Efficacy, Effectiveness and Efficiency of Escitalopram in the Treatment of Major Depressive and Anxiety Disorders
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Efficacy, Effectiveness and Efficiency of
Escitalopram in the Treatment of Major
Depressive and Anxiety Disorders
Raymond W. Lam, Lieven Annemans
Expert Rev Pharmacoeconomics Outcomes Res. 2007;9(6):559-576.
Abstract and Introduction
Abstract
In addition to the large personal challenge that depression and anxiety present, these disorders are
associated with a substantial burden of disability and lost productivity, and are responsible for
considerable strain on healthcare resources and on society. Escitalopram is recommended as first-line
therapy for the treatment of major depressive disorder and severe depression, and is indicated in anxiety
disorders. Compared with other antidepressants, escitalopram has equal or superior efficacy, as proven
in clinical trial settings, equal or superior real-life effectiveness, established in both clinical and
observational studies, and a better tolerability profile. While drug acquisition costs are higher for
escitalopram than for generic drugs such as fluoxetine and citalopram, numerous prospective and
modeled economic analyses show that associated direct and indirect costs of treatment are lower with
escitalopram than with citalopram, fluoxetine, sertraline and venlafaxine. Thus, escitalopram appears to
be more economically efficient than many antidepressants currently available. Escitalopram has a
prominent role in the treatment of major depressive disorder and anxiety disorders, and may also prove
to be important in the treatment of mixed depressive anxiety disorder.
Introduction
Major depressive disorder (MDD) and anxiety disorders are common forms of affective disorder. MDD
has a lifetime prevalence of approximately 16%, and is associated with substantial symptoms and role
impairment.[1] The prevalence of anxiety disorders is 25%, which includes generalized anxiety disorder
(GAD), panic disorder, social anxiety disorder (SAD) and obsessive-compulsive disorder (OCD).[2]
Depression and anxiety are commonly concomitant, with 35-60% of patients with depression also having
an anxiety disorder.[1,3,4] Similarly, the proportion of patients with anxiety disorders who experience at
least one depressive episode can be as high as 70%.[5] Presence of both disorders is linked to poorer
outcome, greater disability, poorer quality of life (QoL) and greater costs compared with either MDD or
anxiety disorder alone.[6-8]Severe depression accounts for approximately one third of all outpatients diagnosed with depression and all hospitalized patients with depression.[9] Severe depression can be defined as a high score on a depression rating scale (e.g., scores of ≥28-30 on the Montgomery-Åsberg Depression Rating Scale [MADRS], of ≥25-28 on the 17-item Hamilton Depression Rating Scale [HAM-D-17] or ≥28 on the 21-item HAM-D).[10] On average, patients with more severe depression have worse clinical outcomes, poorer QoL, take more sick leave and cost more to treat than patients with mild-to-moderate depression.[10] Depression and anxiety also impose a substantial disease and economic burden on patients, caregivers and healthcare providers and services. In Europe, depression accounts for 6% of the burden of all diseases and 30% of the burden of all neuropsychiatric diseases, based on disability adjusted life- years;[11] the cost of treatment, including direct and indirect costs, is estimated to be €118 billion per year (€253 per inhabitant).[12] A breakdown of direct and indirect costs involved in the treatment of MDD and anxiety disorders is shown in Box 1. Drug acquisition costs alone have increased many times over in the last 20 years, mainly owing to increased prescribing and use, and higher cost products. [13] However, drug costs represent only 4-8% of total treatment costs, while 61-65% is accounted for by indirect costs, such as loss of productivity (e.g., sick leave, absenteeism or loss of productivity at work) or premature death.[12,14] The main cost drivers in depression and anxiety disorders are hospitalization, which is influenced by treatment efficacy (lower response and remission rates) and tolerability (side effects and treatment adherence), and work productivity.[15] Differences in antidepressant effectiveness can translate into economic savings: increased response and remission rates can lead to reduced healthcare resource use, including fewer physician visits, fewer referrals for specialist care, a reduced need for dose modification, switching and adjunctive medications, fewer sick days and lower hospitalization rates. [16] Overall cost per patient per year in Europe ranges from €1200 to €8000, of which indirect costs comprise approximately €750-6000.[12] A major aim of treatment for MDD and anxiety disorders is complete sustained remission and the prevention of relapse. Patients with depression who achieve remission (a maintained period of minimal depressive symptoms) have better prognosis, function and a more stable enduring state compared with patients who do not remit.[17] In addition, achieving remission leads to significantly reduced healthcare costs and improved QoL.[18] Selective serotonin reuptake inhibitor (SSRI) and serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressants are the preferred first-line therapy for MDD and anxiety disorders.[8] Escitalopram (Cipralex®, Lexapro®) is the therapeutically active S-isomer of the antidepressant citalopram.[19] It is a second-generation SSRI with activity on only one allosteric site and can, therefore, be classed as an allosteric serotonin reuptake inhibitor. It is the most selective serotonin-specific antidepressant marketed
to date.[19,20] The R-enantiomer is not only inactive but appears to somewhat counteract the antidepressant activity displayed by the S-enantiomer.[21,22] Escitalopram is approved for MDD and anxiety disorders (GAD, SAD, OCD and panic disorder).[23] Dose-ranging placebo-controlled trials showed escitalopram 10 mg/day to be the dose recommended for treatment of depression, titrating to 20 mg/day if required.[24-27] With many of the current pharmacological options being available in generic form (fluoxetine, citalopram, sertraline and paroxetine) in Europe or the USA, proof of value for branded drugs such as escitalopram, venlafaxine extended release (XR) or duloxetine is demanded, in order to justify the additional drug acquisition costs. Most economic studies focus on the overall burden of depression, making it difficult to identify the specific healthcare costs that could be affected by clinical differences between treatments. However, some studies specifically examine the extra cost of not achieving remission, allowing for greater understanding of the specific costs associated with pharmacological treatment. Several economic studies based on success (remission) rates as the main outcome have shown that nonremission is a major driver of the cost of treating MDD. For example, studies by François et al. and Demyttenaere et al. have demonstrated that the cost associated with nonremission is significantly higher than that of remission, mainly owing to additional costs for secondary care required.[28-30] Results from the Health Economics of Depression in Sweden (HEADIS) study, a naturalistic observational study in 426 patients with depression, showed that, over a 6-month observation period, remitting patients had significantly fewer outpatient visits and fewer sick-leave days (leading to €2700 lower total cost per patient; p < 0.01) and significantly improved health-related QoL scores compared with nonremitting patients (p < 0.01).[18] This article is the first to review published literature relating to the clinical efficacy, real-life effectiveness and economic efficiency of escitalopram for the treatment of MDD and anxiety disorders. The manner in which the headings efficacy, effectiveness and efficiency will be used in this review is represented briefly in Figure 1 and further defined below. Efficacy relates to the ability of a treatment or intervention to produce a therapeutic effect, as measured using strict scales (often the primary end point), in a clinical trial setting, in other words, where strict inclusion and exclusion criteria, scheduling, dosing and monitoring processes are applied. Effectiveness is the ability of a treatment or intervention to produce a therapeutic effect, either in a clinical trial setting (but assessed with more real-life clinical practice measures such as remission, patient-reported outcomes (PROs) and productivity - often secondary end points) or in observational studies, where physicians, other allied healthcare professionals and patients are not necessarily required to adhere to strict selection criteria, treatment regimes, or monitoring processes. Efficiency is defined as the cost-effectiveness of a treatment or intervention relative to other treatments or interventions for a given indication.
Figure 1. Overview of the terms efficacy, effectiveness and efficiency. Efficacy A common primary efficacy goal or end point in clinical trials of depression is change from baseline in scores on clinical scales. These scales include the MADRS, which comprises ten items rated from 0 (best) to 6 (worst),[31] and the HAM-D, which can contain varying numbers of items (e.g., 6, 12, 17, 21 or 24).[32] Remission and response to interventions are often additional objectives that can be measured in a clinical trial or clinical practice setting; however, remission as an outcome is the focus of the next section (Effectiveness) and, therefore, will not be discussed here. For anxiety disorders, the 24-item Liebowitz Social Anxiety Scale (LSAS) and the 14-item Hamilton Anxiety Scale (HAM-A) are commonly used investigator-reported measures in a clinical trial setting.[33] Escitalopram in Major Depressive Disorder Escitalopram is an efficacious and well-tolerated treatment for MDD.[24-27] Randomized controlled trials have shown that escitalopram is associated with significantly greater efficacy than placebo in MDD.[24,26,27,34] Escitalopram Versus SSRIs & SNRIs. Randomized controlled trials have also demonstrated escitalopram to be significantly more effective than citalopram in patients with MDD. [35,36] A meta-analysis of four trials (n = 1262) confirmed the superiority of escitalopram to citalopram, and showed the difference to be particularly marked in severely depressed patients.[37] The meta-analysis was recently updated[38] to include a head-to-head trial of escitalopram versus citalopram.[35] In the updated analysis, which included 1971 patients, mean changes in MADRS scores from baseline to end point were significantly higher for escitalopram versus citalopram (estimated mean difference, 1.20; 95% confidence interval [CI]: 0.35-2.05; p = 0.006).[38] Escitalopram produced a significantly greater response rate
(defined as the proportion of patients with a ≥50% reduction in the MADRS score from baseline), with a response rate of 59.0% compared with 52.9% for citalopram (odds ratio [OR]: 1.44; 95% CI: 1.17-1.77; p = 0.001).[38] The efficacy of escitalopram has also been compared with conventional SSRIs and SNRIs. In a meta- analysis of ten studies of antidepressant treatment for MDD, escitalopram (10-20 mg/day; n = 1345) was superior in reducing MADRS score compared with conventional SSRIs (citalopram, 20-40 mg/day; fluoxetine, 20-40 mg/day; paroxetine, 20-40 mg/day; sertraline, 50-200 mg/day; n = 1102) and the SNRI venlafaxine XR (75-225 mg/day; n = 240), with an estimated difference in treatment score of 1.07 (95% CI: 0.42-1.73; p
57.8%; OR: 1.93; 95% CI: 1.41-2.64; p < 0.001) and a higher remission rate (53.8 vs 45.9%; OR: 1.59; 95% CI: 1.16-2.16; p < 0.01) than comparators (citalopram, fluoxetine, paroxetine, sertraline or venlafaxine).[39] The results from these pooled and meta-analyses were supported by data from two randomized, double- blind clinical trials. In patients with severe depression at baseline (MADRS score ≥30), escitalopram 20 mg was found to be statistically significantly superior to citalopram (40 mg/day)[35] and paroxetine (40 mg/day).[36] Escitalopram in Anxiety Disorders Escitalopram is also approved for the treatment of anxiety disorders.[46] Its efficacy has been demonstrated in randomized, placebo- and active comparator-controlled trials in patients with GAD,[47-52] SAD,[53-55] panic disorder[56] and OCD.[57,58] Several trials have evaluated escitalopram for anxiety disorders; there are three trials for which economic analyses are also available, and these are discussed briefly here.[50-52] The data from two of these trials[50,51] were used to develop economic models for escitalopram in GAD[59-61] and one trial evaluated escitalopram for SAD,[52] alongside which a health economic study was conducted.[62] Allgulander et al. evaluated the efficacy and tolerability of escitalopram versus placebo for preventing relapse (following initial open-label escitalopram treatment) in GAD.[51] Time to relapse was longer (p < 0.001) and the proportion of patients who relapsed was lower (p < 0.001), with a 4.04-fold lower risk of relapse (p
negative impact of poor tolerability on adherence to treatment. In MDD, the overall adverse event frequency and the rate of premature discontinuation due to adverse events with escitalopram 10 mg/day do not differ from placebo.[24] A 24-week study showed that escitalopram and citalopram had similar adverse event profiles, but withdrawal rates were significantly higher with citalopram from weeks 9 to 24 (4.0 vs 11.2%; p < 0.05), suggesting that long-term tolerability was better with escitalopram.[63] Escitalopram is better tolerated than the SNRIs venlafaxine and duloxetine; trial withdrawal rates owing to adverse events for escitalopram were significantly lower than venlafaxine (p < 0.05)[39] or duloxetine (p < 0.05).[40-42] Escitalopram tolerability in patients with anxiety disorders is similar to that seen in MDD.[47,53,56] While most of the anxiety studies were 8-12 weeks in duration, and there are no comparative data available in this patient group,[20] escitalopram was also shown to be well tolerated in 24-week studies in SAD[55] and OCD.[57] Long-term tolerability is particularly important in patients with panic disorders owing to the recommended 12-month minimum duration of treatment.[64] Effectiveness The effectiveness of antidepressant treatments can be evaluated using various validated outcomes that are closer to real-life efficacy than those commonly used as primary end points in clinical trials. These include remission rates, QoL measures, PROs and productivity (i.e., how effective a treatment is at reducing the number of sick leave days/absenteeism). In addition to clinical trials, outcomes reported in observational studies can be valuable measures of effectiveness in a real-world setting. Remission Remission has been recognized as a valid and clinically relevant end point for both investigators and practitioners, and is the desired goal of both acute and long-term treatment.[65] Remission can be defined as the absence of (or presence of minimal) major depressive symptoms (sadness and reduced interest/pleasure) plus the presence of less than three of the remaining Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria for three or more consecutive weeks.[17] Remission may also be defined as a score within the normal range on a rating scale (e.g., MADRS score of ≤12 or HAM-D-17 score of ≤7).[31] The effectiveness of escitalopram versus citalopram was evaluated in a double-blind trial, in which outpatients with baseline MADRS scores of 30 or more received fixed doses of escitalopram (20 mg/day; n = 138) or citalopram (40 mg/day; n = 142) for 8 weeks.[35] A secondary end point of the trial was
remission rate (where remission was prospectively defined as MADRS total score ≤12). The remission rate was significantly higher in the escitalopram group versus citalopram group (56.1 and 43.6%, respectively; p = 0.04). The corresponding adjusted number of patients needed to treat for remission was nine (95% CI: 4-117).[35] In the meta-analysis comparing five trials of escitalopram versus citalopram, the remission rates were 47.1 versus 43.3% (OR: 1.27; 95% CI: 1.03-1.57; p = 0.023).[38] Patient-reported Outcomes PRO is a measurement of any aspect of a patient's health status that comes directly from the patient.[66] Measuring PRO in clinical trials can provide evidence of a treatment benefit from the patient perspective. PRO instruments (such as questionnaires) can measure a range of aspects of treatment, from single symptoms to broader concepts, such as QoL. Beyond clinical trials, researchers are also investigating how PROs can be used in clinical practice to improve the treatment of patients.[66] The MADRS-S is a PRO based on the MADRS.[67] This instrument was used to assess treatment effectiveness in the head-to-head study of escitalopram versus citalopram.[35] The mean change from baseline to end point in MADRS-S score was in favor of escitalopram (-9.9 vs -8.6 for citalopram) and the treatment difference of 1.3 was statistically significant (p < 0.05).[35] This difference was also clinically relevant, as it has been suggested that an improvement of 5% on a PRO is meaningful;[67] the MADRS-S range is 0 to 27,[68] therefore, an improvement of 1.3 can be considered clinically relevant. Another PRO instrument, which specifically evaluated the QoL during treatment with escitalopram, is the 15-item Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q15).[69] A secondary analysis of data from the randomized, double-blind, placebo-controlled parallel group trial performed by Burke and colleagues included results of Q-LES-Q15.[24] In this trial, in which citalopram (40 mg/day) was an active reference to two dose levels of escitalopram (10 and 20 mg/day), 20 mg escitalopram was superior on the Q-LES-Q15 to both escitalopram 10 mg and citalopram 40 mg (p ≤ 0.01).[70] The effect of escitalopram on Health Related Quality of Life (HRQoL) in anxiety disorders has been assessed. In an HRQoL evaluation conducted alongside an escitalopram-relapse prevention trial during the 12-week open-label escitalopram treatment period, patients reported significant improvements in HRQoL on all dimensions of the SF-36 health survey (p < 0.001).[71] In a 24-week relapse prevention study in patients with SAD, escitalopram-treated patients reported significant improvement versus placebo on the following SF-36 dimensions: mental health (p < 0.001), social functioning (p = 0.001), role
emotional and vitality (p < 0.05).[62] In panic disorders, escitalopram was significantly better than placebo in improving QoL (measured by the Q-LES-Q total score).[72] Productivity Work productivity is often decreased in patients with depression because they take sick days more often and for a longer duration (increased absenteeism from work), and have reduced productivity during days at work (known as presenteeism).[73] An economic comparison of escitalopram versus citalopram was conducted [74] alongside the head-to- head trial.[35] The percentage of patients taking sick leave days (25.4 and 26.8%) and the average number of sick leave days taken (9.46 and 9.28 days) were similar for both escitalopram and citalopram in the 2-month pre-study period. However, both measures increased slightly in the 2-month study period; the increase was greater in the citalopram group (31.7 and 12.18 days) than the escitalopram group (26.8% and 11.56 days); the difference in number of sick leave days between the two drugs was statistically significant (p < 0.01).[74] The observed increase in sick leave from pre-study period to treatment period may have been due to recall bias (i.e., patients being unable to remember accurately the number of sick days they took in the pre-study period); since the trial was randomized, however, the bias should be equal for both treatment groups. The randomized, double-blind trial comparing 24 weeks of escitalopram with duloxetine treatment[40] incorporated a parallel economic analysis.[75] Escitalopram was associated with 58% shorter duration of sick leave over the 24 weeks compared with duloxetine (p < 0.001).[75] Escitalopram Effectiveness in Observational Studies Results from observational and naturalistic studies support those from randomized clinical trial settings with regards to the effectiveness of escitalopram. In a prospective, naturalistic, 8-week study comparing escitalopram (n = 67) with citalopram (n = 60) for severe MDD (baseline MADRS score ≥30), significantly greater improvements were observed in MADRS score (p < 0.001), response rate (according to Clinical Global Impression of Severity [CGI-S] and Improvement [CGI-I] scales; p < 0.001), and remission rate (MADRS score ≤12; p < 0.001) in patients who received escitalopram versus citalopram.[76] A large (11,760 patients) multicenter German study, evaluating the effectiveness of escitalopram for MDD (all severities), was conducted in private practice clinics.[77] Of the 10,477 patients who completed 8 weeks of escitalopram treatment, 66% were treated in a general practitioner setting, and 33% were
treated by specialists. The response rate was 70% (≥50% decrease in score according to the short
version of the MADRS [svMADRS]) and the remission rate was 56.8% (svMADRS score ≤12) at week
8.[77] Similar to results from clinical trials, a higher response was observed in patients suffering from
severe depression (baseline svMADRS ≥30).
Escitalopram significantly reduced the number of (patient reported) sick leave days (11.0 vs 5.4 days for
the 3-month pre-study period vs the 3-month study period; p < 0.001) in an observational study of 2378
outpatients with mood or anxiety disorders in Austria.[78] CGI-S scores were also significantly improved
between baseline and 3 months of treatment with escitalopram (p < 0.001).[78]
A 12-month study of 590 patients with MDD treated with open-label escitalopram following participation
in double-blind acute trials found a favorable safety and tolerability profile with low withdrawal rates.[79]
Clinical response also steadily increased during the study period, with 86% of patients achieving
remission (MADRS score ≤12) by the end of 52 weeks. Response rates of 68% (measured as score ≤2
on the clinician assessed CGI-I) or 66% (≤2 on the patient global evaluation score) were observed in an
8-week open-label trial of escitalopram in 5433 patients with MDD treated in primary, psychiatric or other
speciality practices.[80]
Efficiency
Given the efficacy and effectiveness of escitalopram in the treatment of MDD and anxiety disorders, its
cost-effectiveness compared with other treatments is an important consideration.
Pharmacoeconomic Analyses of Escitalopram
Economic evaluations of escitalopram for the treatment of depression include three prospective studies,
conducted alongside clinical trials comparing escitalopram with citalopram,[74] venlafaxine[81] or
duloxetine,[40] and ten studies using decision analytical models comparing escitalopram with citalopram
and/or venlafaxine in various countries.[82] summarizes the studies comparing the pharmacoeconomics of
escitalopram with other antidepressants in the treatment of MDD.
Table 1. Summary of Escitalopram Pharmacoeconomic Studies in Patients With Major Depressive
Disorder, Severe Depression and Anxiety Disorders
Escitalo
pram
dose
Country/cu Clinical and Patie Main
rrency data compara nt Study outcome Commen
Study (year) source tor type design measure Results t Ref.Prospective studies
Fantino France/€ RCT ESC: 20 MDD Prospe Remissio Mean Lower [35,74]
mg/day; OP (n ctive n cost per ADR with
CIT: 40 = societal patients escitalop
mg/day 294) perspec were ram due
tive 41% to lower
(direct lower hospitaliz
healthc with ESC ation
are vs CIT rate;
costs (€96 vs ICER
plus 163; p < showed
cost of 0.05) ESC to
sick be more
leave) cost
effective
than CIT
Fernand European RCT ESC: MDD Prospe EQ-5D Total ICER [90,102
ez (UK, 10-20 OP (n ctive costs showed ]
Denmark, mg/day; = CE significan ESC to
Finland, VEN XR: 251) payer tly lower be at
France, 75-150 perspec with ESC least as
Germany, mg/day tive after cost
Spain)/€ (societa adjustme effective
(2001) l nt for as VEN if
perspec other not more
tive in cost
sensitivi drivers (p
ty = 0.007)
analysis
include
d
estimat
ed
costs of
lost
producti
vity)
Modeled analyses
Armstron US/$ Two ESC: MDD 6- Cost per Total ICER [24,85,
g (2005) RCTs 10-20 OP month QALY direct showed 102]
mg/day; CUA gained costs: ESC
SER: model $919 for dominate
50-200 (direct ESC and d SER
mg/day costs $1351 for
only) SER;
QALYs
gained:
0.403 for
ESC and
0.393 for
SER;
Differenc
e mainly
due to
drug
titrationcosts and
adverse
events;
Cost/QA
LY:
$2280 for
ESC and
$3440 for
SER
Demytte Belgium/€ One ESC: MDD 6- Remissio Success [16,28]
naere (2003) MA, ad 10-20 OP month n rates
hoc mg/day; two- (success) (remissio
survey CIT: 20- path rates n at week
and 40 decisio 8
expert mg/day; n sustained
panel VEN XR: analytic at week
75-150 model; 24):
mg/day two 62.3%
parallel with ESC
analyse vs 57.2%
s: ESC with CIT;
vs CIT; 66.6%
ESC vs with ESC
VEN vs 67.0%
with
VEN;
Total
costs
were
lower for
ESC than
CIT from
payer
(€390 vs
411) or
societal
(€1162
vs 1276)
perspecti
ve; Total
costs
were
lower for
ESC than
VEN
from
payer
(€333 vs
350) or
societal
(€1002
vs 1036)
perspecti
ve
François Finland/€ Data ESC: MDD 6- Remissio Overall Sensitivit [29]
(2000) from 10-20 OP month n success y
several mg/day; two- (success) rate analysisRCTs, CIT: 20- path rates higher for showed
literatur 40 decisio (CE, ESC vs that ESC
e review mg/day; n QALY, other was
and FLU: 20- analytic CU) ADs; associate
expert 40 model; Average d with
panel mg/day; CE and expected lower
VEN: CU total costs
75-150 analyse costs and
mg/day s were higher
similar success
for ESC rate than
and VEN CIT or
(€857 FLU;
and 876), ESC
and more
higher for cost
CIT and effective
FLU than
(€990 VEN due
and 959); to lower
Cost/suc costs
cess and
higher similar
with ESC success
than rates
other
ADs;
Cost/QA
LY higher
than with
other
ADs
François Norway/ Data ESC: MDD 6- Remissio Success Sensitivit [30]
NOK from 10-20 OP month n rates y
(2000) several mg/day; two- (success) highest analysis:
RCTs, CIT: 20- path rates with ESC ESC
literatur 40 decisio (64.2 vs remained
e review mg/day; n 58.7, more
and FLU: 20- analytic 58.7 and cost
expert 40 model 62.1% effective
panel mg/day; CE with CIT, than FLU
VEN: (direct FLU and and CIT
75-150 costs VEN, even at
mg/day only) respectiv the
ely); extremes
Total of values
costs and likely
similar to be
for ESC more
and VEN cost
and effective
higher for than
CIT and VEN
FLU;
Total
cost per
success:
ESC30,600N
OK; CIT
38,000N
OK; FLU
38,400N
OK; and
VEN
33,800N
OK
François Sweden/ Compar ESC; MDD 6- Remissio Success Increase [83]
SEK (2000) ative CIT; OP month n rates: drug
trial FLU; two- (success) ESC costs
data, VEN path rates 63.5%; more
publishe decisio CIT than
d n 57.2%; offset by
literatur analytic FLU decrease
e and model; 57.0%; in other
expert CE VEN healthcar
opinion (payer 61.1%; e costs
perspec Cost per
tive) patient:
ESC
SEK15,6
70; CIT
SEK18,8
60; FLU
SEK19,0
50; VEN
16,580
Hemels Austria/€ One ESC: MDD 6- Remissio Success Sensitivit [26,86]
(2002) RCT, 10-20 OP month n rates: y
current mg/day two- (success) ESC analysis:
practice CIT: 20- path rates 64.5%; ESC
and 40 decisio CIT remained
expert mg/day n 59.1%; dominant
opinion analytic Cost per even
model; success: when
CE Payer: CIT drug
(payer €608 vs cost = 0
and 723;
societal Society:
perspec €3034 vs
tive) 3670
Hemels Austria/€ RCT ESC: MDD 6- Remissio Success Sensitivit [90,103
(2002) 10-20 OP month n rates: y ]
mg/day; two- (success) ESC analysis:
CIT: 20- path rates 64.5%; ESC
40 decisio CIT remained
mg/day; n 59.1%; dominant
VEN XR: analytic VEN in both
75-150 model; 62.2%; payer
mg/day CE Cost per and
(payer success societal
and (ESC vs perspecti
societal CIT and ve
perspec VEN): analysestive) Payer:
€608 vs
723 and
650;
Society:
€3034 vs
3670 and
3269
Hemels Denmark/D One ESC: MDD 6- Remissio Success Sensitivit [16,93]
KK (2004) RCT 10-20 OP month n rates: y
current mg/day; two- (success) ESC analysis:
practice CIT: 20- path rates 61.1% vs ESC
and 40 decisio CIT remained
expert mg/day; n 58.9%; dominant
opinion VEN XR: analytic ESC in both
75-150 model; 69.1% vs payer
mg/day two VEN and
parallel 68.6%; societal
analyse Cost per perspecti
s: ESC success: ve
vs CIT; ESC vs analyses
ESC vs CIT;
VEN; Payer:
CE 23,535D
(payer KK vs
and 25,943D
societal KK;
perspec Society:
tive) 75,991D
KK vs
87,926D
KK; ESC
vs VEN;
Payer:
16,767D
KK vs
17,847D
KK;
Society:
56,782D
KK vs
58,717D
KK
Kulp Germany/€ Clinical ESC: 10 MDD 70-day Remissio ESC was ICER [91]
data mg/day; OP CE n associate favored
and VEN XR: Markov (success) d with ESC
physicia 75 model rate similar over
ns mg/day success VEN XR
survey rates and
lower
costs
than VEN
XR
(€7446
vs 9836)
Sørense Denmark/D System ESC: MDD 6- Remissio ESC had Sensitivit [87]n KK (2004) atic 10-20 OP month n a lower y
literatur mg/day; three- (success) cost per analysis
e CIT: 20- path rate success showed
review, 40 decisio than CIT: ESC to
ad hoc mg/day; n Payer: be more
survey VEN XR: analytic 22,323D cost
and 75-150 model; KK vs effective
expert mg/day Payer 25,778D than CIT
opinion and KK; and
societal Societal: similar in
perspec 72,399D cost-
tive KK vs effective
87,786D ness to
KK; VEN
Success
rates and
costs
were
similar
for ESC
and VEN
Sullivan USA/$ Literatur All MDD 6- EQ-5D- ESC was Sensitivit [84]
(2003) e review currently OP month based the least y
markete two- QALY costly of analysis
d SSRIs: path (including all SSRIs showed
ESC, decisio relative and had that ESC
CIT, n rates of the was the
FLU, analytic ADRs) highest most
PAR, model; effectiven likely to
PAR CE and ess be cost
CR, CU effective
SER,
VEN and
VEN XR
Wade UK/£ Meta- ESC: MDD 6- Remissio ESC vs ESC [16,92]
(2003) analysis 10-20 OP month n rates, CIT: dominate
of RCTs mg/day; two- relapse costs d CIT;
and CIT: 24- path rates and were ESC had
GPRD 40 decisio adverse lower lower
data, mg/day; n events and cost per
publishe VEN XR: analytic success success
d 75-150 model; rate than
literatur mg/day Payer higher VEN but
e and and with differenc
expert societal ESC. e was
opinion perspec Costs per not
tive success significan
were 732 t
vs 933
(payer)
and 3635
vs 4519
(societal)
; ESC vs
VEN:
costs
werelower
with ESC
and
success
rates
similar.
Costs per
success
were 546
vs 607
(payer)
and 2640
vs 2693
(societal)
Severe depression
Danchen Norway/NO Data ESC: SD 12- Remissio ESC vs Results [96]
ko K (2006) from 10-20 OP month n rates CIT: robust to
several mg/day; (MAD two- higher changes
RCTs, CIT: 20- RS path effectiven but
literatur 40 ≥30 decisio ess and model
e mg/day; at n lower substanti
review, VEN: baseli analytic costs ally
national 75-225 ne) model; (cost per depende
sources mg/day societal success: nt on
and perspec 113,213 productiv
expert tive NOK vs ity loss
panel 123,971 inputs
NOK);
ESC vs
VEN:
higher
effectiven
ess (1st
line) and
QALYs
(cost per
success:
106,733
NOK vs
115,548
NOK)
Wade UK/ £ Meta- ESC: SD 6- Remissio ESC Sensitivit [44,94]
(2003) analysis 10-20 (MAD month n, costs y
of RCTs mg/day; RS two- discontin were analysis
and CIT: 24- ≥30 path uation lower showed
GPRD 40 at decisio and and that ESC
data, mg/day baseli n response success dominate
publishe ne) analytic rates rate d CIT
d model; higher
literatur payer with ESC
e and and vs CIT;
expert societal Total
opinion perspec cost per
tive success:
ESC
£786 vsCIT £932
(payer)
and
£1283 vs
£1521
(societal)
Hemels Austria/€ Pooled ESC: SD 6- Remissio ESC vs Sensitivit [43,104
(2002) analysis 10-20 (MAD month n rates CIT y ]
of three mg/day; RS two- success analysis
RCTs CIT: 20- ≥30 path rates showed
40 at decisio 53.7 vs that ESC
mg/day baseli n 48.7%; dominate
ne) analytic Total d CIT
model; cost per even if
Payer success: CIT drug
and ESC cost = 0
societal €2879 vs
perspec CIT
tive €3803
(payer);
€5610 vs
€6979
(societal)
Anxiety disorders
Jørgense UK/£ RCT, ESC: GAD 9- Success Success Sensitivit [50,59,
n (2005) epidemi 10-20 month (response rates y 105]
o- mg/day; two- at 12 were analysis
logical PAR: path weeks higher demonstr
study, 20-50 decisio and no and costs ated
publishe mg/day n relapse lower ESC
d analytic after with ESC dominan
literatur model further 24 vs PAR ce over
e and based weeks) (lower PAR
expert on costs due even
opinion NICE to lower when
treatme rates of PAR
nt sick drug cost
guidanc leave, =0
e; secondar
societal y care
perspec and
tive switch
rates);
Total 9-
month
costs:
ESC
£8434 for
ESC vs
£9843
PAR
Servant European/€ RCT ESC: SAD Prospe Relapse Improved Higher [52,62]
(2005) 10-20 ctive preventio PRO with efficacy
mg/day societal n and ESC (p < and
perspec PRO 0.05); lower
tive 2.8-fold costs vs(direct reduced placebo;
costs risk of Costs
and relapse with
sick with ESC ESC, but
leave (p < not
costs) 0.0001); placebo,
Cost per decrease
relapse d over
with ESC study
prevente period
d €400
AD = Antidepressant; ADR = Adverse drug reaction; CE = Cost-effectiveness; CIT = Citalopram; CR =
Controlled release; CU = Cost-utility analysis; EQ-5D = 5-item EuroQoL questionnaire; ESC =
Escitalopram; FLU = Fluoxetine; GAD = Generalized anxiety disorder; ICER = Incremental cost-
effectiveness ratio; MA = Meta-analysis; MADRS = Montgomery-Åsberg Depression Rating Scale; MDD
= Major depressive disorder; NICE = National Institute for Clinical Excellence; OP = Outpatients; PAR =
Paroxetine; PRO = patient-reported outcome; QALY = Quality-adjusted life years; RCT = Randomized
controlled trial; Remission rate = Proportion of patients with MADRS ≤12 at end point; SAD = Social
anxiety disorder; SD = Severe depression; SER = Sertraline; SSRI = Selective serotonin reuptake
inhibitor; VEN = Venlafaxine; XR = Extended release
Escitalopram Versus SSRIs in Major Depressive Disorder
Several studies have shown escitalopram to be cost effective compared with standard SSRIs. [29,30,74,82-85]
The cost-effectiveness of escitalopram versus citalopram has been assessed extensively.
Escitalopram Versus Citalopram
The economic evidence for escitalopram versus citalopram has been generated using three different
methodologies:
A prospective cost-effectiveness analysis[74]
Nine country-specific economic modeled analyses[82]
Simple model based on the evaluation of cost of remission versus nonremission [18]A prospective cost-effectiveness analysis of escitalopram versus citalopram, based on the double-blind randomized clinical trial performed by Moore and colleagues[35] in 294 outpatients with MDD, showed that escitalopram was dominant over citalopram (i.e., that escitalopram was more effective and associated with significant cost-savings).[74] Patients receiving escitalopram were significantly more likely to achieve remission (55 vs 44%; p < 0.05). Mean per-patient costs were 41% lower (€96 vs €163; p < 0.05) for the escitalopram group compared with the citalopram group, mainly accounted for by differences in hospitalization costs.[74] In the cost-effectiveness analysis, bootstrapped CIs on the difference in costs and effectiveness were significantly in favor of escitalopram.[74] The prospective data generated by Fantino et al. are consistent with data from modeled analyses. A qualitative review of eight country-specific economic modeled analyses (seven European countries and Canada), using best practice according to the healthcare system in each country, concluded that escitalopram is cost effective compared with citalopram and may provide cost-savings from both healthcare payer and societal perspectives. Effectiveness measures included remission rates or PRO, and cost-effectiveness was expressed as cost per successfully treated patient. Savings were mainly attributed to lower rates of referral for specialist care and hospitalization.[82] Economic analyses in Finland, Sweden and Norway using a 6-month, two-path decision analysis model developed by François et al. found that escitalopram was cost effective compared with citalopram when used as first-line therapy for MDD.[29,30,83] In the Finnish study, escitalopram dominated citalopram, in other words, escitalopram was associated with lower costs and more quality-adjusted life years (QALYs) gained.[29] Economic studies in Austria[86] and Belgium[28] produced similar results with an adapted 6-month two-path decision analytic model using remission rates as the main outcome. Hemels et al. showed that escitalopram was cost effective compared with citalopram from the perspective of the healthcare insurance system and society.[86] Data from the economic analysis by Demyttenaere et al. also showed that escitalopram was dominant (less costly with more patients in remission) over citalopram. The main cost driver was the difference in remission rates between the two treatments.[28] A recent Danish study also showed significant dominance of escitalopram over citalopram owing to greater clinical benefit and reduced costs for both payers and society.[87] A simple modeling approach to compare the cost-effectiveness of escitalopram with citalopram is to perform a cost analysis of remission. Using the remission rates observed in the meta-analysis by Lançon et al. (escitalopram, 47.1%; citalopram, 43.3%) and the 6-month costs of remission and nonremission estimated in the HEADIS study (cost of remission: €4221 and cost of nonremission: €6894 per patient treated),[18,38] the 6 month cost per 100 patients can be estimated at €563,502 for escitalopram-treated patients versus €573,659 for citalopram-treated patients (a net saving of €10,157 with escitalopram).
Escitalopram Versus SNRIs in Major Depressive Disorder Escitalopram Versus Venlafaxine. A review of clinical and economic studies suggests that, given the fact that escitalopram is at least as effective and better tolerated than venlafaxine XR, it may be more cost effective.[88] A prospective economic study found that escitalopram was at least as cost effective as venlafaxine XR.[81] These results contradict the perception that venlafaxine is superior (in cost- effectiveness terms) to SSRIs, which was possibly gained from data from earlier studies comparing venlafaxine with older SSRIs.[89] Doyle and colleagues performed a multinational (ten countries) pharmacoeconomic analysis comparing venlafaxine immediate release (IR) with SSRIs and tricyclic antidepressants for MDD using a decision analytic model.[89] Venlafaxine IR was less costly per patient success (50% reduction in HAM-D or MADRS score) than SSRIs (each country analysis including at least two of citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline), except in Poland (inpatient setting) and Italy (outpatient setting).[89] The prospective cost-effectiveness analysis of escitalopram versus venlafaxine XR mentioned previously[81] was conducted in tandem with an 8-week, randomized, double-blind, clinical trial that compared escitalopram (10-20 mg/day) with venlafaxine XR (75-150 mg/day) in patients with MDD.[90] The analysis, using the 5-dimension EuroQoL questionnaire (EQ-5D) as the primary efficacy measure, was performed from the perspective of the healthcare payer and included 251 patients from several European countries.[81] Both treatment groups achieved a significant and similar improvement in QoL. Total treatment costs per patient were 32% lower with escitalopram compared with venlafaxine XR (€110 vs 161), as a result of lower drug acquisition costs (€62 vs 84) and fewer hospitalizations (inpatient care costs, €0 vs 46), but this difference was not statistically significant. A multivariate analysis was performed, adjusting for factors associated with healthcare costs (receiving escitalopram, being from French or British sample, male sex, age ≥60 years, living alone or in an urban area, being unemployed or a nonworking spouse, and having at least some problems on EQ-5D self-care, usual activities or pain dimensions); escitalopram was associated with significantly lower costs than venlafaxine XR (40% lower for the average patient; p = 0.007). Both drugs were effective and an analysis of the EQ-5D scores showed no difference between the drugs. Hence, although escitalopram was not found to be dominant (i.e., more effective and less costly), it was associated with lower costs and equal effectiveness compared with venlafaxine XR.[81] The qualitative review of country-specific economic modeled analyses discussed previously (comparing escitalopram with citalopram) also included studies comparing escitalopram with venlafaxine XR.[82] These analyses have indicated that escitalopram treatment is associated with lower total costs than venlafaxine XR treatment in MDD.[28-30,83,91] In Danish and UK modeled analyses of escitalopram- and
venlafaxine-related costs, escitalopram was associated with higher success (remission) rates, and lower total, direct and indirect costs compared with venlafaxine.[92,93] In addition, a US modeled analysis showed that escitalopram was likely to be more cost effective than venlafaxine XR, from the perspective of a US- managed care payer, owing mainly to the lower costs associated with fewer adverse drug reactions. [84] Of the published economic analyses comparing escitalopram with venlafaxine, one report (a country- specific modeled analysis conducted in Denmark) showed that escitalopram was associated with a slightly higher 6-month remission rate and was slightly less expensive than venlafaxine;[87] the other studies showed larger differences in effects and costs. A recent review of head-to-head clinical studies and economic analyses comparing escitalopram and venlafaxine XR concluded that escitalopram is at least as effective as venlafaxine XR in terms of improvements in MADRS score from baseline, response and remission rates and health-related QoL, and may have advantages in terms of tolerability, time to remission and cost-effectiveness. Greater cost- effectiveness has been demonstrated from both a payer and a societal perspective. [88] Escitalopram Versus Duloxetine. The cost-effectiveness analysis conducted alongside the clinical trial comparing 24 weeks of escitalopram with duloxetine in outpatients with MDD[40] revealed that escitalopram appeared to be more effective on the Sheehan Disability Scale and less costly than duloxetine.[75] Among patients who completed 24 weeks of treatment, patients receiving escitalopram had significantly lower total cost (over £1000) compared with duloxetine (p = 0.002), and a 58% reduction of sick-leave duration (p
versus £933 (21.5% lower) from a UK National Health Service perspective, and £3635 versus £4519 (19.6% lower) from a societal perspective.[92] Similarly, in the severe depression study of patients with baseline MADRS score of 30 or more, success (remission) rates were higher and costs were lower with escitalopram compared with citalopram: success rates were 53.7 versus 48.7% and total costs were £422 versus £454 (NHS perspective) and £690 versus £740 (societal perspective). Again, average cost per success for escitalopram versus citalopram were £786 versus £932 (15.7% lower) from an NHS perspective, and £1283 versus £1521 (15.6% lower) from a societal perspective.[94] Multivariate analysis showed that escitalopram was the more effective therapy from both perspectives and, even with citalopram costs given as zero, escitalopram remained the more cost-effective therapy from a societal perspective. Two Norwegian analyses compared the cost-effectiveness of escitalopram with other antidepressants, one in MDD and one in severe depression.[95,96] Both models were probabilistic, two-path decision analytic models, using remission as the outcome and head-to-head clinical trial data, published data, national sources and expert panel estimations for costs and utilization. In the MDD study, escitalopram was compared with citalopram, fluoxetine and venlafaxine: overall success (remission) rates were 64.2, 58.7, 58.7 and 62.1%, respectively. Escitalopram was dominant over all comparators, being more effective and less costly when total, direct or indirect costs were taken into consideration; 6-month cost per success was 6700NOK, 8400NOK, 8550NOK and 8200NOK, respectively, from the payer perspective, and 30,600NOK, 38,000NOK, 38,400NOK and 33,800NOK, respectively, from a societal perspective. [95] In the study of patients with severe depression (baseline MADRS score ≥30), escitalopram was compared with citalopram and venlafaxine from a societal perspective over a 12-month period. Again, escitalopram was more effective and less costly than both citalopram and venlafaxine. For escitalopram versus citalopram, success (remission) rates were 53.6 versus 49.0% and costs per patient were 113,213 versus 123,971NOK. For escitalopram versus venlafaxine, costs per patient were 106,733NOK versus 115,548NOK.[96] Cost-effectiveness of Escitalopram in Anxiety Disorders There have been fewer economic analyses of escitalopram in the treatment of anxiety disorders than for MDD. Results from three analyses of escitalopram for GAD are available; two for escitalopram versus paroxetine (one UK[59] and one US[60,61]), and one for escitalopram versus venlafaxine (US).[97] For SAD, the cost-effectiveness of escitalopram compared with placebo for the prevention of relapse has been analyzed.[98,99] No economic analyses of escitalopram for OCD have been published to date. Generalized Anxiety Disorder. In the UK study comparing the cost-effectiveness of escitalopram and paroxetine in the treatment of GAD, the analysis was performed from a societal perspective using a 9-
month decision analytic model, adapted to the UK setting based on treatment success (defined as response after 12 weeks of treatment and no relapse during the following 24 weeks) as the main outcome measure.[59] The first-line success rate was higher in escitalopram recipients (49.6 vs 35.2%) and discontinuation rates due to adverse events were significantly lower than with paroxetine. Escitalopram was associated with lower total costs and resource use, resulting from lower rates of switching drugs and lower use of secondary care owing to increased work productivity.[59] Erder and colleagues evaluated both escitalopram versus paroxetine and escitalopram versus venlafaxine for GAD in a US setting.[60,61,97] Both studies used cost-minimization models from a US managed-care perspective, and were based on outcomes and costs from randomized, parallel-group, fixed dose, multicenter trials.[50,100] A 13% lower cost was associated with escitalopram versus paroxetine, primarily owing to fewer hospitalization days, a result that was robust, as determined through sensitivity analysis.[60,61] Cost-savings (60%; cost per patient, US$136 vs US$334) were also observed with escitalopram versus venlafaxine XR.[97] Social Anxiety Disorder. In a double-blind, placebo-controlled trial of escitalopram for SAD, there were significant improvements in PRO (SF-36 scores) in the escitalopram group compared with placebo group.[62] The total costs (from a societal perspective) in the escitalopram group decreased significantly from baseline to end of study (p = 0.02), while those in the placebo group remained constant. The incremental cost per relapse prevented with escitalopram was estimated to be €400. [62] Expert Commentary The clinical efficacy of escitalopram is superior to placebo, and equal or superior to the SSRIs and SNRIs currently available, and has a better tolerability profile. The real-life effectiveness of escitalopram, as shown through clinical and observational studies, is also well founded. In terms of economic efficiency, the cost-effectiveness and cost-utility advantages of escitalopram compared with other SSRIs and the SNRI duloxetine has been demonstrated in prospective studies,[62,74,75,81] modeled analyses[28-30,59-61,83,86,87,94,96] and meta-analyses/systematic reviews.[82,88] The cost advantages of escitalopram were independent of the geographical area studied, specific outcomes and sources of costs employed in the analyses, perspective used (payer or societal) and indication or comparator agents investigated. All retrospective modeled analyses were country specific since valid models, using data from more than one country, are difficult to construct, although not impossible. [89] Simple models employing remission data as the primary outcome showed similar results to those using more complex decision trees. Most studies utilized methods of validating the data whether by sensitivity
analyses, data adjustment for baseline factors other than treatment known to impact cost and/or calculation of incremental cost-effectiveness ratios. In both the modeled and the prospective analyses, the main reason for the reduction in overall direct costs with escitalopram therapy was the reduced need for secondary care, particularly hospitalization, and lower product costs than other branded antidepressants. The relative cost-effectiveness of escitalopram was more pronounced when productivity-related costs (sick leave) were included in the model. When the costs of nonremission versus remission are taken into consideration, escitalopram, based on its superior ability to improve remission rates, provides more cost savings relative to other treatments; these cost-savings outweigh cost-savings made through the use of generic versions of drugs. These findings show that escitalopram is more cost effective than other SSRIs and at least as cost effective as venlafaxine in MDD; the single study comparing escitalopram with duloxetine suggests that escitalopram is more cost effective, although further studies are required to confirm this. What is also significant is that many of the analyses included comparisons with generic agents (fluoxetine and citalopram). Compared with these agents, escitalopram was shown to be more cost effective, even when some analyses set the generic drug acquisition cost as zero, suggesting that the drug acquisition cost is not the primary driver of cost of treatment in these disorders. Most cost analyses used a 6-month time frame. Therefore, longer-term prospective economic studies or prolonged modeling analyses are needed to investigate whether the cost benefits achieved with escitalopram are maintained over the longer term. This is important owing to the chronic nature of these disorders and the likelihood of the need for long-term treatment. Another potential limitation is that all these studies (as with most economic analyses of medications) were sponsored by the manufacturer of escitalopram; although the studies were randomized and double-blind, sponsor bias cannot be ruled out entirely. Escitalopram has clearly demonstrated cost-effectiveness benefits for MDD, severe depression and anxiety disorders. This, together with the fact that the majority of patients with depression also have comorbid anxiety, suggest that escitalopram has the potential to provide similar clinical benefits in patients with mixed depressive anxiety disorder and these benefits may translate into greater cost- effectiveness compared with other agents. However, this needs to be formally demonstrated in robust cost analyses in this population. MDD and anxiety disorders are difficult to differentially diagnose in many
patients in the primary care setting, therefore a single, effective and well-tolerated drug for first-line therapy of individual disorders or comorbid disorders is attractive. As has been shown in these analyses, one of the main drivers for the lower costs with escitalopram therapy is its benign tolerability profile. This, together with less titration required compared with sertraline and the SNRIs, facilitates the management of patients with depression and comorbidities. In conclusion, extensive evidence from clinical and economic studies and meta-analyses shows that escitalopram is good value for money. It is effective in reducing symptoms of depression and anxiety, in preventing relapse and improving remission rates, and this can typically be achieved without compromising safety and at lower overall costs of treatment compared with several agents. Five-year View The WHO predicts that by 2020 MDD is expected to move from fourth to second place in terms of greatest global disease burden, therefore increasing attention to the health burden of MDD and anxiety disorders is expected in the next 5 years.[101] Recent improvements in the understanding of the precise distinctions between the different depressive and anxiety disorders should lead to improvement in differential diagnosis based on revised International Classification of Disease classification and revised diagnostic criteria in DSM, particularly in anxiety disorders and mixed depressive-anxiety disorder. Healthcare funding in many countries is coming under increasing pressure, therefore recognition of the main drivers of cost of treatment may need to improve. For example, healthcare payers need to be aware of the relatively low impact of drug cost on total disease costs (direct and indirect) and the high rate and costs of absenteeism and presenteeism in inadequately treated patients. In addition, payers should appreciate the impact of treatments to reduce total health costs rather than the current 'one-eyed' focus on lower drug acquisition costs. More consistent use in economic analyses of clinical outcomes that have been shown to affect total cost, in other words, remission rate, time to remission and tolerability, should give a better overall view of the real costs and benefits of treatments. Evidence of important differences between antidepressant medications in terms of clinical efficacy and tolerability profiles will increase. This, in addition to further recognition of the problems posed by poor treatment adherence and the benefits of a simple dosing regimen, should result in further use of the more effective and better tolerated agents as first-line therapy, leading to a greater potential to reduce total costs in MDD and anxiety disorders. The publication of additional clinical evidence on optimal treatment regimens, including more aggressive treatment for longer durations, may also result in lower overall costs of disease.
Sidebar: Key Issues
The burden of major depressive disorder (MDD) and anxiety disorders on healthcare resources
and society is increasing.
Escitalopram, compared with some selective serotonin reuptake inhibitors (SSRIs), is associated
with greater improvements in Montgomery-Åsberg Depression Rating Scale score, and greater
response and remission rates in MDD; escitalopram is at least as effective as venlafaxine and
duloxetine.
Escitalopram is better tolerated than citalopram, sertraline, fluoxetine, paroxetine, venlafaxine
and duloxetine.
Owing to its beneficial efficacy and tolerability profile, escitalopram may be more cost effective
than other SSRIs and venlafaxine and duloxetine in MDD (including severe depression), mainly
because of savings resulting from lower need for secondary care and fewer sick leave days. The
cost-effectiveness of escitalopram relative to other antidepressants has been demonstrated
using pharmacoeconomic models and prospective analyses using total, direct and indirect costs,
from both a payer and a societal perspective.
Escitalopram has also been shown to be more cost effective than paroxetine in generalized
anxiety disorder.
Further economic studies with robust methodology, particularly prospective randomized studies
or those based on real-life data from registries, are required to confirm the cost-effectiveness
advantages of escitalopram over serotonin-norepinephrine reuptake inhibitors in MDD, and to
provide further evidence for the relative cost-effectiveness of escitalopram in anxiety disorders
and mixed depressive anxiety disorder.Acknowledgments Writing assistance was utilized in the production of this manuscript. The authors would like to thank Natalie Barker, a medical writer funded by H Lundbeck A/S, for writing assistance provided in the preparation of this manuscript. Reprint Address Raymond W Lam, Professor of Psychiatry, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, V6T 2A1, Canada. Email: r.lam@ubc.ca Expert Rev Pharmacoeconomics Outcomes Res. 2007;9(6):559-576. © 2007 Future Drugs Ltd.
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