Drug, Alcohol, and Substance Abuse

Heavy Drinking and Use of Sedative or Anxiolytic Drugs Among

Aging Men: An 1I-Year Follow-Up of the FinDrink Study

Jenni llomakl, J Simon Bell, Jussi Kauhanen, and Hannes Enlund

High rates of concurrent alcohol andpsychotropic drug use havebeen re-

ported in Germany,'> Sweden.v'Spain,'the US,6-Sand Canada,":"Alcohol mayhave additive interactions with psy-chotropic drugs,and concurrent use mayresult in excess sedation andcross-depen-dence."Wehavepreviously reported thatmiddle-aged men who consume >14drinks per week were more likely to usesedative/anxiolytic drugs ." We also re-portedthatmen whoconsume 5 or moredrinks ina single session were more likelyto use sedative/anxiolytic drugs. Heavydrinking and psychotropic drug use mayoccurconcomitantly as theresult of simi-lar geneticand environmental factors, orheavy drinking andpsychotropic drugusemaybecausally related,"

The possible causal relationship be-tween alcohol consumption and psy-chotropic drug usehas not beenassessedin epidemiologic research. However, acausal pathway between alcohol con-sumptionand subsequentmajor depres-sion has been proposed ." A prospectivecohort study in Finlandfound that base-line binge drinking was associatedwithdepressive symptoms 5 years later," Pre-dictors of new-onset long-term use ofsedative/anxiolytic drugs include depres-sive symptoms, hypertension, joint pain,poor self-perceived health, and multi-

Authorinformation provided at endof text.

BACKGROUND: Most studieson heavydrinking and sedalivelanxiolytic drug usehave been cross-sectional, and evidence for a possible temporalassociation Islacking .

OBJECTIVE: To prospectively Investigate whether heavy drinking predictsinitiation, continuation, or disoontinuationof sedalivelanxiolyticdrugsat 4 and 11years and , conversely, whether sedatlve/anxiolytic drug use predicts heavydrinking.

METHOD: Thiswas a longitUdinal population-basedstudy conducted in Kuopio,RnIand . An ag&Stratifled random sample of 1516 men aged 42, 48, 54, and 60years received a structured clinical examination at baseline (August 1986-December 1989). Follow-up cinlcaI examinations were conducIed at 4 (n =1038)and 11 (n • 854) years. MuhinomlaJ logistic regression was used to computeodds ratios and 95°A, confidence intervals lor the association betweensedatlvelanxlotytJc drug use and initiation, continuation, and discontinuationofheavydrinking (01:14 drinkSIWk). The reverse association between heavydrinkingand sedativelanxlolytic drug usewas also Investigated. Regression models wereadjusted for age, WOI1<ing status, smoking, and depressive &ynl)toms.

RESUlTS: At baseline 12.9% (134/1038) of participants were hea~ drinkersand4.0"10 (41/1000)used sedatlvelanxlo/ylic drugs. In muhivarlate analyses, baselineheavydrinkingpredicted initiation of sedalivelanxiolytic drug use at 4 years (OR2.96; 95% CI 1.23 to 7.15). Conversely, baseline sedatlve/anxlolytic drug usepredicted continuation of heavydrinlOOg at 11 years in unadjusted analysis (OR3.30; 95% CI 1.19 to 8.44). However, the association was not statisticallysignificant Inadjusted analyses (OR 2.69; 95% CI 0.86 to8.44).

COHCW8IONS: Themaillinding of this study was the association between heavydrinkingand subsequent Initiationof sedatlveJanxiolytic drugs that was not fullyexplained by baseline depressive symptoms. This may inform strategies tooptinUe the use of sedativelanxlolytic drugs, and assistin the earlyidentilicationof patleRs at riskof heavydrinking. Cinicians shouldconsider a patient's aJc:ohoIconsumption prior to prescribing or dispensing sedatlve/anxiolytic drugs.Cliniciansshould also monitorpatientsprescribedsedatlveJanxiolytic drugs forsubsequent heavydrinking.

KEY WORDS: alcohol drinking, epidemiology, Finland, longitudinal studies,psyctlObopIcdrugs.

Ann Pharmacother 2011;45:1240-7.

PublIshed Online, 6 Sept 2011, the8nnsJs.com. DOl 10.13451aph.1Q375

1240 • TheAnnalsofPharmacotherapy • 2011 October, Volume 45 theannals.com

morbidity.P" A Norwegian study reported that receiptofdisability pensions among people aged 40-42 years pre-dictedbenzodiazepine use 20 yearslater." Similarly, men-tal distress among 40- and 45-year-old people has beenlinked to the subsequent use of anxiolytics." A reversecausalpathway may alsoexist.Baseline depressive symp-tomshave beenassociated with stress-related alcohol con-sumption over a lO-year follow-up period." Psychoactivedrug use among women, but not men, aged 55-65 yearshas been associatedwith drinking problems 10 years lat-er.20 Patients withpainfrequently use psychotropic drugs,"and thesepatients mayincrease theirconsumption of alco-hol as a formof self-medication."

To our knowledge, no longitudinal studies have investi-gatedthe possible causal association between heavydrink-ing and sedative/anxiolytic drug use.The objective of thisstudy was to prospectively investigate whether heavydrinking predicts initiation,continuation,or discontinua-tion of sedative/anxiolyticdrugs at 4 and 11 years and,conversely, whether sedative/anxiolytic drug use predictsheavydrinking.

Methods

STUDY SAMPLE

Data were obtainedfrom the prospectiveKIHD (Kuo-pio Ischaemic HeartDisease RiskFactor) study,23 an ongo-ing population-basedcohort study conducted in EasternFinland that was designed to investigate risk factors forcardiovascular diseases. The FinDrink studyis an ongoingproject supported by the Academyof Finland that is con-ductedin conjunction with the KIHD study. The FinDrinkstudy aims to explore the distribution,determinants, anddynamics of alcohol consumption in Finland. By usingclinical data collected as partof the KIHD study, it aims toinvestigate novel associations betweendrinkingbehaviorandhealth outcomes.

At baseline, an age-stratified random sample of 1935men aged42,48,54, and 60 yearsfrom Kuopio,Finland,was recruited. Of thesemen, 1516 (78%) participated in thebaseline structuredclinical examinationbetween August1986andDecember 1989. The reasons for notparticipatingin the baseline examination wererefusal (n = 186),no con-tact information (n =136),death (n =41), migration (n =30), and severe illness (n =26). Follow-upexaminationswere conductedat 4 years (March 1991-December 1993)and 11 years (March 1998-February 2001). At the 4-yearfollow-up 1038 of aneligible 1229 men(84%) participated.At the l l-yearfollow-up 854of an eligible 1007 men(85%)attended. Eligibleparticipants for the follow-up examina-tionswerethose whohadparticipated in theprevious exami-nation. The participants wereaged46-65years at the4-yearfollow-up and53-73years at the l l-yearfollow-up.

Eightparticipants at the4-yearfollow-up and 22 partici-pants at the ll-year follow-up had missing alcohol con-sumption data.For this reason the study sample comprised1038 and 854 participants when sedative/anxiolytic usewasexamined and 1030and 832 participants whenheavydrinking was examined, at 4 and 11 years, respectively.The studywas approved by theethics reviewboardof theUniversity of Kuopio (University of EasternFinlandsinceJanuary 2010), and informed consent was obtained fromthe participants at the time of examination. All procedureswereconducted in accordance withthe World Medical As-sociation Declaration of Helsinki.

ASSESSMENT OFALCOHOL CONSUMPTION

Alcohol consumption was assessed using the samepar-ticipant self-completed questionnaire at eachtime point. Thequestionnaire included a modified version of theNordic Al-coholConsumption Inventory," whichwas included in theScandinavian Drinking Survey," This IS-iteminventory isbased on the quantity-frequency method that is a widelyusedand validated tool for collecting data on alcohol con-sumption in survey research." Participants wereasked to re-port the averagenumberof glassesor bottlesof alcoholicdrinks they had consumedon one drinking occasionandhowoftentheydrank eachtypeof beverage (beer, wine,andspirits) duringthe preceding year. Average weekly alcoholconsumption wascalculated foreachparticipant. In Finland,1unitis equivalentto 12g of ethanol.

Participants werecategorized as non-heavy drinkers (al-coholconsumption <14 drinks/wk) or heavydrinkers (~14

drinks/wk). This categorization was consistent with ourprevious studyand earlierNorthAmerican research.s" Atfollow-up, participants were categorized as never heavydrinkers (non-heavy drinker at baseline and follow-up),initiating heavydrinkers (non-heavy drinker at baseline butheavy drinker at follow-up), continuing heavy drinkers(heavy drinker at baseline and follow-up), and formerheavydrinkers (heavy drinker at baseline but not at follow-up).

ASSESSMENT OF SEDATIVElANXIOLYTlC DRUG USE

Drug utilization was assessed using the same itemswithin the participant self-completed questionnaire at eachtime point. Participants were asked to list prescription,nonprescription, and complementary and alternativemedicines they were takingon a regularbasis.After com-pleting the questionnaire, participants attended a structuredclinical examination to which they were asked to bringtheir drug packages, containers, and prescription forms.This provided the opportunity for the interviewer to ad-dressany apparent discrepancies in each participant's se1f-reported listof regularly useddrugs.

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J Ilomiiki etal.

Drugs were categorized using the Anatomical Thera-peutic Chemical (ATe) classification system recommend-ed by the World Health Organization." The ATC classifi-cation is a hierarchical categorization of drugs based on theorgan or system on which a drug acts, and also its thera-peutic, pharmacologic, and chemical properties. For thepurpose of the analyses, sedatives and anxiolytics includedanxiolytic drugs in class NOSB (primarily benzodiazepinederivatives used as anxiolytics; eg, diazepam, alprazolam,oxazepam) and hypnotic and sedative drugs in class NOSC(primarily benzodiazepine derivates used as sedatives; eg,temazepam, midazolam; and benzodiazepine-relateddrugs; eg, zolpidem). A participant was classified as asedative/anxiolytic drug user if he reported using I or moredrugs from classes NOSB and NOSe.

At follow-up, participants were categorized as never-users of sedative/anxiolytic drugs (nonuser at baseline andfollow-up), initiating users of sedative/anxiolytic drugs(nonuser at baseline but user at follow-up), continuingusers of anxiolytic/sedative drugs (user at baseline and fol-low-up), and former users of sedative/anxiolytic drugs(user at baseline but not at follow-up).

COVARIATES

Detailed descriptions of the structured clinical examina-tion protocol and the measurement of covariates havebeen reported.P-" Briefly, depressive symptoms were as-sessed with the 18-item Human Population LaboratoryDepression Scale." Participants were defined as havingdepressive symptoms (yes/no) if their score was 3 or high-er," Having a history of cardiovascular disease was de-fined as a self-reported history of myocardial infarction,angina pectoris, other coronary conditions, or stroke(yes/no). Self-reported history of cardiovascular diseasewas verified at the baseline structured clinical examina-tion. A participant was defined as a current smoker if hereported smoking regularly or irregularly at the time ofexamination (yes/no). Working status was defined accord-ing to either full- or part-time work (yes/no). Age at thetime of baseline examination was included as a continu-ous variable (years).

STATISTICAL ANALYSES

Baseline characteristics of the participants were ex-pressed as means and proportions. Multinomial logisticregression models were used to investigate the bidirec-tional unadjusted and adjusted associations between heavydrinking and use of sedative/anxiolytic drugs at the 4- andl l-year follow-up. All drug use and alcohol consumptiondata were paired, so only participants with complete datafor both parameters were included in the analyses. Never-use was treated as the reference group. Models were ad-

justed for age, working status, smoking status, and depres-sive symptoms. These adjustment variables were selectedon the basis of bivariate associations between the exposureand outcome. The results of the multinomial logistic re-gression models were expressed as odds ratios with 9S%confidence intervals. All statistical analyses were per-formed using SPSS version 17.0 (SPSS, Inc., Chicago, IL).

Results

CHARACTERISTICS OFTHESTUDY POPULATION

Among the study participants, 12.9% were heavydrinkers at baseline. There was a greater percentage ofsedative/anxiolytic drug users among the heavy drinkersthan among the nonheavy drinkers at baseline (Table 1). Incontrast, 4% of the participants used a sedative/anxiolyticdrug at baseline. There was a higher percentage of heavydrinkers among the sedative/anxiolytic drug users thanamong the nonusers at baseline.

Twenty-six (2.5%) participants initiated sedative/anxi-olytic drugs between baseline and the 4-year follow-up,and 42 (4.9%) participants initiated sedative/anxiolyticdrugs between baseline and the l l-year follow-up (Table2). Similarly, S4 (S.2%) of the participants initiated heavydrinking between baseline and the 4-year follow-up, and67 (8.1%) of the participants initiated heavy drinking be-tween baseline and the ll-year follow-up.

BASELINE HEAVY DRINKING ANDSEDATlVElANXIOLYTIC

DRUG USEAT4 AND11 YEARS

Baseline heavy drinking was associated with initiationof sedative/anxiolytic drug use at the 4-year follow-up inthe adjusted analysis (OR 2.96; 9S% CI 1.23 to 7.1S)(Table 3). Baseline heavy drinking was not associated withcontinuation or discontinuation of sedative/anxiolytic druguse at the 4-year follow-up. Similarly, baseline heavydrinking was not associated with sedative/anxiolytic druguse at the ll-year follow-up.

BASELINE SEDATIVEIANXIOLYTIC DRUG USEANDHEAVY

DRINKING AT4 AND11 YEARS

Baseline sedative/anxiolytic drug use was not associatedwith heavy drinking at 4 years (Table4). However, there wasa significantassociationbetween baseline sedative/anxiolyticdrug use and continuous heavy drinking at 11 years in theunadjusted analysis (OR 3.30; 9S% CI 1.19 to 9.17). Theassociation was no longer statistically significant when theregression model was adjusted for age, working status,smoking status, and depressive symptoms (OR 2.69; 9S%CI 0.86 to 8.44). The results were nonsignificant for dis-continuation and initiation of heavy drinking.

1242 • The Annals ofPharmacotherapy • 2011 October, Volume 45 theannals.com

Discussion

MAIN ANDINGS

The main finding of this prospectivelongitudinal studywas that baseline heavy drinking predicted initiation ofsedative/anxiolytic drug use at the 4-year follow-up, butnot at the II-year follow-up. There are a numberof possi-ble explanations why alcohol consumption may precedethe initiation of sedative/anxiolytic drugs. First,baselineal-cohol use may be due to initial self-medication with alco-hol of diagnosed or undiagnosed anxiety or depressive dis-orders. Data from the cross-sectionalNational Epidemio-logicSurveyon Alcohol and RelatedConditions in the USrevealed frequent use of alcohol for self-medication ofmoodand anxiety disorders .32,33One quarterof respondentswith mood disordersused alcoholor drugs to relieve theirsymptoms, with men more than twice as likely to engagein self-medication as women.However, the cross-sectionalnature of the survey prevented making assessments con-cerningcausality."

Second, sedative/anxiolytic druguse at follow-up maybeassociated with depressive symptoms. Our analyses wereadjusted for baselinedepressive symptoms; however, alco-hol use may precedethe diagnosis of majordepression," Ithas been suggested that alcohol consumptionmay triggergenetic markers that increase the risk of major depres-sion.34.35 Depressive symptoms were associated withbenzo-diazepineuse in the cross-sectional EuropeanStudy of theEpidemiology of Mental Disorders." Sleepdisturbances aresymptoms of bothdepression and alcohol use disorder,"

Heavy Drinking and UseofSedaJive orAnxiolytic DrugsAmongAgingMen

Third, alcoholdependencehas been associatedwith in-somnia after 10 years," Baseline heavy drinking couldhave prompted the prescription of sedative/anxiolyticdrugs for insomnia at the 4-year follow-up. Finally, it ispossible that use of sedative/anxiolytic drugs reflected, atleast in part, the 'prescription of these drugs for alcoholwithdrawal. Sedative/anxiolytic drugs are widely pre-scribed to treat alcohol withdrawal symptoms. However,evidence in relation to the safetyand effectiveness of seda-tive/anxiolytic drugs for this purpose is mixed,"

While the association between alcohol consumption andthe initiation of sedative/anxiolytic drugswas significant at4 years, there was no corresponding association at IIyears.This may bedue to change in drinking patternsovertime. While there was an overall increase in alcohol con-sumption among younger participants (aged 42 years atbaseline) in our cohort," most previousstudies have indi-cated that total alcohol consumption declines in olderage.41

,42 This is in contrast to the use of sedative and anxi-olytic drugs that typically increases with age." Further-more, heavy drinkers at baseline may have reduced theiralcohol consumption in response to the emergence ofchronic illnesses in mid-to-Iater life.44 We have previouslyreported that 11 % of men aged 65 years and 26% of menaged 53 years in Kuopio,Finland, were heavy drinkers in1998 to 2001.40 Halme et al. reported that 19% of allFinnish men aged 65-69 years consumel S units or moreof alcohol per week,"

Long-term sedative/anxiolytic drug use has beenassoci-ated with an increased risk of depression," In tum, depres-

Table1. Baseline Characteristicsof theStudy Population

Baseline Heavy Baseline sedative!Dri nking" Anx lolyt lc Drug Useb

No Yes No YesCharacterlsllc (n = 904) (n = 134) P Valuec (n = 989) (n=41) p Valuec

Sedative/anxiolytic use, n (%) 34 (3.8) 7 (5.2) 0.417

Heavy drinking, n ("!o) 126 (12.7) 7 (17.1) 0.418

Age (y), n (%) 0.025 0.900

42 192 (21.2) 44 (32.8) 226 (22.9) 9 (22.0)

48 218 (24.1) 29 (21.6) 235 (23.8) 10 (24.4)

54 255 (28.2) 29 (21.6) 269 (27.2) 13 (31.7)

60 239 (26.4) 32 (23.9) 259 (26.2) 9 (22.0)

Married, n (%) 801 (88.6) 114 (85.1) 0.252 875 (88.5) 33 (BO.5) 0.121

Working full or part-t ime, n (%) 620 (68.6) 84 (62.7) 0.173 678 (68.6) 20 (48.8) 0.008

Current smoker, n ("!o) 285 (31.5) 73 (54.5) <0.001 336 (34.0) 20 (48.8) 0.051

Depression (HPL >3), n (%) 135 (14.9) 30 (22.4) 0.028 142 (14.4) 20 (48.8) <0.001

CVD, n (%) 214 (23.7) 34 (25.4) 0.667 231 (23.4) 16 (39.0) 0.021

CVD = cardiovascular disease; HPL = Human Population Laboratory depression scale."Average alcohol consumption ~14 drinkstwk.bClasses NOSS and NOSC of the Anatomical Therapeut ic Chemical classification system.·Calcula ted using Pearson's X2 test.

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J Ilomdki et al.

sion has been linked to increased alcohol consumption."Consistent with these findings , the unadjusted odds ratiofor continuous heavy drinking among baseline seda-tive/anxiolytic drug users was 3 .30 (95% CI 1.19 to9.17) at 11 year s. After the model was adjusted for co-variates this association was no longer statistically sig-nificant. One possible reason why the results did notreach statistical significance may have been the relative-ly small number of sedative/anxiolytic drug users atbaseline (n = 41).

An important strength of this study was that the datawere obtained from a well-characterized cohort. This pro-vided the opportunity to adjust our analyses for a variety ofdemographic and diagnostic parameters. Drug use datawere self-reported by the participants, and then verified bya nurse interviewer. This method of drug exposure assess-ment had several advantages over the use of administra-tive pharmacy data. Our method of drug exposure assess-ment captured only those drugs actually taken by the par-ticipants. It also covered drugs not reimbursed andtherefore not included in administrative pharmacy data(eg, small pack sizes of benzodiazepines)." However. alimitation was that self-reported drug use data may beprone to recall errors. Alcohol consumption was assessed

Table 2. Sedative/Anxiolytic Use and

Heavy Drinking Status attha Fallow-Up Examinations

LoslloFollow-Up

4-Year 11-Year from 4Follow- Follow- Years to

Characterlsllc Up" Upb 11 Years

Sedative/anxiolytic use,cn (%) n = 1038 n =854

never user 971 (93.5) 780 (91.3) 167 (17.2)

initiator 26(2.5) 4~(4 .9) 8 (30.8)

continuous user 26(2.5) 15 (1.8) 5 (19.2)

former user 15 (1.4) 17" (2.0) 4 (26.7)

Heavy drinking," n (%) n = 1030 n=832

never user 843 (81.8) 661 (79.4) 143 (17.0)

Initiator 54(5.2) 60P (8.1) 7 (13.0)

continuous user n(7.5) 54(6.5) 17 (22.1)

former user 56 (5.4) 4]1 (5.6) 15 (26.8)

"At the 4-year follow-up, drug consumption data were available for all1038 participants and alcohol consumption data were availablo lor1030 participants.

bAt the l1-year follow-up, drug consumption data were available for all854 participants and alcohol consumption data were available for 832part icipants.

"Classes N05B and N05C 01 the Anatom ical Therapeulic Chem icalclassification system.

dSeven initiators at 11 years had already initiated at 4 years and 9 for-mer users at 11 years had already quit at 4 years.

"Average alcohol consumption 2:14 drinkslwk .trwenty initiators at 11 years had already initiated at 4 years and 30former users at 11 years had already quit at 4 years .

by a widely used and previously validated quantity-fre-quency method." While this represents a methodologicalstrength , self-reported alcohol consumption data are sub-ject to recall errors. This may be particularly true because

Table 3. Association Between Baseline Heavy Drinking and

Sedative/Anxiolytic Use Status at 4- Year and

11- Year Follow-Up

AnxlolyticlSedallve Baseline Heavy Drlnking,bUse" Sialus OR (95% CI)

4-year follow-up

Initiator Unadjusted 3.83 (1.67 108.78)

AdjustedC2.96 (1.23 to 7.15)

continuous user Unadjusted 1.72 (0.64 to 4.65)

Adjusled" 1.25 (0.44 to 3.54)

former user Unadjusted 1.11 (0.25 to 4.99)

AdjustedC0.76 (0.16 to 3.60)

11-year follow-up

inil iator Unadjusted 1.29 (0.53 to 3.16)

Adjusted" 1.05 (0.42 102.65)

continuous user Unadjusted 1.94 (0.55 to 7.01)

Adjusled" 1.30 (0.34 104.96)

former user Unadjusted 1.66 (0.47 to 5.90)

Adjustedc 1.12 (0.29 to 4.25)

"Classes N05S and NOSCof the Anatom ical Therapeut ic Chemicalclass ification system.

bAverage alcohol consumption 2:14 drinkstwk.CAdjusted for age, smoking, working status, and depression.

Table 4 . Association Between SedativelAnxiolytic Use at

Baseline and Heavy Drinking Status at 4- Year and

11-Year Follow-Up

Heavy Drinking Baseli ne Sedat ive!Sialus' Anxloly1lc Use,b OR (95% CI)

4-year follow-up

Initiator I:lnadjusted 1.54 (0.46 to 5.21)

Adjusted' 1.34 (0.39 to 5.01)

conlinuous user Unadjusted 1.44 (0.49 to 4.18)

Adjusted' 1.00 (0.32 to 3.11)

former user Unadjusled 1.48 (0.44 to 5.01)

AdjustodC0.96 (0.27 to 3.45)

11-year follow-up

initiator Unadjusted 2.05 (0.68 106.12)

Adjusted" 2.32 (0.71 107.52)

continuous user Unadjusted 3.30 (1.19 to 9.17)

Adjusted" 2.69 (0.86 to 8.44)

former user Unadjusted 0.75 (0.10 to 5.74)

Adjusted" 0.32 (0.04 to 2.62)

"Average alcohol consumption :2:14 drinkslwk .bClasses N05B and N05C of the Anatom ical Therapeutic Chemicalclassification system.

CAdjusted for age, smoking, working status, and depression.

1244 • The AnnalsofPharmacotherapy • 2011 October, Volume 45 theannals.com .

of the long recall period of 12 months. Another limitationwas that therewere a numberof dropouts betweenbaselineand the 4- and ll-year examinations. When assessingsedative/anxiolytic drug use at 11 years, 30.8% of the par-ticipants who initiated sedative/anxiolytic drug use at 4years did not attend the ll-year examination. Similarly,26.7% of the men who were former sedative/anxiolyticdrug users at 4 years did not participatein the 11-year ex-amination. When assessing heavy drinking at 11 years,22.1% of those who were continuous heavy drinkers at 4years did not participate in the ll-year examination.Thissuggests that the numberof participants in these categoriesmay have been underestimated at the 11-yearfollow-up.

Our results can be generalizedto countrieswith similardrinkingpatterns to Finland, including other Nordiccoun-tries, the UK, and Germany." Daily drinking in thesecountries is low in general (except in Germany), but theamount of alcohol consumed in each drinking occasion ishigh. In Italyand France,dailydrinkingis commonbut theamount consumed at each occasion is lower than in Fin-land, the UK, Sweden,and Germany.

This study showedthat baselineheavydrinkingpredict-ed initiationof sedative/anxiolytic drugs at the 4-year fol-low-up.This finding may informstrategies to optimizetheuse of sedative/anxiolytic drugs and assist in the earlyidentification of patients at risk of heavy drinking. Clini-cians shouldconsider a patient's alcoholconsumptionbe-fore prescribing sedative/anxiolytic drugs and monitorpa-tients prescribed sedative/anxiolytic drugs for subsequentheavy drinking. Further studies with larger sample sizesare needed to confirm the association between baselinesedative/anxiolytic drug use and initiation of heavy drink-ing.

Jenni lIomakl PhD, Research Fellow, Quality Use of Medicinesand Pharmacy Research Centre, Sansom Institute, School of Phar-macyandMedical Sciences, University of South Australia, Adelaide,Australia; Researcher, Instituteof PublicHealthand Clinical Nutri-tion,Faculty of HealthSciences, University of Eastern Finland, Kuo-pia, FinlandJ Simon Bell PhD,Associate Professor, QualityUseof Medicinesand Pharmacy Research Centre, Sansom Institute, School of Phar-macyand Medical Sciences, University of SouthAustralia; AdjunctProfessor, Clinical Pharmacology and GeriatricPharmacotherapyUnit, Faculty of HealthSciences, University of Eastern FinlandJussl KauhanenMDMPH PhD, Professor, Institute of Public HealthandClinical Nutrition, Faculty of Health Sciences, University of East-ern FinlandHannes Enlund PhD, Professor, Research Director, FinnishMedicines Agency, KuopioCorrespondence: Dr.1I0maki, jennLilomaki@unisa.edu.auReprints/Online Access:www.theannals.comlcgVreprintlaph.1Q375

Conflict of interest: Authors reported none

Dr. llornakl received a research grantfromthe Finnish Cultural Foun-dation. The research described in thismanuscript wasfunded by theAcademy of Finland (grantnumber118551).

Wegratefully acknowledge Kimmo Ronkainen MSc.University ofEastern Finland,for assistance with data management.

Heavy Drinkingand UseofSedative orAnxiolytic DrugsAmongAgingMen

References

1. Du Y,Scheidt-Nave C, KnopfH. Useof psychotropic drugsandalcoholamongnon-institutionalised elderlyadultsin Germany. Pharmacopsychi-atry2008;41 :242-51.

2. John U, BaumeisterSE, VolzkeH, MeyerC, UlbrichtS, Alte D. Seda-tive, hypnotic,anxiolytic and opioid medicament use and its co-occur-rence with tobaccosmokingand alcoholrisk drinkingin a communitysample. BMCPublicHealth 2007;7:337.

3. Blennow G, Romelsjo A, Leifman H, Leifman A, Karlsson G. Sedativesand hypnotics in Stockholm-social factors and kindsof use.AmI Pub-lic Health 1994;84:242-6.

4. Osterling A, BerglundM. Alcoholconsumptionand regular benzodi-azepineuse in 55-year-oldfemaleMalmoresidents: results of a healthscreening. ActaPsychiatr Scand1996;94:141-8.

5. DelRIO MC,Prada C, Alvarez FJ.Do Spanish patients drinkalcohol whileundergoing treatment withbenzodiazepines? Alcohol 2002;26:31-4.

6. AdamsWL.Potential foradverse drug-alcohol interactions amongretire-mentcommunity residents. J Am GeriatrSoc 1995;43:1021-5.

7. PringleKE, Ahern FM. HellerDA, GoldCH, BrownTV.Potentialforalcoholand prescription drug interactions in olderpeople.J Am GeriatrSoc2005;53:1930-6.

8. SatreDO,SterlingSA, MackinRS, WeisnerC. Patternsof alcoholanddrug use among depressedolder adults seeking outpatient psychiatricservices. Am J GeriatrPsychiatry 2011;19:695-703.DOllO.1097/JGP.ObOI3e3181f17fDa

9. Veldhuizen S, Wade TJ, CaimeyJ. Alcohol consumption amongCanadi-ans takingbenzodiazepines and related drugs.Pharmacoepidemiol DrugSaf2009;18:203-10.

10. GrahamK, Vidal-Zeballos D. Analyses of use of tranquilizers andsleep-ingpillsacrossfive surveys of the samepopulation (1985-1991): the re-lationship with gender, age and use of other substances.Soc Sci Med1998;46:381-95.

II. Linnoila MI.Benzodiazepines anda1cohol.J Psychiatr Res1990;24:121-7.12. IlornakiJ, KorhonenMJ, EnlundH, HartzemaAG, KauhanenJ. Risk

drinkingbehavior among psychotropic drug users in an aging Finnishpopulation: theFinDrink study. Alcohol 2008;42:261-7.

13. Fergusson DM, BodenJM, HorwoodU. Testsof causal linksbetweenalcohol abuseor dependence and majordepression. ArchGen Psychiatry2009;66:260-6.

14. PaljarviT, KoskenvuoM, PoikolainenK, Kauhanen I, Sillanmliki L,Makela P.Binge drinking and depressivesymptoms:a 5-year popula-tion-based cohortstudy. Addiction 2009;104:1168-78.

15. FourrierA, Letenneur L,Dartigues IF, MooreN, BegaudB. Benzodiaze-pineuse in an elderlycommunity-dwelling population: characteristics ofusers and factorsassociated withsubsequent use. Eur J Clin Pharmacol2001;57:419-25.

16. LuijendijkHJ, TiemeierH, HofmanA. HeeringaJ, StrickerBH. Deter-minants of chronic benzodiazepineuse in the elderly: a longitudinalstudy. Br I ClinPharmacoI2008;65:593-9.

17. HartzI, Lundesgaard E, Tverdal A, Skurtveit S. Disability pensionis as-sociated with the use of benzodiazepines 20 years later: a prospectivestudy. ScandI PublicHealth 2009;37:320-6.

18. Hausken AM, FumK, Tverdal A, Skurtveit S. Mental distress andsubse-quent use of anxiolyticdrugs-a prospective population-based cohortstudyof 16,000 individuals. ScandI PublicHealth2010;38:465-73.

19. HolahanCJ, MoosRH, HolahanCK,CronkiteRC, Randall PK. Drink-ing to cope and alcoholuse and abusein unipolardepression: a 10-yearmodel.J AbnormPsychol2003;112:159-65.

20. MoosRH,SchutteK, Brennan P,MoosBS.Ten-year patternsof alcoholconsumption anddrinking problemsamongolderwomenand men.Ad-diction 2004;99:829-38.

21. Bonnewyn A, KatonaC, Bruffaerts R, et aI.Painanddepression inolderpeople: comorbidity and patternsof helpseeking.J AffectDisord2009;117:193-6.

22. BrennanPL, SchutteKK, MoosRH.Painand use of alcoholto managepain: prevalenceand 3-year outcomes amongolder problem and non-problem drinkers. Addiction 2005;100:777-86.

theannals.com TheAnnalsofPharmacotherapy • 2011 October, Volume 45 • 1245

J lIomiiki et al.

23. LakkaTA,Venalainen 1M,Rauramaa R, SalonenR, Tuomilehto 1, Salo-

nen IT. Relationof leisure-time physicalactivityand cardiorespiratoryfitness to the risk of acute myocardialinfarction.N Engl1 Med 1994;330:1549-54.

24. National Institute of Alcohol and Drug Research. Bruk av alkoholognarkotika blanttilsatteI forsvaret-Resultater av en sperreskjemaunder-sekelsehasten[Norwegian]. Oslo:1991.

25. HaugeR, Irgens-Jensen O. Theexperiencing of positive consequences ofdrinking in fourScandinavian countries. Br1 Addict1990;85:645-53.

26. HeebJL,GmelG. Measuring alcohol consumption: a comparison of grad-uatedfrequency, quantity frequency, and weekly recall diarymethods in ageneral population survey. AddictBehav2005;30:403-13.

27. WHO Collaborating Centre for Drug Statistics Methodology. TheAnatomical Therapeutic Chemical classification system.WHOCollabo-ratingCentre for Drug StatisticsMethodology. NorwegianInstituteofPublicHealth.2011.www.whocc.no/atcdddl (accessed 2011 Aug2).

28. Lehto SM, RuusunenA, NiskanenL, et al. Elevateddepressivesymp-toms and compositional changes in LDL particlesin middle-aged men.EurJ EpidemioI2010;25:403-9.

29. Valtonen M, Laaksonen DE,Laukkanen 1,et al. Sedentarylifestyleandemergence of hopelessness in middle-aged men. Eur1 Cardiovasc PrevRehabil201O;17:524-9.

30. KaplanGA, Roberts RE,CamachoTC, CoynelC. Psychosocial predic-torsof depression. Prospective evidence fromthe humanpopulation lab-oratorystudies. Am1 Epidemiol 1987;125:206-20.

31. Stamatakis KA, Lynch1, EversonSA, Raghunathan T, SalonenIT, Ka-planGA. Self-esteem and mortality: prospective evidencefroma popu-lation-based study. AnnEpidemiol2004;14:58-65.

32. Bolton1M, Robinson1, Sareen 1. Self-medication of mood disorderswithalcohol anddrugsin the National Epidemiologic Surveyon Alcoholand Related Conditions. 1AffectDisord2009;115:367-75.

33. Leeies M,PaguraJ,Sareen J,Bolton 1M.The useof alcohol anddrugstoself-medicate symptoms of posttraumatic stressdisorder. Depress Anxiety2010;27:731-6.

34. Langbehn DR, Philibert R, Caspers KM, Yucuis R, CadoretRJ. Associa-tion of a D2S2944allelewithdepression specifically among thosewithsubstanceabuse or antisocialpersonality. Drug Alcohol Depend2006;83:33-41.

35. Nurnberger Jl, ForoudT,FluryL, et al. Evidence for a locuson chromo-some I that influences vulnerability to alcoholism and affective disorder.AmJ Psychiatry 2001;158:718-24.

36. Demyttenaere K, Bonnewyn A, Bruffaerts R, et al. Clinical factors influ-encing the prescription of antidepressants and benzodiazepines: resultsfrom the Europeanstudyof the epidemiology of mental disorders(ES-EMeD). 1 AffectDisord2008;110:84-93.

37. WattsM. Understanding the coexistence of alcoholmisuseand depres-sion.Br J Nurs2008;17:696-9.

38. Janson C, LindbergE, GislasonT, ElmasryA, Boman G. Insomniainmen-a IO-year prospective population basedstudy. Sleep2001;24:425-30.

39. AmatoL, MinozziS, Vecchi S, DavoliM. Benzodiazepines for alcoholwithdrawal. Cochrane Database SystRev201O;CDOO5063.

40. Ilomaki 1,Korhonen Ml, Lavikainen P,LiptonR, EnlundH, Kauhanen 1.Changes inalcohol consumption anddrinking patternsduringII yearsoffollow-upamongageing men: the FinDrinkstudy.Eur1 PublicHealth2010;20:133-8.

41. KemmJ. Ananalysis by biIthcohortof alcoholconsumption by adultsinGreatBritain 1978-1998. Alcohol Alcohol 2003;38:142-7.

42. Kerr WC, FillmoreKM, BostromA. Stabilityof alcoholconsumptionover time: evidence from three longitudinal surveys from the UnitedStates. 1 StudAlcohol Drugs2002;63:325-33.

43. Hartikainen S, KIaukka T. Use of psychotropics is highamongveryoldpeople. EurJ ClinPharmacoI2004;59:849-50.

44. Eigenbrodt ML,FuchsPD,Hutchinson RG,PatonCC,GoffDC,CouperOJ. Health-associated changesin drinking: a periodprevalence studyofthe Atherosclerosis Risk In Communities(ARIC)cohort (1987-1995).PrevMed 2000;31:81-9.

45. HaJrne IT,SeppaK, AlhoH, Poikolainen K, PirkolaS, AaltoM. Alcoholconsumption andall-cause monaIity amongelderlyin Finland. DrugAl-coholDepend2010;160:212-8. _

46. van Vliet P,van der Mast RC, van den Broek M, WestendorpRG, deCraen AJ. Useofbenzodiazepines,depressive symptomsand cognitivefunction in old age.Int1 GeriatrPsychiatry 2009;24:500-8.

47. Swendsen10, TennenH, CarneyMA, AffleckG, WillardA, HromiA.Mood andalcohol consumption: an experience sampling testof the self-medication hypothesis. J AbnormPsychoI2000;I09:198-204.

48. Rikala M, Hartikainen S, Sulkava R, Korhonen MI. Validity of theFinnishPrescription Register for measuring psychotropic drugexposuresamongelderlyFinns:a population-based intervention study. DrugsAg-ing2010;27:337-49.

49. Leifrnan H. A comparative analysis of drinking patternsin sixEU coun-triesin year2000.ContempDrugProbl2002;29:501-48.

Consumo Elevado de Alcohol y uso de FarmacosAnsioliticos 0

Sedantes en Hombres de Edad Avanzada: Seguimiento de II Anosde Duraci6n del Estudio FinDrink Study

J Ilomaki, JS Bell, J Kauhanen, y H Enlund

AnnPharmacother 2011;45:1240-7.

EXTRAcro

ANTECEDENTES: La mayorfade los estudios sobre el consumo elevado dealcoholy el uso de farmaeos ansioliticos 0 sedanteshan sidotransversales,y faltan datos que manifiesten una posible relaci6n temporal.

OBJETIVO: Investigarde forma prospectiva si el consumo elevado dealcohol augura el inicio, prosecucion 0 interrupci6ndel uso de farrnacosansioliticos0 sedantes a los 4 y II aiios y, al contrario, si el uso deansiolfticos0 sedantes pronostica el consumo excesivo de alcohol.

Mtrooos: Se realiz6 un estudio plobacionallongitudinal en Kuopio,Finlandia.Se utiliz6 una muestra aleatoriade 1516 hombres con 42,48,54, Y60 aiios que fueron sometidos a un examen clinicoestructurado alinicio (desde agosto 1986 a diciembre 1989).Los examenes clfnicos deseguimiento se realizarona los cuatro (n = 1038)YII afios (n = 854). Seutiliz6 una regresi6n logfstica multinominalpara calcular los odds ratios(DRs) y los intervalosde confianza al 95% (IC) para determinar larelaci6n entre el uso de farmacos ansiolfticos0 sedantes, la continuaci6no interrupci6ndel consumo elevado de alcohol (:!:14 bebidaslsemana).Tambien se investig6 la relaci6n inversa. Los modelos de regresi6nseajustaron por edad, estado laboral, ser 0 no fumador y la presencia0 node sfntornas depresivos.

RESULTADOS: AIinicio,eI12.9% (n = 134),delos participantes presentabaun consumo elevado de alcohol y e14.o% (n =41) utilizaba farmacosansioliticos 0 sedantes. En el analisis mullivarlal,el consurnoelevado dealcohol al principio auguraba el inicio de uso de farmacos ansiolfticos0

sedantes a los 4 afios(OR 2.96; IC 95% 1.23 Y7.15). AIreves, el usa defarmacosansiolilicos 0 sedantesal inicioprosticabala continuaei6n delconsumo elevado de alcohol a los 11aiios en un analisis sin ajustar (OR3.30; IC 95% 1.19Y8.44). No obstante, la relaci6n no pareci6 serestadfsticamentesignificativaen el analisis ajustado (OR 2.69; IC 95%0.86 Y8.44).

CONCLUSIONES: EI principal hallazgo de este estudio longitudinalprospectivo fue la relaci6n entre el consumo elevado de alcohol y elinicio posteriorde uso de farmacos ansiolfticos0 sedantesque no seexplicaba por la existencia al iniciode sfntomasdepresivos.Se debencrearestrategias paraoptirnizarel uso de farmacosansiolfticos 0 sedantesYprocurar identificar10antes posible a pacientes con riesgo de consumoelevado de alcohol. Los medicos deberan considerarel consumo dealcohol de los pacientes antes de prescribirles0 dispensarlefarmacosansiolfticos 0 sedantesYcontrolarel consumode alcoholde los pacientesalos que les ha prescrito farmacos ansioliticos0 sedantes.

Traducido porVioleta LopezSanchez

1246 • TheAnnalsofPharmacotherapy • 2011 October, Volume 45 theannals.com

ConsommationAbusive d'Alcool et Utilisationde MedicamentsSedatifsou Hypnotiqueschez I'Homme: Suivi Apres 11 ans deI'Essai FinDrink

J Ilomaki, JS Bell,J Kauhanen, et H Enlund

Ann Pharmacother 20II ;45: 1240-7.

INTRODUcnON: La plupart desessaissur laconsommation excessived'alcoolet I'abusde medicaments 11 proprietes sedatives/hypnotiques ontetedesetudestransversales et les preuves d'un lientemporel ne sontpasdisponibles.

OBJECTIFS: Realiser uneetudeprospective pourdeterminer si laconsommation excessive d'a1cool peutpredire I'initiation, la poursuiteou l'arret de medicaments aproprietes sedatives/hypnotiques apres4 ouII ans,ou 11 l'inverse,si I'utilisation de medicamentssedatifs/hypnotiques peutpredire la consommation excessive d'a1cool.

METHODE: II s'agit d'une etudelongitudinale de population realisee aKuopio en Finlande. Un echantillon aleatoire, stratifie pourl'age, de1516hommes de 42,48, 54,et 60 ansont subituneevaluation semi-structuree lorsde leur inclusion dansl'etude (aoOt 1986-decembre1989). Desevaluations cliniques ont ererealisees apres4 ans(n = 1038)et 11 ans (n= 854).Uneregression logistique multinomiale a ere utiliseepourcalculerlesrapports de cote (RC)et I'intervalle de confiance 95%(lC)pourI'association entre I'utilisation de medicaments sedatifs!anxioly-tiques et I'initiation,Ia poursuite ou I'arretde laconsomrnation excessive

HeavyDrinkingand Useo/Sedative orAnxiolyticDrugsAmong AgingMen

d'alcool (~I4 consommationslsemaine). L'association inverse entrelaconsommation excessive d'a1cool et I'utilisation de medicaments sedatifs/anxiolytiques a aussieteevaluee. Lesmodeles de regression onteteajustespourI'age,Iestatut d'emploi, Ietabagisme, et pourlessymptCimesdepressifs,

REsULTATS: Audebutde l'etude, 12.9% (n = 134)des participants etaitdegrosbuveurs et 4.0%consommaient des sedatifslhypnotiques. Lesanalyses multivariees ont demontre que la consommation initialed'a1cool predit\'initiation de sedatifs/hypnotiques apres4 ans(RC2.96;IC95%123 1'17.15). Deplus,laconsommation initiale desedatifslhypno-tiques preditla poursuite des habitudes de consommation d'alcool 11 IIansdansuneanalyse sansajustement (RC330; IC 95% 1.1911 8.44).Cependant,l'association n'etaitpas statistiquement significative lorsdesanalyses ajustees (RC2.69;IC 95%0.86a8.44).CONCLUSIONS:Leresultat principal de cetteetudelongitudinale prospectiveestuneassociation entrela consommation excessive d'a1cool et I'initiationsubsequente de sedatifs/hypnotiques, maisquin'est pascompletementexpliquee par la presence de symptomes depressifs aI'origine. Cetteinformation perrnettra de developper des strategies d'utilisation dessedanfs/hypnotiques, et de faciliter Iedepistage precoce des patients arisque d'abuserde l'a1cool. Lescliniciens devraient considerer Iaconsommation d'a1cool de leurspatients avantde prescrire ou de fournirdessedatifs oudeshypnotiques. Lescliniciens devraient doneetrevigilantsfaceal'eventualite d'une consommation d'a1cool accruechezlesutilisateurs de sedatifs/hypnotiques prescrits.

Traduit parMarcParent

theannals.com The AnnalsofPharmacotherapy • 2011 October, Volume 45 • 1247