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Hamre2010 Article HealthCostsInPatientsTreatedFo
Hamre2010 Article HealthCostsInPatientsTreatedFo
Hamre2010 Article HealthCostsInPatientsTreatedFo
DOI 10.1007/s10198-009-0203-0
ORIGINAL PAPER
Received: 23 July 2009 / Accepted: 20 October 2009 / Published online: 13 November 2009
The Author(s) 2009. This article is published with open access at Springerlink.com
123
78 H. J. Hamre et al.
long-term improvement of symptoms and health status modelling, music or speech exercises; or AM
[18]. eurythmy movement exercise therapy; or AM
Anthroposophic treatment for depression differs from rhythmical massage therapy);
ordinary treatment in its use of non-verbal artistic and – or starting AM therapy provided by study physician
physical therapies and special AM medications [18]. (AM-related consultations, AM medication) after
Similar to recent guideline recommendations [19], con- an initial AM-related consultation C30 min.
ventional antidepressant drugs are not used as initial ther-
Further inclusion criteria applied to the three groups
apy for mild depression. In cases of severe depression,
studied:
however, AM therapies are often combined with antide-
pressants [20]. Similar to conventional care, AM physi-
Patients treated for depression (Group 1)
cians may offer counselling and refer patients for
psychotherapy or, if necessary, for inpatient treatment [18].
• Center for Epidemiological Studies Depression Scale,
One research question of the AMOS study concerned
German version (CES-D) C24 points, which is the cut-
the cost-of-illness of depression and other chronic diseases
off point for clinically relevant depressive symptoms
[21]. Here we present a secondary cost analysis from
[22, 23];
AMOS, contrasting patients treated for depression, patients
• physician’s diagnosis of main disorder as depression or
with depressive symptoms treated for another disorder, and
depressive symptoms;
patients without depressive symptoms.
• depressed mood plus at least two of the following
depressive core symptoms [symptoms of dysthymic
disorder, according to Diagnostic and Statistical Manual
Methods
of Mental Disorders, 4th Edition (DSM-IV)]: poor
appetite or overeating, insomnia or hypersomnia, low
Objective and design
energy or fatigue, low self-esteem, poor concentration or
difficulty making decisions, feelings of hopelessness [24].
The objective was to study long-term depression costs in a
German AM outpatient setting from the societal perspec-
tive. For this purpose, we analysed healthcare use and Patients with depressive symptoms, treated for another
productivity loss in a prospective cohort of patients starting disorder (Group 2)
AM therapies (AMOS), and calculated direct and indirect
costs. The cost analysis had two main objectives: • CES-D C 24 points;
• physician’s diagnosis of main disorder is NOT depres-
1. Comparison of patients treated for depression, patients
sion or depressive symptoms.
with depressive symptoms treated for another disorder,
and patients without depressive symptoms.
2. Comparison of the pre-study year to the 1st and Patients without depressive symptoms (Group 3)
2nd years after enrolment.
• CES-D \ 24 points.
Setting, participants, and therapy The patients were treated according to the physician’s
discretion.
Participating physicians were certified by the Physicians’
Association for Anthroposophical Medicine in Germany Outcome measures
and had office-based practices or worked in outpatient
clinics in Germany. The physicians recruited consecutive The primary outcome was overall health costs, regardless of
patients starting AM therapy. Patients enrolled in the per- diagnosis, in the pre-study year and in the 1st and 2nd study
iod 1 January 1999–31 March 2001 were included in the years. Costs included direct health costs (AM therapies, non-
present analysis if they fulfilled the eligibility criteria. AM complementary therapies, physician and dentist visits,
Inclusion criteria for all patients in this analysis were: psychotherapy, medication, physiotherapy, occupational
therapy, inpatient hospital and rehabilitation treatment) and
• age 17–70 years;
indirect costs (sick-leave compensation, early retirement,
• starting AM therapy for a disorder of minimum
mortality) and were assessed from a societal perspective.
6 months’ duration (main disorder):
Depressive symptoms were assessed by the CES-D,
– referral to non-medical therapists (providing AM ranging from 0 (‘‘no depressive symptoms’’) to 60
art therapy involving painting, drawing, clay (‘‘maximum symptoms’’). Patients document the frequency
123
A two-year prospective cohort study 79
of 20 symptoms during the last week, from 0 (‘‘rarely or Helsinki and International Conference on Harmonisation
none of the time & less than 1 day’’) to 3 (‘‘most or all of Good Clinical Practice guidelines. Written informed con-
the time & 5–7 days’’) [22, 23]. sent was obtained from all patients before enrolment.
Baseline health status was assessed with the SF-36
Physical Component summary score, the SF-36 Health Data analysis
Change item [25], disease duration, and disease severity.
Disease severity was assessed by the physicians on a Data analysis [PASW Statistics 17.0 (http://www.spss.
numerical rating scale [26] from 0 (‘‘not present’’) to 10 com/statistics/), StatExact 5.0.3 (http://www.cytel.com/
(‘‘worst possible’’). products/statxact/), S-PLUS 8.0 (http://www.insightful.com/
Medical comorbidity was assessed with the Chronic products/splus/)] was performed on all patients fulfilling the
Disease Score [27]. The Chronic Disease Score is based on eligibility criteria.
medications used to treat chronic diseases, is a good pre-
dictor of future hospitalisations and health costs [28], and Resource use and unit costs (Table 1)
has been used in a number of cost analyses of depression
[6, 29–31]. We used the original version [27] with 17 Costs were analysed from a societal perspective. For all
medication classes (updated for newer medications [32, resource items except non-AM complementary therapies,
33]), which does not include psychotropic medications and costs were calculated by multiplying resource use by the
is not associated with depression or anxiety [27]. The unit cost for the respective item. Out-of-pocket expendi-
Chronic Disease Score has a theoretical range of 0–35 tures for non-AM complementary therapies were docu-
points, the upper range requiring intake of 20 different mented directly.
medications. AMOS study documentation was truncated at Unit costs (Table 1) were calculated from average costs
eight medications per patient and observation period, in Germany for the year 2000 (physicians’ and dentists’
resulting in a range of 0–17 points. fees, medication, hospital, rehabilitation, sick-leave costs
Resource utilisation included AM therapies, medication, [34, 35]) or from reimbursement fees regulated in health-
physician and dentist visits, diagnostic investigations, care benefit catalogues (AM therapies, diagnostic investi-
psychotherapy, physiotherapy, occupational therapy, and gations, psychotherapy, physiotherapy, occupational
inpatient hospital and rehabilitation treatment. therapy [36–38]).
Productivity loss included sick-leave, early retirement, Hospital costs were calculated from average costs in
and deaths regardless of the cause of death. each German federal state [39]. Physicians’ fees were
calculated from average fees of general practitio-
Data collection ners plus 12 specialist categories in the Accounting Data
Record Panel of the Central Research Institute of Ambu-
All data were documented with questionnaires returned in latory Health Care in Germany [40]. Costs for diagnostic
sealed envelopes to the study office. Physicians documented investigations (X-rays, computer tomography scans,
name, duration and severity of main disorder, comorbid nuclear magnetic resonance imaging and scintigrams) were
disorders, and (Group 1 only) depressive core symptoms; all calculated separately [36]. Costs of AM medication (any
other items were documented by patients. Patient responses medication produced by the pharmaceutical companies
were not made available to physicians. Resource use and Abnoba Arzneimittel, Pforzheim, Germany; Helixor Heil-
productivity loss in the pre-study year were documented at mittel, Rosenfeld Germany; Wala Heilmittel, Bad Boll/
study enrolment; in the 1st and 2nd study years these items Eckwälden, Germany; and Weleda, Arlesheim, Switzer-
were documented after 3 months (medication only), and land) were calculated from average costs in 51 different
after 6, 12, 18, and 24 months. Physicians were compen- price groups. Costs of other medications were calculated
sated €40 per included and fully documented patient, while from national average costs in 86 Anatomical Therapeutic
patients received no compensation. Chemical Classification Index subgroups [41].
Data were entered twice by two different individuals into Costs of productivity loss included costs for sick-leave,
Microsoft Access 97. The two datasets were compared and early retirement, and deaths. Costs for sick-leave and early
discrepancies resolved by checking with the original data. retirement were calculated from national average gender-
specific earnings for civil servants, salaried employees, and
Quality assurance, adherence to regulations wage earners (100% compensation for days 1–42, 70%
compensation thereafter) [35]. Mortality costs (4.3% of all
The study was approved by the Ethics Committee of the costs of productivity loss) were calculated with the same
Faculty of Medicine Charité, Humboldt University Berlin, method.
and was conducted according to the Declaration of Unless otherwise stated, costs were not discounted.
123
80 H. J. Hamre et al.
Anthroposophic therapies Therapy session Eurythmy, art, rhythmical 19.9–32.2 Health insurance
massage company data
Anthroposophic medication Daily dose Price groups (51) 0.1–5.2 Manufacturer’s
price lists
Non-anthroposophic Euro (out-of-pocket Not applicable
complementary therapies expenditures)
Physician visit Visit Specialist categories (12) 12.3–28.6 [40]
Dentist visit Visit (excluding dental prosthesis) 62.4 [34]
Psychotherapy Therapy session 56.1 [36]
Diagnostic investigation Investigation X-rays, computer tomography 17.4–200.3 [36]
scans, nuclear magnetic
resonance imaging,
scintigrams
Non-anthroposophic Daily dose Anatomical Therapeutic 0.1–37.1 [41]
medication Chemical Classification
Index groups (86)
Physiotherapy Therapy session Remedial gymnastics, exercise 5.7–13.7 [37]
therapy, massage, fango
packs, aerothermotherapy,
other
Occupational therapy Therapy session 24.9 [38]
Inpatient hospitalisation Day German Federal states (16) 271.0–411.0 [39]
Inpatient rehabilitation Day 58.0 Health insurance
company data
Sick-leave, early Day Days 1–42 vs days [ 42/self- 41.5–113.1 [35]
retirement, mortality employed, civil servants,
salaried employees, wage
earners, unemployed/males
vs females
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A two-year prospective cohort study 81
unadjusted analyses were considered explorative, with comparisons between Groups 1, 2 and 3 were corrected
significance criteria P \ 0.05 and 95% CI not including 0. with the sequential Bonferroni method. For all 11
variables in the models the variance inflation factors
were \1.2, suggesting that multicollinearity was not a
Adjusted analyses
problem. The model for the 1st year showed a good fit
with a ratio deviance/df of 1.024, while the models for
Total costs in the three groups and 3 years were adjusted
the pre-study year and 2nd year showed signs of some
for socio-demographic characteristics, comorbidity, and
overdispersion with ratios deviance/df of 1.387 and
baseline health status. Since the three groups were defined
1.685, respectively. Scatter plots of standardised devi-
by their depression status, we did not adjust for depressive
ance residuals, Pearson residuals, and Likelihood
symptoms (baseline CES-D) and included only those
residuals vs predicted mean revealed 2–4 outliers for
independent variables that showed low or minimal corre-
each model. According to Cook’s distance and leverage
lation to baseline CES-D, defined as Spearman-Rho \ 0.3.
values, 0–2 of these outliers were potentially influential
The following 11 variables were included in the main
for each model, respectively. Data inspection showed
analysis: patient group (1, 2 or 3), age, gender, education,
no evidence of documentation errors of the cost values
engagement in economic activity, living in the former
for the identified outliers. Moreover, the exclusion of
German Democratic Republic, disease duration, Chronic
outliers from the models led to only minimal changes
Disease Score, baseline disease severity, baseline SF-36
(with the exception of one change in the 1st year; see
Physical Component, and baseline SF-36 Health Change.
Results section). Hence all outliers were retained in the
In an alternative analysis, stricter criteria for inclusion of
main analysis.
independent variables were used, with a correlation to
• A supplementary fourth model was built using general-
baseline CES-D \0.2 instead of \0.3. This lead to exclu-
ised estimating equations with average total costs across
sion of 1 of the 11 variables (SF-36 Health change) from
the 3 years as dependent variable, study year as within-
the models, although the overall results were very similar.
subject variable, and model specifications analogous to
In another alternative analysis, the impact of a 12th
the three generalised linear models described above.
variable, household income, was explored. This variable
was available for only 84% of patients, was not a signifi-
cant predictor in any models, and was not included in the Sensitivity analyses
main analysis.
The following adjustment models were used: Two sensitivity analyses were performed, for the following
reasons:
• In a preliminary analysis, general linear models with
repeated measures were used, with the natural loga- 1. A previous sensitivity analysis of cost units in the
rithm of total costs as dependent variable and study AMOS study [17] had identified one item for which
year as within-subject variable. Results were similar to uncertainty in the assumptions could have a relevant
results of the other adjusted analyses but are of lesser impact on costs: inpatient hospital treatment. Hospital
utility due to the use of the logarithm of costs [45]. costs will vary according to hospital specialisation,
Results are therefore not shown. which was not documented in the study; therefore
• For the main analysis, generalised linear modelling was average costs across hospital specialties were used.
used to build three models with total costs in the pre- Costs in German psychiatric and neurological hospitals
study year, 1st, and 2nd years, respectively, as depen- are lower (average €203 per day) than in general
dent variable [46–48]. Since costs were highly skewed, hospitals (€309). Accordingly, hospital costs in
a gamma distribution with a log link was used. The depressed patients (Groups 1 and 2) were analysed
influence of the 11 independent variables on the costs under the extreme assumption that 100% of hospital
was analysed in a main effects model, using a robust days were spent in psychiatric or neurological hospi-
covariance matrix, estimation of scale parameters by tals (instead of 7%—the German average) [35, 49].
the maximum likelihood method, testing for model 2. The inclusion criteria for Group 1 required fulfilment
effects and between-group differences with Wald chi- of all depression criteria, which can be considered a
square statistics, and estimation of marginal means with narrow definition, as AM physicians may treat patients
Wald type 95% CI. (An alternative model included the for depressive symptoms regardless of diagnostic
interaction of age and gender, which was a significant criteria. Accordingly, total costs were analysed using
predictor in the pre-study year only. Results were less restrictive criteria for Group 1, including all
otherwise changed only minimally, and this interaction patients aged 17–70 years starting therapy for depres-
was not used in the main analysis). Multiple sive symptoms.
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82 H. J. Hamre et al.
Excluded: n = 296
Not eligible: n = 90
Duration of main disorder < 6 months: n = 86
Another eligibility criterion not fulfilled: n = 4
Included: n = 487
Fig. 1 Patient recruitment. CES-D Center for Epidemiological Studies Depression Scale, German version
123
A two-year prospective cohort study 83
123
84 H. J. Hamre et al.
123
Table 3 Health resource use and productivity loss. Values are mean ± standard deviation
A two-year prospective cohort study
Anthroposophic therapy sessions 2.7 ± 8.1 0.6 ± 2.1 1.3 ± 4.7 0.338 18.5 ± 17.9 12.2 ± 11.4 12.3 ± 10.9 0.002 5.6 ± 9.8 4.7 ± 8.5 6.2 ± 11.2 0.818
Anthroposophic medication, daily 0.4 ± 0.7 0.3 ± 0.8 0.4 ± 0.8 0.137 0.8 ± 0.9 0.7 ± 0.9 0.8 ± 0.9 0.548 0.4 ± 0.7 0.4 ± 0.7 0.5 ± 0.9 0.106
doses
Other medication, daily doses 1.0 ± 1.2 1.0 ± 1.0 0.7 ± 1.0 0.001 1.0 ± 1.3 1.0 ± 1.1 0.9 ± 1.1 0.394 0.9 ± 1.4 0.9 ± 1.2 0.9 ± 1.4 0.451
Physician and dentist visits 24.9 ± 21.4 24.5 ± 28.7 17.2 ± 16.2 \0.001 24.7 ± 18.0 23.3 ± 20.6 18.5 ± 15.6 0.001 22.7 ± 20.6 21.5 ± 21.2 19.3 ± 53.0 0.003
Diagnostic investigations 1.2 ± 1.6 1.7 ± 2.4 1.1 ± 1.6 0.254 0.9 ± 1.4 1.3 ± 2.6 1.1 ± 2.2 0.769 0.8 ± 1.2 1.3 ± 2.1 0.9 ± 1.7 0.052
Psychotherapy sessions 7.0 ± 11.7 8.9 ± 23.2 2.1 ± 9.0 \0.001 11.5 ± 23.8 5.8 ± 12.8 2.7 ± 8.6 \0.001 11.0 ± 26.0 5.5 ± 13.3 3.5 ± 12.6 \0.001
Physiotherapy and occupational 7.7 ± 12.8 13.6 ± 34.2 9.4 ± 17.8 0.626 6.9 ± 14.8 16.4 ± 45.9 8.9 ± 16.9 0.074 6.1 ± 11.8 18.2 ± 47.0 9.0 ± 19.6 0.035
therapy sessions
Hospital days 10.4 ± 30.7 3.3 ± 12.2 4.0 ± 13.3 0.233 7.9 ± 38.5 2.0 ± 5.6 2.3 ± 10.1 0.212 3.4 ± 15.6 2.6 ± 11.8 2.7 ± 12.1 0.864
Rehabilitation days 4.5 ± 12.0 2.9 ± 9.5 1.9 ± 8.6 0.075 1.2 ± 5.4 1.4 ± 6.5 1.9 ± 7.7 0.806 0.0 ± 0.0 1.2 ± 6.0 1.4 ± 7.0 0.139
Sick-leave daysa (all days) 44.2 ± 85.8 37.0 ± 68.7 22.3 ± 54.3 0.442 30.6 ± 58.3 37.7 ± 78.0 20.0 ± 55.0 0.746 31.2 ± 67.0 27.3 ± 74.1 27.9 ± 70.6 0.286
Sick-leave daysa (day 1–42) 14.9 ± 18.3 15.1 ± 16.8 12.6 ± 15.1 0.535 13.5 ± 18.0 13.8 ± 16.8 10.3 ± 14.1 0.800 14.1 ± 16.0 10.4 ± 15.3 12.1 ± 15.3 0.306
Sick-leave daysa (day 43?) 29.2 ± 73.5 21.9 ± 59.7 9.8 ± 46.4 0.043 17.2 ± 45.6 23.8 ± 66.6 9.6 ± 47.0 0.044 17.1 ± 57.1 16.9 ± 64.5 15.8 ± 61.7 0.925
Early retirement (n, cumulative) 0 1 3 3 2 7 3 2 11
Deaths (n, cumulative) 0 0 0 0 1 0 0 3 3
a
Economically active patients
85
123
86
123
Table 4 Unadjusted health costs (€). Values are mean ± standard deviation
Item Pre-study year 0–12 Months 12–24 Months
Group 1 Group 2 Group 3 Group 1 Group 2 Group 3 Group 1 Group 2 Group 3
Anthroposophic therapies 84 ± 254 20 ± 68 41 ± 150 569 ± 568 382 ± 356 390 ± 349 170 ± 297 144 ± 251 195 ± 348
Anthroposophic medication 82 ± 221 49 ± 121 49 ± 112 101 ± 209 119 ± 259 92 ± 205 72 ± 191 57 ± 122 63 ± 140
Total costs anthroposophic treatment 166 ± 339 69 ± 134 90 ± 197 670 ± 641 501 ± 450 481 ± 428 243 ± 343 201 ± 303 258 ± 396
Complementary non-anthroposophic 119 ± 274 249 ± 413 123 ± 346 177 ± 301 386 ± 705 190 ± 389 142 ± 248 272 ± 509 158 ± 438
treatment
Physician services 279 ± 268 319 ± 288 255 ± 248 265 ± 211 296 ± 278 256 ± 245 246 ± 270 280 ± 274 275 ± 1,023
Psychotherapy 391 ± 659 499 ± 1,303 119 ± 503 645 ± 1,338 325 ± 721 152 ± 482 619 ± 1,461 311 ± 747 195 ± 709
Dental treatment 199 ± 269 187 ± 306 147 ± 201 208 ± 374 191 ± 250 145 ± 161 193 ± 249 169 ± 224 132 ± 163
Physiotherapy, ergotherapy 80 ± 129 143 ± 322 96 ± 189 73 ± 150 174 ± 432 93 ± 179 64 ± 117 192 ± 471 96 ± 213
Non-anthroposophic medication 319 ± 412 332 ± 501 247 ± 1,028 300 ± 402 333 ± 549 278 ± 502 272 ± 446 275 ± 446 306 ± 846
Total outpatient healthcare costs 1,553 ± 1,153 1,799 ± 1,917 1,079 ± 1,366 2,338 ± 1,924 2,206 ± 1,848 1,595 ± 1,110 1,778 ± 1,731 1,700 ± 1,595 1,421 ± 1,772
Inpatient hospital treatment 3,006 ± 8,948 1,015 ± 3,633 1,232 ± 4,117 2,402 ± 12,058 642 ± 1,756 743 ± 3,523 1,015 ± 4,616 803 ± 3,632 886 ± 4,148
Inpatient rehabilitation 262 ± 697 168 ± 551 113 ± 496 70 ± 313 81 ± 379 108 ± 447 0±0 72 ± 348 83 ± 404
Total inpatient healthcare costs 3,268 ± 9,056 1,184 ± 3,861 1,344 ± 4,173 2,472 ± 12,051 723 ± 1,773 851 ± 3,562 1,015 ± 4,616 875 ± 3,657 969 ± 4,177
Total direct costs 4,821 ± 9,275 2,983 ± 4,893 2,423 ± 4,675 4,810 ± 12,993 2,930 ± 2,617 2,446 ± 3,892 2,793 ± 4,926 2,575 ± 4,084 2,390 ± 4,990
Sick-leave compensation (Day 1–42) 888 ± 1,328 934 ± 1,537 617 ± 1,090 1,028 ± 1,994 846 ± 1,629 584 ± 1,170 998 ± 1,907 690 ± 1,492 698 ± 1,429
Sick-leave compensation (Day 43?) 1,038 ± 3,665 654 ± 2,355 287 ± 1,954 477 ± 1,969 526 ± 2,132 214 ± 1,404 442 ± 2,196 371 ± 2,023 326 ± 1,855
Early retirement 0±0 197 ± 1,996 268 ± 2,724 516 ± 2,669 270 ± 2,128 432 ± 3,194 689 ± 3,565 344 ± 2,486 727 ± 4,124
Mortality 0±0 152 ± 1,547 0±0 0±0 369 ± 2,918 152 ± 2,273
Total indirect costs 1,926 ± 4,570 1,784 ± 3,860 1,172 ± 3,685 2,020 ± 4,299 1,795 ± 4,221 1,229 ± 3,826 2,129 ± 4,959 1,775 ± 4,824 1,904 ± 5,356
Total costs (mean ± SD) 6,747 ± 11,531 4,768 ± 6,581 3,595 ± 6,828 6,830 ± 14,427 4,725 ± 5,551 3,676 ± 5,607 4,922 ± 7,884 4,349 ± 6,672 4,294 ± 7,910
Total costs (bootstrap mean, 6,739 4,763 3,588 6,825 4,715 3,683 4,926 4,328 4,300
95% Confidence interval) 5,898–9,971 4,395–6,388 3,344–4,419 6,026–11,872 4,391–5,914 3,485–4,391 4,439–7,413 3,968–5,819 3,993–5,345
H. J. Hamre et al.
A two-year prospective cohort study 87
Table 6 Adjusted analyses: estimated marginal means for total costs (€). P-values are based on Wald chi-square statistics and indicate if
between-group differences are significant
Year (analysis) 0 (GZLM) 1 (GZLM) 2 (GZLM) 0–1–2 (GEE)
a a a
Group Mean 95% CI Mean 95% CI Mean 95% CI Mean 95% CIa
Group 1 7,129 4,770 to 9,489 6,029 3,689 to 8,369 4,929 3,156 to 6,702 6,069 4,301 to 7,837
Group 2 4,371 3,180 to 5,563 3,522 2,748 to 4,296 3,792 2,621 to 4,963 3,880 3,145 to 4,614
Group 3 3,532 2,812 to 4,251 3,353 2,782 to 3,924 4,031 3,136 to 4,927 3,691 3,081 to 4,301
Group 1 vs 2 vs 3 P = 0.008 P = 0.083 P = 0.460 P = 0.026
Groups 2 ? 3 3,734 3,052 to 4,417 3,391 2,873 to 3,908 3,986 3,165 to 4,808 3,748 3,222 to 4,275
Group 1 minus Group 2 2,758 67 to 5,449 2,507 -220 to 5,234 1,137 -1,082 to 3,356 2,190 199 to 4,181
P = 0.043b P = 0.079b P = 0.659b P = 0.027b
Group 1 minus Group 3 3,597 775 to 6,490 2,676 -200 to 5,552 897 -1,132 to 2,927 2,378 266 to 4,490
P = 0.007b P = 0.078b P = 0.659b P = 0.021b
Group 1 minus Groups 2 ? 3 3,350 1,112 to 5,588 2,619 298 to 4,939 964 -650 to 2,578 2,338 648 to 4,027
P = 0.003 P = 0.027 P = 0.242 P = 0.007
a
Wald type 95% confidence interval
b
Corrected for multiple comparisons with the sequential Bonferroni method
variable (patient group) was significant in all models 2 (€4,371) and 102% higher than in group 3 (€3,532).
except the 2nd year. Four variables (SF-36 Health Change, Cost differences in the pre-study year were significant
Chronic Disease Score, gender, engagement in economic between Groups 1 and 2 (mean difference €2,758, 95%
activity) were significant in the pre-study year only. The CI €67 to €5,449, P = 0.043) and Groups 1 and 3 (mean
remaining four variables (living in the former German difference €3,597, 95% CI €775 to €6,490, P = 0.007),
Democratic Republic, disease duration, age, education) but not between Groups 2 and 3 (P = 0.180).
were not significant predictors in any model. Removing • In the 1st study year, costs in Group 1 (€6,029) were
these four variables from all models—or removing all non- 71% higher than in Group 2 (€3,522) and 80% higher
significant variables in each model—affected results only than in Group 3 (€3,353). No between-group differences
minimally, thus all 11 variables were retained in all four were significant in the 1st year, although group assign-
models. Estimated marginal means for total costs are pre- ment was a significant predictor (P = 0.019). However,
sented in Table 6 and Fig. 2: when two potentially influential outliers were removed
from the model of the 1st year, cost differences between
• In the pre-study year, costs in Group 1 (estimated
Groups 1 and 3 became significant (P = 0.032).
marginal mean €7,129) were 63% higher than in Group
123
88 H. J. Hamre et al.
Adjusted total health costs main analysis, total costs in Group 1 were reduced by 13%
10000 (€901), 12% (€798), and 7% (€321) in the pre-study year,
1st, and 2nd study years, respectively; while costs in Group
8000 2 were reduced by 11% (€533), 5% (€228), and 6% (€274),
respectively (P = 0.002 or lower for all comparisons).
6000
In the second analysis, the eligibility criteria for Group 1
Euro
Sensitivity analyses Fig. 3 Healthcare costs in the 1st year in Group 1 and in a subgroup
of the Salize Study [50]. Group 1: Patients treated for depression
In the first sensitivity analysis, unadjusted hospital costs in (n = 81). Costs of 1st study year (2000) were discounted by ?5%.
Salize subgroup: Primary care patients (n = 89), costs in year 2001.
Groups 1 and 2 were calculated on the basis of average Outpatient treatment: physician visits, diagnostic examinations,
costs of neurological and psychiatric hospitals in Germany, psychotherapy, physiotherapy, occupational therapy; in Group 1 also
instead of average costs for all hospitals. Compared to the anthroposophic therapies and medications
123
A two-year prospective cohort study 89
123
90 H. J. Hamre et al.
criteria for DSM-IV dysthymic disorder. In our analysis, Cost comparisons between the three groups were
the distinction between Groups 1 and 2 was associated adjusted for ten potentially relevant variables pertaining to
with large cost differences in the pre-study year and 1st socio-demographics, comorbidity, and baseline health sta-
year (63 and 71% higher in Group 1 in the pre-study year tus. Four of these variables were not significant predictors
and 1st year, respectively). Groups 2 and 3 differed by the in any models, and of the remaining six variables, only
cut-off point for ‘‘relevant depressive symptoms’’ on three measures of baseline health status (disease severity,
the CES-D, German version [23]. The cut-off point for the SF 36 Physical Component, SF-36 Health Change) differed
original English CES-D version has been used to define significantly between the groups. Our models are of course,
depression in several cost analyses [30, 58]. The cut-off like all statistical adjustment models, imperfect represen-
value for the German version (24 points) is one standard tations of reality [46]; they do not prove causality, and
deviation above the average score in the German popu- residual confounding cannot be ruled out. Furthermore, the
lation and is a highly sensitive marker for depressive confidence intervals for unadjusted (Table 4) as well as
symptoms, insofar as 94% of patients with a DSM-III-R adjusted (Table 6) cost estimates were relatively wide,
diagnosis of an acute depressive episode but only 17% of particularly in Group 1. This may be due to the skewed cost
the general population will have elevated CES-D scores. distribution in all three groups, and a relatively modest
On the other hand, the specificity of high CES-D scores sample size for the analysis of skewed data in Group 1 [60].
for a depression diagnosis is low [23]. In our analysis, the Among the three main models in the present analysis, the
distinction between Groups 2 and 3 was associated with best model fit was observed for the 1st study year, while the
modest and non-significant costs differences (24 and 5% models for the pre-study year and the 2nd year showed
higher in Group 2 in the pre-study year and 1st year, signs of some overdispersion. This finding could have
respectively). Groups 1 and 3 differed regarding the several possible explanations: as noted above, the longer
physician’s decision to start treatment for depressive documentation period for resource use in the pre-study year
symptoms (100 vs 12% of patients) and our criteria for could lead to more recall bias and more errors in resource
depression (100 vs 0%). These criteria included the documentation for this period. Also, since most of the
CES-D cut-off value (see above) and the core criteria for significant predictors in the cost models referred to the
DSM-IV dysthymic disorder [24]. In our analysis, this baseline status, predictors could have a more direct rela-
distinction was associated with the largest cost differences tionship to costs in the ensuing 1st year than to costs in the
(102 and 80% higher in Group 1 in the pre-study year and pre-study year and in the 2nd year.
1st year, respectively).
A limitation of the study documentation of inpatient Agreement with other studies, and interpretation
hospitalisation is that hospital specialisation was not
recorded. German psychiatric and neurological hospitals The patients treated for depression in this study (Group 1)
have average 33% lower costs than general hospitals. differed from other depression cohorts in two aspects: at
Accordingly, we performed an extreme-scenario sensitivity enrolment, 100% of patients in Group 1 started artistic or
analysis, assuming all hospital days in depressed patients complementary therapies (AM), combined with antide-
(Groups 1 and 2) were spent in psychiatric or neurological pressants and/or psychotherapy in 45% of patients [18]. In
hospitals. This resulted in only modest reductions of total other treated depression cohorts, 100% of patients usually
costs (range 5–13% for all time periods). start treatment with antidepressants and/or psychotherapy,
Like most depression cost analyses conducted outside while up to 50% of subjects with depression reportedly use
the United States [3], our study was based on patient self- complementary therapies [12, 13]. In Group 1, comple-
reporting of resource use. All resource items were docu- mentary treatment (AM and non-AM) amounted to 12% of
mented over 3 years and continuous diary-keeping was not all costs in the 1st year, while conventional outpatient
feasible. Therefore, patient documentation of use during treatment amounted to 22%, and inpatient hospital treat-
the preceding 12 months (at study enrolment) and pre- ment amounted to 35% of costs. A few other depression
ceding 6 months (at 6-, 12-, 18-, and 24-month follow-up) cost studies have included costs for complementary treat-
might be affected by recall bias. Since patient recall of ment [14–16], but none allow for direct comparison to our
resource use declines over time with a net tendency study, as these costs were either not presented separately
towards under-reporting [59], under-reporting is more [14, 16] or because the only costs for complementary
likely for the 12-month pre-study period than for the treatment included were costs for spinal manipulation [15],
shorter periods after study enrolment. Therefore, cost which is classified as conventional treatment in Germany.
reductions from the pre-study year to subsequent years The costs of complementary treatment for depression
might be larger than reported (and cost increases may be in this study (12% of total costs and 18% of treatment costs
lower than reported). in the 1st year) suggest that depression cost analyses in
123
A two-year prospective cohort study 91
settings with significant use of complementary therapies (unadjusted) respectively 31% (adjusted), compared to the
should account for the costs of complementary treatment. pre-study year, and reduced by 28 and 18%, respectively,
Another difference to other studies was observed regarding compared to the 1st year. We are aware of three other
the female-to-male ratio, which was much larger in Group depression cost analyses providing cost data for at least 2
1 with 90% primary care patients (7.1/1.0) than in other consecutive years [6, 10, 51]: in 290 primary care patients
German primary care depression cohorts (1.3–3.0/1.0) [61– starting antidepressant therapy for major depression,
65]. Possibly, more women than men with depression health-care costs were analysed according to clinical status
might be motivated to engage in artistic or complementary after 12 months, whereby 41% of patients had undergone
therapies. Otherwise, patients in Group 1 were recruited remission, 47% were improved, and 12% had persistent
from all but one German federal states and resembled other depression. Compared to the 1st year, costs in the 2nd year
primary care depression cohorts regarding symptom were reduced by 48% and 33% in improved and remitted
severity and functional impairment [18]. Nevertheless, patients, respectively, while costs in patients with persis-
study results might not be generalisable to men and to tent depression were increased by 169% [6]. This would
patients receiving conventional care only. correspond to a 26% cost reduction in the whole sample. In
Healthcare costs in the 1st study year in Group 1 were a randomised trial of systematic depression treatment for
similar to corresponding costs in another German primary 329 patients with diabetes and coexisting major depression,
care depression cohort [50]. The relative contribution of costs for outpatient treatment in the 2nd year were reduced
outpatient, hospital, and sick-leave costs in this study as by 6% in the intervention group and increased by 12% in a
well as the skewed cost distribution are also similar to usual care control group, compared to the 1st year [10]. In
findings from other studies [3, 16, 56, 66]. 492 subjects in a health maintenance organisation with
In our study, adjusted costs in patients with depression high healthcare costs in 2 consecutive years, direct costs in
(Group 1) were twice as high as costs in patients without the 3rd year were increased by 5% in depressed subjects
depression (Group 3) in the pre-study year and 80% higher and reduced by 21% in non-depressed subjects, compared
in the 1st year. This large difference is in accordance with to the 1st year [51].
findings from several other studies with follow-up periods The cost reduction in Group 1 could be attributed lar-
between 6 and 12 months [52, 54, 55, 67, 68]. gely to a reduction in hospital costs and long-term sick-
Among study patients with relevant depressive symp- leave. The reduction in resource use was paralleled by an
toms, those starting treatment for chronic depression improvement in depressive symptoms and health status
(Group 1) had higher costs than patients starting treatment [18] and might thus be related to the complementary and
for another chronic disorder (Group 2). The differences conventional therapies used. Since this study is a com-
were large in the pre-study year and 1st year (63 and 71%, parison by diagnosis in treated patients without an
respectively) and were significant in the pre-study year, but untreated control group, one has to consider other causes
were not significant in the 1st year except if outliers were for these changes, such as natural recovery, regression to
removed from the analysis. It is difficult to explain this the mean, and secular trends: for improvement in symp-
difference by differences in baseline CES-D scores, since toms, regression to the mean due to sample truncation of
baseline CES-D differed by only 10% or 3.0 points (34.4 Group 1 (CES-D C 24 points at inclusion) or due to
and 31.4 points in Groups 1 and 2, respectively), and since symptom fluctuation and preferential self-selection to
there was no significant correlation between baseline CES- therapy and study inclusion at symptom peaks is a possible
D and costs in these two groups. Notably, all patients in explanation [18, 69]. However, these phenomena relate to
Group 1 had at least three core depression symptoms at symptoms not costs, and baseline symptoms (CES-D) did
baseline, while fulfilment of this criterion was not docu- not correlate with costs. Moreover, when Group 1 was
mented for Group 2. At baseline, a physician’s diagnosis of reanalysed without truncation (second sensitivity analysis,
depression (ICD-10 F30-39) was documented in 100% and with extension of eligibility criteria to include patients with
25% of patients in Groups 1 and 2, respectively, while baseline CES-D scores \ 24 points) costs were comparable
physicians referred to new therapy for depression in 100% to costs in the main analysis. Altogether, regression to the
and 0% of patients, respectively. Possibly, in depressed mean cannot be ruled out but seems unlikely as a cause of
patients, the physician’s decision to initiate new therapy for the cost reduction in Group 1.
depression is an independent marker for high costs. We are The cost reduction in Group 1 cannot be explained by
not aware of other cost studies comparing depressed pri- secular trends towards a reduction in inpatient hospital
mary care patients starting treatment either for depression days and long-term sick-leave during the study (1999–
or for another disorder. 2003). In this period, the average number of hospital
In our study, costs of patients treated for depression days per person-year in Germany decreased by only
(Group 1) in the 2nd study year were decreased by 27% 0.21 days (from 2.07 to 1.86 days) [70]. This reduction of
123
92 H. J. Hamre et al.
0.11 days per 2 years corresponds to only 3% of the 8. Katon, W., Russo, J., von Korff, M., Lin, E., Simon, G., Bush, T.,
observed reduction of 8.26 days per 2 years (from pre- et al.: Long-term effects of a collaborative care intervention in
persistently depressed primary care patients. J. Gen. Intern. Med.
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1. In the same period, the annual number of sick-leave 9. Katon, W., Unutzer, J., Fan, M.Y., Williams Jr., J.W.,
days paid by the statutory health insurance (sick-leave Schoenbaum, M., Lin, E.H., et al.: Cost-effectiveness and net
beyond 42 days) was reduced by 0.35 days (from benefit of enhanced treatment of depression for older adults with
diabetes and depression. Diabetes Care 29(2), 265–270 (2006)
5.23 to 4.88 days) [71], i.e. by 0.18 days per 2 years, 10. Simon, G.E., Katon, W.J., Lin, E.H., Rutter, C., Manning, W.G.,
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12.13 days (from 29.24 to 17.11 days). treatment among people with diabetes mellitus. Arch. Gen. Psy-
chiatry 64(1), 65–72 (2007)
11. Unutzer, J., Katon, W.J., Fan, M.Y., Schoenbaum, M.C., Lin,
E.H., la Penna, R.D., et al.: Long-term cost effects of collabo-
Conclusions rative care for late-life depression. Am. J. Manag. Care 14(2),
95–100 (2008)
This study in a complementary outpatient setting under- 12. Kessler, R.C., Soukup, J., Davis, R.B., Foster, D.F., Wilkey, S.A.,
Van Rompay MI, M.I., et al.: The use of complementary and
lines the importance of depression for health costs and alternative therapies to treat anxiety and depression in the United
suggests that treatment of depression could be associated States. Am. J. Psychiatry 158(2), 289–294 (2001)
with long-term reduction of costs. 13. Wu, P., Fuller, C., Liu, X., Lee, H.C., Fan, B., Hoven, C.W.,
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Acknowledgments This study was funded by the Software-AG women with depression: results of a national survey. Psychiatr.
Stiftung and the Innungskrankenkasse Hamburg with supplementary Serv. 58(3), 349–356 (2007)
grants from the Deutsche BKK, the Betriebskrankenkasse des Bun- 14. Hawthorne, G., Cheok, F., Goldney, R., Fisher, L.: The excess
desverkehrsministeriums, the Dr. Hauschka Stiftung, the Mahle cost of depression in South Australia: a population-based study.
Stiftung, and the Zukunftsstiftung Gesundheit. The sponsors had no Aust. N. Z. J. Psychiatry 37(3), 362–373 (2003)
influence on study design or planning; on collection, analysis, or 15. Trivedi, D.N., Lawrence, L.W., Blake, S.G., Rappaport, H.M.,
interpretation of data; on the writing of the manuscript; or on the Feldhaus, J.B.: Study of the economic burden of depression. J.
decision to submit the manuscript for publication. We thank W. Pharm. Finance Econ. Policy 13(4), 51–66 (2004)
Tröger for valuable help and advice. Our special thanks go to the 16. Goldney, R.D., Fisher, L.J., Grande, E.D., Taylor, A.W.,
study physicians, therapists, and patients for participating. Hawthorne, G.: Have education and publicity about depression
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Open Access This article is distributed under the terms of the excess costs in South Australia: 1998 and 2004. Aust. N. Z. J.
Creative Commons Attribution Noncommercial License which per- Psychiatry 41(1), 38–53 (2007)
mits any noncommercial use, distribution, and reproduction in any 17. Hamre, H.J., Becker-Witt, C., Glockmann, A., Ziegler, R.,
medium, provided the original author(s) and source are credited. Willich, S.N., Kiene, H.: Anthroposophic therapies in chronic
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