Medication-related inpatient falls: a critical review

Ribeiro, Tatiane Bomfim; Melo, Daniela Oliveira de; Maia, Flávia de Oliveira Motta; Ribeiro, Eliane

doi:10.1590/s2175-97902018000117355

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Brazilian Journal of Pharmaceutical Sciences

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Review • Braz. J. Pharm. Sci. 54 (01) • 2018 • https://doi.org/10.1590/s2175-97902018000117355 copy

Medication-related inpatient falls: a critical review

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Falls are the second leading cause of accidental and unintentional injury deaths worldwide. Inpatient falls in hospital settings are likely to prolong the length of stay of patients in nearly 6.3 days, leading to increased hospitalization costs. The causes of fall incidents in healthcare facilities are multifactorial in nature and certain medications use could be associated with these incidents. This review seeks to critically evaluate the available literature regarding the relationship between inpatient falls and medication use. A comprehensive search was performed on MEDLINE, EMBASE and Lilacs with no time restriction. The search was filtered using English, Spanish or Portuguese languages. Our study evaluated medication use and inpatients falls that effectively happen, considering all ages and populations. An assessment of bias and quality of the studies was carried out using an adapted tool from the literature. The drugs were classified according to the Anatomic Therapeutics Chemical Code. The search strategy retrieved 563 records, among which 23 met the eligibility criteria; ninety three different pharmacological subgroups were associated with fall incidents. Our critical review suggests that the use of central nervous system drugs (including anxiolytics; hypnotics and sedatives; antipsychotics; opioids; antiepileptics and antidepressants) has a greater likelihood of causing inpatient falls. A weak relationship was found between other pharmacological subgroups, such as diuretics, cardiovascular system-related medications, and inpatient fall. Remarkably, several problems of quality were encountered with regard to the eligible studies. Among such quality problems included retrospective design, the grouping of more than one medication in the same statistical analysis, limited external validity, problems related to medication classifications and description of potential confounders.

Keywords:
Accidental Fall/hospitals; Therapeutic Uses; Inpatients; Central Nervous System Agents.

Author, publication year	Country	n fallers/ n control group (or comparative group); Special sample condition	Median age (fallers)	Follow-up period	Type of study	Other factors related to fall (statistically significant)	ATC - Pharmacological subgroup	Medication	P value Univariate analysis (UA) and Multivariate analysis (MA)	Odds ratio Univariate analysis (UA) and Multivariate analysis (MA)
*O’Neil et al. (2015*O'Neil C, Krauss M, Bettale J, Kessels A, Costantinou E, Dunagan W, et al. Medications and patient characteristics associated with falling in the hospital. J Patient Safety. 2015;1.)	US	228 fallers/ 678 control; NA	61.5	4.5 months	Case control	Underweight, history of falls, fall was the reason for admission, weak gait, assistive device, person assistance, incontinence, syncope, dizziness and confusion.	Anxiolytics	lorazepam, diazepam, clonazepam (as antiepileptics)	UA: S MA: NS	UA: OR: 2.65 (CI:1.88-3.73); MA: NI
							Antidepressants	amitriptyline, nortriptyline, clomipramine, doxepin, desipramine, phenylpiperazine	UA: S UA for antidepressant phenylpiperazines: S	UA: OR: 1.37 (CI: 0.98-1.90),
							Antiepileptics	Phenytoin (hydantoins)	UA: S MA: NI	UA: OR: 4.93 (CI:2.27-10.70), M A: OR: 3.25 (CI: 1.33-7.95)
							Centrally-acting Antiadrenergic agents	clonidine and methyldopa	UA: S MA: NI	UA: OR: 1.89 (CI:1.01-3.52) MA: NI
							Antipropulsives	loperamide	UA:S MA: NI	UA: OR: 2.31 (CI: 1.02-5.48) MA: NI
							Insulin and analogues	insulin	UA: NS MA: NI	UA:NI MA: OR: 1.46 (CI: 1.01-2.13)
*Tapper et al. (2015*Tapper E, Risech-Neyman Y, Sengupta N. Psychoactive medications increase the risk of falls and fall-related injuries in hospitalized patients with cirrhosis. Clin Gastroenterol Hepatol. 2015;13(9):1670-1675.)	US	55 fallers/ 1749 controls; Cirrhotic	55	3.5 years	Retrospective Cohort	Score MELD (hepatic disease), hepatic encephalopathy and length of stay.	Anxiolytics	diazepam, lorazepam, clonazepam, alprazolam, zolpidem, chlordiazepoxide and zolpidem	UA: S MA: NI	UA: ORa: 6.59 (CI: 3.76 -11.59) MA: NI
	US	55 fallers/ 1749 controls; Cirrhotic	55	3.5 years	Retrospective Cohort		Antipsychotics	olanzapine, risperidone, quetiapine and haloperidol.	UA: S MA: NI	UA: ORa:3.72 (CI:1.9-7.06) MA: NI
*Hayakawa et al. (2014*Hayakawa T, Hashimoto S, Kanda H, Hirano N, Kurihara Y, Kawashima T, et al. Risk factors of falls in inpatients and their practical use in identifying high-risk persons at admission: Fukushima Medical University Hospital cohort study. BMJ Open. 2014;4(8):e005385-e005385.)	Japan	230 fallers/ 9240 controls; NA	60.5	2 months	Prospective Cohort	History of falls, cognitive dysfunction, wheelchair use, needs help to move, rehabilitation and need help with activities of daily life .	Antipropulsives	Antipropulsives NE	UA: S MA: NS	UA: N MA NI
							Psychotropics¹	Psychptropics NE*	UA: S MA: S	UA: N MA: OR 3.64 (men)
							Hypnotics and sedatives	hypnotics NE	UA: S A; S	UA: N MA: ; OR 1.65 (women)
*Dauphinot et al. (2014*Dauphinot V, Faure R, Omrani S, Goutelle S, Bourguignon L, Krolak-Salmon P, et al. Exposure to anticholinergic and sedative drugs, risk of falls, and mortality. J Clin Psychopharmacol. 2014;34(5):565-570.)	France	21 fallers/ 317 controls; Exposure to anticholinergic and sedative Drugs	85.33 +- 6.68	11.6 months	Prospective Cohort	Dementia and Parkinson disease.	Opioids	tramadol	UA with increased DDD: S MA: NI	UA: OR: 2.59; (CI: 1.05-6.35) MA: NI
							Anxiolytics	alprazolam e oxazepam	UA with increased DDD for alprazolam and oxazepam: S UA with increased DDD for meprobamate (without BZD): S MA: NI	UA with increased DDD for alprazolam and oxazepam: OR: 2.59 (CI: 1.05-6.35) UA with increased DDD for meprobamate (without BZD): OR: 2.59 (CI: 1.05-6.35) MA: NI
							Hypnotics and sedatives	zopiclone e zolpidem	UA with increased DDD: S MA: NI	UA with increased DDD: OR: 2.59 (CI: 1.05-6.35) MA: NI
							Antipsychotics	olanzapine. risperidone. amisulpiride. tiaprida.ciamemazine	UA with increased DDD: S MA: NI	UA with increased DDD: OR: 2.59 (CI: 1.05-6.35) MA: NI
							Antiepileptics	Phenobarbital	UA with increased DDD: S MA: NI	UA with increased DDD: OR: 2.59 (CI: 1.05-6.35) MA: NI
*Costa-Dias et al. (2014*Costa-Dias M, Oliveira A, Martins T, Araújo F, Santos A, Moreira C et al. Medication fall risk in old hospitalized patients: A retrospective study. Nurse Edu Today. 2014;34(2):171-176.)	Portugal	214 falls (193 fallers); Elderly	75	3.5 years	Retrospective Cohort	Age, oncologic patient, neurodegenerative disease, male gender, chronic and palliative inpatient wards	Antiepileptics	Antiepileptics (clonazepam 19%)	UA for fall CNS meds: S UA for recurrent fall with valproic acid: S UA for recurrent fall with levetiracetam: S MA: NI	UA for fall CNS meds: OR 7.14 (CI:NI) UA for recurrent fall with valproic acid: OR 3.33 (CI: 1.39-5.4) UA for recurrent fall with levetiracetam: OR 5.67 (CI: 1.91-13.53) MA: NI
*Costa-Dias et al. (2014*Costa-Dias M, Oliveira A, Martins T, Araújo F, Santos A, Moreira C et al. Medication fall risk in old hospitalized patients: A retrospective study. Nurse Edu Today. 2014;34(2):171-176.)	Portugal	214 falls (193 fallers); Elderly	75	3.5 years	Retrospective Cohort	Age, oncologic patient, neurodegenerative disease, male gender, chronic and palliative inpatient wards	Antiepileptics	Antiepileptics (clonazepam 19%)	UA for fall - psychotropic meds: S UA for recurrent fall: S MA:NI	UA for fall - psychotropic meds: OR 8.68 (CI:NI) UA for recurrent fall: OR: 2.74 (CI: 1.36-43.29) MA: NI
							Hypnotics and sedatives	Hypnotics and sedatives NE	UA for fall - psychotropic meds: S UA for recurrent fall: S MA: NI	UA for fall - psychotropic meds: OR 8.68 (CI: NI) UA for recurrent fall: OR: 2.74 (CI 1.36-43.29) MA: NI
							Antipsychotics	Antipsychotics (haloperidol 53%)	UA for falls: S UA for recurrent falls: S UA for recurrent fall with haloperidol: NI UA for recurrent fall with clozapine: NI MA: NI	UA for falls: OR: 7.27 UA for recurrent falls: OR: 5.08 (CI: 2.24-10.84) UA for recurrent fall with haloperidol: OR: 3.32 (IC 2.62-10.50) UA for recurrent fall with clozapine: OR: 7.67 (CI:1.81-8.74) MA: NI
							Antidepressants	Antidepressants NE	UA for fall: S UA for recurrent falls: S UA for recurrent fall with trazadone: NI MA: NI	UA for fall: OR: 6.34 (CI: NI) UA for recurrent falls: OR:4.93 (CI: NI) UA for recurrent fall with trazadone OR:5.25(CI: NI) MA: NI
							Opioids	Opioids (tramadol 40%)	UA for falls: S UA for recurrent falls: S UA for recurrent fall with tramadol: S MA:NI	UA for falls:OR: 7.14(CI: NI) UA for recurrent falls: OR:3.97 (CI 1.36-43.29) UA for recurrent fall with tramadol: OR:3.10 (CI: NI) MA: NI
							Diuretics²	Diuretics (furosemide 59%)	UA for recurrent falls: S MA:NI	UA for recurrent falls: OR 2.37 (CI: NI) MA:NI
							Agents acting on the renin-angiotensin	Angiotensin-converting-enzyme inhibitor inhibitors (captopril 30%)	UA for recurrent falls: S MA: NI	UA for recurrent falls: OR 7.67 (CI: NI) MA:NI
							Blood glucose lowering drugs. excluding insulin	Oral Antidiabetic drugs (metformin 15%)	UA for recurrent falls: S UA for recurrent fall with metformin: S UA for recurrent fall with gliclazide: S MA:NI	UA for recurrent falls: OR: 2.54 (CI 1.21-5.34) UA for recurrent fall with metformin: OR 2.82 (CI: 1.27-6.20) UA for recurrent fall with gliclazide: OR: 5.36 (CI 2.07-13.90) MA:NI
*Kolla et al.* (2013**Kolla B, Lovely J, Mansukhani M, Morgenthaler T. Zolpidem is independently associated with increased risk of inpatient falls. J Hosp Med. 2013;8(1):1-6.)	US	151 falls; NA	56.84 +- 17,24	12 months	Retrospective Cohort	Insomnia, Delirium, age, Charlson index ,Hendrich’s fall risk score and zolpidem dose.	Hypnotics and sedatives	zolpidem	UA: S MA: S	UA: OR: 4.37 (CI: 3.33 -5.74) MA: OR: 6,39 (CI: 3.34-5.76)
*Pierce et al.* (2013**Pierce JR, Shirley M, Johnson EF, Kang H. Narcotic administration and fall-related injury in the hospital: Implications for patient safety programs and providers. Int J Risk Safety Med. 2013;25(4):229-234.)	US	251 fallers; NA	NM	12 months	Retrospective Cohort	Pre-fall confusion. Other not evaluated.	Opioids	Opioids NE	UA: S MA: S	UA: OR: 5,12 (CI: 1.96-13.41) MA: OR: 5.38 (CI: 2.07-13.98)
*Obayashi et al. (2013*Obayashi K, Araki T, Nakamura K, Kurabayashi M, Nojima Y, Hara K, et al. Risk of falling and hypnotic drugs: retrospective study of inpatients. Drugs in R D. 2013;13(2):159-164.)	Japan	116 fallers / 3.683 control ; NA	64.7 ± 19.5	3 months	Case control	Age. Others not evaluated.	Hypnotics and sedatives	Zolpiclone, brotizolam, estazolam	UA: NI MA for hypnotics: S MA for zopiclone: NS MA for brotizolam: S MA for estazolam: NS	UA: NI MA for hypnotics: OR: 2.17 (CI: 1.44-3.28) MA for zopiclone: OR: 3.773 (CI: 1.36-10.4); MA for brotizolam: OR: 2.43 (1.61- 3.68) MA for estazolam: OR: 4.027 (1.35-12.1)
							Antiepileptics	Antiepileptics NE	UA: NI MA: S	UA: NI MA: OR 5.06 (CI: 2.70-9.46)
							Anti-dementia drugs	Anti-Alzheimer NE	UA: NI MA: S	UA: NI MA: OR: 3.08 (CI:1.63-5.84)
							Anti-Parkinson drugs²	Anti-Parkinson drugs NE	UA: NI MA: S	UA: NI MA: OR: 5.06 (CI:1.58-16.24)
							Diabetic drugs ²	Diabetic drugs NE	UA: NI MA: S	UA: NI MA: OR: 5.06 (CI:1.58-16.24)
							Drugs for Cardiovascular system²	Antihypertensives NE	UA: NI MA: S	UA: NI MA: OR: 2.24 (CI: 1.41-3.56)
							Antiarrhythmic drugs class I and III	Antiarrhythmic drugs class I and III NE	UA: NI MA: S	MA: p=0.005; OR: 2.82 (CI:1.36-5.86)
*Lamis et al. (2012*Lamis R, Kramer J, Hale L, Zackula R, Berg G. Fall risk associated with inpatient medications. Am J Health-Syst Pharm. 2012;69(21):1888-1894.)	US	96 fallers/ 96 control; NA	70 +- 13,9	12 months	Case control	Not mentioned or evaluated	Other Analgesics e Antipyretics	Analgesics e Antipyretics NE	UA for CNS meds: S MA for CNS meds: S	UA for CNS meds: NI MA: OR:1.4 (CI: 1.09-1.71)
							Antiepileptics	Antiepileptics NE	UA for CNS meds: S MA for CNS meds: S	UA for CNS meds: NI MA: OR:1.4 (CI: 1.09-1.71)
							Antidepressants	Antidepressants NE	UA for CNS meds: S MA for CNS meds: S	UA for CNS meds: NI MA: OR:1.4 (CI: 1.09-1.71)
							Antipsychotics	Antipsychotics NE	UA for CNS meds: S MA for CNS meds: S	UA for CNS meds: NI MA: OR:1.4 (CI: 1.09-1.71)
							Anxiolytics	Anxiolytics NE	UA for CNS meds: S MA for CNS meds: S	UA for CNS meds: NI MA: OR:1.4 (CI: 1.09-1.71)
							Hypnotics and sedatives	Hypnotics and sedatives NE	UA for CNS meds: S MA for CNS meds: S	UA for CNS meds: NI MA: OR:1.4 (CI: 1.09-1.71)
*Chang et al. (2011*Chang C, Chen M, Tsai C, Ho L, Hsieh H, Chau Y, et al. Medical conditions and medications as risk factors of falls in inpatient older people: a case-control study. Int J Geriat Psych. 2011;26(6):602-607.)	Taiwan	165 fallers/ 165 controls; Elderly	76.2	12 months	Case control	Oncologic patients. Others not evaluated.	Anxiolytics	Benzodiazepines NE	UA: S MA: S	UA: OR: 2.26 (CI:1.21-4.23) MA: OR: 2.63 (CI:1.55-4.46)
*Chang et al. (2011*Chang C, Chen M, Tsai C, Ho L, Hsieh H, Chau Y, et al. Medical conditions and medications as risk factors of falls in inpatient older people: a case-control study. Int J Geriat Psych. 2011;26(6):602-607.)	Taiwan	165 fallers/ 165 controls; Elderly	76.2	12 months	Case control	Oncologic patients. Others not evaluated.	Opioids	Opioids NE	UA: NI MA: S	UA: NI MA: OR: 2.13 (CI:1.16-3.94)
							Antihistamines for systemic use	Antihistamines NE	UA: NI MA: S	UA: NI MA: OR: 3.00 (CI:1.19-7.56)
							Hypnotics and sedatives	zolpidem	UA: NI MA: S	UA: NI MA: OR: 2.38 (CI: 1.04-5.43)
Cashin, Yang (2011Cashin R, Yang M. Medications prescribed and occurrence of falls in general medicine inpatients. Can J Hosp Pharm. 2011;64(5):321-326.)	Canada	151 falls; NA	73.5	12 months	Cross sectional study	Not mentioned or evaluated	Anxiolytics	Alprazolam, bromazepam, chlordiazepoxide, clobazam. Clonazepam, clorazepate. Diazepam,flurazepam. Lorazepam,midazolam, nitrazepam,oxazepam, temazepam,triazolam	UA: NI MA: NI	UA: NI MA: NI
Bun, Serby, Friedmann (2011Bun S, Serby M, Friedmann P. Psychotropic medication use, hyponatremia, and falls in an inpatient population. J Clin Psychopharmacol. 2011;31(3):395-397.)	US	15 fallers/ 233 control; Psychiatric population with hyponatemia	55,8	12 months	Case control	Age and hyponatermia. Others not evaluated.	Antipsychotics	Antipsychotics NE	UA: S MA: NI	UA: OR: 3.85 (CI: 1.17 -12.73) MA: NI
*Shuto et al. (2010*Shuto H, Imakyure O, Matsumoto J, Egawa T, Jiang Y, Hirakawa M, et al. Medication use as a risk factor for inpatient falls in an acute care hospital: a case-crossover study. Brit J Clin Pharmacol. 2010;69(5):535-542.)	Japan	349 fallers	71.5± 14.8	2,5 years	Case-crossover	Not mentioned or evaluated	Antihypertensives	amlodipine, atenolol , benidipine ,betaxolol, bisoprolol, candesartan, captopril, carvedilol, clonidina , diltiazem, doxazosin, efonidipine, enalapril, imidapril losartan, etoprolol, nicardipine, nifedipine, nilvadipine, nisoldipine, perindopril, prazosin, propranolol, temocapril, valsartan, verapamil	UA: NI MA: S MA for candersartan: S	UA: NI MA: OR: 8.42 (CI: 3.12-22.72) MA for candersartan: OR: 13.92 (CI: 1.71 - 113.69)
							Anti-Parkinson drugs²	amantadine, biperiden, cabergoline, droxidope, levodopa, pergolid), pramipexole,selegiline, tiapride, trihexifenidil	UA: NI MA: S MA for biperiden: S	UA: NI MA: OR: 4,18 (CI: 1.75 -10.02) MA for biperiden: OR: 4.34 (IC: 1.57 - 11.99)
							Anxiolytics	alprazolam, bromazepam, clotiazepam,cloxazolam, diazepam, etil loflazepate, etizolam, lorazepam, tandospirona	UA: NI MA: S MA for etizolam: S	UA: NI MA: OR: 3.25 (IC: 1.62 - 6.50) MA for etizolam: OR: 6.83 (IC: 1.92 - 24.26)
							Hypnotics and sedatives	brotizolam, flunitrazepam, lormetazepam),midazolam, nitrazepam, quazepam, rilmazafone, triazolam, zolpidem, zopiclone	UA: NI MA: S MA for zopiclone: S	UA: NI MA:;OR:2.44 (CI: 1.32 - 4.51) MA for zopiclone: OR: 4.20 (CI: 1.55 - 11.40)
Mamun, Lim (2009Mamun K, Lim J. Association between falls and high-risk medication use in hospitalized Asian elderly patients. Geriatr Gerontol Int. 2009;9(3):276-281.)	Singapore	298 fallers/ 298 control; Asian elderly	75.8	12 months	Case control	Normal mental state on admission, length of stay, Morse scale, history of falls, walking independently and number of medications	Anxiolytics	benzodiazepines and anxiolytics	UA: S MA: S	UA: NI MA: NI
							Cough supressant	Cough preparations NE	UA: S MA: S	UA: NI MA: NI
							Antithrombotic agents	Anti-platelet agents NE	UA: S MA: S	UA: NI MA: NI
							Vasodilators used for treating heart-related diseases	Nitrates	UA: S MA: NI	UA: NI MA: NI
							Calcium channel blockers²	Calcium channel blockers	UA: S MA: NI	UA: NI MA: NI
							Opioids	Weak opioids	UA: S MA: NI	UA: NI MA: NI
							Diuretics²	Diuretics NE	UA: S MA: NI	UA: NI MA: NI
Mamun, Lim (2009Mamun K, Lim J. Association between falls and high-risk medication use in hospitalized Asian elderly patients. Geriatr Gerontol Int. 2009;9(3):276-281.)	Singapore	298 fallers/ 298 control; Asian elderly	75.8	12 months	Case control	Normal mental state on admission, length of stay, Morse scale, history of falls, walking independently and number of medications	Lipid- modifying agents. plain	Lipid -regulating drugs NE	UA: S MA: NI	UA: NI MA: NI
							Beta-blocking Agents	Beta-blockers	UA: S MA: NI	UA: NI MA: NI
							Alpha and beta adrenoreceptor agonist	Alpha-agonist	UA: S MA: NI	UA: NI MA: NI
							Corticosteroids for systemic use	Steroides	UA: S MA: NI	UA: NI MA: NI
*Tanaka et al. (2008*Tanaka M, Suemaru K, Ikegawa Y,Tabuchini N, Araki H. Relationship between the risk of falling and drugs in an academic hospital. Yakugaku Zasshi. 2008;128(9):1355-1361.)	Japan	65 fallers/ 4084 control; NA	68.1±13.1	7 months	Case control	Age >70 years . Other non-specified conditions.	Anxiolytics	Anxiolytics NE	UA: S MA: S	UA: OR: 3.35 (CI: 1.83-5.82) MA: OR: 2.36 (CI: 1.24-4.28)
							Anti-Parkinson drugs	Anti-Parkinson drugs NE	UA: NI MA: S	UA: OR: 5.7 (CI: 1.71 -14.80) MA: OR: 5.04 (CI: 1.44-13.43)
							Hypnotics and sedatives	Hypnotics and sedatives NE	UA: S MA: NS	UA: OR:2.12 (CI: 1.25-3.52) MA: NI
							Opioids	Opioids NE	UA: NI MA: NS	UA: OR: 3.08. (CI: 1.06 -7.11) MA: NI
							Diuretics²	Diuretics NE	UA: NI MA: NI	UA: OR: 2.39 (CI: 1.42- 3.95) MA: NI
Angalakuditi, Gomes, Coley (2007Angalakuditi M, Gomes J, Coley K. Impact of drug use and comorbidities on in-hospital falls in patients with chronic kidney disease. Ann Pharmacother. 2007;41(10):1638-1643.)	US	635 fallers/ 1270 control; With chronic kidney disease	68 ± 15	5.5 years	Case control	Dementia, diabetes and pneumonia.	Antiepileptics	Anticonvulsant NE	UA: S MA: S	UA: NI MA: OR: 1.52 (CI: 1.13-2.03)
							Antidepressants	Antidepressants NE	UA: S MA: S	UA: NI MA: OR: 1.65 (CI: 1.32-2.08)
							Anxiolytics	Benzodiazepines NE	UA:S MA: S	UA: NI MA: OR: 0.69 (CI: 0.55- 0.86)
Vassalo et al. (2006)	UK	825 falls; Confused patients	81.9	17 months	Case control	Confused patients. Others not evaluated.	Anxiolytics	Benzodiazepines NE	UA for falls on tranquilizers (benzodiazepines and antipsychotics): S UA for recurrent falls in confused: S MA: NI	UA for falls on tranquilizers (benzodiazepines and antipsychotics): OR: 0.63 (CI: 047-0.82) UA for recurrent falls in confused: NI MA: NI
Vassalo et al. (2006)	UK	825 falls; Confused patients	81.9	17 months	Case control	Confused patients. Others not evaluated.	Antipsychotics	Antipsychotics NE	UA for falls on tranquilizers (benzodiazepines and antipsychotics): S UA for recurrent falls in confused: S MA: NI	UA for falls on tranquilizers (benzodiazepines and antipsychotics): OR: 0.63 (CI: 047-0.82) UA for recurrent falls in confused: NI MA: NI
Walker (2005Walker P. Medication use as a risk factor for falls among hospitalized elderly patients. Am J Health-Syst Pharm. 2005;62(23):2495-2499.)	US	62 fallers/ 62 control; NA	74.54 ± 6.03	12 months	Case control	Mean ± S.D. no. medications received within 24 hr preceding fall and Dementia.	Other Analgesics e Antipyretics	Aspirin 85 e 325 (77%). aspirin+celecoxibe. aspirin+ibuprofen, celecoxib, ibuprofen, ketorolac, indometacin	UA: S MA: NI	UA: OR: 10.02 (2.6-38.58) MA: NI
	US	62 fallers/ 62 control; NA	74.54 ± 6.03	12 months	Case control		Opioids	Opioids NE	UA: S MA: NI	UA:OR: 0.33 (IC: 0.11-0.96) MA: NI
Walker (2005Walker P. Medication use as a risk factor for falls among hospitalized elderly patients. Am J Health-Syst Pharm. 2005;62(23):2495-2499.)	US	62 fallers/ 62 control; NA	74.54 ± 6.03	12 months	Case control	Mean ± S.D. no. medications received within 24 hr preceding fall and Dementia.	Urological drugs	Oxybutynin and tolterodine	UA for other medication that can produce sedation or postural hypotension: S MA: NI	UA for other medication that can produce sedation or postural hypotension: OR: 13.85 (IC:3.6-52.83) MA: NI
							Blood glucose lowering drugs, excluding insulin	glimepiride, glipizide, insulin, rosiglitazone	UA for other medication that can produce sedation or postural hypotension: S MA: NI	UA for other medication that can produce sedation or postural hypotension: OR: 13.85 (IC:3.6-52.83) MA: NI
							Antiepileptics	carbamazepine, gabapentin, lamotrigine, oxcarbazine, phenytoin, topiramate, valproate.	UA for other medication that can produce sedation or postural hypotension: S MA: NI	UA for other medication that can produce sedation or postural hypotension: OR: 13.85 (IC:3.6-52.83) MA: NI
							Antihistamines for systemic use	cyclizine, fexofenadine	UA for other medication that can produce sedation or postural hypotension: S MA: NI	UA for other medication that can produce sedation or postural hypotension: OR: 13.85 (IC:3.6-52.83) MA: NI
							Drugs for alimentary tract and metabolism²	dolasetron, metoclopramide, omeprazole, ondansetron, ranitidine	UA for other medication that can produce sedation or postural hypotension: S MA: NI	UA for other medication that can produce sedation or postural hypotension: OR: 13.85 (IC:3.6-52.83) MA: NI
							Drugs for Cardiovascular system²	Amlodipine, diltiazem, nitrates	UA for other medication that can produce sedation or postural hypotension: S MA: NI	UA for other medication that can produce sedation or postural hypotension: OR: 13.85 (IC:3.6-52.83) MA: NI
*Krauss et al. (2005*Krauss M, Evanoff B, Hitcho E, Ngugi K, Dunagan W, Fischer I, et al. A case-control study of patient, medication, and care-related risk factors for inpatient falls. J Gen Internal Med. 2005;20(2):116-122.)	US	98 fallers/ 318 controls; NA	ND (50-69 years - 37.8%)and >=70 (38.8%)	6 weeks	Case control	Age>50 years, gait/balance deficit or lower extremity, incontinence, diabetes, fallen in the past 6 months, depression, impaired memory, confused, and care-related factors (assistance, patient-to-nurse ration)	Hypnotics and sedatives	Hypnotics and sedatives NE	UA: NI MA: NI	UA: OR: 2.1 (CI: 1.2 - 3.7) MA: OR: 4.3 (CI: 1.6 - 11.5)
							Antiarrhythmics class I and III	Antiarrhythmics class I and III NE	UA: NI MA: NI	UA: OR: 2.1 (CI :1.2 - 3.7) MA: NI
							Diabetic drugs²	Diabetic drugs NE	UA: NI MA: NI	UA: OR: 2.1 (CI: 1.2 - 3.5) MA: OR: 3.2 (CI: 1.3 - 7.9)
							Other Analgesics e Antipyretics	Non-narcotic analgesics - NE	UA: NI MA: NI	UA: OR:2.0 (CI:0.9 - 3.3) MA: NI
Vassalo et al. (2004)	UK	136 fallers/ 463 control ; With unsafe-safe gait	81.9	12 months	Prospective Cohort	Unsafe gait, previous fall and confusion .	Anxiolytics	Tranquilizers NE	UA: S MA: NI	UA: OR: 1.73 (CI:1.08-2.75) MA: NI
Frels (2002Frels C. Iatrogenic causes of falls in hospitalised elderly patients: a case-control study. Postgrad Med J. 2002;78(922):487-489.)	UK	181 fallers/ 181 controls; Elderly	73.3	4 months	Case control	Stroke, previous fall, disoriented in time/place or person and needs maximum assistance.	Anxiolytics	Benzodiazepines NE	UA: S MA: S	UA: NI MA: OR: 2.3 (CI:1.4-3.7)
	UK	181 fallers/ 181 controls; Elderly	73.3	4 months	Case control		Diuretics²	Diuretics NE	UA: S MA: NS	UA: NI MA: NI
Mendelson (1996Mendelson WB. The use of sedative/hypnotic medication and its correlation with falling down in the hospital. Sleep. 1996;19(9):968-701.)	US	253 falls/ 84 control; NA	57.4±1.3	12 months	Case control	Not mentioned or evaluated.	Antidepressants	Amitriptyline.clomipramine, doxepin, fluoxetine, imipramine, nortriptyline and sertraline	UA for antidepressants: S UA for Nortriptyline: S UA for sertraline: S MA: NI	UA: NI UA for Nortriptyline: NI UA for sertraline: NI MA: NI
							Hypnotics and sedatives	Chloral hydrate, temazepam andtriazolam	UA for hypnotics: S UA for temazepam:S MA: NI	UA for hypnotics: NI UA for temazepam:NI MA: NI
							Anxiolytics	Alprozolam,chlordiazepoxide, Chlorazepate, diazepam e lorazepam	UA for benzodiazepines: S UA for alprozolam. diazepam and lorazepam: S MA: NI	UA for benzodiazepines: NI UA for alprozolam. diazepam and lorazepam: NI MA: NI
							Antipsychotics	Clorpromazine, droperidol. Haloperidol,prochlorperazinam, Tioridazinam,tiotixene and trifluoerazine	UA for general: S UA for haloperidol and prochlorperazine: S	UA for general: NI UA for haloperidol and prochlorperazine: NI
Aisen, Deluca, Lawlor (1992Aisen P, Deluca T, Lawlor B. Falls among geropsychiatry inpatients are associated with prn medications for agitation. Int J Geriat Psych. 1992;7(10):709-712.)	UK	33 falls (17 fallers)/ 30 control; Geropsychiatry inpatients	75.3±7	12 months	Case control	Length of stay, dementia, history of falls and assistance required	Anxiolytics	Benzodiazepines NE	UA: S MA: NI	UA: NI MA: NI
	UK		75.3±7	12 months	Case control		Antipsychotics	Neuroleptics NE	UA: S MA: NI	UA: NI MA: NI

Pharmacological Subgroup related to inpatient fall	Studies “n”	% based on total number of studies n=23
Anxiolytics	17	74
Hypnotics and sedatives	11	48
Antipsychotics	8	35
Opioids	7	30
Antiepileptics	7	30
Antidepressants	5	22
Diuretics²	4	17
Anti-Parkinson drugs²	3	13
Other Analgesics e Antipyretics	3	13
DiabetIC drugs²	2	8,7
Drugs for cardiovascular system²	2	8,7
Antipropulsives	2	8,7
Antihistamines for systemic use	2	8,7
Antiarrhythmic drugs - class I and III	2	8,7
Agents acting on the renin-angiotensin system	1	4,3
Urological drugs	1	4,3
Blood glucose lowering drugs, excluding insulin	1	4,3
Beta-blocking agentes	1	4,3
Drugs for alimentary tract and metabolism²	1	4,3
Alpha and beta adrenoreceptor agonist	1	4,3
Centrally-acting antiadrenergic agents	1	4,3
Anti-dementia drugs	1	4,3
Antihypertensives²	1	4,3
Antithrombotic agents	1	4,3
Blood glucose lowering drugs, excluding insulin	1	4,3
Calcium channel blockers ²	1	4,3
Corticosteroids for systemic use	1	4,3
Cough supressant	1	4,3
Insulin and analogues	1	4,3
Lipid modifying agents, plain	1	4,3
Psychotropics¹	1	4,3
Vasodilators used for treating heart-related diseases	1	4,3
Total	93	-

Universidade de São Paulo, Faculdade de Ciências Farmacêuticas Av. Prof. Lineu Prestes, n. 580, 05508-000 S. Paulo/SP Brasil, Tel.: (55 11) 3091-3824 - São Paulo - SP - Brazil
E-mail: bjps@usp.br

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[1] *Correspondence: T. B. Ribeiro. Hospital Universitário, Universidade de São Paulo. Av. Prof. Lineu Prestes, 2565, 05508-000, Butantã, São Paulo - SP. E-mail: tatianeribeiro6@gmail.com

Database	Search Strategy
PUBMED.MEDLINE	(((((inpatients[MeSH Terms]) OR inpatient[Title]) OR hospital[Title])) AND (((therapeutic uses[MeSH Terms]) OR drug[Title]) OR medicat[Title])) AND ((accidental falls[MeSH Terms]) OR fall*[Title])
EMBASE	inpatient:ti OR ‘hospital patient’:de,ti OR hospital:ti AND (drug:ti OR ‘drug therapy’/exp OR medicat:de,ti) AND (‘fall risk’:de OR falling:de OR fall:ti)
BVS.LILACS	(mh:inpatients OR ti:inpatient* OR ti:hospital) AND (mh:”therapeutic uses” OR ti:drug OR ti:medicat* OR mh:drug* OR mh:medicat) AND (mh:”accidental falls” OR ti:fall)

Clear definition and representation of population	-The population, the eligibility criteria and methods of selection were clearly described; -The sample was representative of the population or group studied
Adequate selection of cases and control (or comparative group)	-The case and control(or comparative group) selection criteria were clearly described; -The control (in case it is control case) reflects the case population (characteristics and number); - The same indicators were evaluated for both groups.
Full identification of potential confounders	- All confounders (or at least 80%) were identified (we considered the main confounders to fall: history of fall, age, ambulatory aid, gait, mental status (dementia, confusion, disorientation, impulsivity), symptomatic depression), according to Hendrich II Fall Risk Model and Morse Fall Scale.
Accurate measure of all important relevant exposure, potential confounders and outcomes	-Accurate measure and description of the relevant exposure, potential confounders and outcomes, sample characteristics, follow-up period and clear outcomes.
Adequate statistical analysis	-Description and accurate analysis of the statistical methods chosen.