Introduction
Selective serotonin reuptake inhibitors (SSRI) like escitalopram are mainly used for
drug treatment of depression and anxiety disorders. For escitalopram like for many
other SSRI’s efficacy data for major depression (MDP) and most anxiety disorders are
available. Due to their good efficacy and tolerability, they have largely replaced
tricyclic antidepressants [1]
[2]. Differences between individual SSRIs with regard to effectiveness and adverse effect
profile mainly occur due to pharmacokinetic factors and different affinities for the
serotonin transporter.
In order to provide scientific evidence of efficacy in controlled randomised clinical
studies (RTC’s), only patients with one disorder are usually included. However, comorbid
anxiety disorders and depression occur frequently in daily practice. Especially generalised
anxiety disorder (GAD) rarely occurs alone: 90% of patients with GAD also report other
psychiatric disorders in their medical history; in two-thirds of the cases, they also
suffer from depression [3]. Inversely, it is also estimated that 20–30% of the patients with major depression
also suffer from GAD [4]. The results of a prospective, longitudinal cohort study in New Zealand [5] even showed somewhat higher values: 48% of the patients with depression also suffered
from anxiety disorders at some point in time in their lives and, inversely, 72% of
the patients with GAD also had a history of depression. Altogether, 12% of the 1037
persons examined were comorbid with depression and anxiety disorder. The authors concluded
that the proportion of the population suffering from comorbid depression and anxiety
disorder is larger than usually assumed.
A summary of methodical requirements on controlled, randomised double-blind studies
on the treatment of anxiety disorders can be found in Broich [6].
Within the scope of a post-marketing surveillance (PMS) study, the practically relevant,
naturalistic use of a drug can be better evaluated than in a typical RTC. Thus, the
present study examines the usefulness and tolerability of escitalopram under routine
conditions in Germany in outpatients with comorbid anxiety and depression.
Patients and Methods
Patients
The data in this multicentre study were collected from November 2005 until December
2006 in Germany. A total of 994 registered physicians of different specialties (general
physicians, practical physicians, internists and specialists for psychiatry) treated
2 911 patients with escitalopram over a period of 16 weeks. The participating patients
were outpatients and at least 18 years old. Patients were comorbid and suffered from
depression and anxiety. In this context, comorbidity of depression and anxiety was
defined as a combination of the diagnosis “depression” on the basis of ICD-10 classification
F32 or F33 and a baseline svMADRS>12 with the diagnosis “anxiety” on the basis of
ICD-10 classification F40 or F41 and a baseline HAMA≥10. Patients were not treatment
resistant defined as showing no response to 2 previous different antidepressants in
sufficient dosing over a period of at least 2 weeks. Patients with known intolerability
to escitalopram or citalopram or a contraindication for treatment with escitalopram
were not included. Patients were not permitted to simultaneously participate in other
studies.
Study design
Patients were treated (tablets or drops) for 16 weeks. The dose was decided by the
attending physician. During this period, 4 examinations were performed within the
scope of the study: 1 examination at the time of the inclusion into the study (week
0), 2 follow-up examinations (week 2 and week 8) and 1 final examination (week 16).
During the inclusion examination, the following data were collected: demographics,
height, weight, diagnosis, psychotropic pre-treatment, concomitant diseases and medication,
and medical history.
This study did not influence physicians’ individual decision concerning diagnosis,
dosing, or course of treatment.
Assessments
In order to determine the therapeutic effect of escitalopram, validated and established
scales were used in this study. Quality of the recorded data was assured by double
data entry and analysis by a clinical research organisation (CRO). Physicians were
familiar with the used scales or they had the possibility to train the use of the
rating scales to assure a good data quality.
Severity of disease was assessed using the Clinical Global Impression of Severity
Scale (CGI-S), change in condition was assessed using the Clinical Global Impression
of Improvement Scale (CGI-I) [7]. The CGI-I is a 7 point-scale ranging from “condition is much worse” (7 points)
to “condition is much better” (CGI-I=2) and “condition is very much better” (CGI-I=1).
Patients who described their condition to be “much better” or “very much better” after
treatment were considered to be responders.
Severity of anxiety or depression was measured using the German versions of established
third-party (clinician) rating scales, the Hamilton Anxiety Scale (HAMA) [7] and the Montgomery-Åsberg Depression Rating Scale (MADRS) [8], which comprises 10 items assessed by the physician from 0 to 6, giving a maximum
of 60 points. The svMADRS (sv=short version) is a modified version in which anchor
points are not used and the symptoms are not defined but only mentioned. For the original
version of the MADRS, a score ≥30 points usually corresponds to severe depression,
a score between 13 and 21 to mild depression in individual cases, and a score ≤12
to remission.
The maximum HAMA total score is 56; patients with a mild anxiety disorder have a score
of 10 or less, and patients with generalised anxiety disorder (GAD) have a score of
20 or more [9]. The German version of the Hospital Anxiety Depression Scale (HADS-D) [7] was used for self-assessment of anxiety and depression symptoms by the patients.
This questionnaire consists of 14 items including 7 items referring to depression
(HADS-D “depression”) and 7 items referring to anxiety (HADS-D “anxiety”). Both HADS-D
scales have a score range of 0–21.
The dosage of escitalopram was individually determined by the attending physician
after the initial visit. Escitalopram could be used as coated tablets 10 mg and 20 mg
and escitalopram 10 mg/mL solution. Depending on the patient response to treatment,
the dosage adaptation was allowed at any time during the study. The primary endpoints
included remission using the svMADRS (total score≤12) and HAMA scale (HAMA≤10). Secondary
endpoints included the time course of changes in symptom severity and responder rates
(≥50% decrease from baseline in svMADRS and HAMA scores; CGI-I of 1 or 2=“very much
better” or “much better”). At the end of the observation period, patients and physicians
separately evaluated efficiency and tolerability ranging from “insufficient”, to “moderate”,
“good”, and “very good”.
All unexpected events were considered “adverse events”, even if they did not have
any apparent causal relationship with treatment. This included the deterioration of
an existing condition, but not lack of therapeutic effect. Serious adverse events
were defined as symptoms that led to death or permanent disability, were life-threatening,
required or extended a hospital stay, and to congenital anomalies or birth defects.
Events which required medical intervention in order to prevent one of the above mentioned
criteria were classified as severe and adverse.
During every follow-up examination and at final examination patients were asked for
adverse events. In the case of a serious adverse event it had to be sent within 24 h
to the selected CRO responsible for collecting and handling of all adverse events
in this post-marketing surveillance study.
Statistical analyses
This post-marketing surveillance study was evaluated using methods of descriptive
statistics using last-observation-carried-forward (LOCF) analysis. Multiple linear regression and covariance analytical models were
used to analyse the dose groups (10 mg/day and 20 mg/day) for continuous parameters;
logistic regressions were used to compare the dose groups (10 mg/day and 20 mg/day)
regarding binary parameters (e. g., remission rates). Categorical data were analysed
using the chi-square test. Linear regression, using stepwise backward elimination
(p>0.15), was used to model change from baseline to week 16 on the svMADRS, HAMA and
HADS-D. The following factors were tested: age, sex, BMI, mono-diagnosis of depression
or anxiety, classification by diagnostic group, somatic disorders, other psychiatric
disorders, total duration of illness, duration of current episode, pre-treatment of
current episode, marital status, concomitant diseases, baseline scores on the svMADRS,
HAMA and CGI-S, and escitalopram dose.
The Statistical Software Package SAS® was used for the formal statistical analyses.
Results
Demographic data
Altogether, 2911 patients treated with escitalopram were included in the study, comprising
the all-patient-treated set (APTS) or safety population. Two-thirds (68.0%) of the patients were women, with
a mean weight of 69.8±12.4 kg and a mean height of 167±6 cm. Male patients had a mean
weight of 82.1±11.6 kg and a mean height of 178±6 cm. There were 193 patients who
prematurely withdrew from the study; thus 2718 patients (93.4%) of the APTS completed
16-weeks treatment ([Fig. 1]).
Fig. 1 Patient flow and reasons for withdrawal during the treatment period.
There were 2185 patients who met the inclusion criteria: comorbidity in the sense
of an ICD-10 diagnostic classification of F32/F33 plus F41/F40, a baseline svMADRS>12
and a baseline HAMA≥10, as well as documented assessments during the study. This group
of patients was designated as the “full-analysis set” (FAS) and was evaluated separately. Early study withdrawal occurred for 109
patients, resulting in a completion rate of 95.0%.
The APTS (n=2 911) could be divided into 4 diagnostic groups: comorbid depression
and anxiety disorder (n=2 371: 81.4%), exclusively depression (n=284: 9.8%), exclusively
anxiety (n=188: 6.5%) and other diagnoses (n=68: 2.3%). [Table 1] provides an overview of the demographic data of the patients at baseline. The median
age at the first depressive episode was 35 years, and the median length of the disease
was 10 years. The severity of previous episodes was predominantly moderate. The median
age at first occurrence of an anxiety disorder was 38 years, with a median length
of disease of 6 years. Treatment of previous depression or anxiety conditions was
reported by 55.8% of the patients. The median length of the current episode was 6
weeks, for which 35.7% of the patients had received treatment. In addition, 39.5%
of the patients of the comorbid group suffered from a somatic syndrome, and 11.1%
from an additional mental disorder.
Table 1 Demographic and clinical data (FAS, n=2 185).
|
Parameter
|
Mean
|
|
*Based on the APTS (n=2 911); CGI-S: Clinical Global Impression of Severity scale,
HADS-D: Hospital Anxiety and Depression Scale – German version, HAMA: Hamilton Anxiety
Scale (assessment of the severity of anxiety), svMADRS: Montgomery-Åsberg Depression
Rating Scale – short version, FAS: Full-Analysis Set
|
|
age±SD
|
47.3±14.1 years
|
|
– ≤30 years
|
12.9%
|
|
– 31–40 years
|
20.5%
|
|
– 41–50 years
|
25.6%
|
|
– 51–65 years
|
31.4%
|
|
– >65 years
|
9.7%
|
|
BMI±SD*
|
25.3±4.1 kg/m2
|
|
single*
|
30.2%
|
|
clinical assessments±SD
|
|
– svMADRS
|
33.8±8.9
|
|
– HAMA
|
29.5±8.5
|
|
– HADS-D
|
30.1±6.1
|
|
– CGI-S
|
5.02±0.74
|
Medication
Prior to initiation of treatment with escitalopram, 35.7% of patients had been treated
with at least one of the following: tri- or tetracyclic antidepressants (n=385), SSRIs
(n=250), noradrenergic and specific serotonergic antidepressants (n=183), serotonin
and noradrenergic reuptake inhibitors (n=90), phytotherapeutic antidepressants (n=82),
noradrenergic antidepressants (n=13), monoamine oxidase inhibitors (n=9), or psychotherapy
(n=6). For 23 patients, the treatment was not recorded, and 259 patients were treated
with other medications.
At the beginning of the study, 70.4% of patients (n=2 049) were treated with 10 mg/day
escitalopram, 21.5% (n=626) received 20 mg/day, and 7.0% (n=203) received 5 mg/day
(APTS). Only 3 patients took more than 20 mg/day, 12 patients took 15 mg/day, and
the remaining patients (n=18) took less than 10 mg/day. By the end of the study, the
dose had been changed at least once: for 1 355 of the 2 270 patients in the 10 mg
group (59.7%) and for 171 of the 641 patients in the 20 mg group (26.7%) (APTS). For
the FAS, 1 687 patients were initially treated with 10 mg/day and 498 received 20 mg/day
escitalopram.
For 2 546 patients (87.5%, APTS), escitalopram was subsequently used for maintenance
treatment, with 48.8% of the patients being treated with 10 mg/day (n=1 242) and 43.3%
with 20 mg/day (n=1 103). A few patients continued maintenance therapy on 5 mg (n=68),
15 mg (n=72), 30 mg (n=42), or 40 mg escitalopram (n=13). At the end of the study,
9.6% of patients (n=277) did not continue treatment, 85.8% of patients (n=2 473) continued
with escitalopram alone, 2.5% of patients (n=73) combined escitalopram with another
antidepressant, and 1.4% of patients (n=40) switched to another antidepressant (APTS).
Severity of depression (svMADRS)
At the beginning of the study, severe depression (svMADRS≥29) was diagnosed in 70.8%
of the patients with comorbid depression, moderate depression in 20.0% of patients
(svMADRS 22–28), and mild depression (svMADRS ≥21) in 9.2% of patients (FAS). During
the course of this 16-week surveillance study, the mean baseline svMADRS of 33.8±8.9,
decreased to 24.5±10.0 at week 2, 13.5±8.9 at week 8, and 8.2±7.8 at week 16, corresponding
to a mean improvement of 25.5±10.8 ([Table 2], FAS, LOCF). The response rate was 16.9% at week 2, 67.5% at week 8, and 86.7% at
week 16; and the remission rate was 11.6% at week 2, 51.4% at week 8, and 76.0% at
week 16 (FAS, LOCF). For patients treated with 10 mg escitalopram (n=1 687), the mean
baseline svMADRS was 33.2±8.8, decreasing to 24.5±10.0 at week 2, 13.5±8.8 at week
8, and 8.2±7.8 at week 16, corresponding to a mean improvement of 25.0±10.6 (FAS,
LOCF). For patients treated with 20 mg escitalopram (n=498), the mean baseline svMADRS
was 35.5±9.1, decreasing to 24.9±10.1 at week 2, 13.7±9.2 at week 8, and 8.3±7.9 at
week 16, corresponding to a mean improvement of 27.1±11.0 (FAS, LOCF).
Table 2 Difference in total scores between inclusion and after 16 weeks, remission and response
rates [%] (FAS, LOCF).
|
svMADRS
|
HAMA
|
HADS-D
|
CGI-I
|
|
‡ The CGI-I describes a change in condition compared with the beginning of the study.
Negative numbers indicate an improvement. Remission: svMADRS≤12, HAMA<10, HADS-D≤10.
CGI-I: Clinical Global Impression of Improvement scale, HADS-D: FAS: full analysis
set, Hospital Anxiety and Depression Scale – German version, HAMA: Hamilton Anxiety
Scale (assessment of the severity of anxiety), LOCF: last observation carried forward,
svMADRS: Montgomery-Åsberg Depression Rating Scale – short version.
|
|
change in total score
|
− 25.5±10.8
|
− 21.2±9.3
|
− 20.1±8.9
|
− 1.57±0.75‡
|
|
response rate
|
86.7%
|
83.8%
|
–
|
92.0%
|
|
remission rate
|
76.0%
|
66.3%
|
57.7%
|
–
|
For the safety population (APTS), the severity of depression decreased from a mean
svMADRS total score of 33.0±9.4 to 8.9±8.7, corresponding to a mean difference of
− 24.0±11.6 (APTS, LOCF). The corresponding response rate (≥50% improvement from
baseline in the svMADRS score) was 83.1% and the remission rate (svMADRS≤12) was 72.9%
(LOCF).
Severity of anxiety (HAMA)
At the beginning of the study, 99.3% of patients had a HAMA >10. For patients with
comorbid depression, the mean baseline HAMA was 29.5±8.5, decreasing to 8.3±7.2, corresponding
to a mean difference of 21.2±9.3 (FAS, LOCF). For patients with comorbid depression,
the response rate was 15.0% at week 2, 63.5% at week 8, and 83.8% at week 16; the
corresponding remission rates were 7.9% at week 2, 38.8% at week 8 and 66.3% at week
16 ([Table 2], FAS, LOCF).
For the safety population (APTS), the severity of anxiety decreased from a mean HAMA
total score of 28.8±8.6 to 8.8±7.9, corresponding to a mean improvement of 20.0±10.0
(LOCF). The response rate (≥50% improvement from the baseline HAMA total score) was
80.2%, and the remission rate (HAMA<10) was 63.9% (LOCF).
Self-assessment of anxiety and depression (HADS-D)
At the beginning of the study, 99.6% of patients had self-assessment total scores>10.
For patients with comorbid depression, the mean baseline HADS-D score was 30.1±6.1,
decreasing to 10.0±7.1, corresponding to a mean improvement of 20.1±8.9 (FAS, LOCF).
For patients with comorbid depression, remission was achieved by 3.2% of patients
at week 2, 28.2% at week 8, and 57.7% at week 16 (FAS, LOCF). For the safety population
(APTS), the total mean HADS-D score decreased from 29.6±6.4 to 10.7±7.8, corresponding
to a mean improvement of 18.9±9.5 (LOCF). The remission rate was 55.2% after 16 weeks
(HADS-D≤10) (LOCF).
Severity and change in condition (CGI-S, CGI-I)
The CGI-S score decreased from 4.97±0.76 to 2.57±1.17, corresponding to a mean difference
of 2.41±1.30 (APTS, LOCF). For patients with comorbid depression, the CGI-S score
was 5.02±0.74 at the beginning of the study, 4.30±0.97 at 2 weeks, 3.18±1.06 at 8
weeks and 2.48±1.11 at the final examination, corresponding to a mean difference to
baseline of 2.54±1.22 (FAS, LOCF). The mean CGI-I scores were 2.84±0.83 at week 2,
1.95±0.75 at week 8 and 1.57±0.75 at the end of the study. At the first follow-up
examination (week 2), 31.8% of patients could be classified as responders (CGI-I≤2)
(FAS). After 8 weeks, 82.1% of patients were responders, increasing to 92.0% at 16
weeks (FAS, LOCF). The response rates at 16 weeks were not significantly different
(p=0.5234) for patients taking 10 mg/day (92.2%) and 20 mg/day (91.3%).
Dosage
Patients treated with 20 mg/day (n=498) had significantly higher mean total scores
(svMADRS, HAMA, HADS-D) at baseline than patients treated with 10 mg/day (n=1 687)
– svMADRS: 35.5±9.1 vs. 33.2±8.8, HAMA: 31.0±8.7 vs. 29.1±8.3, HADS-D: 31.5±5.7 vs.
29.7±6.1, respectively (p<0.0001 for all). For patients whose dosage was fixed at
20 mg/day escitalopram at the beginning of the study, the decrease in the mean total
scores was greater than for patients treated with 10 mg/day ([Table 3]), even after adjustment for baseline scores.
Table 3 Difference in the mean total scores between the beginning and the end of the study
in the dose groups 10 mg/day and 20 mg/day (FAS, LOCF).
|
Escitalopram 10 mg/day (n=1 687)
|
Escitalopram 20 mg/day (n=498)
|
|
*svMADRS: p=0.0033
|
|
**HAMA: p=0.0011
|
|
***HADS-D: p<0.0001, CGI-S: p=0.0157, 20 mg vs. 10 mg
|
|
CGI-S: Clinical Global Impression of Severity scale, HADS-D: FAS: full analysis set,
Hospital Anxiety and Depression Scale – German version, HAMA: Hamilton Anxiety Scale
(assessment of the severity of anxiety), LOCF: last observation carried forward, svMADRS:
Montgomery-Åsberg Depression Rating Scale – short version
|
|
svMADRS
|
− 25.0±10.6
|
− 27.1±11.0*
|
|
HAMA
|
− 20.8±9.2
|
− 22.7±9.7**
|
|
HADS-D
|
− 19.6±8.7
|
− 21.8±9.2***
|
|
CGI-S
|
− 2.50±1.21
|
2.69±1.25‡
|
Factors
Higher baseline levels of the svMADRS, HAMA and CGI-S scales and a higher escitalopram
dose were significantly correlated with a greater decrease in the mean total scores
from baseline. Three factors with a significantly unfavourable influence on the decrease
in the mean total scores from baseline were the presence of other psychiatric disorders
or pre-treatment of the current episode. Age, total disease duration, and duration
of the current episode also had a negative effect on treatment outcome, but to a lesser
degree. Sex, BMI, mono-diagnosis of anxiety or depression, somatic symptoms, and classification
by diagnostic group (ICD-10) were without significant influence on outcome.
Adverse events
In the course of the study, 346 adverse events were reported by 189 patients (6.5%)
(APTS). In 157 (5.4%) instances, a causal relationship with escitalopram was at least
considered possible. A significantly higher incidence of adverse events was reported
in the group of patients who were stabilised on 10 mg/day escitalopram in the beginning.
In this group, 171 out of 2 270 patients (7.5%) reported adverse events, compared
to 18 out of 641 patients (2.8%) in the group that started treatment on 20 mg/day
escitalopram in the beginning (p<0.0001). The adverse event was not considered to
be severe in 172 of the 189 cases. In 58 cases, escitalopram was stopped due to adverse
events. Adverse events with at least a possible relationship with escitalopram are
shown in [Table 4].
Table 4 Adverse events with at least a possible relationship with escitalopram.
|
Preferred term
|
Escitalopram 10 mg/day (n=2 270)
|
Escitalopram 20 mg/day (n=641)
|
APTS (n=2 911)
|
|
nausea
|
43 (1.89%)
|
3 (0.47%)
|
46 (1.58%)
|
|
agitation
|
31 (1.37%)
|
1 (0.16%)
|
32 (1.10%)
|
|
diarrhoea
|
15 (0.66%)
|
2 (0.31%)
|
17 (0.58%)
|
|
hyperhidrosis
|
16 (0.70%)
|
–
|
16 (0.55%)
|
|
dizziness
|
15 (0.66%)
|
–
|
15 (0.52%)
|
|
fatigue
|
12 (0.53%)
|
1 (0.16%)
|
13 (0.45%)
|
|
weight gain
|
7 (0.31%)
|
1 (0.16%)
|
8 (0.27%)
|
|
vomiting
|
7 (0.31%)
|
1 (0.16%)
|
8 (0.27%)
|
|
sleep disorder
|
7 (0.31%)
|
–
|
7 (0.24%)
|
|
anxiety
|
7 (0.31%)
|
–
|
7 (0.24%)
|
|
palpitations
|
6 (0.26%)
|
–
|
6 (0.21%)
|
|
loss of libido
|
4 (0.18%)
|
2 (0.31%)
|
6 (0.21%)
|
Severe adverse events
17 patients reported 19 severe adverse events. 2 patients attempted suicide, with
suicidal thoughts registered in one case, and acute suicidal tendency in another case.
A causal relationship with medication was evaluated as “possible” in 2 cases (suicidal
thoughts, one attempted suicide). The other severe adverse events were deterioration
of condition (3 cases), lack of effect (3 cases), hospitalisation (2 cases), and one
case of renal cell carcinoma, myocardial infarction with ST-segment elevation, abnormal
gynaecological examination, alcohol abuse, agitation and anxiety, and continuous vaginal
bleeding. No deaths were reported in the course of the study.
Concerning the cardiac adverse events no cases of QTc-prolongation were reported.
Therapeutic effect and tolerability of escitalopram
Therapeutic effects and tolerability were described as “good” or “very good” by most
physicians and patients. In the APTS (n=2 911), 92.2% of physicians and 89.6% of patients
assessed the therapeutic effects of escitalopram to be “good” or “very good”, whereas
2.5% of physicians and 3.8% of patients described it “insufficient”.
For the full analysis set (n=2 185), 94.8% of physicians and 92.6% of patients described
the therapeutic effects as “good” or “very good”, compared to 1.2% of physicians and
1.8% of patients with “insufficient”. Most physicians (97.4%) and patients (96.1%)
evaluated tolerability as “good” or “very good”, and 0.9% of physicians and 1.5% of
patients considered the tolerability of escitalopram “insufficient”. At the end of
the study, 87.5% of the patients continued maintenance treatment with escitalopram.
Discussion
The therapeutic efficacy of escitalopram in patients with depression or different
anxiety disorders was demonstrated in several placebo-controlled, randomised and blind
clinical studies [10]
[11]
[12]
[13]
[14]. Significant improvements of anxiety symptoms in depressive patients could also
be shown by means of pooled data from double-blind placebo-controlled studies [15]
[16].
The present PMS examined under relevant conditions of daily practice and by means
of standardised methods, the use of escitalopram in patients with both indications,
i. e., depression and anxiety disorder, a combination which is common in daily clinical
practice. In this context, the therapeutic usefulness and good tolerability of escitalopram,
which was already known from controlled clinical studies, including patients with
comorbid depression and anxiety [17], was confirmed.
In the group of patients who were stabilised on 20 mg/day escitalopram at the beginning
of the study, the decrease in the mean total scores (svMADRS, HAMA, HADS-D) was clearer
in the course of the study than in the group treated with 10 mg/day in the beginning.
The difference could only be partially explained by the higher level of total scores
in the 20 mg group at the beginning of the study. Even after adjustment for baseline
severity, a significantly clearer decrease in the total scores on all 3 scales was
shown with initial treatment with 20 mg/day.
The adverse events spectrum was similar to that reported in controlled clinical studies
with escitalopram and citalopram; however, the incidence was slightly lower. Nausea
was the dominant side effect in this study (1.6% of patients), as in controlled studies
in which the reported incidence was 6–17% [9]
[10]
[11]
[13]
[14]
[18]
[19]
[20]. A significant higher rate of adverse events was notable in the group of patients
who were stabilised on the lower dose of 10 mg/day escitalopram in the beginning.
This result, which was surprising, might be attributed to the fact that patients who
were treated with 20 mg/day escitalopram perceived a greater improvement in their
symptoms at week 2 (a decrease of 11.0 vs. 8.3 svMADRS points for 10 mg) and thus
subjectively suffered less from the possible side effects at the beginning of the
therapy.
The incidence of severe adverse events was 1.7%. Attempted suicide was reported in
2 cases, and a relationship with escitalopram could not be excluded in one case. As
the majority of the study participants suffered from severe depression and/or anxiety
disorders, the occurrence of attempted suicide is not surprising [21].
The low incidence of cardiac adverse events (0.2% of patients) confirms the good tolerability
of Escitalopram as shown in clinical practice.
Efficiency and tolerability of escitalopram were significantly higher in the group
of patients with the higher initial dose of 20 mg/day compared with the lower initial
dose of 10 mg/day. These results suggest to start treatment with 20 mg/day for the
acute therapy of patients with comorbid depression and anxiety disorder and to consider
reducing the dose in the maintenance phase.
The present data are based on a post-marketing surveillance (PMS) study or non-interventional
study (NIS). The methodology of PMS comprises series of intrinsic problems (e. g.,
inter-rater reliability, handling of missing data, comedication, heterogeneous patient
population, inclusion and exclusion criteria). Moreover, PMS do not provide evidence
of efficacy, but provide information on adverse events, dosage, medication adherence,
and therapeutic effects indifferent group of patients usually not included in RTC’s
[12]
[22]
[23]
[24]. Response and remission rates in this PMS were rather high, which agrees with other
PMS using escitalopram. In a naturalistic sample test among employed persons with
affective and anxiety disorders, a clear reduction of the conditions was shown with
escitalopram, together with an improvement of the severity of the disease according
to CGI-S from 4.7 to 2.4 [25]. In another open, multicentric PMS, more than 11 700 outpatients were treated with
escitalopram over a period of 8 weeks. The response rate was 70%, the remission rate
57% [26]. 83% of the patients described the efficiency as “good/very good”, and 22% assessed
the tolerability as “good/very good”. On the other hand, these remission and response
rates are within the range reported for escitalopram in RTC’s vs. placebo or comparator
in depression or anxiety ([Table 5]).
Table 5 Response and remission rates from RCTs with Escitalopram (ESC) and the PMS study.
|
Study
|
Response rate (%)
|
Remission rate (%)
|
|
ESC
|
CIT
|
PBO
|
ESC
|
CIT
|
PBO
|
|
Response=svMADRS ≥50% improvement from baseline, Remission=svMADRS ≤12 (1 after 8/16 weeks, 2, 3, 5 after 8 weeks, 4 after 8/24 weeks, 6after 6 weeks)
|
|
ITT, LOCF (*OC analysis, **FAS), CIT: Citalopram, PMS: Post-Marketing Surveillance
|
|
°p<0.01 vs. PBO, ′p<0.05 vs. CIT, ″p<0.01 vs. CIT, ″′p<0.001 vs. CIT
|
|
1
PMS study**
|
67.5/86.7
|
–
|
–
|
51.4/76.0
|
–
|
–
|
|
2
Burke WJ et al. 2002
|
51.2°
|
45.6°
|
27.7
|
–
|
–
|
–
|
|
3
Lepola UM et al. 2003*
|
63.7°′
|
52.6
|
48.2
|
52.1′
|
42.8
|
no data
|
|
4
Colonna L et al. 2005
|
63.0′/80.0
|
55.0/78.0
|
–
|
55.0/76.0
|
45.0/71.0
|
–
|
|
5
Moore N et al. 2005
|
76.1″
|
61.5
|
–
|
56.1′
|
43.6
|
–
|
|
6
Yevtushenko VY et al. 2007
|
95.4″′
|
83.3
|
–
|
89.8″′
|
50.9
|
–
|
Some of the latest controlled, double-blind studies provide response rates (under
escitalopram) for depression between 63 and 70% and remission rates between 55 and
62% [27]
[28]
[29]. Pooled results from double-blind placebo-controlled studies on the treatment of
generalised anxiety disorders with escitalopram resulted in response rates of almost
48%, and remission rates of 26% [30].
