were anxiety disorder, oppositional defiant disorder, mood disorder, impulse control disorder, posttraumatic stress disorder, intermittent explosive disorder, oppositional defiant disorder, impulse control disorder, adjustment disorder, and psychotic disorder.
Effectiveness and measure of outcome following pro re nata administration
Out of fourteen studies reviewed, six did not report the effectiveness of PRN psychotropic medications.,,,,, Effectiveness due to pharmacological effects of PRN psychotropic medications was reported in four studies and ranged from 30% to 50%.,,, A prospective study  and a case–control study  reported the effectiveness of intramuscular ziprasidone as a PRN psychotropic medication. Olanzapine, lorazepam, and chlorpromazine were found to be effective in a prospective study. Nonpharmacological factors (time of PRN psychotropic medication administration, familiarity of staff and patient with the institution, positive expectations of the medication and collaborative effort between patient and nurse to resolve crisis) accounted for reported 70% effectiveness in one of the studies. Ineffectiveness of PRN psychotropic medications was reported in three studies.,, One of the studies reported 14% ineffectiveness, another reported lack of clear evidence base  and the only controlled study reviewed, which had small sample size (n = 21), reported no significant difference between placebo and diphenhydramine PRN administration, however, reported that diphenhydramine when administered by intramuscular route is more effective than oral route which was attributed to placebo effect.
Out of seven studies that reported means to measure outcome following the administration of PRN medications, three studies reported nurse observation documented on the chart.,, Behavioral Activity Rating Scale (BARS) was used to assess the improvement of agitation in two studies; there was significant decrease in BARS score at 30 min (P < 0.05) and thereafter (P < 0.01) which lasted up to 120 min, the second study reported a statistical significant decrease in mean BARS scores from baseline to end (mean baseline [standard deviation (SD)] = 6.5 ± 0.7 and end mean [SD] = 3.1 ± 1.3, P < 0.0001). Clinical Global Impression-Severity (CGI-S) was used to assess the overall severity of illness, in one study, it was reported that CGI rating determined 81% of PRN injections led to the improvement of agitation. Similarly, in another study, there is decline in CGI rating regardless if patent received diphenhydramine or placebo (CGI severity, F = 0.5, df = 3, 51, P = 0.68; CGI improvement, F = 0.1, df = 2,34, P = 0.87). Reported in one of the studies, test-retest reliability evaluated the effectiveness of PRN injection (P ≤ 0.001).
| Discussion|| |
The analysis of PRN psychotropic medications administration among children and adolescent patients and examination of effectiveness of this practice in child and adolescent psychiatry care facilities is the aim of this systematic review. This review afforded the opportunity to learn about psychotropic PRN psychotropic medications from different regions of the world. While the reasons for administration of PRN psychotropic medications are quite similar across studies, the practice seemed to be same. We made the determination that haldol and thioridazine are most popular based on the result of the review. However, there did not seem to be any studies that addressed the efficacy of these medications in detail. Many of these studies only used them based on the effectiveness. While some of the studies determined that these medications are effective in the study population, there was no scientific basis for this. For some of the studies, it was difficult to determine the difference between effectiveness and efficacy of psychotropic PRN psychotropic medications, for other studies, both concepts seemed to be for the same purpose; other studies reported on the effectiveness of the administration of PRN psychotropic medications but is was based on nonscientific reports and observation by the nurses, bringing to question the validity and reliability of the reported effectiveness by these studies, few studies however reported effectiveness based on validated scale. There was no comparative study on the effectiveness of PRN psychotropic medications among child and adolescent patient population as studies in the literature are among adults. The studies seemed to highlight how important the practice of administration of PRN psychotropic medications and the convenience of the practice without heeding to a protocol. Comparing this to the clinic where it is either a refill of medications or medications for established psychiatric conditions for which the patient is “deserving,” psychotropic PRN psychotropic medications might be described as given easily or convenient irrespective of the indication. For these reasons, we categorically neither suggest nor recommend any of the medications in the administration of PRN psychotropic medications.
While some of the studies acknowledged the side effects of the PRN psychotropic medications, the circumstances surrounding these side effects leaves much to be desired. Patients have the right to accept or refuse the prescription and administration of PRN psychotropic medications; while we understand that this might not have been the focus of the respective studies, this makes the studies incomplete because the side effects of currently prescribed psychotropic medications may determine if patients would refuse or accept repeat administration of similar medications administered based on the present indication or diagnosis for the medication or another indication. In addition, the administration of psychotropic medications is not without significant risks. Serious side effect profile such as respiratory arrest, severe sedation, or seizures have been reported in studies in which IM ziprasidone was used. Because of varying side effects, it would have been great to see changes in medication administration pattern from one medication to another based on the side effect profile of the index medication, however, considering that across the studies different indications were documented, this may not be a very strong point. Notwithstanding, there did not seem to be any analysis of rescue medications or antidotes in the event of any adverse event and for this reason, it is difficult to generalize about the effectiveness or consistency of justification of PRN psychotropic medications.
It is possible that some of the patients in the respective cohorts across all the studies may have had one other medical condition such as liver or renal impairment affecting the distribution of the medications. At this juncture, we may suggest that just like there is currently a protocol for reporting drug-induced liver injury case reports, we suggest that for any study performed on PRN psychotropic medications that reporting of side effects be the standard. Considering these, recommending the quality of some of these studies might be a dilemma. Furthermore, the issue of polypharmacy is brought to the fore. Many of the studies did not make any comments about polypharmacy and the multiplied effects of this practice making it difficult to make conclusions about the effectiveness of this practice. The indications for the use of PRN psychotropic medications and the diagnoses seemed to be the same across all the studies; however, the consideration of behavioral therapy in conjunction with psychotropic PRN psychotropic medication administration seemed to be missing, only one study evaluated the nonpharmacological approach toward the management of aggressive and agitated patient that should have required PRN psychotropic medication. In the determination of the indications for PRN psychotropic medications, the study of repeat patients versus malingering patients might have significantly added some more knowledge across the studies. It would have been helpful to observe the patterns of administration of psychotropic PRN psychotropic medications in the day versus night. Many of the studies did not analyze this. The observation of this pattern would have helped to determine whether the administration at night is borne out of necessity or convenience. In addition, considering that the locations of the studies vary, i.e., emergency psychiatric facility versus inpatient psychiatric facility, there is a possibility that locations might bias or impact the justification for the administration of these medications. In addition, it would be difficult to compare the effectiveness or efficacy or pharmacokinetics of psychotropic PRN psychotropic medications across the studies because the routes of administration varied significantly.
Considering the effectiveness of this practice i.e., the administration of PRN psychotropic medications, there was no single scale or outcome measure across the studies. There were a lot of variations. Some studies used BARS, others used observation, and others used CGI-S. It is imperative to note that some of these ratings or scales are subjective, generic, or not adjusted for certain patients. This raises questions as to whether there are accurate outcome measures or tools in the determination of outcomes for these studies. We would agree with one of the studies that could not determine a clear evidence for determining outcome measures. For the variety of outcome measures or measuring instruments, we daresay this may be because of the varying locations of the studies. There is a possibility that different countries have their different instruments/tools of measurement; however, the power of the studies and the significantly varying sample sizes may be responsible. We, therefore, suggest a single-measuring tool that might be useful for measuring outcomes. Furthermore, chart review leaves little much to be desired in the obtaining of information for a study such as this one. Incomplete documentation may also be responsible for a paucity of clinical information required to have a standard measuring tool across all the studies.
Across the studies, there is a significant variation based on the selection of study participants, methods used in the studies, time frame of the study, and accumulating and analysis of data. For these reasons, making a conclusion about these studies from a general standpoint would be inappropriate.
It was interesting to note that many of the studies showed that older women and younger male patients were the most likely candidates to receive these medications.,,, The reason for this association is difficult to determine. This might be partly because the studies are not necessarily homogenous across, besides considering various locations: Europe, Australia, and America, it would be difficult to categorically determine which studies are homogenous. Considering socioeconomic class, it would also be difficult to compare studies across different countries and continents because of significant variations in patterns and lifestyle. Inner city dwellings may be more likely to have patients who are in and out of the psychiatric emergency compared to patients from other parts of the city or the world. This would create a bias in the determination of the effect of socioeconomic class in the effectiveness of psychotropic PRN medications.
| Conclusion|| |
Findings of the reviewed articles show the imperativeness of more controlled study to evaluate the safety and effectiveness of PRN psychotropic medications among child and adolescent population. Moreover, considering the side effect profile of the studied psychotropic medications, the practice should be based on a careful assessment of risks, benefit, and alternatives to PRN administration.
- There were no comparative studies among PRN psychotropic medications to assess effectiveness
- There were no studies to assess the safety of the psychotropic medications, effective dosing and choice of medication
- There was a dearth of studies comparing use of psychotropic medication versus nonpharmacological interventions
- The use of PRN psychotropic medications among psychiatrists is largely based on unscientific observation and reports which intentionally or unintentionally make psychiatrists engage in a practice that leads to unintentional exposure of patients to psychotropic medications leading to untoward side effects.
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Conflicts of interest
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