psychotropic medication use and accidents, injuries and cognitive failures

human psychopharmacology

Hum Psychopharmacol Clin Exp 2005; 20: 391–400.

Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/hup.709

REVIEW

Psychotropic medication use and accidents, injuriesand cognitive failures

E. J. K. Wadsworth*, S. C. Moss, S. A. Simpson and A. P. Smith

Centre for Occupational and Health Psychology, Cardiff University, 63 Park Place, Cardiff CF10 3AS, UK

Background Psychotropic medication has the potential to impair psychomotor and cognitive function, and several med-ications have well documented links to increased accident and injury susceptibility. Those developed more recently havemany fewer side effects. However, there is little work examining any association between psychotropic medication use andsafety within the context of other demographic, health and lifestyle factors.Aims To examine and compare any associations between psychotropic medication use (including benzodiazepines, tricyc-lics and SSRIs) and accidents, injuries and cognitive failures in a community sample.Methods A postal questionnaire survey was conducted among people selected at random from the electoral registers ofCardiff and Merthyr Tydfil.Results Psychotropic medication use was associated with accidents, injuries and cognitive failures, particularly amongthose who already had higher levels of other risk factors and/or continuing mental health problems.Conclusions The well established associations between accidents and injuries and older psychotropic medications werereplicated. SSRIs, however, were relatively safer. The study also highlighted the need to consider any effect of psychotropicmedication within the context of both mental health status and other factors. Copyright # 2005 John Wiley & Sons, Ltd.

key words— SSRIs; tricyclics; benzodiazepines; accidents; injuries; mental health

INTRODUCTION

Links between psychotropic medication and cognitiveand psychomotor function impairment are well docu-mented (Paterniti et al., 1999; Edwards, 1995). Thereis also some evidence for an association between med-ication use and accidents (Tinetti et al., 1988; Osteret al., 1990; Ray et al., 1992; Leveille et al., 1994;Wadsworth et al., 2003a). In particular, this isapparent for medications such as benzodiazepines(Stenbacka et al., 2002; Macdonald, 1999; Ellinwoodand Heatherly, 1985; Currie et al., 1995; Oster et al.,1990) and tricyclic antidepressants (Ray et al., 1987;

1992; Leveille et al., 1994; Currie et al., 1995). Thelink between psychotropic medication use andaccidents has been studied extensively in the elderly(Kallin et al., 2002; van Laar et al., 2002; Leveilleet al., 1994; Liu et al., 1998; Pacher and Ungvari,2001; Ray et al., 1992; Tinetti et al., 1988), amongwhom sensitivity to side effects is more likely, anddepression more common (Beekman et al., 1999).Selective serotonin reuptake inhibitors (SSRIs), how-ever, which were developed partly in response to suchside effects, have a much better safety record (vanLaar et al., 2002).

The UK prevalence of treated depression and anxi-ety has risen in recent years. In 1998, 29 per thousandmales were treated by their GP for depression and23.8 per thousand for anxiety. Corresponding figuresfor females were higher at 70.1 per thousand and54.4 per thousand respectively (Key Health Statistics,2000). This represents around 3.5% of the adult popu-lation (Ohayen et al., 1998).

Received 9 February 2005

Copyright # 2005 John Wiley & Sons, Ltd. Accepted 1 June 2005

* Correspondence to: Dr E. J. K. Wadsworth, Centre for Occupa-tional and Health Psychology, Cardiff University, 63 Park Place,Cardiff CF10 3AS, UK. Tel: 029 2087 6599. Fax: 029 2087 6399.E-mail: [email protected]

Contract/grant sponsor: Health and Safety Executive; contract/grantnumber: 4280/R54.080.

However, it is likely that the prevalence of depres-sive and anxiety disorders is considerably higher. TheUK ONS survey (Singleton et al., 2001), and similarstudies (Kadam et al., 2001), suggest an adult preva-lence of 9–16%. Untreated, or ineffectively treated,anxiety, depression and sleeplessness can also impaircognitive function (Alvarez-Rueda et al., 2001; Wonget al., 2000) and increase accident proneness (Nino-Murcia, 1992; Edwards, 1995). Similarly, demo-graphic, health and other factors are also associatedwith poorer safety (Cherpitel et al., 1995; Chipman,1995; Health and Safety Commission, 2001; Schelpand Svanstrom, 1986; Dobson et al., 1999; Kirkcaldyand Furnham, 2000; Davies and Elias, 2000; diLorenzo et al., 1998; Simpson et al., 2005). However,there is very little work assessing the effect of psycho-tropic medication use on accidents after adjusting forthe influence of both any underlying psychopathologyand other possible confounding factors (Edwards,1995; Allgulander and Evanhoff, 1990), particularlywithin a community sample.

The aim of this study was to consider the relation-ships between psychotropic medication use and acci-dents, injuries and cognitive failures among acommunity sample within the context of other poten-tially confounding factors.

MATERIALS AND METHODS

A postal questionnaire survey was conducted amongpeople selected at random from the electoral registersof Cardiff and Merthyr Tydfil. This has been describedin detail elsewhere (Smith et al., 2004a, b; Wadsworthet al., 2004a, b).

Participants

Questionnaires were sent to 30 000 people selected atrandom from the 2001 electoral registers for Cardiffand Merthyr Tydfil (22 500 and 7500, respectively).This is a sample of just over 10% of those on the reg-isters. The areas were selected for their differingsocial and economic conditions.

Procedure

Questionnaires and covering letters were posted in earlyMay 2001. No identifiers were attached, precluding anyfollow-up procedure. The questionnaire’s content hasbeen described previously (Smith et al., 2004a, b) andincluded demographic, personality, health, lifestyleand occupational factors. The factors included in theanalyses described here are outlined in Table 5.

Incident measures

Participants were asked about four incident types:

* accidents—during the previous year whichrequired medical attention

* road traffic accidents (RTAs)—during the previousyear where the respondent was the driver

* minor injuries—during the previous year whichdid not require medical attention (quite and veryfrequent minor injuries were compared with none,rare or occasional minor injuries)

* cognitive failures—problems of memory, attentionor action (quite and very frequent cognitive failureswere compared with none, rare or occasionalcognitive failures).

They were asked about each incident type both out-side work and at work (in the case of traffic accidentsthis included driving to and from work as well as driv-ing as part of work).

Medication use

Participants were asked about their medication useover three periods: the previous 14 days, month andyear. They were asked for the names of each medica-tion they had used, the amount taken daily, and whatthe medication was taken for. These details were scru-tinized and categorized individually. To correspondwith the incident measures, the analyses presentedhere focus only on psychotropic medication used inthe previous year.

Mental health status

Depression and anxiety were defined using the clinicalcut-points of the hospital anxiety and depression scale(Zigmond and Snaith, 1983). In addition, those whoreported having difficulty sleeping in the previous14 days were categorized as having sleep problems.

Ethical approval

The study was approved by the Cardiff UniversitySchool of Psychology Ethics Committee. It was alsoscrutinized by the Local Research Ethics Committee,which deemed that formal ethical approval was notnecessary.

RESULTS

Participants

In total 7979 people completed and returned a ques-tionnaire, giving a response rate of 27%. Respondents

392 e. j. k. wadsworth ET AL.

Copyright # 2005 John Wiley & Sons, Ltd. Hum Psychopharmacol Clin Exp 2005; 20: 391–400.

were predominantly female (n¼ 4601, 58%), theirmean age was 45.61 (SD¼ 18.00, range 16–97),most were working (n¼ 4620, 58%), most werewhite (n¼ 7584, 97%) and 26% had a degree orhigher educational qualification, while 18% had noeducational qualifications.

Overall 11% of respondents reported an accident,2% a road traffic accident, 14% quite or very frequentminor injuries, and 18% quite or very frequent cogni-tive failures. In total 2661 (38%) respondents reportedone or more of these incidents.

In total 2045 (26%) reported taking at least one psy-chotropic medication in the previous year (Table 1).

Both opioids and non-sedating antihistamines wereexcluded from the analyses; the former as they mayhave been used as a result of an accident or injury,and the latter as they are both non-sedating and oftenused seasonally. Analyses were also restricted to med-ications for which numbers reporting exclusive use inthe previous year were large enough (Table 2).

More of the medication users were female (bothoverall (62%, p¼ 0.002), and considering just thosemedications included in the analyses (62%,p¼ 0.03) compared with 58%). They were also lesslikely to be working (37%, p< 0.0001) overall, and42% (p< 0.0001) for the medications included inthe analyses compared with 62%), and were older(mean 53.29 (SD¼ 17.12) overall (p< 0.0001) and

53.60 (17.58) for those medications included in theanalyses (p< 0.0001) compared with 44.29 (17.82)among those who had not used any medication duringthe previous year). There were also some demo-graphic differences between the groups of medicationusers: more SSRI users were female, and their meanage was younger, while fewer beta blocker users wereworking (Table 3).

Overall 19% (1418) of respondents suffered fromanxiety, 6% (458) depression (both defined at the clin-ical cut-points of HADS) and 36% (2839) reported dif-ficulty sleeping in the previous 14 days. A little underhalf (45%, 3419) had at least one of these problems.Among those taking the medications used in the ana-lyses these rates were higher (anxiety 31%, depression12%, sleep problems 46%, any 59%). They also variedby medication type (Table 4). Those taking beta block-ers had similar rates to those taking no medication,reflecting their likely use. Similarly, more of those tak-ing hypnotics reported sleeping difficulties, and levelsof poor mental health were generally higher amongthose using SSRIs, benzodiazepines and tricyclics.

Logistic regression analyses were carried out to testfor associations between medication use and the inci-dent measures. Each model also included demo-graphic, personality, health, lifestyle and othervariables selected because of their established asso-ciation with the dependent variables and/or with med-ication use (Table 5).

Odds ratios and confidence limits for the dichoto-mous medication variables for each model are pre-sented in Table 6. Significant positive associationsare shown in bold. These indicate that the odds ratiofor medication use is significantly higher than 1 (i.e.the odds ratio for the reference non-medication use

Table 1. Reported psychotropic medication (n (%)) use in theprevious year by sex

Male Female All

Anya 736 (22) 1309 (29) 2045 (26)Any excludingb 436 (13) 724 (16) 1160 (15)Opioids 278 (8) 531 (12) 809 (10)Beta blockers 231 (7) 247 (5) 478 (6)SSRIs 98 (3) 255 (6) 353 (5)Benzodiazepines 72 (2) 148 (3) 220 (3)Non-sedating antihistamines 67 (2) 132 (3) 199 (3)TCAs 58 (2) 106 (2) 164 (2)Hypnotics 28 (1) 40 (1) 68 (1)SNRIs 11 (< 1) 20 (< 1) 31 (< 1)Sedating antihistamines 9 (< 1) 16 (< 1) 25 (< 1)MAOIs 2 (< 1) 1 (< 1) 3 (< 1)

aIncludes those not classified above.bExcludes those taking opioids and non-sedating antihistamines.

Table 2. Numbers (%) reporting exclusive use of those medica-tions included in the analyses

n (%)

Beta blockers 350 (5)SSRIs 235 (4)Benzodiazepines 79 (1)Tricyclics 66 (1)Hypnotics 30 (1)

Table 3. Age, sex and work status by medication use

None Beta blockers SSRIs Benzodiazepines TCAs Hypnotics

Female n (%)a 3877 (58) 177 (51) 176 (76) 52 (68) 45 (68) 15 (52)Mean (SD) agea 44.29 (17.82) 63.02 (13.01) 39.78 (13.78) 57.17 (18.66) 51.55 (15.42) 47.10 (18.57)Working n (%)a 4191 (62) 100 (29) 138 (59) 24 (31) 34 (52) 19 (63)

ap< 0.0001.

medication, accidents and cognitive failures 393


group), as indicated by both the upper and lower con-fidence limits being greater than 1. There were noassociations between either hypnotics or beta blockersand accidents, injuries and cognitive failures. Simi-

larly there were no associations with incidents occur-ring at work, and the numbers reporting both RTAsand medication use were clearly too small for mean-ingful analyses. However, SSRI use was associated

Table 4. Mental health status (n (%)) by medication use

None Beta blockers SSRIs Benzodiazepines TCAs Hypnotics

Anxiety 1012 (16) 39 (12) 110 (49) 31 (42) 31 (53) 10 (33)Depression 280 (4) 14 (4) 39 (17) 17 (24) 13 (22) 7 (23)Sleep problems 2229 (33) 111 (32) 121 (52) 53 (67) 37 (56) 25 (83)Any 2679 (41) 134 (41) 164 (72) 62 (81) 47 (77) 25 (83)

Table 5. Factors included in logistic regression analyses

Factor Categorization Included because of previous association with

DemographicsAge > 25, 25> 40, 40> 60, 60þ Accidentsc, injuries a,b,c, cognitivea,b,c, medicationd

Sex Male, female Accidentsa,b, cognitiveb, medicationd

Income > £10k, £10k> £20k, £20k> £30k, £30kþ Injuriesa,b, cognitiveb,c, medicationd

Education No qualifications, O level or equivalent, A level or Cognitivec, RTAc

equivalent, City & Guilds, degree or high degree,professional qualification

PersonalityNeuroticism Quartiles of EPI-N Injuriesc, cognitiveb,c

Risk takin None, rare, occasional compared with quite Accidentsc, injuriesb,c, cognitiveb,c, RTAc

or very frequentMental health

Anxiety Clinical cut-point of HADSa Injuriesc, cognitivea,b,c, medicationd

Depression Clinical cut-point of HADSd Cognitiveb,c, medicationd

Sleep problems Difficulty sleeping in the last 14 days Accidentsc, injuriesa,b,c, cognitivea,c, RTAc, medicationd

Physical health14-day symptoms 3 or more compared with fewer from checklist Accidentsc, injuriesb,c, cognitivea,b,c, RTAc, medicationd

12-month symptoms 2 or more compared with fewer from checklist Accidentsb,c, injuriesc, cognitivec, medicationd

Chronic symptoms 1 or more compared with fewer from checklist Accidentsb, injuriesb,c, cognitivec, medicationd

General Health Very good, good, moderate compared with Accidentsb,c, medicationd

bad or very badLifestyle

Smoking Current smokers compared with non-smokers Accidentsa, injuriesa, cognitiveb, medicationd

Alcohol Those in the top 10% (calculated separately for men Accidentsb, medicationd

and women) compared with those belowOther

Work status* Workers compared with non-workers Injuriesc, cognitivec, RTAc

Combined Combinations of other accidents, injuries and cognitive Accidentsb, injuriesb, cognitiveb

incidents failures reported at work or outside work as appropriateOccupationaly

Risk taking at work None, rare, occasional compared with quite Accidentsb

or very frequentWork stress None, mild, moderate compared with very or extreme Injuriesb, cognitivea,b, medicationd

Total negative score Quartiles of negative occupational characteristics Accidentsa,b, injuriesa,b, cognitivea, medicationd

Social class Manual compared with non-manual Accidentsb, injuriesb

Employment Self-employed compared with others Injuriesb

Experience Less than 6 months in post compared with longer Cognitiveb

*Excluded from models for work-related incidents.yIncluded only in models for work-related incidents.aWadsworth et al., 2003b.bSimpson et al., 2005.cSimpson et al., in preparation.dWadsworth et al., 2003a.



with accidents outside work, benzodiazepine use withinjuries outside work and tricyclic use with accidentsgenerally (i.e. outside work and at work combined).There were also trends towards associations betweenSSRIs and both injuries and cognitive failures (bothoutside work and generally), between benzodiaze-pines and injuries, as well as both accidents outsidework and accidents generally, and between tricyclicsand accidents outside work.

Next analyses were carried out to try to clarifythe associations between medication use and inci-dents over and above any associations between inci-dents and both mental health status and level of otherassociated risk factors. Factors associated with eachincident type were established using backward step-wise logistic regression models which excluded boththe medication and mental health variables. Respon-dents were then categorized into two groups: thosewith lower levels of associated risk factors; andthose with higher levels of associated risk factors.Within each of these groups they were further cate-gorized according to both their medication use andmental health status: those who used no medicationand had no mental health problems; those who usedmedication and had no mental health problems;those who used no medication and had mentalhealth problems; and those who used medicationand had mental health problems. The resulting eightlevel variables were included in further logisticregression analyses. As there were no associationswith beta blockers or hypnotics (Table 6), modelswere restricted to SSRIs, benzodiazepines and tri-cyclics. Similarly, the analyses focused on incidents(excluding RTAs) outside work and incidentsgenerally (i.e. at work and outside work combined)as there were no overall associations between med-ication use and either incidents at work or RTAs(Table 6).

Odds ratios and confidence limits for the polyto-mous medication variables for each model are pre-sented in Table 7. Significant positive associationsare again shown in bold. However, in this case signif-icance was assessed using repeated measures con-trasts. These indicate that the odds ratio for aparticular category of the variable (e.g. higher risksand medication use) is significantly greater than theodds ratio for the previous category (e.g. higher risksand neither medication use nor mental health pro-blems). These analyses suggested associationsbetween: benzodiazepine use and non-work injuries(among those with both higher levels of other asso-ciated risk factors and mental health problems), andcognitive failures (among those with both higherlevels of other associated risk factors and mentalhealth problems); tricyclic use and accidents (amongthose with higher levels of other associated risk fac-tors), cognitive failures (among those with higherlevels of other associated risk factors and mentalhealth problems), and cognitive failures outside work(among those with higher levels of other associatedrisk factors and mental health problems); and SSRIuse and non-work injuries (among those with higherlevels of other associated risk factors), cognitive fail-ures (among those with both lower and higher levelsof other associated risk factors and mental health pro-blems), and non-work cognitive failures (among thosewith both higher levels of other associated risk factorsand mental health problems) (Table 7). All the asso-ciations were apparent among those with higher levelsof other associated risk factors. Table 7, therefore,gives one example of the full eight-level variable,and then presents odds ratios and confidence limitsfor the reference and higher risk categories only foreach model with a significant association.

To try to clarify the relationships between safety,mental health and medication further, a final series

Table 6. Associations (OR (CI)) between medication use and incident type

Beta blockers SSRIs Benzodiazepines TCAs Hypnotics

Non-work accident 0.65 (0.26–1.66) 1.90 (1.10–3.29) 2.41 (0.87–6.70) 2.62 (0.88–7.80) 0.01 (0.00–151180.18)Non-work injury 1.22 (0.57–2.63) 1.42 (0.87–2.32) 4.43 (1.89–10.38) 0.60 (0.14–2.63) 1.37 (0.29–6.49)Non-work cognitive failure 1.20 (0.74–1.97) 1.17 (0.79–1.76) 0.80 (0.31–2.04) 0.86 (0.37–1.98) 0.42 (0.08–2.12)Non-work RTA 1.29 (0.15–10.94) 1.72 (0.57–5.20) 0.00 (0.00–2.27E31) 0.00 (0.00–5.48E31) 0.00 (0.00–8.31E47)Any accident 0.74 (0.33–1.66) 1.69 (1.01–2.82) 2.01 (0.71–5.67) 3.07 (1.18–7.96) 0.64 (0.08–5.05)Any injury 0.96 (0.48–1.93) 1.12 (0.71–1.75) 2.17 (0.89–5.32) 0.63 (0.20–1.95) 0.74 (0.16–3.49)Any cognitive failure 1.15 (0.69–1.91) 1.04 (0.69–1.56) 1.47 (0.59–3.63) 0.95 (0.41–2.18) 0.36 (0.07–1.88)Any RTA 1.62 (0.36–7.33) 1.41 (0.51–3.88) 0.01 (0.00–1.21E12) 0.00 (0.00–3.96E10) 0.01 (0.00–3.44E9)Work accident 0.67 (0.15–2.98) 0.96 (0.28–3.28) 1.36 (0.13–14.58) 2.68 (0.52–13.86) 2.67 (0.28–25.09)Work injury 0.68 (0.16–2.96) 1.01 (0.46–2.18) 1.85 (0.38–9.08) 0.49 (0.06–4.03) 0.00 (0.00–1.36E12)Work cognitive failure 0.49 (0.14–1.68) 0.95 (0.51–1.78) 2.22 (0.50–9.77) 0.45 (0.10–2.09) 0.02 (0.00–10613.97)Work RTA 0.00 (0.00–9.41E63) 2.64 (0.27–26.26) 0.00 (0.00–1.44E148) 0.00 (0.00–1.37E115) 0.00 (0.00–2.34E155)



of analyses was carried out. Models were createdexcluding those with lower levels of other associatedrisk factors for each of the significant results inTables 6 and 7. Each model included medication use

and mental health status together with the interactionterm medication by mental health status. Backwardsstepwise regression was applied. Table 8 shows thefinal step from each model. It suggests associations

Table 7. Significant associations between medication use categorized by mental health status and accidents, minor injuries and cognitivefailures

OR CI

Non-work injury and benzodiazepinesLower risks and neither 1.00Lower risks and benzodiazepines 0.07 0.00–1.92E8

Lower risks and mental health problems 1.98 1.25–3.14Lower risks and both 4.62 0.56–38.33Higher risks and neither 3.10 2.19–4.38Higher risks and benzodiazepines 6.47 0.74–56.49Higher risks and mental health problems 5.03 3.62–7.00Higher risks and both 16.18a 6.24–41.94

Any cognitive failure and benzodiazepines*Lower risks and neither 1.00Higher risks and neither 2.33 1.79–3.02Higher risks and benzodiazepines 0.08 0.00–10042996Higher risks and mental health problems 5.15 4.08–6.52Higher risks and both 18.09b 6.17–53.04

Any accident and tricyclics*Lower risks and neither 1.00Higher risks and neither 1.92 1.48–2.49Higher risks and TCAs 14.45b 2.01–103.67Higher risks and mental health problems 2.51c 1.94–3.24Higher risks and both 2.89 0.82–10.15

Any cognitive failure and tricyclics*Lower risks and neither 1.00Higher risks and neither 2.33 1.79–3.02Higher risks and TCAs 6.78 1.23–37.44Higher risks and mental health problems 5.15 4.08–6.52Higher risks and both 12.06c 4.56–31.86

Non-work cognitive failure and tricyclics*Lower risks and neither 1.00Higher risks and neither 2.24 1.68–2.97Higher risks and TCAs 2.64 0.32–21.71Higher risks and mental health problems 4.61 3.56–5.99Higher risks and both 9.85c 4.06–23.91

Non-work injury and SSRIs*Lower risks and neither 1.00Higher risks and neither 3.10 2.19–4.38Higher risks and SSRIs 6.86c 2.89–16.31Higher risks and mental health problems 5.03 3.62–7.00Higher risks and both 6.25 3.45–11.33

Any cognitive failure and SSRIs*Lower risks and neither 1.00Higher risks and neither 2.33 1.79–3.02Higher risks and SSRIs 3.80 1.61–8.98Higher risks and mental health problems 5.16 4.08–6.52Higher risks and both 8.41b 5.17–13.70

Non-work cognitive failure and SSRIs*Lower risks and neither 1.00Higher risks and neither 2.24 1.68–2.97Higher risks and SSRIs 4.11 1.65–10.22Higher risks and mental health problems 4.61 3.56–5.99Higher risks and both 8.48a 5.15–13.98

a< 0.01; b< 0.05; c< 0.10 using repeated measures contrasts. *Odds ratios and confidence limits not shown for categories: lower risks andmedication, lower risks and mental health problems, lower risks and both.



between benzodiazepine use and minor injuries out-side work, tricyclic use and both accidents and cogni-tive failures, and SSRI use and accidents outsidework, cognitive failures and cognitive failures outsidework. It also suggests interactions between mentalhealth status and: benzodiazepine use for cognitivefailures; tricyclic use for cognitive failures outsidework; and SSRI use for accidents. The strong associa-tion between mental health status and reported inci-dents is also clear.

DISCUSSION

Just over a quarter of the respondents reported havingused at least one psychotropic medication in the pre-vious year. This is considerably higher than previousestimates (Ohayen et al., 1998), in part, because allmedications with a CNS effect have been included.However, even considering just those most often usedto treat anxiety and depression, the rate of reported usewas 8%. This may reflect the increase in psychotropic

medication prescriptions in recent years, and is similarto the 7% taking prescribed medication for symptomsof anxiety or depression in more recent work (Parslowand Jorm, 2004).

Medication use varied with both age and sex. Thispattern has been described elsewhere (Ohayen et al.,1998). It seems to correspond with higher rates ofmental health problems with increasing age andamong women (Paterniti et al., 1999, Kessler, 2003).

Excluding opioids (because of their likely use fol-lowing an accident or injury) beta blockers were themost commonly reported medication, followed bySSRIs. The use of beta blockers was highest amongthose over 60 years, which probably largely reflectstheir treatment of conditions such as hypertension,rather than depression and anxiety. SSRIs are usedsolely to treat a variety of mental health problemsincluding anxiety, depression and sleep problems(Ohayen et al., 1998; Rouillon et al., 1996). Theirsafety and effectiveness relative to other, older treat-ments, has meant that SSRIs have become the most

Table 8. Associations among those with higher levels of other associated risk factors between accidents, injuries and cognitive failures, andboth medication use and mental health status, including the interaction term

Model Independent variables OR CI

Benzodiazepines: minor injuries outside work Benzodiazepines No 1.00Yes 3.06 1.32–7.10

Mental health None 1.00status Problems 1.67 1.28–2.17

Benzodiazepines: any cognitive failures Mental health None 1.00status Problems 2.14 1.69–2.70Benzodiazepinesx 3.66 1.26–10.66health

Tricyclics: any accident Tricyclics No 1.00Yes 2.05 0.75–5.59

Tricyclics: cognitive failures outside work Mental health None 1.00status Problems 2.00 1.58–2.53Tricyclicsx health 2.17 0.91–5.18

Tricyclics: any cognitive failures Tricyclics No 1.00Yes 2.55 1.10–5.92


SSRIs: any accident SSRIsx health 1.89 1.08–3.33SSRIs: accidents outside work SSRIs No 1.00

Yes 1.68 0.98–2.90SSRIs: minor injuries outside work Mental health No 1.00

status Problems 1.63 1.27–2.10SSRIs: cognitive failures outside work SSRIs No 1.00

yes 1.85 1.22–2.81Mental health None 1.00status Problems 2.01 1.59–2.53

SSRIs: any cognitive failures SSRIs No 1.00Yes 1.69 1.12–2.55




prescribed medication for mental health problems(Bellantuono et al., 2002). Sales of antidepressantshave increased rapidly (Barbui et al., 1999), withGPs in the UK spending approximately £160 millionannually (Eccles et al., 1999). Recent NICE guide-lines, however, do not recommend antidepressantsfor the initial treatment of mild depression, becauseof the poor risk–benefit ratio (NICE 2004). Ratherthey recommend ‘watchful waiting’, guided self-helpand short-term psychological treatment (NICE, 2004).When an antidepressant is required, though, it shouldbe an SSRI as they are as effective as tricyclics and areless likely to be discontinued because of side effects(NICE, 2004).

In this study associations between medication useand accidents, injuries and cognitive failures weremost often with incidents occurring outside the work-place. This seemed to reflect the employment status ofthe medication users, who were less likely to be work-ing.

Associations were suggested between benzodiaze-pines and injuries and cognitive failures, and betweentricyclics and accidents and cognitive failures.Similar associations have been reported previously(Hartley, 1992; Curran, 1992; Stenbacka et al., 2002;Macdonald, 1999; Ellinwood and Heatherly, 1985;Currie et al., 1995; Oster et al., 1990; Ray et al.,1987; 1992; Leveille et al., 1994; Currie et al., 1995).

Some association between SSRIs and accidents,injuries and cognitive failures was also apparent.Kallin et al. (2002) suggested that SSRI use was amore important risk factor for falls among older peo-ple than depression. This may be the result of a car-diac effect (Pacher and Ungvari 2001). The risk offalling may be greatest for new users (Liu et al.,1998), perhaps because of agitation and activation atthe start of treatment (Wessely and Kerwin, 2004).However, most studies have concluded that SSRIs havefewer adverse effects (Nutt, 2003; Hindmarch, 1995),both in the short- and long-term (Cassano and Fava,2004), are relatively free from cognitive and psychomo-tor effects (Hindmarch 1995) and do not impair drivingperformance (Hale, 1994). The side-effect profiles ofindividual SSRIs do, of course, vary (Goldstein andGoodnick, 1998; Goodnick and Goldstein, 1998), asdo their specific effects on cognitive function (Oxmanet al., 1996). In this study fluoxetine and paroxetinewere most commonly used, but individual analyseswere not possible because of small numbers.

The associations between medication use and inci-dents were apparent primarily among those who alsohad higher levels of other risk factors associated withthat incident type. Unfortunately, the numbers were

not sufficient to allow us to consider which other fac-tors may be most important. However, interactions,perhaps with other drugs (prescribed or otherwise)(Akin and Chaturvedi, 2003), have been suggestedelsewhere. Here factors common to all or most ofthe risk variables included physical health, age, risktaking, other incidents, stress and neuroticism. Theprecise nature of the relationships between medicationuse, safety and other associated risk factors dependson the variables included in the analyses and, in thiscase, the way in which they have been combined toform an overall measure of risk.

The results also indicated a clear, independent asso-ciation between mental health status and reportedincidents, particularly among those with higher levelsof other associated risk factors. Mental illness hasbeen associated with accidents, injuries and cognitiveimpairment elsewhere (Alvarez-Rueda et al., 2001;Wong et al., 2000; Nino-Murcia, 1992; Edwards,1995; Curran, 1992). The safety effects of medicationuse relative to those of the condition they are treatingare more meaningful than any absolute associations.Attempting to ‘benchmark’ the impact of medicationuse on accidents, injuries and cognitive failuresagainst that of depression, anxiety and sleep problemsallows this comparison.

Further analyses, focusing only on the more ‘atrisk’ group, suggested that the links between benzo-diazepine use and injuries, and tricyclic use and bothaccidents and cognitive failures, reflected independentassociations between medication use and safety.Furthermore, these medication effect sizes were largerthan the mental health effect sizes. For SSRIs inde-pendent associations were apparent with accidentsand cognitive failures. However, for the latter, medi-cation effect sizes were smaller than those for mentalhealth.

These associations may reflect links between med-ication use and safety for particular groups, such asolder respondents or those who had not been takingthe medication for long. For SSRIs, for example, boththese factors may be influential (Kallin et al., 2002,Liu et al., 1998). This could not be pursued withinthe current study (because of small numbers withincertain age groups and the lack of information onduration of medication use). There were interactionsbetween all three medications and mental health statusfor cognitive failures, and with SSRIs for accidentsgenerally. This may reflect the relative timings of inci-dents, illness, medication use and the study, but againthis could not be pursued.

Taken together the findings suggest that, for allmedications, associations with poorer safety were



most apparent among those with higher levels of otherassociated risk factors. Among this higher risk group,older medications seemed to be linked to accidentsand injuries more strongly than mental illness. Asso-ciations between SSRIs and cognitive failures, how-ever, seemed to be weaker than corresponding linkswith mental illness, suggesting that SSRIs are com-paratively safer than benzodiazepines and tricyclics.

The study had several limitations. First, theresponse rate was low. Comparisons with census datafor Cardiff and Merthyr Tydfil suggest that those whodid respond were broadly representative of their com-munities, though younger people, particularly males,were under-represented in both areas. In addition, nodata were collected about the relative timings of med-ication use, psychopathology and accidents, injuriesand cognitive failures. This also required that thosewho had taken more than one psychotropic medica-tion in the previous year be excluded from the ana-lyses. Furthermore, the data were all self-reported.Numbers were too small in some categories to allowcomparisons between medication types, and were alsoinsufficient for consideration of specific medicationswithin a particular type. Comparisons of the severityof mental illness between medication groups, andamong those who were untreated, were not possible.

In spite of these limitations, this study represents anattempt to consider the impact of psychotropic medi-cation use on safety within the context of other riskfactors, and with specific focus on the comparativeimpacts of medication and mental illness. It suggeststhat, particularly among those with higher levels ofother associated risk factors, psychotropic medicationuse may be linked to accidents, injuries and cognitivefailures. However, comparisons with the effects ofpsychopathology suggest that SSRIs are relativelysafer than tricyclics and benzodiazepines. It alsoemphasizes the importance of studying the effects ofpsychotropic medication within the context of bothmental health status and other potential risk factors.

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