Cost-effectiveness of cognitive-behavioural therapy and drug interventions for major depression

Cost-effectiveness of cognitive behavioural therapy and selective serotonin reuptake inhibitors for major depression in children and adolescents

Michelle M. Haby, Bruce Tonge, Lyn Littlefield, Rob Carter, Theo Vos

Objective:

To assess from a health sector perspective the incremental cost-effectiveness ofcognitive behavioural therapy (CBT) and selective serotonin reuptake inhibitors (SSRIs) forthe treatment of major depressive disorder (MDD) in children and adolescents, compared to‘current practice’.

Method:

The health benefit is measured as a reduction in disability-adjusted life years(DALYs), based on effect size calculations from meta-analysis of randomised controlled trials.An assessment on second stage filter criteria (‘equity’; ‘strength of evidence’, ‘feasibility’ and‘acceptability to stakeholders’) is also undertaken to incorporate additional factors that impacton resource allocation decisions. Costs and benefits are tracked for the duration of a newepisode of MDD arising in eligible children (age 6–17 years) in the Australian population inthe year 2000. Simulation-modelling techniques are used to present a 95% uncertaintyinterval (UI) around the cost-effectiveness ratios.

Results:

Compared to current practice, CBT by public psychologists is the most cost-effective intervention for MDD in children and adolescents at A$9000 per DALY saved (95%UI A$3900 to A$24 000). SSRIs and CBT by other providers are less cost-effective but likelyto be less than A$50 000 per DALY saved (> 80% chance). CBT is more effective than SSRIsin children and adolescents, resulting in a greater total health benefit (DALYs saved) thancould be achieved with SSRIs. Issues that require attention for the CBT intervention includeequity concerns, ensuring an adequate workforce, funding arrangements and acceptability tovarious stakeholders.

Conclusions:

Cognitive behavioural therapy provided by a public psychologist is the mosteffective and cost-effective option for the first-line treatment of MDD in children andadolescents. However, this option is not currently accessible by all patients and will requirechange in policy to allow more widespread uptake. It will also require ‘start-up’ costs andattention to ensuring an adequate workforce.

Key words:

antidepressive agents, cognitive behaviour therapy, cost effectiveness,

Australian and New Zealand Journal of Psychiatry 2004; 38:579–591

depressive disorder, meta-analysis.

Michelle M. Haby, Senior Epidemiologist (Correspondence); Theo Vos,Senior Epidemiologist

Health Surveillance and Evaluation Section, Public Health, Departmentof Human Services, Melbourne, Victoria, Australia. Email: [email protected]

Bruce Tonge, Head of School

School of Psychology Psychiatry and Psychological Medicine, MonashUniversity, Melbourne, Victoria, Australia

Lyn Littlefield, Executive Director

Australian Psychological Society, Melbourne, Victoria, Australia

Rob Carter, Deputy Director

Program Evaluation Unit, University of Melbourne, Melbourne, Vic-toria, Australia

Received 29 August 2003; revised 19 March 2004; accepted 22 March 2004.

580 INTERVENTIONS FOR CHILDHOOD DEPRESSION

Major depressive disorder (MDD) affects 2.3% ofAustralian children and adolescents [1]. However, thecost-effectiveness of recommended treatments has notbeen assessed in this population. Clinical practice guide-lines recommend cognitive behavioural therapy (CBT)as the treatment of first choice because its efficacy issupported by evidence from randomised controlled trials(RCTs) [2,3].

Pharmacological intervention is currently recom-mended as a second-line treatment [2,3]. However, amore recent review of the research literature suggeststhat selective serotonin reuptake inhibitors (SSRIs)might also be considered as a first-line treatment [4].

As part of the Australian Assessing Cost-Effectiveness(ACE) – Mental Health project [5] we assessed theincremental cost-effectiveness of CBT and SSRIs forthe treatment of MDD in children and adolescents.Both treatments were assessed as first-line therapy withcurrent practice as the comparator. Selective serotoninreuptake inhibitors have also been assessed as asecond-line treatment with no further treatment as thecomparator.

Method

The incremental cost-effectiveness ratio (ICER) is calculated as thecost (A$) per disability-adjusted life year (DALY) saved. Children andadolescents eligible for the intervention are those aged 6–17 years inthe Australian population in the year 2000 who are currently seekingcare (‘consulting’) for MDD, but would have received types of careother than evidence-based medicine (EBM) under current practice(Fig. 1). All incident episodes of MDD in the year 2000 are included.For SSRIs as a second-line treatment, the eligible group is thosechildren who do not remit by the end of treatment with CBT or do notadhere to treatment with CBT (Fig. 2). Of these, we assume thatbetween 50% and 90% will actually be offered treatment with SSRIs.

Health benefits are measured for the duration of the episode ofMDD. Costs are measured for the duration of the intervention. Sincethe time horizon is less than one year, costs are not discounted. Theperspective is that of the health sector, including government costs(both Commonwealth and states/territories) and out-of-pocket costs forpatients and their families, that is drug and service costs.

Interventions

CBT

We model 12

×

1 hour individual sessions of CBT plus twoparent/family sessions over 14 weeks (based on expert opinion and

Figure 1. Pathway analysis for current practice (white boxes) and for cognitive behavioural therapy (CBT) and selective serotonin reuptake inhibitors (SSRIs) interventions (light and dark boxes, respectively). EBM, evidence-based

medicine; GP, general practitioner; MDD, major depressive disorder; YLD, years lived with disability.

M.M. HABY, B. TONGE, L. LITTLEFIELD, R. CARTER, T. VOS 581

randomised controlled trials of CBT). A general practitioner (GP) visitfor diagnosis and referral is also included. Four different providerscenarios are costed, with only the cost of the intervention and whobears the cost (government or patient) differing between scenarios.These are: private psychologist; public psychologist; private psychi-atrist; and public psychiatrist.

SSRIs

We model 9 months of treatment with an SSRI, which includes3 months for the acute phase and 6 months for continuation treatment

(based on expert opinion and clinical practice guidelines [3]). The doseper day modelled is 20 mg fluoxetine, citalopram or paroxetine, 50 or100 mg sertraline or 100 mg fluvoxamine [6,7]. Fourteen doctor visitsare included, assuming weekly visits in the first month, every twoweeks for two months, and then monthly visits (based on expertopinion). We assume the proportion of patients consulting with aGP, paediatrician or private psychiatrist is the same as currentlyhappening in those consulting (i.e. 53%, 31% and 16%, respectively[1]). Two different scenarios for the intervention are analyzed: SSRIsoffered as a first-line treatment; and SSRIs offered as a second-linetreatment.

Figure 2. Pathway analysis for selective serotonin reuptake inhibitors offered as a second-line treatment (shaded boxes). The comparator is no further treatment following treatment with cognitive behavioural therapy (CBT). YLD,

years lived with disability.


Current practice

Current practice for the treatment of MDD was determined from the1998 National Survey of Mental Health and Wellbeing – Child andAdolescent Component (NSMHW-CA) [1] in those with MDD in theprevious 12 months (n = 88). A consult is defined as an attendance foremotional or behavioural problems during the past 6 months with afamily doctor, private paediatrician, private psychiatrist, private psy-chologist or social worker, mental health clinic, hospital emergencydepartment, hospital-based department of psychiatry, any other hos-pital based outpatient department or stayed overnight in a hospital.

Of those who consulted (35%), these were further split into treat-ment with EBM (12%) or non-EBM (23%). We defined treatment withSSRIs and/or CBT as EBM. Since there is not a specific questionasking about CBT in the survey, we assumed that those who statedthey had received counselling and had made at least four visits in theprevious 6 months to a private psychiatrist, private psychologist orsocial worker, hospital psychiatry department or mental health clinic,had received CBT [1], which applies to 9% of the survey sample.Consultation with experts suggests that even these conservativeassumptions are likely to have overestimated the number of childrenactually receiving CBT. Children and adolescents who we defined asreceiving non-EBM under current practice each averaged 4.4 visits toa GP, 0.8 visits to a paediatrician, 0.1 visits to a private psychiatrist and0.2 visits to a private psychologist or social worker [1].

Assessment of benefit

Benefits are calculated by a two-stage process. The first stageinvolves the estimation of the health gain that could be attributed toeach intervention using the DALY. The second stage involves theassessment of issues that either influence the degree of confidence thatcan be placed in the cost-effectiveness ratios (such as the level of avail-able evidence), or broader issues that need to be taken into account indecision-making about resource allocation (such as equity and accept-ability to stakeholders).

Stage one: measurement of the health gain

There is no evidence in the literature that CBT or SSRIs can cause orprevent death, so only a change in the years lived with disability (YLD)component of the DALY is modelled. YLD are calculated asincidence

×

duration

×

the disability weight (DW).

YLD for the current practice comparator

To estimate the number of incident cases in the year 2000 weassumed that the prevalence rates calculated from the 1998 NSMHW-CA [1] still apply in 2000 and that incidence can be derived from prev-alence by using the formula: 1-year incidence = 1-year prevalence/(1 + average duration). This 1-year incidence figure (1.5%) is appliedto Australian population figures for 6–17 year-olds in June 2000(Australian Bureau of Statistics, Time series spreadsheet 3201.0) togive 48 552 incident episodes of MDD.

The average duration of an episode of MDD was calculated usingthe spread of durations found in the Oregon Adolescent DepressionProject [8]. While the average duration of an episode of MDD is

26.7 weeks there is a difference in the average duration of an episodebetween those consulting and those not consulting for their MDD. Weassume that there is a lag from onset of MDD to treatment of 4 weeks(range 2–6 weeks) so that children with episodes of 4 weeks or lesswould remit before getting to treatment (25.5%). Conversely, all chil-dren treated would have durations greater than the lag. Thus, we derivean average duration of 20.8 weeks in those children not consulting and34.8 weeks in those consulting.

The disability weights (DW) used are based on the Dutch weightingsystem [9]. These are 0.14 for mild, 0.35 for moderate and 0.76 forsevere MDD. Composite DWs were calculated separately for thosewho: did not consult; consulted and received EBM; and consulted andreceived non-EBM under current practice, based on the spread ofseverities in the Australian population. We extrapolated this severityinformation from the young adults (18–34 years) in the adult NationalSurvey of Mental Health and Wellbeing [10] because the numbers withdepression in the NSMHW-CA [1] were too small to obtain reliableestimates of the spread of severity of depression. We used the MentalComponent Score of the SF-12 [11], which has a mean populationvalue of 50 and a standard deviation of 10. We classified cases into:severe (> 2.5 SD below mean, i.e. < 25); moderate (> 1.5–2.5 SDbelow mean, i.e. 25–34.9); and mild (> 0.5–1.5 SD below mean,i.e. 35–44.9). The proportion of cases in each severity category ismultiplied by the appropriate DW for the category to get a weightedaverage DW for those in each group. The resulting DWs are: ‘didnot consult’ = 0.270; ‘received EBM’ = 0.397; and ‘received non-EBM’ = 0.417.

YLD for the comparator for SSRIs as a second-line treatment

To derive the average duration of an episode of MDD before becom-ing eligible for treatment with SSRIs under this scenario we assumedan average of 2 weeks treatment with CBT before being treated withSSRIs for those who do not adhere to CBT and 14 weeks of CBT forthose who adhere but do not remit. This is in addition to the 4-week lagto treatment with CBT. This gives an average duration of 41.4 weeks inthose not adhering to treatment with CBT and 74.0 weeks in those notremitting by the end of treatment with CBT. We assumed no healthbenefit from the prior treatment with CBT, so used a disability weightof 0.417 at baseline, consistent with the modelling of SSRIs as a first-line treatment.

Determining the reduction in YLD with treatment

The reduction in severity, and hence YLD, was modelled using theeffect size and both the ‘conversion factor method’ and the ‘surveyseverity method’ [5] to translate the effect size into a reduction in theDW. For the ‘conversion factor method’ we multiplied the effect sizeby the DW conversion factor. This conversion factor is an averagechange in the DALY disability weights for the equivalent of a standarddeviation change in severity for the particular mental disorder [12]. Forthe ‘survey severity method’ the effect size is applied directly to theMental Component Score, which was used to determine the averageDW at baseline. The severity of respondents is then reclassified and anew average DW calculated. The difference in average DW is thechange attributed to treatment [5].


The effect size was calculated from a meta-analysis of the relevantRCTs. Although the interventions do impact on the duration of theepisode of MDD, we assumed that the effect size captures the effectsof both the reduced severity and duration. Reductions in the DW wereonly applied to the time from the commencement of the intervention.For cases not adherent to treatment no reduction in DW has beenmodelled (although they do incur costs of the treatment provided).

Meta-analysis

Trials of CBT and SSRIs were identified from published meta-analyses, searches of the Cochrane Controlled Trials Register andMedline, from reference lists in included trials, review articles, booksand clinical practice guidelines and from authors of published trials. Tobe included, trial participants had to be less than 18 years and havediagnosed depression (MDD or dysthymia). For CBT seven studiesfitted the inclusion criteria [13–19]. However, the study by Reed [14]could not be included in the calculation of the effect size for CBT dueto lack of continuous outcome measures. For SSRIs four RCTs fittedthe inclusion criteria [20–23].

The effect size (standardized mean difference) was calculated usingHedges’ g and the random effects method of DerSimonian and Laird[24]. We first calculated an effect size for each study by averagingacross the relevant outcome measures within the study. All continuousoutcome measures related to depression (including anxiety and mood)and health-related quality of life were included. Clinician, parent andchild/adolescent reported measures were included. Some outcomemeasures that were considered to be relevant could not be includedbecause data were not presented in a way that could be incorporatedinto the calculation of the effect size (e.g. data presented in figuresonly). For the study by Simeon

et al

. [20] no data were presented in thepaper but it was stated that there were no significant differencesbetween the treatment and control groups. Thus, an effect size of zerowas assumed. The weighted mean effect size for CBT is 0.41 (95%CI = 0.15–0.67) and for SSRIs is 0.29 (95% CI = 0.11–0.46). Someunexplained heterogeneity was present in the effect size for CBT(Q = 12.04, df = 7, p = 0.099) but not for SSRIs (Q = 0.90, df = 3,p = 0.8).

Adherence

It was assumed that the completion rate of the treatment group in theRCTs reflects the best possible adherence with treatment. No longitu-dinal studies measuring adherence to CBT or SSRIs were available forMDD in children and adolescents so a minimum adherence rate of 50%was used in the uncertainty analysis (Table 1). This was done to betterreflect what could be expected under routine health service conditionswhere results may vary due to the motivation of clinicians and patients,the availability of skilled clinicians and the capacity to vary the inter-vention to suit the needs of the patient.

Stage two: the second stage filter criteria

The first stage of measuring benefit described above is characterizedby a reliance on data sets and the application of quantitative methodsbased on health economics and epidemiology. The second stage incor-porates, explicitly, broader aspects where decisions rest heavily on

judgement and notions of ‘due process’. The filters chosen for theACE–MH study were ‘strength of evidence’, ‘equity’, ‘feasibility’ and‘acceptability to stakeholders’ [5].

Assessment of costs

Pathway analysis was used to identify the component activities of theinterventions and their current practice comparator (Figs 1 and 2).Resource usage (i.e. dosage, number of visits, etc.) for the componentactivities was estimated from the published literature and supplementedby expert advice. Unit costs and data sources are shown in Table 2.Costs that would have been incurred under current practice are sub-tracted from the intervention (and non-adherence) costs to obtain theincremental cost.

Children and adolescents who don’t adhere to treatment with CBTor SSRIs incur some costs but no health benefit. However, there are nodata available on their care-seeking behaviour. Thus, it is assumed thatthe cost of non-adherence is (on average) the same as the cost of non-EBM. However, for SSRIs as a second-line treatment, we assume thatthese patients behave differently from the average patient receivingnon-EBM. Thus, for those not adherent to SSRIs as a second-linetreatment, we model the cost of filling one or two scripts of the SSRIand 1–3 doctor visits (in addition to the GP visit for referral to apaediatrician or psychiatrist).

Uncertainty analysis

Simulation-modelling techniques were used to allow the presenta-tion of an uncertainty range around the health benefits, costs and ICERs(Table 1). @RISK software [25] was used to conduct Monte Carlosimulations, which allow multiple recalculations of a spreadsheet, eachtime choosing a value from the specified distribution for each inputvariable (shown in Table 1). We used 2000 iterations for each of thetwo methods for translating the effect size into a change in the DW(i.e. the ‘conversion factor method’ and the ‘survey severity method’).Thus, the final results are based on the 2000 + 2000 iterations. Medianvalues were calculated because results are not normally distributed. Theranges presented can be interpreted as the range within which the trueresult lies with 95% certainty.

Uncertainty analyses are used to address issues of uncertainty in theresults due to sampling error (e.g. in the meta-analyses) and the needto make assumptions due to the lack of evidence for some parameters(e.g. the lag to treatment).

In addition to the uncertainty range, the @RISK analysis can alsoshow which model parameters contribute most to the uncertainty in theresults. We list the input variables that contribute to overall uncertaintyaround the cost-effectiveness ratios with a regression coefficient of

±

0.30 or greater.

Results

Cognitive behavioural therapy by public psychologists (or othereffective providers at a similar salary level) is the most cost-effectiveintervention for child and adolescent depression at A$9000 per DALYsaved (95% UI A$3900 – A$24 000) and is also the second mostaffordable first-line treatment option for the government at anincremental cost of A$3.7 million (95% UI A$1.9 – A$6.7 million)


Tabl

e 1.

Cri

tica

l par

amet

er v

alue

s, u

ncer

tain

ty d

istr

ibut

ions

and

sou

rces

of i

nfor

mat

ion

for

dete

rmin

ing

the

heal

th b

enefi

t and

cos

ts

Par

amet

erV

alu

esU

nce

rtai

nty

d

istr

ibu

tio

n

†

So

urc

e an

d a

ssu

mp

tio

ns

Pre

vale

nce

an

d c

urr

ent

pra

ctic

e:

‡

1-ye

ar p

reva

lenc

e of

MD

D2.

3%, S

E 0

.24%

Nor

mal

NS

MH

W-C

A [1

]P

ropo

rtio

n th

at c

onsu

lted

and

rece

ived

non

-E

BM

und

er c

urre

nt p

ract

ice

23%

, SE

4.4

%N

orm

alN

SM

HW

-CA

[1].

Ass

umes

that

pat

ient

s w

ho a

nsw

ered

‘yes

’ to

coun

selli

ng in

the

surv

ey

and

had

mad

e at

leas

t 4 v

isits

in th

e pr

evio

us 6

mon

ths

to a

priv

ate

psyc

hiat

rist,

priv

ate

psyc

holo

gist

or

soci

al w

orke

r, ho

spita

l psy

chia

try

depa

rtm

ent o

r m

enta

l hea

lth c

linic

re

ceiv

ed C

BT.

Pro

port

ion

of c

ases

like

ly to

be

offe

red

trea

tmen

t with

SS

RIs

afte

r tr

eatm

ent w

ith

CB

T

min

50%

, max

90%

Uni

form

Est

imat

e

Hea

lth

ben

efit:

Lag

to tr

eatm

ent

min

2 w

eeks

, mea

n 4,

m

ax 6

Tria

ngul

arE

stim

ate

base

d on

con

sulta

tion

with

exp

erts

Effe

ct s

ize:

CB

T:

min

0.1

5, m

ean

0.41

, m

ax 0

.67

Tria

ngul

arR

CT

s of

CB

T [1

3,15

–19]

and

SS

RIs

[20–

23].

Min

imum

and

max

imum

val

ues

are

from

the

95%

con

fiden

ce in

terv

al.

SS

RIs

: m

in 0

.11,

mea

n 0.

29,

max

0.4

6D

isab

ility

wei

ght c

onve

rsio

n fa

ctor

min

0.1

39, m

ax 0

.172

Uni

form

San

ders

on

et a

l

. 200

4 [1

2]. T

he m

inim

um is

from

the

Tim

e Tr

ade-

Off

met

hod

and

the

max

imum

is fr

om th

e V

isua

l Ana

logu

e S

cale

met

hod.

Red

uctio

n in

the

disa

bilit

y w

eigh

t usi

ng th

e su

rvey

sev

erity

met

hod:

CB

T:

min

0.0

6, m

ean

0.11

, m

ax 0

.22

Tria

ngul

arM

etho

d de

scrib

ed b

y H

aby

and

colle

ague

s [5

].

SS

RIs

: m

in 0

.05,

mea

n 0.

08,

max

0.1

2

Adh

eren

ce w

ith:

CB

T:

min

50%

, max

85%

Uni

form

Min

imum

val

ue is

an

estim

ate

base

d on

exp

ert a

dvic

e. M

axim

um v

alue

s ar

e ob

tain

ed fr

om

the

RC

Ts

of C

BT

and

SS

RIs

.S

SR

Is:

min

50%

, max

76%

Pro

port

ion

rem

itted

by

the

end

of tr

eatm

ent

with

CB

T62

%, S

E 3

.4%

Nor

mal

RC

Ts

of C

BT

[13–

18],

incl

uded

in a

sys

tem

atic

rev

iew

[35]

Co

sts:

Cos

t to

patie

nt o

f priv

ate

psyc

holo

gist

vis

its

and

cost

to g

over

nmen

t of p

ublic

ps

ycho

logi

st a

nd p

ublic

psy

chia

tris

t vis

its

varia

tion

fact

or

mea

n 1,

SE

0.1

Nor

mal

Uni

t cos

ts a

nd s

ourc

es o

f dat

a ar

e sh

own

in T

able

2. T

hese

cos

ts a

re a

ssum

ed to

var

y to

geth

er, i

.e. i

n th

e sa

me

dire

ctio

n.

On-

cost

s fo

r pu

blic

psy

chol

ogis

t or

publ

ic

psyc

hiat

rist (

%)

min

25,

mea

n 30

, m

ax 3

5Tr

iang

ular

On-

cost

s in

clud

e di

rect

sal

ary

cost

s (s

uper

annu

atio

n, w

ork

cove

r, le

ave,

allo

wan

ces)

and

co

rpor

ate

cost

s (e

lect

ricity

, hum

an r

esou

rces

, etc

.) a

nd a

re b

ased

on

pers

onal

co

mm

unic

atio

n w

ith r

esou

rce

man

ager

s at

3 m

ajor

Vic

toria

n ho

spita

ls/M

enta

l Hea

lth

Ser

vice

s an

d th

e V

icto

rian

Men

tal H

ealth

Bra

nch.

Num

ber

of d

aily

pat

ient

con

tact

s by

pub

lic

psyc

holo

gist

min

5, m

ean

6, m

ax 7

Tria

ngul

arE

stim

ate

base

d on

con

sulta

tion

Num

ber

of p

atie

nt c

onta

cts

for

CB

T b

y pu

blic

ps

ychi

atris

t per

ses

sion

min

2.5

, mea

n 3,

m

ax 3

.5Tr

iang

ular

Est

imat

e ba

sed

on c

onsu

ltatio

n

Num

ber

of s

crip

ts fi

lled

for

thos

e no

n-ad

here

nt to

SS

RIs

(sc

enar

io 2

)1

or 2

Dis

cret

eE

stim

ate

Num

ber

of d

octo

r vi

sits

for

thos

e no

n-ad

here

nt to

SS

RIs

(sc

enar

io 2

)m

in 1

, max

3U

nifo

rmE

stim

ate


(Tables 3 and 4). CBT by other providers is likely to have ICERs< A$50 000 per DALY (> 80% chance). SSRIs are a cost-effectiveoption, both as first-line and second-line treatments (Table 4). How-ever, CBT has greater effectiveness in children and adolescents thanSSRIs and therefore greater total YLD saved (Tables 3 and 4). Note thatthe costs and benefits of SSRIs as a second-line treatment are additionalto those incurred from first-line treatment with CBT.

The major contributors to uncertainty around the ICERs for CBT arethe effect size and the variation factor around the cost to patient ofprivate psychologist visits and cost to government of public psychol-ogist and public psychiatrist visits. For SSRIs, the effect size is themajor contributor to uncertainty around the ICERs. Other parameterscontributing to uncertainty around the health benefit (YLD) and totalcost of CBT and SSRIs are the proportion of children and adolescentscurrently receiving non-EBM, adherence with treatment and the prev-alence of MDD.

A consideration of the second stage filters for each intervention isshown in Table 5.

Discussion

Economic analysis raises important issues as to whatconstitutes ‘value-for-money’. It is not uncommon for athreshold ICER (or ‘shadow price’) to be set as a guideto assist decision-making. In ACE–MH, for example, anICER of A$50 000 per DALY has been used. However,this should not be over-interpreted or taken out of con-text. It is important to reflect, for example, on how wellthe ICER captures the various dimensions of ‘benefit’ inmental health. The second stage filters are designed toallow the ICERs to be placed within a broader decisioncontext.

Cognitive behavioural therapy is a cost-effective inter-vention for major depression in children and adolescents(Table 3). Whether delivered by private or public psy-chologists or psychiatrists the cost-effectiveness ratiosare likely to be below our threshold of $50 000 perDALY saved (> 80% chance). Clearly, CBT deliveredby a public psychologist is the most cost-effective optionand is also the second most affordable option for thegovernment at about $3.7 million per year if all eligiblepatients were offered treatment (Table 3). From the per-spective of the government, CBT delivered by a privatepsychologist is the cheapest option. However, the factthat all treatment costs are borne by the patient and totalmore than A$1600 per episode suggests that the inter-vention would be unaffordable for many patients. This islikely to have a significant impact on both uptake andadherence to the treatment. SSRIs are also a cost-effective intervention both as a first-line treatment and asa second-line treatment for MDD in children and adoles-cents (Table 4). However, SSRIs are less effective thanCBT, resulting in lower total health benefit.

Tabl

e 1.

Con

tinu

ed

Par

amet

erV

alu

esU

nce

rtai

nty

d

istr

ibu

tio

n

†

So

urc

e an

d a

ssu

mp

tio

ns

Num

ber

of d

octo

r vi

sits

for

thos

e no

n-ad

here

nt to

SS

RIs

(sc

enar

io 2

)m

in 1

, max

3U

nifo

rmE

stim

ate

Cos

t of n

on-E

BM

var

iatio

n fa

ctor

min

0.5

, mea

n 1,

m

ax 1

.5Tr

iang

ular

Est

imat

e

†

In a

uni

form

dis

trib

utio

n ev

ery

valu

e in

the

spec

ified

ran

ge h

as a

n eq

ual p

roba

bilit

y of

bei

ng c

hose

n in

eac

h ite

ratio

n of

the

sim

ulat

ion.

In a

tria

ngul

ar d

istr

ibut

ion,

the

grea

test

pr

obab

ility

of b

eing

cho

sen

is th

e va

lue

repr

esen

ting

the

top

of th

e tr

iang

le (

i.e. t

he m

ean

valu

e sh

own

in c

olum

n 2)

, whi

le th

e pr

obab

ility

of o

ther

val

ues

bein

g ch

osen

tape

rs o

ff to

war

ds th

e ex

trem

es o

f the

bas

e of

the

tria

ngle

(i.e

. the

min

imum

and

max

imum

val

ues)

.

‡

Ass

umpt

ions

mad

e fo

r pr

eval

ence

and

cur

rent

pra

ctic

e es

timat

es w

ould

affe

ct th

e to

tal

num

ber

elig

ible

for

the

inte

rven

tion

and

henc

e to

tal c

osts

and

ben

efit b

ut h

ave

no e

ffect

on

the

cost

-effe

ctiv

enes

s ra

tio.


Tabl

e 2.

Sum

mar

y of

uni

t cos

t inf

orm

atio

n, d

ata

sour

ces

and

assu

mpt

ions

Ele

men

t co

sted

Co

st t

o

gov

t (A

$)C

ost

to

p

atie

nt

(A$)

So

urc

eA

ssu

mp

tio

ns

1 m

onth

sup

ply

of a

n S

SR

I$3

2.23

$10.

08P

BS

dat

a fr

om D

HA

Pat

ient

s ta

ke th

eir

med

icin

e as

pre

scri

bed.

The

pro

port

ion

of s

crip

ts o

f eac

h ty

pe a

nd fo

rm o

f SS

RI a

re th

e sa

me

for

child

ren

as fo

r al

l pat

ient

s ac

cess

ing

thes

e dr

ugs

unde

r th

e P

BS

in th

e 19

99/2

000

finan

cial

yea

r. A

ll br

ands

with

in

the

SS

RI c

lass

are

ass

umed

to h

ave

sim

ilar

effic

acy.

1 G

P v

isit

of 2

0–40

min

s$3

9.51

$1.8

7M

BS

dat

a fr

om D

HA

MB

S it

em 3

6 –

for

initi

al v

isit

and/

or fo

r re

ferr

al/d

iagn

osis

.

1 G

P v

isit

of <

20 m

ins

$21.

88$2

.21

MB

S d

ata

from

DH

AM

BS

item

23

– fo

r se

cond

and

sub

sequ

ent v

isits

for

SS

RI i

nter

vent

ion

and

for

non-

EB

M.

1 pa

edia

tric

ian

visi

t – 1

st v

isit

$97.

92$1

7.79

MB

S d

ata

from

DH

AT

his

is a

vera

ged

over

pae

diat

ricia

n vi

sits

und

er it

ems

104

(spe

cial

ist)

and

110

(c

onsu

ltant

) in

pro

port

ion

to th

e nu

mbe

r of

ser

vice

s pr

oces

sed

in th

e 19

99/

2000

fina

ncia

l yea

r.

1 pa

edia

tric

ian

visi

t –

subs

eque

nt v

isits

$49.

06$9

.90

MB

S d

ata

from

DH

AT

his

is a

vera

ged

over

pae

diat

ricia

n vi

sits

und

er it

ems

105

(spe

cial

ist)

and

116

(c

onsu

ltant

) in

pro

port

ion

to th

e nu

mbe

r of

ser

vice

s pr

oces

sed

in th

e 19

99/

2000

fina

ncia

l yea

r.

1 ps

ychi

atris

t vis

it of

45–

75 m

in$1

17.0

2$1

6.47

MB

S d

ata

from

DH

AM

BS

item

306

– fo

r C

BT,

non

-EB

M a

nd fo

r in

itial

vis

it fo

r S

SR

I int

erve

ntio

n.

1 ps

ychi

atris

t vis

it of

15–

30 m

in$5

6.38

$5.9

5M

BS

dat

a fr

om D

HA

MB

S it

em 3

02 –

sub

sequ

ent v

isits

for

SS

RI i

nter

vent

ion.

1 se

ssio

n of

46–

60 m

ins

with

a

priv

ate

psyc

holo

gist

$0$1

15.0

0A

ustr

alia

n P

sych

olog

ical

Soc

iety

The

Aus

tral

ian

Psy

chol

ogic

al S

ocie

ty r

ecom

men

ded

fee

is $

161

(as

of 1

Jul

y 20

01)

but p

erso

nal c

omm

unic

atio

n w

ith th

e E

xecu

tive

Dire

ctor

sug

gest

s th

e fe

e m

ost c

omm

only

cha

rged

is $

110-

$120

.

1 se

ssio

n of

60

min

s w

ith a

pub

lic

psyc

holo

gist

$47.

05$0

Bas

e sa

lary

from

Vic

toria

n H

ospi

tals

’ Ind

ustr

ial

Ass

ocia

tion

Gra

de 3

, Yea

r 2

psyc

holo

gist

(P

L2).

Sal

ary

effe

ctiv

e fr

om 1

Jul

y 20

00: $

1085

.80

per

wee

k. O

n-co

sts

of 3

0% h

ave

been

add

ed. T

he p

sych

olog

ist h

as 6

pat

ient

co

ntac

ts p

er d

ay w

ith th

e re

mai

nder

of t

he w

orki

ng d

ay u

sed

for

prep

arat

ion,

ad

min

istr

atio

n, p

rofe

ssio

nal d

evel

opm

ent,

etc.

1 se

ssio

n of

60

min

s w

ith a

pub

lic

psyc

hiat

rist

$129

.64

$0B

ase

sala

ry fr

om th

e A

ustin

&

Rep

atria

tion

Med

ical

Cen

tre

Hum

an R

esou

rces

The

psy

chia

tris

t is

paid

as

a vi

sitin

g m

edic

al o

ffice

r (V

MO

). A

n av

erag

e sa

lary

pe

r se

ssio

n ha

s be

en u

sed

from

the

rang

e: S

peci

alis

t to

Sen

ior

Spe

cial

ist.

Sal

ary

effe

ctiv

e fr

om 1

Jul

y 20

00: $

260.

76 to

$33

7.60

per

ses

sion

. The

ps

ychi

atris

t has

3 p

atie

nt c

onta

cts

per

sess

ion

(of 3

.5 h

). O

n-co

sts

of 3

0%

have

bee

n ad

ded.

DH

A, A

ustr

alia

n D

epar

tmen

t of H

ealth

and

Age

ing;

PB

S, P

harm

aceu

tical

Ben

efits

Sch

eme;

MB

S, M

edic

are

Ben

efits

Sch

edul

e.


The higher effect size for CBT (compared to SSRIs)may reflect the greater remission with CBT, and henceshorter duration of the episode of depression. WithCBT 62% of patients remitted by the end of treatmentcompared to 39% of the control groups [13–18]. WithSSRIs 46% of patients remitted by the end of treatmentcompared to 30% of the placebo control groups [21–23].

Thus, the odds of remission are 2.59 (95% CI =1.66–4.03) with CBT and 2.03 (95% CI = 1.40–2.95)with SSRIs. Both CBT and SSRIs have lower effectsizes (and hence are less cost-effective) in childrenand adolescents than in adults (i.e. 0.41

vs.

0.82 inadults [26] for CBT and 0.29

vs.

0.55 [27] in adults forSSRIs).

Table 3. The incremental benefits, costs and cost-effectiveness of cognitive behaviour therapy for major depression in children and adolescents compared with current practice

Private psychologist Public psychologist Private psychiatrist Public psychiatristHealth benefit

YLL 0 0 0 0YLD 360 (120–920) 360 (120–920) 360 (120–920) 360 (120–920)DALYs 360 (120–920) 360 (120–920) 360 (120–920) 360 (120–920)

Intervention costs (A$ millions):

Government 0.9 (0.5–1.6) 5.7 (3.2–9.2) 13 (7.2–20) 14 (7.5–23)Patient 12 (6.3–20) 0.15 (0.1–0.3) 1.8 (1.0–2.9) 0.15 (0.1–0.3)Total 13 (6.9–21) 5.8 (3.3–9.4) 15 (8.3–23) 14 (7.6–24)

Incremental costs

†

(A$ millions):

Government

–

1.0 (– 2.0– –0.4) 3.7 (1.9–6.7) 11 (6.0–18) 12 (6.2–21)Patient 11 (6.0–19) –0.3 (–0.5– –0.1) 1.4 (0.8–2.3) –0.3 (–0.5– –0.1)Total 10 (5.5–17) 3.4 (1.7–6.3) 12 (6.7–20) 12 (6.1–20)

Cost-effectiveness ratio (A$ thousand per DALY)

28 (13–70) 9 (3.9–24) 34 (16–82) 32 (14–79)

Proportion of iterations that fall below A$50 000 per DALY saved

‡

88% 100% 80% 81%

YLL, years of life lost; YLD, years lived with disability; DALYs, disability-adjusted life years (YLL + YLD);

†

This is the cost of the intervention reduced by the cost of non-EBM not given;

‡

Calculated from the 4000 iterations generated in the uncertainty analysis for the cost-effectiveness ratio; values are medians; figures in brackets show the 95% uncertainty interval; negative values are savings from the reduction in non-EBM treatments. Cost savings can result from a reduction in total cost of health services and/or from a shifting of costs between providers, i.e. government

versus

patient.

Table 4. The incremental benefits, costs and cost-effectiveness of selective serotonin reuptake inhibitors (SSRIs) for major depression in children and adolescents

SSRIs as first-line treatment compared to current practice

SSRIs as second-line treatment compared to no further treatment

Health benefit:

YLL 0 0YLD 230 (88–510) 130 (47–320)DALYs 230 (88–510) 130 (47–320)

Intervention costs (A$ millions):

Government 6.5 (3.8–10) 2.6 (1.3–4.6)Patient 1.3 (0.8–2.0) 0.5 (0.3–0.9)Total 7.8 (4.6–12) 3.1 (1.6–5.5)

Incremental costs

†

(A$ millions):

Government 4.6 (2.6–7.2) As abovePatient 0.9 (0.5–1.4)Total 5.4 (3.1–8.6)

Cost-effectiveness ratio (A$ thousand per DALY)

23 (13–53) 23 (13–54)Proportion of iterations that fall below A$50 000

per DALY saved

‡

96% 96%

YLL, years of life lost; YLD, years lived with disability; DALYs, disability-adjusted life years (YLL + YLD); values are medians; figures in brackets show the 95% uncertainty interval;

†

this is the cost of the intervention reduced by the cost of non-EBM not given;

‡

calculated from the 4000 iterations generated in the uncertainty analysis for the cost-effectiveness ratio.


We could find only two other studies of the cost-effectiveness of CBT for depression in the literature andnone looking at its cost-effectiveness for children andadolescents [28,29]. There are several economic evalua-tions of SSRIs for the treatment of depression (reviewedin Frank

et al

. [30]) but no studies in children andadolescents. However, the applicability of the overseasstudies in adults needs to be carefully assessed, due todifferences in health system design and cultural context.

When deciding to model alternative scenarios for theprovider of CBT, we assumed that psychologists andpsychiatrists have equal efficacy but this has not beenproven. Nor is it clear whether other providers, such asGPs, social workers and nurses, are as effective orwhether this is dependant on the amount of training theyhave in CBT. For the SSRI intervention we have assumedequal efficacy of the different types of SSRI although theevidence is limited to fluoxetine and paroxetine.

In the course of this analysis, several gaps in theresearch were noted. In terms of defining the CBT inter-vention there are no RCTs that investigate the optimumduration of treatment with psychological therapy in

children and adolescents. Most of the studies in ourmeta-analysis investigate a set course of CBT, rangingfrom 5–16 sessions for patients and 0–8 sessions forparents. Only one study has looked at continuation treat-ment [18], with inconclusive results, and none havelooked at the effect of varying the length of treatmentor the number of sessions of CBT. This is importantbecause it has implications for the cost, uptake andadherence to treatment. In terms of defining the SSRIintervention, there are no RCTs that investigate theoptimum duration of treatment in children and adoles-cents. Most studies are limited to the acute phase ofMDD and last for a maximum of 9 weeks. We are awareof only one longer-term study, which continues foralmost one year, but the results have not yet been pub-lished in a peer-reviewed journal [31]. Finally, there areno RCTs in children and adolescents that compare theefficacy of combining pharmacological therapy withpsychological therapy compared to treatment with asingle therapy.

A significant issue in this cost-effectiveness analysis isthe use of mean values to describe the natural history of

Table 5. Consideration of second stage filters

Filter CBT intervention SSRIs intervention

Evidence Sufficient evidence of adequate quality, noting however, that there are:

●

few trials in NESB groups

●

few trials for providers other than psychologists

●

no trials amongst the indigenous population

●

only one trial in children < 13 years

Sufficient evidence of adequate quality.

Equity Moderate equity concerns require attention, i.e.

●

appropriateness for minority groups (e.g. NESB, indigenous)

●

access for rural/remote consumers and in outer metropolitan areas (computer-based CBT may address this issue)

●

inequity in access if ‘user pays’ (e.g. for private providers)

No important equity issues.

Feasibility Possible but challenging to implement in short-term. Issues include:

●

ensuring an adequate workforce, i.e. appropriately trained and accredited providers; adequate distribution

●

ability of health funding to enable adequate access via primary care

●

development of implementation arrangements (cost-effectiveness assumes ‘steady-state’ operation)

Feasible within current workforce and institutional arrangements.

Acceptability Some issues that require resolution:

●

cost to consumers if private providers

●

acceptance of treatment by clinicians and consumers

●

acceptance of a shift towards non-pharmacological treatments

Issues that require resolution:

●

Parental concern about using drugs in children and adolescents

●

Ethical concerns about drugs (which have side-effects) as first-line treatment (particularly in children) while more effective treatment (i.e. CBT) is available with no side-effects

NESB, non-English speaking background; CBT, cognitive behaviour therapy; SSRIs, selective serotonin reuptake inhibitors.


MDD. For example, we use a mean duration of anepisode of 27 weeks, although the duration probablyvaries from as little as 2 weeks to more than 5 years [8].This use of mean values was necessary for a number ofreasons, the most important being the limited data avail-able on the natural history of depression (in children andadolescents particularly) and the limited informationavailable from the treatment literature. Randomized con-trolled trials of treatment often exclude children withcomorbid conditions and/or do not present the resultsstratified by subgroups. Thus, attempts to incorporate theheterogeneity of depression into our results are not sup-ported by data. However, the results are likely to be agood reflection of what would happen ‘on average’ andallow meaningful comparisons between treatments. Theresults of these analyses are not intended to be a pre-scription for individual patients and we caution againstgeneralizing the results to the most severe patients(e.g. inpatients) as these patients are not included in thepublished RCTs or the community study of depressionduration [8] used in these analyses.

Another issue for this analysis has been the use of anepisode-based analysis of MDD, which was necessarydue to the limited data on the natural history of depres-sion in children and adolescents. The disadvantage ofthis method is that the longer-term health benefits relatedto prevention of new episodes or delay in relapse orrecurrence due to the intervention cannot be measured.This is particularly important for CBT, which in adultstudies has been shown to prevent new episodes whilenot incurring ongoing costs [32].

The strengths of the current analysis include the use ofthe best available evidence for all parameters, the useof Australian data, calculation of ICERs for local cir-cumstances and extensive uncertainty analyses. We havealso undertaken steps through the second stage filters toincorporate a broader range of considerations that impacton resource allocation decisions. The limitations of thestudy are the lack of overall quality of life data inthe calculation of the effect size, which is mostly limitedto symptom measures, and the measurement of severityin DALY disability weights [5]. While the cost side ismore straightforward, there are two issues to note. First,the estimation of cost offsets for CBT is very conserva-tive (e.g. does not include impact of reduced use ofantidepressants on PBS or resource savings resultingfrom reduction in relapse and severity of depression).Second, the economic analysis assumes ‘steady-state’operation and costs associated with implementation (e.g.costs associated with ensuring adequate training andaccreditation of providers) have not been factored in.

For several parameters, we could not find any data,and have relied on the advice of experts (Table 1).

Because only 31 children and adolescents with MDD inthe NSMHW-CA [1] had sought treatment in the pre-vious 6 months estimates of the proportion of childrentreated with CBT, SSRIs and non-EBM are uncertain.The collection of further data on the treatment of depres-sion in children and adolescents in Australia is required.However, it is important to note that these parametersonly impact on the total cost and total benefit of theintervention because they influence the total number ofchildren eligible for the intervention. They do not affectthe cost-effectiveness ratio.

In conclusion, there are strong economic groundsto improve access to CBT as a first-line treatment forchild and adolescent depression, especially for publiclyfunded psychologists as providers. The Commonwealthinitiative to improve access to psychologists throughGPs (as being piloted in the ‘Better outcomes in mentalhealth care’ initiative [33]) shows that funding mecha-nisms outside of Medicare are feasible. Should nofurther action be taken, SSRIs may become the first-linetreatment by default due to their greater affordability forconsumers and easier access. However, readers shouldalso note the debate that has arisen since this researchwas conducted over the efficacy and safety of anti-depressants in children and adolescents [34]. Key deci-sion points for policy makers regarding the CBTintervention are: public or private provider; psychologistor psychiatrist; or a mix of providers including othersuitably trained health professionals (social workers,nurses, GPs). However, use of providers other than psy-chologists requires attention to training and accreditationif similar effectiveness is to be achieved. Greater use ofpublicly funded psychologists will require attention toensuring an adequate workforce, particularly in outermetropolitan and rural regions.

Caveat

The ACE–Mental Health project was jointly funded bythe Australian Department of Health and Ageing, MentalHealth and Suicide Prevention Branch and the Depart-ment of Human Services, Mental Health Branch, Vic-toria in recognition of the importance of research into thecost-effectiveness of interventions in mental health treat-ment and care. This work draws upon, but is also limitedby the available research and the assumptions necessaryto complete the work.

The results of the analyses provide valuable material,likely to contribute to future policy deliberations by allservice providers. Conclusions drawn from the eco-nomic evaluations should be considered within thecontext of the second stage filter process, which qualifiesthe results, taking into account issues of equity, feasibility,


strength of evidence and acceptability to stakeholders.This second stage filter process addresses some of thepractical considerations required for changes in actualservice practice.

Acknowledgements

Principal investigators for the project are: Theo Vos,Rob Carter and Gavin Andrews. Analyses draw on theChild and Adolescent Component of the NationalSurvey of Mental Health and Wellbeing which wassponsored by the Mental Health and Suicide PreventionBranch of the Department of Health and Ageing, facili-tated by the National Collaborating Group, and con-ducted by staff in the Department of Psychiatry at theUniversity of Adelaide. The average cost of varioustypes of medical attendances and the various forms ofSSRI were obtained from Medicare Benefits Scheduleand Pharmaceutical Benefits Scheme data from theDepartment of Health and Ageing. We thank KristySanderson, Jeremy Anderson, Peter Birleson, Colin Brown,Neil Coventry, Michael Gordon, Richard Harrington, TonyLawrence and Jenny Smith for advice on various aspectsof the analysis.

We thank members of the ACE–Mental Health steer-ing committee for their input into the project: DavidBarton, Graham Burrows (Chair), Sue Caleo, VaughanCarr, Dermot Casey, Joy Easton, William Hart, HelenHerrman, Barbara Hocking, Assen Jablensky, AnthonyJorm, Lyn Littlefield, Patrick McGorry, John McGrath,Paul Morgan, Lorna Payne, Deb Podbury, KristySanderson, Suzy Saw, Bruce Singh, Bruce Tonge, RuthVine, Harvey Whiteford.

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Cost-effectiveness of cognitive-behavioural therapy and drug interventions for major depression

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