Vol.2, No.6, 620-624 (2010) Health
Copyright © 2010 SciRes. Openly accessible at http://www.scirp.org/journal/HEALTH/
A comparison of duloxetine hydrochloride with
fluoxetine hydrochloride in major depressive disorders:
a pilot study
Ravinder Kumar Sah1, Harmeet Singh Rehan2, Kannanore Eloremadathil Sadanandan Unni3,
Deepti Chopra1*, Seema Manak1, Preeta Kaur Narula1
1Senior resident, Department of Pharmacology, Lady Hardinge Medical College, New Delhi, India;
*Corresponding Author: drdeeptichopra@yahoo.co.in
2Professor and Head, Department of Pharmacology, Lady Hardinge Medical College, New Delhi, India
3Professor and Head, Department of Psychiatry, Lady Hardinge Medical College, New Delhi, India
Received 23 December 2009; revised 11 January 2010; accepted 13 January 2010.
To compare remission rate, relapse rate and
tolerability of duloxetine, a dual reuptake in-
hibitor of 5-hydroxy serotonin (5-HT) and nore-
pinephrine (NE), versus fluoxetine, a reuptake
inhibitor of 5-HT during follow up period of 16
weeks in major depressive disorder (MDD) a
open label comparative trial was conducted.
Trial was comprising of 60 patients, diagnosed
with MDD, were allocated to fluoxetine group
(n*-30, 20-60mg od) or duloxetine group (n*-30,
40-60mg od) for 16 weeks. The end points were
remission and relapse assessed by Hamilton
Rating scale for Depression-24 items (HAMD-24).
In results the mean fall in HAMD-24 scores be-
tween groups was comparable till 4 weeks.
Thereafter, at 8 weeks the mean fall in HAMD-24
score was significantly greater in duloxetine
group (p value < 0.05). At 16 weeks the mean fall
was highly significant (p value < 0.01) in du-
loxetine group. Thirty percent patients in du-
loxetine group achieved remission in compari-
son to none in fluoxetine group. None of the
patient, in any group, reported relapse. Adverse
effects were mild to moderate in severity.In
conclusion duloxetine has a better pharmacol-
ogical profile over fluoxetine in terms of efficacy
and safety.
Keywords: Major Depressive Disorder; Duloxetine;
Remission; Relapse
Major depressive disorder (MDD) represents one of the
most serious conditions encountered in clinical practice
affecting 340 million people globally [1]. It is currently
estimated to be the fourth leading cause of disability
adjusted life years (DALY) in all age groups. Selective
serotonin reuptake inhibitors (SSRIs) are the treatment
of choice for moderate to severe depression [2]. How-
ever, studies have shown that up to half of all depressed
patients fail to respond to SSRIs treatment. Thus there
exists need for alternatives with multiple mechanisms
along with avoidance of unwanted effects of tricyclic
antidepressants (TCA) [3].
Duloxetine, a newer antidepressant which belongs to
selective serotonin nor-epinephrine reuptake inhibitor
(SSNRI) group, has been approved for MDD [4]. In
double blind, placebo controlled multicentre, random-
ized, 9 weeks trials Gartlehner et al. [5] and Detke et al.
[6] concluded that, for treatment of MDD Duloxetine is
safe and effective. In 8 weeks, fluoxetine comparator
trial, remission rates were high in duloxetine group, but
not statistically significantly than fluoxetine group [7].
For long term treatment of MDD duloxetine has been
shown to be effective in 52 weeks non-comparator open
label multicentre trial [8].
As previous studies indicate that duloxetine may have
some advantages in MDD, however there are limited
numbers of studies which assess SSRIs as active com-
parators [9]. These studies are lacking with data’s either
duo to of short duration of study or duo to of lack of
standard comparator. Therefore the current study was
planned to compare remission rate, relapse rate and
safety of oral duloxetine (SSNRI) with fluoxetine (SSRI)
in 16 weeks comparative study.
An open label study was conducted in the Department of
R. K. Sah et al. / HEALTH 2 (2010) 620-624
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Pharmacology in collaboration with the Department of
Psychiatry, Lady Hardinge Medical College and associ-
ated Smt. Sucheta Kriplani (SSK) Hospital, New Delhi.
Sixty six Patients, aged between 18 and 65 years with
either sex, presenting with MDD, as per ICD-10 DCR
criteria [10], on an outpatient basis, were included after
obtaining an informed consent. The study protocol was
approved by Institution Ethics Committee. Baseline dis-
ease severity was defined by patients’ scores on the
Hamilton Rating Scale for Depression-24 items (HAMD-
24) [11]. Exclusion criteria were history of psychosis or
bipolar disorder, substance abuse disorder, intake of
psychoactive medication during past two weeks. Patients
with serious medical illness, serious suicidal risk requir-
ing hospitalization and pregnant or lactating women
were also excluded from study. A complete workup was
done for all patients with respect to history, baseline in-
vestigations (weight, blood pressure, hemoglobin, com-
plete blood count, blood sugar, serum electrolyte, kidney
and liver function test) and clinical examinations.
All patients were randomly assigned to Fluoxetine
20-60 mg per oral (FLX) and Duloxetine 40-60 mg per
oral (DLX) group. Both the study drugs were adminis-
tered daily for 16 weeks and dose was titrated as per the
need of patient.
Clinical response of the patients was assessed at baseline
(0 week), 1 week, 2 week, 4 week, 8 week and 16 week
by using HAMD-24 scale. Improvement in HAMD-24
score from baseline was used as the primary efficacy
measure to assess remission and relapse. Remission was
defined as a total score on HAMD-24 of 7 and relapse
was defined as an episode of MDD that occurs within 6
months after either response or remission [12].
The patients were monitored for any adverse drug effects
during the course of study. The patients as well as the
informants were asked in detail about any adverse drug
effects the course of treatment on each visit.
Baseline and end-point HAMD-24 scores were com-
pared within groups using the paired student’s t-test.
Unpaired student’s t-test was used for comparison of
parameters between two study groups. Safety profile and
response rate were compared between two treatment
groups by Fisher’s exact test. P value of < 0.05 was
taken to be significant.
A total of 66 patients enrolled, out of which 60 com-
pleted the study. Biosocial and demographic characteris-
tics of patients were comparable (Table 1). Baseline
bodyweight, pulse rate, blood pressure and biochemical
parameters in both the groups were matching. On com-
pletion of treatment there were reduction in mean body
weight in both groups which was statistically significant
(P < 0.05). In FLX group bodyweight reduced from
59.27 ± 1.93 kg to 58.84 ± 1.84 kg (p value < 0.05)
while in DLX group body weight reduced from 57.37 ±
1.53 kg to 56.77 ± 1.52 kg after 16 weeks. In DLX group
blood sugar levels also reduced significantly (p value <
0.05) from 104.60 ± 2.33 mg/dl to 102.73 ± 2.03 mg/dl
while there was statistically significant rise in hemoglo-
bin at end of the study. The mean values of other pa-
rameters after16 week were comparable within as well
as between the both groups.
Baseline HAMD-24 scores in FLX and DLX groups
were 17.46 ± 0.13 and 17.70 ± 0.08 respectively (Table
2). In FLX group the HAMD-24 scores reduced signify-
cantly from 17.46 ± 0.13 to 16.16 ± 0.19 (p value < 0.05)
after first week followed by 16.3 ± 0.19, 14.8 ± 0.19, 12
± 0.15 and 9.9 ± 0.14 HAMD-24 scores respectively at 2
weeks, 4 week, 8 week and 16 week. Similarly in DLX
group the score reduced significantly from 17.70 ± 0.08
to 16.80 ± 0.21 after first week, there after 15.96 ± 0.16,
14.86 ± 0.20, 11.10 ± 0.24 and 8.06 ± 0.15 HAMD-24
Table 1. Comparison of biosocial characteristics of study pa-
Characteristics FLX DLX
No. of patients 30 30
Age (years) Mean ± SEM34.06 ± 1.76 32.50 ± 2.01
Sex [n]
Male (n = 18) 12 (40.0%) 6 (20.0%)
Female (n = 42) 18 (60.0%) 24 (80.0%)
Marital status [n (%)]
Married 20 (66.66%) 20 (66.66%)
Unmarried 5 (16.6%) 8 (26.6%)
Divorce 5 (16.6%) 2 (06.6%)
R. K. Sah et al. / HEALTH 2 (2010) 620-624
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Table 2. Mean fall in HAMD-24 scores with time in both
groups (Mean ± SEM).
Baseline (0 week) 17.46 ± 0.13 17.70 ± 0.08
1 week 16.16 ± 0.19 16.80 ± 0.21
2week 16.30 ± 0.19 15.96 ± 0.16
4 week 14.83 ± 0.19 14.86 ± 0.20
8 week 12.06 ± 0.15 11.10 ± 0.24٭
16 week 9.96 ± 0.14 8.06 ± 0.15٭٭٭
٭P < 0.05 (Student’s t-test), ٭٭٭ P < 0.01(Student’s t-test).
scores were recorded at 2 week, 4 week, 8 week and 16
week respectively.
On comparing FLX and DLX groups the mean fall in
HAMD-24 scores were comparable till 4 weeks. There-
after, at 8 weeks the mean fall in HAMD score was sig-
nificantly greater in DLX group i.e. 11.10 ± 0.24 (p <
0.05). At 16 weeks the mean fall was highly significant
(p value < 0.01) in DLX group vs. the FLX group (Table
In FLX group there was no remission till 16 weeks of
treatment, where as in DLX group 9 patients remitted
with in 16 weeks. None of the patient, in any group, re-
ported relapse of any sign or symptoms of MDD during
study period.
A total of 99 adverse events were recorded in FLX group
as compared to 37 adverse events in DLX group. Nausea
was frequent adverse events in FLX group as compared
to DLX. Insomnia, sweating and diarrhoea were the
other frequent adverse events observed in FLX group.
Nausea, dry mouth, diarrhoea and fatigue constituted the
frequent adverse events in DLX group. These adverse
effects were mild to moderate and there were no serious
adverse event in both the groups (Table 3).
After one week of treatment, overall fall in HAMD-24
score was greater in DLX group than FLX group. In
DLX (20 mg twice daily) group, reduction in HAMD-24
score at 8 and 16 weeks from baseline value was –6.6
and –9.64 whereas in FLX (20 mg once daily) fall was
–5.4 and –7.5. Similarly, Goldstein et al. (2002) reported
a higher fall in HAMD scores with duloxetine
Table 3. Adverse drug events observed in the two treatment
Adverse Event FLX (n-99) DLX (n-37)
Nausea 17 (17.1%) 8 (21.6%)
Dry mouth 7 (7%) 5 (13.5%)
Constipation 5 (5%) 4 (10.8%)
Diarrhoea 13 (13.1%) 4 (10.8%)
Vomiting 7 (7%) 2 (5.4%)
Anorexia 12 (12.1%) 2 (5.4%)
Fatigue 1 (1%) 3 (8.1%)
Dizziness 2 (2%) 3 (8.1%)
Somnolence 0 2 (5.4%)
Sweating 14 (14.1%) 3 (8.1%)
Insomnia 15 (15.1%) 1 (2.7%)
Anxiety 3 (3%) 0
Ejaculation delayed 3 (3%) 0
(n- Number of total adverse events)
(–9.73) than with fluoxetine (–7.75) or placebo (–6.6) in
an 8 week study [7]. Hudson et al. (2007) reported
higher reduction in HAMD-24 scores at 12 weeks with
duloxetine (60 mg/day) [1]. The early and higher re-
sponse rate may be due to higher dose of duloxetine. In
present 16 week study and previous short period studies,
duloxetine shown to have better efficacy than SSRIs,
which may be due to its combined effects on both the
serotonin and norepinephrine systems. This dual mecha-
nism makes duloxetine potent (4.5 times) and to act
faster than SSRIs [1,13]. Also, when compared with
other dual action antidepressants like venlafaxine, du-
loxetine appears to be more balanced inhibitor of sero-
tonin and norepinephrine reuptake. Further, experimental
data predicted that dual serotonin and norepinephrine
exert analgesic effects via descending pain pathways;
therefore duloxetine is more suitable in depression with
somatic symptoms [1].
In this study response rate from one week onward was
100% in both the groups and remission rate was 33%
and 0% in DLX and FLX group respectively at end of 16
weeks. Goldstein D.J. et al. (2002) also reported re-
sponse and remission rate of 64% and 56% respectively
for du- loxetine (20 mg twice daily), compared with 52%
and 30% for fluoxetine (20 mg once daily) and 48% and
32% for placebo, indicates superior efficacy of duloxet-
ine over Fluoxetine [7]. In another 8 weeks trial, Gold-
stein DJ (2004) showed response and remission rates
were 54% and 37% for duloxetine (40 mg once daily),
60% and 58% for duloxetine (80 mg) in comparison to
R. K. Sah et al. / HEALTH 2 (2010) 620-624
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50% and 34% for paroxetine (20 mg once daily) and
30% and 28% for placebo [14]. In a metanalysis by Jen-
nifer et al. (2006) the remission rate was found to be
superior for duloxetine as compared to SSRIs (43% vs.
38%). Also when alternative definition of remission
(MADRS score 12) was used, duloxetine was found to
be sig- nificantly better than SSRIs [9].
In both groups there was no relapse till 16 weeks. Al-
though the study duration of 4 months is not sufficient to
comment upon relapse rate but as per definition of re-
lapse there was no reoccurrence of sign and symptoms
after response has been establish in both groups. Relapse
rate for the fluoxetine group was found to be 35.2% after
6 month and 45.9% after 1 year of treatment [15]. In
randomized double blind, multicenter, placebo con-
trolled, parallel group study, David G.P. et al. (2006)
showed that duloxetine (60 mg once daily) was effective
in the prevention of relapse of MDD during continuation
of treatment [16]. Geddes et al. (2003) had concluded on
systemic review of 31 antidepressant trials that continu-
ing with antidepressant reduced the odds of depressive
relapse by 70% compared to placebo. This suggests con-
tinued antidepressant treatment has ability to reduce the
chances of depressive relapse [17].
Duloxetine has better adverse effect profile. In DLX
group 30% of patients experienced adverse events in
which nausea (26.7%) and dry mouth (16.7%) were
principally reported. Other adverse events were diarrhea,
fatigue, dizziness and vomiting. Sharma A. et al. (2000)
have also reported similar adverse effect profile for du-
loxetine [18]. As a reuptake inhibitor of norepinephrine,
duloxetine has been found to be associated with mean
increase in heart rate as well as blood pressure (less than
2 mmHg) [8]. No such cardiovascular adverse effect was
observed in this study .In FLX group, patients mainly
reported nausea (56.6%) and insomnia (50%) followed
by other adverse events which includes sweating, diar-
rhea, anorexia, vomiting, dry mouth and anxiety. In a
study of 6 months, Zajecka et al. (1999) have reported
similar adverse events [19].
Ejaculation delayed was reported by 3 male patients
(10%) in FLX group. Similarly Harman J.B. et al. (1990)
also reported frequent sexual dysfunction with Fluoxet-
ine [20]. Comparatively in DLX group, there was no
sexual dysfunction occurred in any patients although it
has been reported by Detke M.J. et al. (2002) [21].
All the adverse effects during study period were mild
to moderate severity. On the WHO casualty assessment
scale they were classified as possible. Favorable adverse
effect profile of duloxetine may be because of its less
affinity for dopaminergic, adrenergic, cholinergic, his-
taminergic, opioid, glutamate and GABA receptors [1].
In this comparative study duloxetine was found to be
more efficacious than fluoxetine in reducing HAMD-24
score in 16 weeks as well as found to have better adverse
effect profile than fluoxetine. This suggests that for
treatment of MDD duloxetine is better option over
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