RESEARCH ARTICLE
Effectiveness of agomelatine on anhedonia in depressed
patients: an outpatient, open‐label, real‐world study
Pedro Damian Gargoloff1,2 | Ricardo Corral3 | Luis Herbst4 | Miguel Marquez5 |
Giovanni Martinotti6 | Pedro Rafael Gargoloff2
1Hospital Alejandro Korn, Melchor Romero, La
Plata, Argentina
2Clinica City Bell, La Plata, Argentina
3Departamento de Docencia e Investigacion,
Hospital Jose T Borda, CABA, Argentina
4Hospital Jose T. Borda, CABA, Argentina
5ADINEU, CABA, Argentina
6Department of Neuroscience, Imaging and
Clinical Science, Chieti, Italy
Correspondence
Pedro Damian Gargoloff, Hospital Alejandro
Korn, Melchor Romero, La Plata, Argentina.
Email: pdgargoloff@yahoo.com.ar
Abstract
Objective The aim of this real‐world study was to evaluate the effect of agomelatine on anhedonia as primary endpoint in outpatients under treatment of major depressive episodes.
Methods The study was an open‐label, multicenter, 8‐week phase IV trial. Two hundred fifty‐
seven (257) patients were recruited, and 143 patients were included in the analysis. Agomelatine
was administered orally as a 25‐mg tablet. The dose could be increased to 50 mg after 2 weeks of
treatment.
Results An improvement in the severity of anhedonia (Snaith‐Hamilton Pleasure Scale total
score) was observed from 8.5 points at baseline to 4.1 at week 8, statistically significant
(p < 0.05) from the first week. Significant decreases in scores on the severity of depression (Quick
Inventory of Depressive Symptomatology 16‐item Self‐Report [QIDS‐SR‐16]), anxiety (Generalized Anxiety Disorder 7‐item scale), and in overall clinical status (CGI) were also found over
8 weeks, independently from the presence of a first or recurrence episode. Response (QIDS‐
SR‐16 score ≥ 50% of baseline) at week 8 was observed in 65.7% of the patients, while
49.6% of the patients achieved remission (QIDS‐SR‐16 score ≤ 5).
Conclusion Agomelatine was shown to be effective on anhedonia, depression, and anxiety in
subjects with major depression. The pragmatic design of the study reflects real‐world clinical
practice providing interesting insights into routine care management.
KEYWORDS
agomelatine, anhedonia, open‐label, real‐world
1 | INTRODUCTION
Depression is a major mood disorder with 12% prevalence over lifetime (Sadock & Sadock, 2009). The World Health Organization estimated that depression makes a large contribution to the overall
burden of disease, being at third place worldwide and at first place in
middle‐ and high‐income countries. By the year 2030, depression is
estimated to be the first cause of disability‐adjusted life years among
the world’s population.
While various pharmacological treatment options are available,
there are still unsatisfied needs, including the lack of consistent evidence of improvement in anhedonia, identified as a loss of interest
and lack of reactivity to pleasurable stimuli in daily life, being one of
the two core symptoms of depression (Treadway & Zald, 2011). Anhedonia has been considered crucial for the diagnosis of depression
(Klein, 1984; Schrader, 1997), and is a transnosographic condition
reported in several psychiatric disorders (Hatzigiakoumis, Martinotti,
Di Giannantonio, & Janiri, 2011; Millan, Fone, Steckler, & Horan,
2014; De Berardis et al., 2015; Di Nicola et al., 2013, Pettorruso
et al., 2014a), including alcohol, and substance abuse (Martinotti,
Cloninger, & Janiri, 2008) and neurological disorders (Pettorruso
et al., 2014b). In major depression, anhedonia persistence is associated
with the prediction of unsatisfactory outcomes in the treatment of
depression, as patients do not achieve appropriate clinical remission,
with functional and quality‐of‐life impairment (McMakin et al., 2012;
Vrieze et al., 2013).
Agomelatine is an antidepressant with an novel mode of action. It is
antagonist at 5‐HT2C receptors, and antagonist at MT1 and MT2 receptors (Audinot et al., 2003, Millan et al., 2003, De Berardis et al., 2013b).
These receptors act in synergy increasing dopamine and norepinephrine
Received: 17 May 2016 Revised: 29 July 2016 Accepted: 13 September 2016
DOI 10.1002/hup.2557
Hum Psychopharmacol Clin Exp 2016; 1–7 Copyright © 2016 John Wiley & Sons, Ltd. wileyonlinelibrary.com/journal/hup 1
neurotransmission (Millan et al., 2003; Chenu, El Mansari, & Blier, 2013),
and there is a potentiation of dopamine and norepinephrine release in
the prefrontal cortex. Agomelatine has shown antidepressant efficacy in
several randomized placebo‐controlled studies and in studies versus
active controls (see Taylor, Sparshatt, Varma, & Olofinjana, 2014 and
Khoo et al., 2015 for a review and network meta‐analyses). Its effects
have been shown in different psychopathological conditions, well
beyond the diagnosis of major depression (Fornaro et al., 2013; De
Berardis et al., 2013a; Guglielmo, Martinotti, Di Giannantonio, & Janiri,
2013; De Berardis et al., 2012). Agomelatine has showed good
tolerability profile including low sexual dysfunction (Kennedy, Rizvi,
Fulton, & Rasmussen, 2008) and lack of discontinuation syndrome
(Montgomery, Kennedy, Burrows, Lejoyeux, & Hindmarch, 2004).
Agomelatine not only reduces negative affects such as depressed
mood or anxiety but also has particularly clinical actions on improving
positive affect, namely, targeting the improvement of anhedonia,
emotional blunting, and daytime sleepiness among others, which
differentiates agomelatine from serotonergic antidepressants (Stahl,
2014). To date, there are only two published studies that have
described the efficacy of agomelatine in the treatment of anhedonia
among depressive patients in which specific rating scales have been
used to assess these symptoms (Di Giannantonio et al., 2011;
Martinotti et al., 2012). In the first, an open‐label 8‐week study, the
primary endpoints were the effect on depressive and anxiety
symptoms while the effect on anhedonia was a secondary endpoint.
In the second, an open‐label 8‐week study, the effects of agomelatine
on anhedonia were compared with venlafaxine XR and anhedonia was
evaluated as primary endpoint and significant difference between
groups was observed in favor of agomelatine.
The aim of this study was to evaluate the effect of agomelatine on
anhedonia as primary endpoint in outpatients under treatment for
major depressive episode (MDE) under usual clinical practice conditions, in a real‐world setting. Secondary endpoints were changes in
depression and anxiety in MDE patients.
2 | METHODS
This study was an open‐label, multicenter, 8‐week, phase IV trial of
agomelatine in outpatients with MDE.
All patients provided written informed consent prior to participation in the study, and the protocol was approved by a local ethic committee and conducted in accordance with the principles of good clinical
practice.
All planned procedures relating to this noninterventional/observational study were carried out only as part of the routine of diagnosis and
treatment of usual clinical practice. No intervention was undertaken
on or with the patient other than that related to usual clinical practice.
Forty‐six psychiatrists from the city of Buenos Aires, Argentina,
participated in this study.
Outpatients aged 25–65 years, diagnosed with MDE as defined by
the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, and treated with agomelatine were included in this
study. Diagnosis of major depressive disorder was confirmed by the
Mini International Neuropsychiatric Interview (Sheehan, Lecrubier, &
Sheehan, 1998). Only patients who provided written informed consent
were included, and each participant was assigned a number by which
he/she was identified to keep his or her privacy.
Study visit were scheduled for weeks 1, 4, and 8 after treatment
initiation. Only data collected in the respective windows intervals at
follow‐up visits (week 1 ± 3 days, week 4 ± 1 week, and week
8 ± 2 weeks) after treatment initiation were included.
Exclusion criteria were represented by hypersensitivity to
agomelatine or the excipients, hepatic failure (cirrhosis or active liver
disease), any kind of transaminase abnormalities, concomitant use of
potent CYP1A2 isoenzyme inhibitors (e.g., fluvoxamine, ciprofloxacin),
dementia, history of bipolar disorder, mania, or hypomania.
Agomelatine was administered orally as a 25‐mg tablet before
sleep. The dose could be increased at the discretion of the physician
to 50 mg after 2 weeks of treatment.
Anhedonia was evaluated by the Snaith–Hamilton Pleasure Scale
(SHAPS), the primary objective of this study (Snaith et al., 1995; Fresán
& Berlanga, 2013; Franken, Rassin, & Muris, 2007). It is a brief 14‐item
self‐report questionnaire designed to measure hedonic tone and its
absence, anhedonia.
Depression was assessed by The Quick Inventory of Depressive
Symptomatology 16‐item Self‐Report (QIDS‐SR‐16), a common self‐
reporting procedure used to establish inclusion criteria and to measure
changes to the medical treatment (Rush et al., 2003; Trivedi et al.,
2004). Response was defined as an improvement of ≥50% in QIDS‐
SR‐16 score from baseline, and remission was defined as a QIDS‐SR‐
16 score ≤ 5 at end point (Trivedi et al., 2006).
The Generalized Anxiety Disorder 7‐item scale (GAD‐7) is a self‐
reporting tool for the Assessment of anxiety disorders and to record
changes in anxiety severity (Spitzer, Kroenke, Williams, & Löwe,
2006; García‐Campayo et al., 2010).
The Clinical Global Impression of Severity (CGI‐S) and Improvement (CGI‐I) were administered by the physician and constitute a general measure of the patient’s psychopathological state before and after
treatment implementation (Guy, 1976).
Each physician managed his patients according to their usual clinical practice and recorded the visit follow‐up by using the electronic
medical report form provided. Safety Assessments were performed by
recording spontaneously reported adverse events and measurement
of aspartate transaminase and alanine transaminase levels according
to recommended intervals at baseline and at week 1, 4, and 8 of
treatment.
Data was expressed as mean ± SD. Primary and secondary analysis
were performed on the intention‐to‐treat population, which was
defined as all patients who took at least one dose of agomelatine. Data
were analyzed for normal distribution using the Kolmogorov–Smirnov
test and one‐way analysis of variance for repeated measure (Friedman
test) using the last‐observation‐carried‐forward was performed. Correlation was analyzed with Spearman correlation. The difference was
considered significant if p < 0.05.
3 | RESULTS
Two hundred fifty‐seven (257) patients were recruited for the study,
and data of 143 patients were included in the analysis (81 were
2 GARGOLOFF ET AL.
excluded due to unconfirmed start date of treatment and 33 because
all visits were outside the recommended intervals; Figure 1).
Sixteen patients (11.2%) dropped out of treatment: eight patients
were lost to follow up and eight subjects because of adverse events,
three due to lack of efficacy, two due to insomnia, one due to somnolence, one due to muscular pain, and one due to compulsions. The dose
of agomelatine was increased from 25 to 50 mg in two patients (1.4%).
The main characteristics of the study population are shown in Table 1.
A significant reduction in the severity of anhedonia (SHAPS total
score) was observed (Figure 2), from 8.5 points at baseline to 4.1 at
week 8 (p < 0.001). This improvement was evident from the first week
(p < 0.01).
A significant decrease in scores on the severity of depression
(QIDS‐SR‐16) from 15.5 points at baseline to 6.9 at week
8 (p < 0.001) and anxiety (GAD‐7) from 14.0 points at baseline to 7.3
at week 8 (p < 0.001) was found (Figure 2).
The CGI‐I score improved from 2.9 in the first week to 2.0 at week
8. The CGI‐S score improved from 4.5 at baseline to 3.3 at week 8 with
a statistically significant difference found from the first week of
treatment.
In order to analyze the relation between percentages of changes in
SHAPS, QIDS‐SR‐16, and GAD‐7 scores at week 8 with agomelatine
treatment, Spearman correlation were carried out between these
parameters and a significant positive correlation was found in all cases
(SHAPS versus QIDS‐SR‐16:r = 0.5532, p < 0.0001; SHAPS versus
GAD‐7:r = 0.5383, p < 0.0001; QIDS‐SR‐16 versus GAD‐7:
r = 0.6513, p < 0.0001).
The proportion of patients achieving the given criteria for
response (QIDS‐SR‐16 score ≥ 50% of baseline) and remission
(QIDS‐SR‐16 score ≤ 5) is shown in Figure 3. Response at week
8 was observed in 65.7% of the patients while 49.6% of the patients
achieved remission.
Change in the QIDS‐SR‐16 was analysed excluding sleep items. A
significant improvement from the first week was also observed in this
analysis (p < 0.001), demonstrating that the decrease of the total score
was not driven by the decrease of the sleep items.
Data were analyzed in the subgroup of patients with recurrence
(n = 78) or first MDE episode (n = 65). Agomelatine showed a similar
and statistically significant (p < 0.05) improvement in SHAPS after
4 weeks of treatment. Improvements in QIDS‐SR‐16 and GAD‐7 were
FIGURE 1 Diagram of subject recruited and included
TABLE 1 Baseline clinical characteristics of patients (n = 143)
Age (years, range) 47.8 ± 11.3 (25–65)
Female (%) 64
Recurrent MDE (%) 54.5
Melancholic MDE (%) 88.8
Average length of current MDE (month) 8.9 ± 23.3
Concomitant treatment at baseline with
other antidepressant (%)
35.7
Concomitant treatment at baseline
(other psychotropic drug) (%)
74.8
Note. MDE = major depressive episode.
FIGURE 2 Mean change of SHAPS, QIDS‐SR‐16, and GAD‐7
scores. Results are expressed as mean ± SD, analysis of variance for
repeated measure (LOCF), p < 0.05. * indicates significant differences
with baseline
GARGOLOFF ET AL. 3
also similar between both groups and were statistically significant from
the second week of treatment (Table 2).
When considering the results obtained in monotherapy with
agomelatine or with concomitant use of other antidepressants
(Table 3), a statistically significant (p < 0.05) SHAPS improvement
was observed from the first week in patients treated with agomelatine
only (n = 92), while in those with concomitant use of other antidepressant (n = 51) the significant improvement was observed from week 4
(p < 0.05). An improvement in QIDS‐SR‐16, GAD‐7, and CGI was also
observed in both groups from the first week of treatment.
The improvements in scores of all the scales evaluated (SHAPS,
QIDS‐SR‐16, GAD‐7, CGI‐S, CGI‐I) were observed both in patients
with moderate anxiety (GAD‐7 ≥ 10, n = 116) and in patients with
severe anxiety (GAD‐7 ≥ 15, n = 69) (data not shown).
Taking into account the whole population (n = 257), 27 adverse
drug reactions (ADR) were reported (10.5%). Seventeen corresponded
to nonserious ADR: headache (n = 4), insomnia (n = 3), nausea (n = 2),
somnolence (n = 2), epigastralgia (n = 2); two of them were upgraded
to serious ADR by the sponsor: dizziness and hypersomnia. Six adverse
events (AE) were informed, and two of them corresponded to an event
included in the risk management plan (transitory increase of liver
enzymes‐ < 1.5 ULN). However, both of them were not considered
as connected to use of agomelatine.
Three cases of lack of efficacy were reported. One pregnancy was
reported (with normal, spontaneous delivery, and no abnormalities
reported in the child). Two cases of elevation of liver enzimes (GGT)
were reported but both of them were not considered as AE connected
to use of agomelatine.
Among the 27 ADR, agomelatine was definitively discontinued in
six cases, the dose was reduced in four subjects, reintroduced in one
patient (in which the drug was interrupted by patient’s decision), and
maintained with no change in 16 cases. There were no clinically significant changes in body weight, blood pressure, or heart rate.
4 | DISCUSSION
To our knowledge, this is the first study in Argentina evaluating anhedonia in depression and the effect of an antidepressant treatment as
the primary endpoint. The main finding of this real‐world, observational, multicenter 8‐week study was that agomelatine produced, as
early as the first week following the treatment initiation, a significant
improvement in anhedonia in a population of depressed patients. This
positive effect on anhedonia is consistent with previous reports (Di
Giannantonio et al., 2011; Martinotti et al., 2012) despite the higher
baseline SHAPS score in our study, which reflects a more severe
anhedonic population.
Agomelatine improved depressive symptoms measured by the
QIDS‐16 SR and anxiety symptoms as seen with the GAD‐7, in both
cases statistically significant since the first week. The beneficial effects
in depression and anxiety symptoms are also in line with previous studies (Stein, Picarel‐Blanchot, & Kennedy, 2013, Taylor et al., 2014; De
Berardis et al., 2013b; Di Giannantonio and Martinotti, 2012), and positive significant correlations between SHAPS, QIDS‐SR‐16, and GAD‐7
were found in the total population. However, when the patients in
monotherapy were evaluated, SHAPS improved faster than depression
or anxiety scales in comparison to patients with concomitant treatments. Drug–drug interaction appears unlikely to have happened
because there are no pharmacodynamic interactions known between
agomelatine and other antidepressive agents, and there were no antidepressants inhibitors of CYP 1A2 in the market in Argentina at the
time the study was performed. A possible explanation lies in the pharmacology of the antidepressants used in the study: We hypothesize
that the effect of agomelatine in anhedonia is due to its mode of
action, by releasing noradrenaline and dopamine in specifically limbic
FIGURE 3 Response and remission rate
TABLE 2 Assessment in MDE patients with first MDE and with recurrent MDE
First MDE Recurrent MDE
Baseline Week 1 Week 4 Week 8 Baseline Week 1 Week 4 Week 8
SHAPS 9.9 ± 3.9 8.2 ± 4.4 6.0 ± 5.0* 4.1 ± 4.9* 7.4 ± 4.5 6.2 ± 4.5 6.2 ± 3.8* 4.1 ± 4.3*
QIDS‐SR‐16 15.0 ± 5.1 11.9 ± 6.4* 8.8 ± 7.1* 6.1 ± 6.2* 16.0 ± 4.2 11.0 ± 5.8* 8.0 ± 5.9* 6.9 ± 5.5*
GAD‐7 13.0 ± 4.8 10.8 ± 4.8* 8.0 ± 5.2* 6.2 ± 4.9* 14.7 ± 4.1 11.3 ± 4.6* 8.6 ± 5.1* 8.3 ± 5.3*
CGI‐S 4.5 ± 0.7 4.2 ± 0.9 3.8 ± 1.1* 3.5 ± 1.4* 4.4 ± 0.7 3.9 ± 0.9* 3.3 ± 1.1* 3.0 ± 1.2*
CGI‐I — 2.8 ± 0.8 2.5 ± 1.0 2.0 ± 1.0 — 2.9 ± 0.9 2.3 ± 1.0 2.0 ± 1.4
Note. CGI‐I = Clinical Global Impression of Improvement; CGI‐S = Clinical Global Impression of Severity; GAD‐7 = Generalized Anxiety Disorder 7‐item scale;
MDE = major depressive episode; QIDS‐SR‐16 = Quick Inventory of Depressive Symptomatology 16‐item Self‐Report; SHAPS = Snaith–Hamilton Pleasure
Scale.
Results are expressed as mean ± SD, analysis of variance for repeated measure (LOCF), p < 0.05.
*Significant differences with baseline.
4 GARGOLOFF ET AL.
areas, namely, prefrontal cortex without influence in extracellular serotonin levels (Millan et al 2003). Enhancement of dopaminergic and noradrenergic neurotransmission has been related to the improvement of
interest and pleasure (Nutt et al., 2006), while SSRIs increasing the
extracellular serotonin levels may dampen the activity of NA and DA
neurons (Blier & Briley, 2011). In this study, most of the coadministrations occurred with SSRIs and they may dampen the effect of
agomelatine when administered concomitantly to depressed patients.
This peculiar effect of agomelatine on anhedonia may be determined
by an interaction with neurotrophic factors, a hypothesis recently proposed in other studies (Martinotti, Orsolini, et al., 2016a).
These results are consistent with a significant number of other trials, but with the relevant parameter of the real‐life setting. Daily clinical practice requires a complex interplay between experience and
judgment and must draw on data not only from classical randomized
controlled trials but also from pragmatically designed studies that better reflect real‐life clinical practice, as the case of this study run by 46
psychiatrists from the city of Buenos Aires. Studies designed to reflect
a more naturalistic, real‐life management approach can provide interesting insights into the differences between randomized clinical trials
management and routine care management, and the potential implications of ecology of care on treatment outcomes.
An interesting finding is the significant clinical improvements
detected in anhedonia, depression, and anxiety symptoms observed
both in first episode as in patients with a story of multiple episodes.
This data show and confirm how agomelatine effect is independent
from the presence of subjects in a drug‐naive condition, and may
represent a good possibility also in patients with a long psychiatric
history.
In our study, when the items of the QIDS‐SR‐16 were analyzed
separately, an improvement from the first week was still observed
despite of excluding the sleep, suggesting that the score of the QIDS
was not driven by the score of the sleep items. In fact, naturalistic
studies have revealed that the relief of sleep complains with
agomelatine had a very low predictive value for treatment response
(Gorwood et al., 2013).
The results of agomelatine on anhedonia from this study in comparison to those from large clinical trials in major depressive disorder
should be interpreted with caution, where anhedonia was considered
only as one of the many depressive symptoms and precisely it was
not included as primary or secondary study endpoint. From the mode
of action of agomelatine, it could be expected that its effect on anhedonia is specific and not due to the remission in depression because
improvement in anhedonia appears earlier than the efficacy on depression scales in patients treated with monotherapy with agomelatine.
These results confirm those obtained in a previous pilot randomized
study versus venlafaxine, where both products had similar efficacy in
the decrease of the Hamilton Depression rating scale (HAMD) and
Hamilton Anxiety rating scale (HAMA) scores over the 8 weeks of
treatment while agomelatine showed a significant greater efficacy than
venlafaxine from the first week of treatment in anhedonia measured
by the SHAPS scale (Martinotti et al., 2012).
In contrast, and in line to the mode of action of SSRI, a study with
sertraline administered to depressed patients showed that depression
and anxiety responded earlier to the antidepressant than the improvement of anhedonia (Boyer, Tassin, Falissart, & Troy, 2000).
The absence of a placebo group, the open design, and the exclusive
use of self‐report scales are limitations of the study. However, a high
number of patients (n = 143) were enrolled and considered for the analysis, with consistent results compared with previous studies (n = 30 in
each) (Di Giannantonio et al., 2011; Martinotti et al., 2012). Although
there was a significant number of patients that could not be included in
the analysis for unconfirmed start date of treatment (n = 81), we observed
that this group had similar response compared to included patients in all
parameters considered in the study. On the other hand, observational
real‐world studies include more heterogeneous populations with a
variety of medical conditions and interventions, as is the case of this
study, which could reflect more closely the daily clinical practice.
In conclusion, this real‐world study confirms the effectiveness of
agomelatine in the improvement of anhedonia in a cohort of depressed
patients in Argentina and supports the data that demonstrated the efficacy of agomelatine in depression and in anxiety within depression. The
efficacy of available antidepressants in anhedonia has been poorly evaluated in the past, even though anhedonia is considered, together with
depressed mood, as one of the two symptoms of depression essentials
for the diagnosis of the disease (DSM IV, 5). Some psychotropic drugs,
also outside the class of antidepressants, have some good potentiality
for this core dimension (Jaehne, Corrigan, Toben, Jawahar, & Baune,
2015; Martinotti, Pettorruso, et al., 2016b; Lally et al., 2015), but data
are still insufficient to draw any conclusion. Even if the results of
TABLE 3 Assessment in MDE patients with or without concomitant use of other antidepressants.
Without concomitant use of other ATD With concomitant use of other ATD
Baseline Week 1 Week 4 Week 8 Baseline Week 1 Week 4 Week 8
SHAPS 8.5 ± 4.5 6.7 ± 4.5* 4.6 ± 4.5* 3.7 ± 4.5* 8.6 ± 4.4 7.8 ± 4.6 5.6 ± 4.5* 4.8 ± 4.7*
QIDS‐SR‐16 14.8 ± 4.5 10.3 ± 5.7* 7.4 ± 5.8* 5.6 ± 5.1* 16.8 ± 4.7 13.4 ± 6.3* 10.1 ± 7.2* 8.2 ± 6.7*
GAD‐7 13.6 ± 4.8 10.7 ± 4.7* 8.3 ± 5.1* 7.1 ± 5.2* 14.6 ± 3.9 11.8 ± 4.6* 8.4 ± 5.3* 7.7 ± 5.5*
CGI‐S 4.4 ± 0.7 4.0 ± 0.8* 3.6 ± 1.0* 3.3 ± 1.3* 4.5 ± 0.7 4.1 ± 1.0 3.6 ± 1.3* 3.2 ± 1.3*
CGI‐I — 2.8 ± 0.7 2.4 ± 0.9 1.9 ± 1.1 — 2.9 ± 1.0 2.4 ± 1.2 2.1 ± 1.4
Note. ATD = antidepressant; CGI‐I = Clinical Global Impression of Improvement; CGI‐S = Clinical Global Impression of Severity; GAD‐7 = Generalized Anxiety Disorder 7‐item scale; MDE = major depressive episode; QIDS‐SR‐16 = Quick Inventory of Depressive Symptomatology 16‐item Self‐Report;
SHAPS = Snaith–Hamilton Pleasure Scale.
Results are expressed as mean ± SD, analysis of variance for repeated measure (LOCF), p < 0.05.
*Significant differences with baseline.
GARGOLOFF ET AL. 5
agomelatine in this important symptom deserve to be confirmed in larger
real‐life studies, they offer a very important property to this novel antidepressant that can have an impact in the management of depressed
patients especially while considering quality of life and remission.
CONFLICT OF INTEREST
The authors have declared no conflict of interest.
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How to cite this article: Gargoloff, P. D., Corral, R., Herbst, L.,
Marquez, M., Martinotti, G., and Gargoloff, P. R. (2016), Effectiveness of agomelatine on anhedonia in depressed patient: an
outpatient, open‐label, real‐world study, Hum Psychopharmacol
Clin Exp, doi: 10.1002/hup.2557
GARGOLOFF ET AL. 7

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