insomnia symptoms and subsequent psychotropic medication: a register-linked study with 5-year...

ORIGINAL PAPER

Insomnia symptoms and subsequent psychotropic medication:a register-linked study with 5-year follow-up

Peija Haaramo • Tea Lallukka • Eero Lahelma •

Christer Hublin • Ossi Rahkonen

Received: 11 October 2013 / Accepted: 28 February 2014

� Springer-Verlag Berlin Heidelberg 2014

Abstract

Purpose This study examined the associations of

insomnia symptoms with subsequent psychotropic medi-

cation, reflecting mental health.

Methods Postal baseline surveys among 40- to 60-year-

old employees of the city of Helsinki, Finland, were col-

lected in 2000–2002 (N = 6,227, response rate 67 %, 78 %

women) and longitudinally linked with national register

data on prescribed reimbursed medication. Insomnia

symptoms at baseline comprised difficulties in initiating

and maintaining sleep, and non-restorative sleep. All pur-

chased psychotropic medication 5–7 years prior to and

5 years after baseline was included. Outcomes were any

psychotropic medication; antidepressants; and anxiolytics,

hypnotics, and sedatives. Covariates included socio-

demographic and work-related factors, health behaviors,

lifetime mental disorders, and prior psychotropic medica-

tion. Logistic regression analysis was used to calculate

odds ratios (OR) and their 95 % confidence intervals (CI).

Results Insomnia symptoms were associated with higher

frequency of subsequent psychotropic medication pre-

scriptions. The associations were strongest for frequent

insomnia symptoms (women OR 3.55, 95 % CI 2.64–4.77;

men OR 4.64, 95 % CI 2.49–8.66, adjusted for age and

prior medication), but also rare and occasional symptoms

were associated with psychotropic medication. Further

adjustments had negligible effects.

Conclusions Insomnia symptoms were associated with

prescribed psychotropic medication during follow-up in a

dose–response manner. Attention should be given to the

prevention of insomnia symptoms to curb subsequent

mental problems.

Keywords Insomnia symptoms � Psychotropic

medication � Follow-up study � Survey � Register data �Occupational cohort

Introduction

Insomnia is the most common sleep disorder, with a

prevalence of occasional insomnia symptoms around 30 %

and clinical and chronic insomnia around 10 % among

working-aged adults in affluent societies [1]. Psychotropic

medication is also prevalent, with an increasing trend [2,

3]. Previous studies suggest an association between

insomnia symptoms and subsequent mental health [4, 5].

Nonetheless, associations between insomnia symptoms and

subsequent psychotropic medication are still poorly known.

Examining these associations helps deepen our knowledge

of the role of insomnia in the etiological pathways to

mental disorders, assisting in their prevention and

decreasing psychotropic medication use.

Previous, mainly cross-sectional studies suggest that

insomniacs use more psychotropic medication than the

general population or those without insomnia [6–8]. A

cross-sectional study examining psychotropic medication

and its associations with sleep and mental and physical

disorders in France, Germany, Italy, and the United

Kingdom found that the prevalence of psychotropic

P. Haaramo (&) � T. Lallukka � E. Lahelma � O. Rahkonen

Department of Public Health, Hjelt Institute,

University of Helsinki, Mannerheimintie 172, PO Box 41,

00014 Helsinki, Finland

e-mail: [email protected]

T. Lallukka � C. Hublin

Finnish Institute of Occupational Health, Topeliuksenkatu

41 a A, 00250 Helsinki, Finland

123

Soc Psychiatry Psychiatr Epidemiol

DOI 10.1007/s00127-014-0862-8

medication among insomniacs varied between 17 and

38 %, depending on whether there was some other condi-

tion comorbid with insomnia, comorbidity increasing the

medication prevalence [9]. Psychotropic medication

increased with age and was more common among women

than men. In a cross-sectional study on the Norwegian

adult population insomnia symptoms were positively

associated with sleep medication, sedatives, and antide-

pressants [8]. In the British 1946 birth cohort insomnia

symptoms were positively associated with psychotropic

medication at ages 36 and 43 but no longer at age 53 [10].

In a longitudinal US study on primary care patients,

insomnia was found to be associated with excess health

care utilization, including psychotropic medication, during

a 3-month follow-up [7]. Insomnia symptoms were also

positively associated with subsequent treatment for

depression in a recent Finnish study using a combined

measure of antidepressant medication, psychotherapy, or

hospitalization due to depression [11].

Most of the previous studies on the associations between

insomnia symptoms and psychotropic medication have

been cross-sectional [6, 8–10, 12, 13], although there are

also a few longitudinal studies [7, 11, 14, 15]. The follow-

up periods varied in the longitudinal studies from 3 months

to 3.3 years. In most studies insomnia symptoms were self-

reported [6, 8, 10, 11, 14, 15], while in some studies

diagnostic interviews were conducted by lay interviewers

[7, 9, 12, 13]. In the majority of studies psychotropic

medication was self-reported [6, 8–10, 12, 13]. In three

studies the information on medication was derived from

primary care records [7, 14, 15] and in one Finnish study

from a national register on prescribed medication [11].

Large-scale epidemiological follow-up studies on the

associations of insomnia symptoms with subsequent psy-

chotropic medication are still lacking. As most previous

studies are based on self-reported medication, more objective

and accurate outcomes are needed. The aim of this study was

to examine the association of insomnia symptoms with sub-

sequent psychotropic medication among middle-aged women

and men using national register data on prescribed medication

over a five-year follow-up. In addition to the longitudinal

design, this study expands the current knowledge with the

examination of the dose–response nature of the association

using a four-category measure of insomnia symptoms. As

both the indications and pharmacodynamic effects vary

between different psychotropic medications, in addition to

examining any psychotropic medication we separately ana-

lyzed antidepressants and the group combining anxiolytics,

hypnotics, and sedatives. Several covariates, including pre-

vious medication, were controlled for. The main hypothesis

of the study was that those suffering from insomnia symp-

toms, compared with those without such symptoms, are more

likely to have subsequent psychotropic medication.

Data and methods

This study is part of the Helsinki Health Study examining

the employees of the city of Helsinki, Finland. Baseline

survey data were collected in 2000–2002 (N = 8,960,

response rate 67 %) [16]. The surveys were carried out by

postal questionnaires among all employees of the city

turning 40, 45, 50, 55 or 60 in each survey year.

Data on insomnia symptoms and covariates were derived

from the baseline surveys. For the participants with written

informed consent to register linkage (74 %, N = 6,606) the

survey data were longitudinally linked to register data on

prescribed reimbursed psychotropic medication purchases,

obtained from the Social Insurance Institution of Finland.

Unique personal identification numbers issued to all Finnish

residents were used in linking the datasets. The total number

of participants consenting to the data linkage and for whom

complete data on insomnia symptoms and adequate

responses to all covariates were available amounted to

6,227. The proportion of women (78 %) reflects the gender

distribution among the employees of the city of Helsinki, as

well as in the Finnish municipal sector on the whole [17].

Insomnia symptoms

Insomnia symptoms were assessed using the Jenkins Sleep

Questionnaire [18]. This questionnaire measures difficul-

ties in initiating and maintaining sleep, and non-restorative

sleep by asking, ‘‘How often during the previous 4 weeks

did you (1) have trouble falling asleep; (2) wake up several

times per night; (3) have trouble staying asleep (including

waking far too early); and (4) wake up after your usual

amount of sleep feeling tired and worn out?’’ Six response

alternatives were included: not at all; 1–3 days; 4–7 days;

8–14 days; 15–21 days; and 22–28 days. The frequency

was categorized into no insomnia symptoms; rare (any of

the symptoms 1–3 times); occasional (4–14 times); and

frequent (at least 15 times) insomnia symptoms. Those

with no insomnia symptoms were used as the reference

group in the analyses. The Jenkins Sleep Questionnaire has

been validated and developed for clinical and epidemio-

logical research purposes [18]. In this study its Cronbach’s

alpha was 0.83 and intercorrelations of the four items

varied between 0.47 and 0.70.

Psychotropic medication

Follow-up data on psychotropic medication contain

detailed information about all prescribed reimbursed

medication purchases. The term ‘‘psychotropic medica-

tion’’ is here used to describe this outcome. Formation of

the data follows these steps: (1) One’s own recognition of

psychological distress and seeking professional help. (2)


123

Visiting a physician who, based on a medical examination,

finds psychotropic medication to be a suitable treatment for

the patient and writes a prescription for it. (3) Purchasing

the prescribed medication and seeking for reimbursement.

(4) If the medication is reimbursable, the reimbursement is

generally made automatically at the time of the purchase.

Information of prescribed reimbursed purchases is for-

warded from all pharmacies in the country to the register of

the Social Insurance Institution of Finland.

Psychotropic medication was classified according to the

WHO Anatomical Therapeutic Chemical (ATC) classifi-

cation system [19]. Our main outcome was any psycho-

tropic medication consisting of medication coded as

psycholeptics (N05) or psychoanaleptics (N06), excluding

medication for dementia (N06D). More in detail, the

included medication classes were antipsychotics (N05A),

anxiolytics (N05B), hypnotics and sedatives (N05C),

antidepressants (N06A), psychostimulants, agents used for

ADHD and nootropics (N06B), and psycholeptics and

psychoanaleptics in combination (N06C). Separate analy-

ses were carried out for antidepressants (N06A) and the

psycholeptics group including anxiolytics, hypnotics, and

sedatives (N05B and N05C combined). The psychotropic

medication outcomes were used as dichotomous measures,

classified into (1) no purchases and (2) at least one pur-

chase during follow-up.

Current users of psychotropic medication at baseline

(N = 319 of the 6,606 participants consenting to the register

linkage) were identified on the basis of the date and defined

daily dose of their last medication purchase. These partici-

pants were excluded from the analyses to be better able to

examine the incidence of psychotropic medication over the

follow-up. All other prior psychotropic medication (starting

from 1 January 1995) was adjusted for in the analyses.

Other covariates

All survey-based covariates were measured at baseline.

Age was adjusted for in all analyses. Marital status was

classified as single; married or cohabiting; and previously

married (divorced, separated, or widowed). Socioeconomic

position included four hierarchical occupational classes:

professionals and managers, semi-professionals, routine

non-manual employees, and manual workers.

Mental and physical strenuousness of work were

assessed using single-item questions with four response

alternatives ranging from very light to very strenuous.

Work arrangements included shift work and working

overtime. Shift work was categorized into regular day-time

work, shift work with no night shifts, shift work with night

shifts (including regular night work), and other working

arrangements. Working more than 40 h per week was used

as the cut-off point for overtime.

Self-reported lifetime physician-diagnosed mental dis-

orders included depression, anxiety, and other mental dis-

orders. Obesity was measured by body mass index (BMI)

of at least 30 kg/m2 and was calculated from self-reported

height and weight. Classification of heavy alcohol drinking

was based on Finnish current care guidelines [20]. The cut-

off point for women was 140 grams of absolute alcohol per

week and for men 280 grams.

The above-mentioned covariates were included as pre-

vious studies have shown them to be associated with both

insomnia symptoms and psychotropic medication [4, 10,

13, 21–26].

Statistical methods

Descriptive analyses were performed using cross-tabula-

tions with Cochran-Armitage trend test and Chi-square test

for heterogeneity. The associations of baseline insomnia

symptoms with psychotropic medication during the five-

year follow-up were examined using logistic regression

analysis. The results are presented as odds ratios (OR) and

their 95 % confidence intervals (CI). No gender interac-

tions were detected. Nevertheless, we chose to conduct the

analyses stratified by gender because of the unequal gender

ratio in the data and moderate gender differences in the

studied associations, suggested by the initial analyses.

Bivariate associations of the covariates with insomnia

symptoms and psychotropic medication were tested in the

initial analyses, and the covariates with the strongest

associations were chosen for the actual analyses. In these

analyses the covariates were entered in a hierarchical way,

adjusting for age in Model 1 and in addition for psycho-

tropic medication before baseline in Model 2. Model 3 was

built on Model 2, adding marital status, socioeconomic

position, mental and physical strenuousness of work, shift

work, and working overtime. Model 4 was also built on

Model 2, adding physician-diagnosed mental disorders,

obesity, and heavy drinking.

We conducted several sensitivity analyses to examine

the associations between insomnia symptoms and psycho-

tropic medication more in detail. First, antipsychotic

medication (ATC code N05A) was used as an additional

outcome. Second, associations between different insomnia

symptoms and subsequent psychotropic medication were

examined. Third, all participants with any psychotropic

medication before baseline were excluded from the anal-

yses. Fourth, multinomial analyses were conducted to

examine the associations of insomnia symptoms with the

number of psychotropic medication purchases during fol-

low-up. The purchases were classified into an outcome

measure with four classes: no purchases, one purchase, two

to three purchases, and four or more purchases. Fifth, some

additional adjustments were tested. Sixth, the medication


123

outcomes were examined with relation to self-reported

lifetime physician-diagnosed mental disorders.

All analyses were conducted using SAS software, ver-

sion 9.2 (SAS Institute Inc, Cary, NC, USA).

Ethical considerations

The Helsinki Health Study protocol was approved by the

ethics committees of the Department of Public Health at

the University of Helsinki and the health authorities of the

city of Helsinki.

Results

Prevalence of insomnia symptoms and psychotropic

medication

Insomnia symptoms were more prevalent among women,

as only 13 % of them reported altogether lacking such

symptoms, compared with 18 % of men (P \ 0.001)

(Table 1). Frequent insomnia symptoms were reported by

20 % of women and 16 % of men. Among both women

and men waking up several times per night was the most

common insomnia symptom and trouble falling asleep the

least common (data not shown).

Also psychotropic medication during the five-year

follow-up was more prevalent among women (23 %) than

men (17 %) (Table 1). Antidepressants were the largest

medication group. In all studied medication groups the

higher the frequency of insomnia symptoms, the higher

the prevalence of psychotropic medication (all P values

for trend \0.001). Among women reporting frequent

insomnia symptoms 39 % had psychotropic medication,

the respective prevalence being 30 % among men. Any

psychotropic medication 5–7 years prior to baseline

showed a prevalence of 24 % among women and 16 %

among men (data not shown). Three-fourths of those with

psychotropic medication during follow-up had more than

one purchase, the median number being two prior to

baseline and four during the follow-up in both genders

(data not shown).

Associations between insomnia symptoms

and psychotropic medication

Any psychotropic medication

Compared with those reporting no insomnia symptoms at

baseline, women with insomnia symptoms were more

likely to have subsequent psychotropic medication

(Table 2). Adjusted for age (Model 1), medication was

most likely for frequent insomnia symptoms, followed by

occasional and rare symptoms. Adjusting additionally for

prior psychotropic medication, lifetime mental disorders,

obesity, and heavy drinking weakened most the studied

association. Further analyses of the individual effects of

the covariates showed that prior psychotropic medication

had the strongest contribution to the examined associa-

tion, followed by lifetime mental disorders (data not

shown).

The association of insomnia symptoms with subsequent

psychotropic medication was somewhat stronger among

men than women (Table 2). After adjusting for age (Model

1), reporting frequent, occasional, and rare insomnia

symptoms were associated with subsequent psychotropic

medication. Adjustments (Models 2–4) attenuated the

studied association, but did not abolish it.

Table 1 Prevalence of

subsequent psychotropic

medication by the frequency of

baseline insomnia symptoms

among 40- to 60-year-old

employees during a 5-year

follow-up (%) (women

N = 4,868, men N = 1,359)

DF degrees of freedoma P value for gender difference

from the Pearson Chi-square

testb P value for trend from the

Cochran–Armitage trend test

Insomnia symptoms Total Pearson DF P value

No Rare Occasional Frequent Chi-square

Prevalence of insomnia symptoms (%)

Women 13 35 32 20

Men 18 33 33 16 27.244 3 \0.001a

Prevalence of medication (%)


Women 11 17 26 39 23 \0.001b

Men 6 12 20 30 17 \0.001b

Antidepressants

Women 7 10 17 28 16 \0.001b

Men 5 8 16 21 12 \0.001b

Anxiolytics, hypnotics, and sedatives

Women 5 9 13 21 12 \0.001b

Men 4 8 10 16 9 \0.001b


123

Antidepressants

Women with frequent insomnia symptoms were most

likely to have subsequent antidepressant medication, but

the likelihood was increased also for those with occasional

or rare symptoms (Table 2). Adjusting for prior psycho-

tropic medication (Model 2) weakened the studied associ-

ation which still remained. Adjusting for socioeconomic

and work-related factors (Model 3) and lifetime mental

disorders, obesity, heavy drinking and health behaviors

(Model 4) attenuated the association somewhat further.

The association of insomnia symptoms with subsequent

antidepressant medication was slightly stronger among

men than women, as for any psychotropic medication

(Table 2). Adjusting for age (Model 1), medication was

most likely among those with frequent insomnia symp-

toms, followed by occasional and rare symptoms. The

effects of adjustments were similar among men and

Table 2 Associations of

insomnia symptoms with


medication among 40- to

60-year-old employees during a

5-year follow-up, OR from

logistic regression analyses and

their 95 % CI (women

N = 4,868, men N = 1,359)

ref. reference group

Model 1, adjusted for age

Model 2, adjusted for age and

psychotropic medication before

baseline

Model 3, Model 2 ? marital

status, socioeconomic position,

mental and physical

strenuousness of work, shift

work, and working overtime

Model 4, Model 2 ? lifetime

physician-diagnosed mental

disorders, obesity, and heavy

drinking

Any insomnia symptom

during previous

4 weeks

Model 1 Model 2 Model 3 Model 4

OR 95 % CI OR 95 % CI OR 95 % CI OR 95 % CI


Women

No insomnia

symptoms (ref.)

1.00 1.00 1.00 1.00

Rare 1.54 1.16 2.04 1.40 1.04 1.87 1.36 1.02 1.83 1.34 1.00 1.80

Occasional 2.70 2.06 3.55 2.21 1.66 2.94 2.15 1.61 2.86 2.04 1.53 2.73

Frequent 4.96 3.74 6.57 3.55 2.64 4.77 3.45 2.56 4.65 3.12 2.31 4.21

Men

No insomnia

symptoms (ref.)

1.00 1.00 1.00 1.00

Rare 2.05 1.13 3.71 1.93 1.04 3.55 1.92 1.03 3.58 1.93 1.04 3.58

Occasional 3.72 2.10 6.60 3.09 1.71 5.59 3.08 1.68 5.66 2.97 1.63 5.39

Frequent 6.61 3.63 12.01 4.64 2.49 8.66 4.53 2.38 8.61 4.10 2.17 7.72

Antidepressants

Women

No insomnia

symptoms (ref.)

1.00 1.00 1.00 1.00

Rare 1.55 1.10 2.20 1.42 0.99 2.02 1.39 0.97 1.98 1.34 0.93 1.91

Occasional 2.77 1.97 3.87 2.23 1.58 3.16 2.18 1.54 3.08 1.99 1.40 2.82

Frequent 5.31 3.77 7.47 3.76 2.64 5.35 3.66 2.56 5.22 3.10 2.16 4.44

Men

No insomnia

symptoms (ref.)

1.00 1.00 1.00 1.00

Rare 1.83 0.91 3.65 1.74 0.86 3.52 1.68 0.83 3.43 1.76 0.86 3.58

Occasional 3.75 1.94 7.24 3.23 1.66 6.31 3.11 1.57 6.15 3.12 1.58 6.14

Frequent 5.72 2.87 11.38 4.17 2.06 8.44 3.86 1.87 7.98 3.56 1.73 7.34


Women

No insomnia

symptoms (ref.)

1.00 1.00 1.00 1.00

Rare 1.78 1.20 2.66 1.60 1.07 2.40 1.59 1.05 2.38 1.57 1.04 2.35

Occasional 2.87 1.95 4.24 2.26 1.52 3.37 2.21 1.48 3.30 2.17 1.45 3.24

Frequent 5.06 3.41 7.50 3.38 2.26 5.07 3.30 2.19 4.96 3.16 2.10 4.76

Men

No insomnia

symptoms (ref.)

1.00 1.00 1.00 1.00

Rare 2.24 1.06 4.73 2.08 0.97 4.47 2.13 0.98 4.64 2.07 0.96 4.44

Occasional 2.90 1.39 6.05 2.23 1.05 4.73 2.28 1.05 4.94 2.14 1.01 4.56

Frequent 5.06 2.37 10.79 3.15 1.44 6.93 3.27 1.45 7.39 2.81 1.27 6.23


123

women, with prior psychotropic medication (Model 2)

showing the strongest contribution to the examined

association.


Insomnia symptoms were associated with subsequent

anxiolytic, hypnotic, and sedative medication among

women (Table 2). The age-adjusted association (Model 1)

was strongest for frequent insomnia symptoms, with an

association for occasional and rare symptoms, as well.

Similar to antidepressants, adjustments (Models 2–4)

attenuated the association which remained.

Among men the association of insomnia symptoms with

anxiolytic, hypnotic, and sedative medication was similar

to women (Table 2). The strongest age-adjusted associa-

tion (Model 1) was for frequent insomnia symptoms and

the association remained after the further adjustments

(Models 2–4).

Sensitivity analyses

Prevalence of at least one antipsychotic medication pur-

chase during the 5-year follow-up was 1.2 % among

women and 1.7 % among men (data not shown). The

sensitivity analyses suggested that the associations of

insomnia symptoms with subsequent antipsychotic medi-

cation were similar to other psychotropic medication. The

associations were especially strong among men. However,

statistical significance was not reached in the analyses due

to the low prevalence of antipsychotic medication.

Associations of the measured four different insomnia

symptoms were separately examined with subsequent

psychotropic medication (data not shown). All symptoms

were associated with subsequent medication. Among

women psychotropic medication was most likely among

those reporting waking frequently up feeling tired or hav-

ing trouble falling asleep. The latter symptom was among

men most strongly associated with subsequent psychotro-

pic medication, along with having trouble staying asleep.

In one of the sensitivity analyses all participants with

any psychotropic medication before baseline (N = 1,398)

were excluded (data not shown). Among men the associ-

ations attenuated but remained for any psychotropic med-

ication and antidepressants; among women the effects of

the exclusion were minor and all the associations remained

practically unaffected, if not strengthened.

Multinomial regression analysis was conducted to

examine the associations of baseline insomnia symptoms

with the number of any psychotropic medication purchases

during follow-up (Fig. 1). Among the participants with rare

or occasional insomnia symptoms the risk of subsequent

psychotropic medication did not differ by the number of

medication purchases. Among those with frequent insom-

nia symptoms the association with subsequent psychotropic

medication followed a gradient by the number of medica-

tion purchases. Similar to the main results the overall

associations were slightly stronger among men than women

(data not shown).

The analyses were additionally adjusted for the regu-

larity of alcohol use, living with children under 18 years of

age, and limiting long-term illnesses. Adjusting for these

factors attenuated the studied associations only slightly

(data not shown).

Psychotropic medication during follow-up was exam-

ined with relation to self-reported lifetime mental disor-

ders. Psychotropic medication was more prevalent (52 vs.

17 %) among those with previous mental disorders than

among those without (data not shown). Different types of

psychotropic medication were prevalent among those with

self-reported depression, as well as anxiety. Congruence

between these two measures is not total, due to several

reasons. The compared time periods are different, as are the

data sources. There is also high comorbidity of mental

disorders, and we do not have information of the diagnoses

on which the prescriptions were based.

Discussion

Main results

Insomnia symptoms were associated with subsequent

psychotropic medication in a dose–response manner, i.e.

the more frequent the insomnia symptoms, the higher the

likelihood of medication. The associations were similar

concerning the different psychotropic medication sub-

groups. The associations of insomnia symptoms with psy-

chotropic medication were stronger among men than

among women regarding any psychotropic medication and

antidepressant medication. Adjusting for previous psycho-

tropic medication and lifetime mental disorders had the

strongest effects on the studied associations. However, the

associations remained for occasional and frequent insom-

nia symptoms even after the adjustments, which mostly

attenuated the associations for rare insomnia symptoms.

Comparisons to previous studies

Our findings confirm in a longitudinal setting the results of

earlier cross-sectional studies [8, 10]. The findings are also

in accordance with previous follow-up studies with out-

comes including wider use of healthcare in addition to

psychotropic medication [7, 11]. Earlier studies reporting

the associations of insomnia symptoms with psychotropic

medication have mostly used dichotomous measures of


123

insomnia symptoms. Our measure of insomnia symptoms

included a scale of four classes, permitting the dose–

response nature of the associations to be examined.

The associations of insomnia symptoms with psycho-

tropic medication were consistent throughout the subgroups

of medication studied. The strong association of insomnia

symptoms with antidepressant medication is likely to be due

to the association of insomnia with depression. Recent

studies have emphasized the role of insomnia preceding

depression [27]. In the medication group of anxiolytics,

hypnotics, and sedatives the association is evident between

insomnia symptoms and the sleep promoting hypnotics.

Also other mental disorders such as anxiety have been

found to be associated with preceding and co-morbid

insomnia symptoms [28]. We conducted sensitivity analy-

ses using antipsychotic medication as an outcome to con-

firm whether the found results apply also to the medication

for more severe mental disorders. We found similar asso-

ciations for antipsychotic medication, as for other medica-

tion groups examined. Antipsychotics are included in the

outcome measure ‘‘any psychotropic medication’’.

The pattern of the associations of insomnia symptoms

with subsequent psychotropic medication was similar

among women and men. In previous studies women have

been more likely users of psychotropic medication than

men, but these studies have not examined the dose–

response association with insomnia symptoms or different

subgroups of psychotropic medication stratified by gender

[10, 13]. As the women in our data had somewhat more

prescriptions of psychotropic medication than men, their

share was also larger among those excluded from the study

due to current medication at baseline—84 vs. 78 % in the

analyzed sample. Nevertheless, as the total number of

excluded participants was fairly low (N = 319), the gender

effect caused by the exclusion was likely negligible,

causing no serious bias in the results. Further studies

examining the associations between insomnia symptoms

and psychotropic medication are warranted using samples

including more men.

Adjusting for prior psychotropic medication and mental

disorders had the strongest effects on the studied associa-

tions. Mental disorders requiring psychotropic medication

are often persistent and chronic in nature [13], and the

effect of prior medication and mental disorders could be

expected. This has been noted also in previous studies [10].

Many of our study participants with medication during the

follow-up had it before baseline as well (data not shown).

Nevertheless, as the studied associations remained after

adjusting for prior medication, this supports the indepen-

dence of the association of insomnia symptoms with sub-

sequent psychotropic medication. We performed also

sensitivity analyses by excluding all the participants who

had any psychotropic medication before baseline. The main

results of the study remained also after this exclusion. By

adjusting for lifetime mental disorders rather than survey-

assessed baseline mental health we aimed at a broader view

of the mental health trajectories of participants. Because

this lifetime information concerned specifically mental

diagnoses by a physician, it could be assumed to include

somewhat more serious mental disorders and to be also

more concordant with our outcome, psychotropic medica-

tion prescribed by a physician.

The sensitivity analyses showed that, in addition to

having a high risk of psychotropic medication per se, those

with frequent insomnia symptoms were also likely to have

larger number of medication purchases during the 5-year

0

1

2

3

4

5

6

1 2-3 4+ 1 2-3 4+ 1 2-3 4+

No Rare Occasional Frequent

Number of psychotropic medication purchases

OR

Insomnia symptoms at baseline

Fig. 1 Associations of

insomnia symptoms with


medication among 40- to

60-year-old employees during a

5-year follow-up, OR from

multinomial regression analysis

and their 95 % CI (N = 6,227).

Adjusted for gender, age, and

psychotropic medication before

baseline


123

follow-up, compared with the participants with no insom-

nia symptoms or only more rarely experienced ones. This

further underlines the notably increased mental health risks

among those with frequent insomnia symptoms.

The possible pathways from insomnia symptoms to

mental disorders include neurobiological mechanisms, e.g.

dysregulation of the hypothalamic–pituitary–adrenal (HPA)

axis [11]. Chronic sleep loss, often associated with insomnia

symptoms, may also lead to diminishing pleasure in life,

which is one of the characteristics of depression, the most

prevalent of mental disorders [29]. Insomnia symptoms may

be associated with mental disorders also via impaired

emotion regulation [27]. Comorbidities between different

mental disorders are common, one disorder increasing the

risk of another. For example, people with insomnia symp-

toms become often anxious about not sleeping and anxiety is

in its turn associated with increased risk of depression [28].

There is accumulating evidence on the potential adverse

side effects of psychotropic medication [30, 31], coupled

with a growing concern for more careful controlling of

medication practices. Previous studies have shown that

early detection and treatment of insomnia symptoms may

contribute to prevention of subsequent mental health

problems, especially depression [32, 33]. Thus, when

pursuing better prevention of mental problems it is essen-

tial to pay more attention to issues associated with them,

including preceding insomnia.

Limitations and strengths of the study

There are limitations and strengths of this study that

deserve to be acknowledged. First, generalization of the

results to the wider Finnish working-aged population is not

warranted as our study participants were all employed at

baseline and thus presumably healthier than the general

population. A healthy worker effect is likely as the severely

ill and disabled tend to be excluded from employment [34].

Furthermore, the participants were middle-aged and came

from the greater Helsinki area. However, the city of Hel-

sinki is the largest single employer in Finland with

approximately 40,000 employees, encompassing a wide

range of non-manual and manual occupations. Non-

response analyses conducted with our data confirm that the

data satisfactorily represent the target population [16, 35].

Non-response was slightly more common among men,

younger employees, those in lower socioeconomic posi-

tions, and those with medically confirmed sickness absen-

ces. Consenting to register linkage followed largely similar

patterns.

Second, a recent study found that respondents had fewer

psychotropic prescriptions than non-respondents [36].

Medication was not examined in our non-response analy-

ses, but the associations between other study variables and

participation did not differ by health status, suggesting that

the results are unlikely to be biased to any larger extent

[35].

Third, the assessment of insomnia symptoms was based

on self-reports measured at baseline. Self-report measures

are regarded as suitable for the study of insomnia symp-

toms, especially in epidemiological settings [37]. A limi-

tation is that the Jenkins Sleep Questionnaire does not

include daytime effects of insomnia. The prerequisite for

primary insomnia diagnosis stated in the DSM-IV-TR is

that ‘‘the sleep disturbance or daytime fatigue causes

clinically significant distress or impairment in social,

occupational, or other important areas of functioning’’ [38].

The used questionnaire, although validated [18], is not

specific to insomnia and these symptoms could be related

to other sleep disturbances, as well. The studied associa-

tions might be stronger for those with a diagnosed

insomnia, as compared to these self-reported and less

specific symptoms. Also, data on other common sleep

disturbances, such as obstructive sleep apnea or restless

legs syndrome, were unavailable. It is also worth noting

that especially in our insomnia symptom class of occa-

sional symptoms the range of the frequency of symptoms is

wide, 4–14 times per month, making this class possibly

quite heterogenic. Still, more than half of the participants

in this class reported at least two different insomnia

symptoms; in other words, these symptoms might be for

them occasional, but not coincidental.

Fourth, we used as our outcome only psychotropic

medication prescribed by a physician and only if purchased

and later on reimbursed by the Finnish Social Insurance

Institution. Strictly speaking, the use of psychotropic

medication was not directly measured. Previous studies

show considerable nonadherence to psychotropic medica-

tion [39], but the adherence may be assumed to be higher

among those who have purchased the medication. As the

medication data came from national health register, they

are likely to be extensive, objective, and accurate since the

information is originally collected for administrative pur-

poses and used as the basis for monetary reimbursements.

Additional advantages of examining mental health with

objective, register-based measures are the reliable assess-

ment of mental health made by the prescribing physician,

and the fact that no recall-bias or social desirability affects

the outcomes, as is the risk with self-reports. Over-the-

counter medications or non-reimbursed prescribed medi-

cation purchases were not included, the prevalence of

especially the latter being marginal in Finland. We do not

aim to make any specific diagnostic deductions based on

the medications. There are numerous intended indications

for each of the studied medications, and mismatch between

medication and symptom profile is common in the case of

mental disorders [9], as is also not seeking for treatment at


123

all [40]. Other possible causes for selection in the medi-

cation data include differences in treatment recommenda-

tions and practice styles, as well as unevenly distributed

economic barriers in purchasing medication. Nevertheless,

it is unlikely that the aforementioned factors were sub-

stantially associated with the frequency of insomnia

symptoms and as such causing serious bias in the exami-

nation. Thus, although there is possible selection in the

outcome measure used in this study, we still consider the

physician-written prescriptions to be a relatively valid—

although indirect—proxy for mental health. Our outcome

measure was defined as at least one purchase of psycho-

tropic medication during follow-up. Compared with more

continuous medication one reimbursed prescription is not a

very strong indicator of mental health problems, especially

as we lack diagnostic information. Nevertheless, even one

purchase of psychotropic medication is quite likely to

reflect some kind of mental health problem, and most of

those with such medication had several purchases.

Fifth, we focused on the associations of insomnia

symptoms preceding psychotropic medication. While

examining these associations we controlled for prior

medication. Irrespective of whether those with medication

during the follow-up had also pre-baseline medication or

not, reporting insomnia symptoms at baseline was associ-

ated with subsequent medication. The results were similar

in the sensitivity analyses in which we included only those

with no psychotropic medication before baseline. It is

possible that some of our participants have had psycho-

tropic medication even earlier on during their lifetime. As a

precaution we controlled also for the lifetime physician-

diagnosed mental disorders but the associations still

remained strong. However, the insomnia symptoms may

equally have started early on, since they tend to be per-

sistent and chronic in nature [41].

Finally, a wide array of covariates was included in our

study. Nevertheless, the possibility of residual confounding

cannot be ruled out as there may be unmeasured covariates

that were unavailable to us.

Conclusion

Our study interests were in understanding the associations of

insomnia symptoms on the one hand with particularly psy-

chotropic medication and on the other hand with mental

health in a broader sense, which the medication stands proxy

for. We found insomnia symptoms to be strongly associated

with subsequent psychotropic medication. These dose–

response associations remained among women and men, as

well as throughout various psychotropic medication sub-

groups and extensive adjustments for covariates. Attention

should be given to the identification and prevention of

insomnia to be able to curb the related mental problems.

Acknowledgments This work was supported by the following

grants: Peija Haaramo is supported by the Emil Aaltonen Foundation,

the Juho Vainio Foundation, and the Doctoral Programs in Public

Health; Tea Lallukka is supported by the Academy of Finland (grant

1133434); and the Helsinki Health Study is supported by the Acad-

emy of Finland (grants 1129225 and 1257362).

Conflict of interest The authors declare that they have no conflict

of interest.

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