enzodiazepine and SSHs have sedative, hypnotic, anx-iolytic, muscle relaxant, and anticonvulsant properties.In addition to their therapeutic properties, BDZ–SSHs areassociated with adverse effects, including cognitive prob-lems,
anincreasedfrequencyof motor vehicle accidents,
and dependence and abuse.
For the most part, the pharmacoepidemiologic literature isrestricted to estimates of the prevalence and cross-sectionalcorrelates of BDZ–SSH use.
For example, the ESEMeDfoundthatanxietyanddepressivedisorders,femalesex,older age,helpseekingfor emotionalproblems,loweducation,and pain predicted BDZ use in 6 European countries.
Similarly,in Canada, cross-sectional correlates of BDZ use includefemale sex, (higher) age, low income, low education, and the presence of mood or anxiety disorders.
Few longitudinalstudies have examined BDZ use in Canada.Zopiclone (a cyclopyrrolone derivative) and zaleplon (a pyrazolopyrimidine) are non-BDZ–SSHs that share pharma-cological properties, adverse effects, and risks withBDZ.
However, these medications are used more spe-cifically for insomnia and less frequently for anxiety. Bothzopiclone and zaleplon are listed under Schedule IV by theInternational Narcotics Control Board.
However, neither zopiclone nor zaleplon are classified as controlled drugs inCanada, whereas BDZs are.TreatmentwithBDZ–SSHsisofteninitiatedduringtreatmentof depressive disorders, particularly when symptomsof anxi-ety are present.
Such use is often intended to be brief, withdiscontinuation of the BDZ–SSH being intended when acoprescribedADbeginstowork.SomecoursesofBDZ–SSHtreatment may become prolonged if there are residual symp-toms of depression or comorbidities that lead to longer-termtreatment. Some ADs, may cause insomnia or agitation as anadverse effect and this may also lead to an increased or more prolonged coprescribingofBDZ–SSHs.Toleranceandabusemay also lead to prolonged BDZ–SSH exposure. Theobjectives of our study included estimation of the incidenceand pattern of new use and the frequency and pattern of dis-continuation of BDZ–SSH medications in relation to MDEsand the use of ADs.
TheNPHSisalongitudinalstudybasedonanationallyrepre-sentative sample of 17 276 respondents selected from theCanadianhouseholdpopulationbyStatisticsCanadain1994.The NPHS longitudinal cohort has been interviewed every2 years since thattime.The NPHS methodology is describedin previous publications.
The estimated response rate to2006 is 77.0%.
This response rate does not include NPHSrespondents who left the sampling frame (died or were insti-tutionalized) during follow-up as they were considered tohave been successfully followed. The 1994 baseline inter-viewswereconductedinperson(75%),but99%offollow-upinterviews were conducted over the phone.TheNPHSinterviewincludesitemscovering demographics,health status, health care use, and health determinants.Respondents were also asked to retrieve containers (boxes, bottles,tubes,orpackages)ofmedicationstakeninthe2days preceding an interview. Specific medications were recordedusingATCcodes.TheseATCcodeswereusedinthecurrentanalysis to identify respondents who were taking aBDZ–SSH and to identify the use of ADs. We examined theincidence of new use of BDZ–SSH as the frequency of reporteduseatsubsequentcyclesafternotreportinguseataninitial cycle. A particular concern is the pattern of persistentBDZ–SSH use, as this may be more problematic thanshort-term use. An analysis was therefore performed requir-ing2consecutivecyclesofnewuse.Asthepatternsofinitia-tion and discontinuation maydiffer depending on the typeof medication, additional analyses were performed in whichzopiclone and zaleplon were analyzed separatelyfrom BDZ.As the 2-day record of use covers a brief period of time, wealso examined (for comparative purposes) the incidence of use of sleeping pills in the preceding month, as documented by responses to a different item: “In the past month, did youtake sleeping pills?”ToexaminetrendsinthefrequencyofBDZ–SSHuse,weini-tially tabulated unadjusted frequencies by year of interview.We also tabulated the types of medications used and the fre-quency of use of more than one BDZ–SSH at the same time.To examine the impact of ADs and MDEs on initiation anddiscontinuation of BDZ–SSHs, we used discrete (grouped)time proportional hazard models to estimate HRs. Thesemodelsincludedbothageandsextogenerateestimatesoftheeffect of ADs and MDE on subsequent BDZ–SSHs adjustedfor these nonmodifiable determinants of use. We also devel-oped modelsincorporating additional potentialdeterminantstoassesspossibleconfoundingeffects.Aswewereinterestedin the effects of AD use on subsequent BDZ–SSH use, ADuse was incorporated into these models as a time-varying
Pharmacoepidemiology of Benzodiazepine and Sedative–Hypnotic Use in a Canadian General Population Cohort During 12 Years of Follow-upThe Canadian Journal of Psychiatry, Vol 55, No 12, December 2010
Abbreviations used in this article
AD antidepressant ATC Anatomic Therapeutic ClassificationBDZ benzodiazepineCIDI-SFMD Composite International DiagnosticInterview—Short Form for Major DepressionDSM Diagnostic and Statistical Manual of MentalDisordersESEMeD European Study of the Epidemiology of MentalDisordersHR hazard ratioMDE major depressive episodeNPHS National Population on Health StudySSH similar sedative–hypnotic