Effects of benzodiazepines, antidepressants and opioids on driving: a systematic review and meta-analysis of epidemiological and experimental evidence.
BACKGROUND
Many individuals in the community are prescribed psychoactive drugs with sedative effects. These drugs may affect their daily functions, of which automobile driving is a major component.


OBJECTIVE
To examine the association of three classes of commonly used psychoactive drugs (viz. benzodiazepines and newer non-benzodiazepine hypnotics, antidepressants and opioids) with (i) the risk of traffic accidents (as indexed by epidemiological indicators of risk); and (ii) driving performance (as indexed by experimental measures of driving performance).


METHODS
A literature search for material published in the English language between January 1966 and January 2010 in PubMed and EMBASE databases was combined with a search for other relevant material referenced in the retrieved articles. Retrieved articles were systematically reviewed, carrying out meta-analyses where possible. Twenty-one epidemiological studies (13 case-control and 8 cohort studies) fulfilled the inclusion criteria by estimating the accident risk associated with drug exposure (ascertained by blood/urine analysis or prescription records). Sixty-nine experimental studies fulfilled the inclusion criteria by testing actual or simulated driving performance after administering a single dose or multiple doses.


RESULTS
Two meta-analyses showed that benzodiazepines are associated with a 60% (for case-control studies: pooled odds ratio [OR] 1.59; 95% CI 1.10, 2.31) to 80% (for cohort studies: pooled incidence rate ratio 1.81; 95% CI 1.35, 2.43) increase in the risk of traffic accidents and a 40% (pooled OR 1.41; 95% CI 1.03, 1.94) increase in 'accident responsibility'. Co-ingestion of benzodiazepines and alcohol was associated with a 7.7-fold increase in the accident risk (pooled OR 7.69; 95% CI 4.33, 13.65). Subgroup analysis of case-control studies showed a lower benzodiazepine-associated accident risk in elderly (>65 years of age) drivers (pooled OR 1.13; 95% CI 0.97, 1.31) than in drivers <65 years of age (pooled OR 2.21; 95% CI 1.31, 3.73), a result consistent with age-stratified risk differences reported in cohort studies. Anxiolytics, taken in single or multiple doses during the daytime, impaired driving performance independent of their half-lives. With hypnotics, converging evidence from experimental and epidemiological studies indicates that diazepam, flurazepam, flunitrazepam, nitrazepam and the short half-life non-benzodiazepine hypnotic zopiclone significantly impair driving, at least during the first 2-4 weeks of treatment. The accident risk was higher in the elderly (>65 years of age) who use tricyclic antidepressants (TCAs); however, the evidence for an association of antidepressants with accident risk in younger drivers was equivocal. Sedative but not non-sedative antidepressants were found to cause short-term impairment of several measures of driving performance. Limited epidemiological research reported that opioids may be associated with increased accident risk in the first few weeks of treatment.


CONCLUSIONS
Benzodiazepine use was associated with a significant increase in the risk of traffic accidents and responsibility of drivers for accidents. The association was more pronounced in the younger drivers. The accident risk was markedly increased by co-ingestion of alcohol. Driving impairment was generally related to plasma half-lives of hypnotics, but with notable exceptions. Anxiolytics, with daytime dosing, impaired driving independent of their half-lives. TCAs appeared to be associated with increased accident risk, at least in the elderly, and caused short-term impairment in driving performance. Opioid users may be at a higher risk of traffic accidents; however, experimental evidence is limited on their effects on driving.
School of Psychology, The University of Newcastle, Newcastle, New South Wales, Australia. Tharaka.Dassanayake@newcastle.edu.au
Tharaka
T
Dassanayake
Patricia
P
Michie
Gregory
G
Carter
Alison
A
Jones
D000063:Accidents, Traffic / Q000706:statistics & numerical data*; D000701:Analgesics, Opioid / Q000009:adverse effects* / Q000627:therapeutic use; D000928:Antidepressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001334:Automobile Driving; D001569:Benzodiazepines / Q000009:adverse effects* / Q000627:therapeutic use; D016021:Epidemiologic Studies; D005260:Female; D006801:Humans; D008297:Male; D012107:Research Design; D012307:Risk Factors; D012309:Risk-Taking
D000701:Analgesics, Opioid; D000928:Antidepressive Agents; D001569:Benzodiazepines
J Clin Psychiatry. 2005;66 Suppl 2:9-13
15762814
Eur J Clin Pharmacol. 2000 Sep;56(6-7):453-8
11049006
J Psychopharmacol. 2002 Dec;16(4):345-54
12503834
Psychopharmacology (Berl). 1977 Nov 24;55(1):9-12
414266
Eur J Clin Pharmacol. 1990;39(1):83-7
1980464
Neuropsychopharmacology. 2002 Aug;27(2):260-9
12093599
J Clin Psychiatry. 2008 Dec;69(12):1880-6
19203476
Pain Med. 2004 Mar;5(1):42-9
14996236
Accid Anal Prev. 2007 Sep;39(5):1050-5
17854578
Acta Psychiatr Scand Suppl. 1983;308:141-6
6230888
Neuropsychobiology. 1995;31(2):81-8
7760989
Psychopharmacology Suppl. 1984;1:182-92
6147840
Curr Drug Saf. 2007 Sep;2(3):220-6
18690971
Lancet. 1998 Oct 24;352(9137):1331-6
9802269
Br J Clin Pharmacol. 1995 Apr;39(4):397-404
7640146
Am J Epidemiol. 2000 Sep 1;152(5):424-31
10981455
Psychopharmacology (Berl). 2001 Mar 1;154(2):189-97
11314681
Acta Psychiatr Scand Suppl. 1986;332:112-8
2883818
Pharmacol Toxicol. 1994 Aug;75(2):91-8
7971743
Am J Public Health. 1981 Dec;71(12):1399-400
7316007
J Clin Psychiatry. 1982 Dec;43(12 Pt 2):45-55
6130073
Psychopharmacology (Berl). 2009 Dec;207(3):461-7
19798483
Acta Pharmacol Toxicol (Copenh). 1986 Mar;58(3):182-6
3716812
Am J Epidemiol. 1992 Oct 1;136(7):873-83
1442753
J Clin Psychopharmacol. 2009 Oct;29(5):432-8
19745642
Accid Anal Prev. 2000 Sep;32(5):623-32
10908134
Pharmacopsychiatry. 1984 Mar;17(2):36-43
6145169
J Clin Psychopharmacol. 2002 Dec;22(6):576-83
12454557
Acta Psychiatr Scand Suppl. 1986;332:95-104
3554901
J Clin Psychiatry. 2003 Jan;64(1):20-9
12590619
J Clin Psychiatry. 2005 Apr;66(4):436-43
15816785
Drug Alcohol Depend. 1993 Jun;33(1):19-22
8103737
Epidemiology. 1994 Nov;5(6):591-8
7841240
J Psychopharmacol. 2006 Nov;20(6):782-8
16401650
Br J Clin Pharmacol. 1984;18 Suppl 1:121S-129S
6525328
Br Med J (Clin Res Ed). 1982 Sep 25;285(6345):852
6126244
Psychopharmacology (Berl). 1981;73(4):340-4
6789355
Sleep Med. 2003 Nov;4(6):553-61
14607350
Ann Epidemiol. 1995 May;5(3):239-44
7606314
Br Med J. 1980 Nov 15;281(6251):1309-12
7437776
Clin Neuropharmacol. 1994;17 Suppl 1:S9-18
7954488
Accid Anal Prev. 2004 Mar;36(2):239-48
14642878
Clin Pharmacol Ther. 1974 Apr;15(4):368-73
4595291
J Clin Psychiatry. 2009 Mar;70(3):370-7
19192466
Br J Clin Pharmacol. 1980 Aug;10(2):145-50
6107116
Clin Pharmacol Ther. 2009 Jun;85(6):596-9
19279562
Br Med J. 1979 Apr 7;1(6168):917-9
35267
Traffic Inj Prev. 2008 Oct;9(5):404-13
18836950
Int Clin Psychopharmacol. 1988 Apr;3(2):157-65
3397523
J Am Geriatr Soc. 2006 Jan;54(1):77-84
16420201
Br J Clin Pharmacol. 1979;7 Suppl 1:85S-90S
35213
Psychiatry Clin Neurosci. 2008 Oct;62(5):610-6
18950383
Psychopharmacology (Berl). 2007 May;191(4):951-9
17219217
Psychopharmacology (Berl). 2005 Oct;181(4):790-8
16025317
Sleep Med. 2008 Dec;9(8):818-22
18226959
Science. 1969 Mar 28;163(3874):1467-8
5773113
Hum Psychopharmacol. 2008 Jul;23(5):385-97
18350566
Hum Psychopharmacol. 2008 Dec;23(8):693-705
18763235
Int J Clin Pharmacol Res. 1983;3(5):323-9
6678826
Int J Environ Res Public Health. 2009 Mar;6(3):1041-54
19440432
CNS Drugs. 2004;18(5):297-328
15089115
Psychopharmacology (Berl). 1977 Mar 23;52(1):103-6
15295
Accid Anal Prev. 2004 Jul;36(4):631-6
15094417
J Clin Psychiatry. 2008 Jul;69(7):1099-103
18588362
Br J Clin Pharmacol. 1977 Oct;4(5):573-8
20918
Am J Epidemiol. 2009 Mar 15;169(6):761-8
19181876
JAMA. 1997 Jul 2;278(1):27-31
9207334
Sleep. 2002 Mar 15;25(2):224-31
11905433
Science. 1982 Jul 2;217(4554):79-81
7089544
J Clin Psychiatry. 2009 Apr 21;70(5):663-73
19389334
Clin J Pain. 2006 Jun;22(5):499-504
16772806
Psychopharmacology (Berl). 1999 Apr;143(4):373-9
10367554
Forensic Sci Int. 2003 Apr 23;133(1-2):79-85
12742692
J Sleep Res. 2009 Dec;18(4):387-96
19552733
Eur Neuropsychopharmacol. 1995 Mar;5(1):35-42
7613099
Accid Anal Prev. 1989 Aug;21(4):341-53
2669785
Ann Epidemiol. 2007 Aug;17(8):597-602
17574863
Neurosci Biobehav Rev. 1995 Fall;19(3):479-93
7566749
Int J Clin Pharmacol Ther. 2002 Jul;40(7):304-9
12139207
J Clin Psychopharmacol. 1998 Jun;18(3):212-21
9617980
J Clin Psychopharmacol. 1992 Apr;12(2):86-95
1573045
Psychopharmacology (Berl). 2006 Jan;183(4):462-70
16292592
Hum Psychopharmacol. 2008 Jul;23(5):399-407
18383000
Psychopharmacology (Berl). 2001 Apr;154(4):356-61
11349388
J Clin Psychopharmacol. 1995 Feb;15(1):30-40
7714226