RESEARCH ARTICLE
\nEffectiveness of agomelatine on anhedonia in depressed
\npatients: an outpatient, open\u2010label, real\u2010world study
\nPedro Damian Gargoloff1,2 | Ricardo Corral3 | Luis Herbst4 | Miguel Marquez5 |
\nGiovanni Martinotti6 | Pedro Rafael Gargoloff2
\n1Hospital Alejandro Korn, Melchor Romero, La
\nPlata, Argentina
\n2Clinica City Bell, La Plata, Argentina
\n3Departamento de Docencia e Investigacion,
\nHospital Jose T Borda, CABA, Argentina
\n4Hospital Jose T. Borda, CABA, Argentina
\n5ADINEU, CABA, Argentina
\n6Department of Neuroscience, Imaging and
\nClinical Science, Chieti, Italy
\nCorrespondence
\nPedro Damian Gargoloff, Hospital Alejandro
\nKorn, Melchor Romero, La Plata, Argentina.
\nEmail: pdgargoloff@yahoo.com.ar
\nAbstract
\nObjective The aim of this real\u2010world study was to evaluate the effect of agomelatine on anhedonia as primary endpoint in outpatients under treatment of major depressive episodes.
\nMethods The study was an open\u2010label, multicenter, 8\u2010week phase IV trial. Two hundred fifty\u2010
\nseven (257) patients were recruited, and 143 patients were included in the analysis. Agomelatine
\nwas administered orally as a 25\u2010mg tablet. The dose could be increased to 50 mg after 2 weeks of
\ntreatment.
\nResults An improvement in the severity of anhedonia (Snaith\u2010Hamilton Pleasure Scale total
\nscore) was observed from 8.5 points at baseline to 4.1 at week 8, statistically significant
\n(p < 0.05) from the first week. Significant decreases in scores on the severity of depression (Quick
\nInventory of Depressive Symptomatology 16\u2010item Self\u2010Report [QIDS\u2010SR\u201016]), anxiety (Generalized Anxiety Disorder 7\u2010item scale), and in overall clinical status (CGI) were also found over
\n8 weeks, independently from the presence of a first or recurrence episode. Response (QIDS\u2010
\nSR\u201016 score \u2265 50% of baseline) at week 8 was observed in 65.7% of the patients, while
\n49.6% of the patients achieved remission (QIDS\u2010SR\u201016 score \u2264 5).
\nConclusion Agomelatine was shown to be effective on anhedonia, depression, and anxiety in
\nsubjects with major depression. The pragmatic design of the study reflects real\u2010world clinical
\npractice providing interesting insights into routine care management.
\nKEYWORDS
\nagomelatine, anhedonia, open\u2010label, real\u2010world
\n1 | INTRODUCTION
\nDepression 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
\nburden of disease, being at third place worldwide and at first place in
\nmiddle\u2010 and high\u2010income countries. By the year 2030, depression is
\nestimated to be the first cause of disability\u2010adjusted life years among
\nthe world’s population.
\nWhile various pharmacological treatment options are available,
\nthere are still unsatisfied needs, including the lack of consistent evidence of improvement in anhedonia, identified as a loss of interest
\nand lack of reactivity to pleasurable stimuli in daily life, being one of
\nthe two core symptoms of depression (Treadway & Zald, 2011). Anhedonia has been considered crucial for the diagnosis of depression
\n(Klein, 1984; Schrader, 1997), and is a transnosographic condition
\nreported in several psychiatric disorders (Hatzigiakoumis, Martinotti,
\nDi Giannantonio, & Janiri, 2011; Millan, Fone, Steckler, & Horan,
\n2014; De Berardis et al., 2015; Di Nicola et al., 2013, Pettorruso
\net al., 2014a), including alcohol, and substance abuse (Martinotti,
\nCloninger, & Janiri, 2008) and neurological disorders (Pettorruso
\net al., 2014b). In major depression, anhedonia persistence is associated
\nwith the prediction of unsatisfactory outcomes in the treatment of
\ndepression, as patients do not achieve appropriate clinical remission,
\nwith functional and quality\u2010of\u2010life impairment (McMakin et al., 2012;
\nVrieze et al., 2013).
\nAgomelatine is an antidepressant with an novel mode of action. It is
\nantagonist at 5\u2010HT2C receptors, and antagonist at MT1 and MT2 receptors (Audinot et al., 2003, Millan et al., 2003, De Berardis et al., 2013b).
\nThese receptors act in synergy increasing dopamine and norepinephrine
\nReceived: 17 May 2016 Revised: 29 July 2016 Accepted: 13 September 2016
\nDOI 10.1002\/hup.2557
\nHum Psychopharmacol Clin Exp 2016; 1\u20137 Copyright \u00a9 2016 John Wiley & Sons, Ltd. wileyonlinelibrary.com\/journal\/hup 1
\nneurotransmission (Millan et al., 2003; Chenu, El Mansari, & Blier, 2013),
\nand there is a potentiation of dopamine and norepinephrine release in
\nthe prefrontal cortex. Agomelatine has shown antidepressant efficacy in
\nseveral randomized placebo\u2010controlled studies and in studies versus
\nactive controls (see Taylor, Sparshatt, Varma, & Olofinjana, 2014 and
\nKhoo et al., 2015 for a review and network meta\u2010analyses). Its effects
\nhave been shown in different psychopathological conditions, well
\nbeyond the diagnosis of major depression (Fornaro et al., 2013; De
\nBerardis et al., 2013a; Guglielmo, Martinotti, Di Giannantonio, & Janiri,
\n2013; De Berardis et al., 2012). Agomelatine has showed good
\ntolerability profile including low sexual dysfunction (Kennedy, Rizvi,
\nFulton, & Rasmussen, 2008) and lack of discontinuation syndrome
\n(Montgomery, Kennedy, Burrows, Lejoyeux, & Hindmarch, 2004).
\nAgomelatine not only reduces negative affects such as depressed
\nmood or anxiety but also has particularly clinical actions on improving
\npositive affect, namely, targeting the improvement of anhedonia,
\nemotional blunting, and daytime sleepiness among others, which
\ndifferentiates agomelatine from serotonergic antidepressants (Stahl,
\n2014). To date, there are only two published studies that have
\ndescribed the efficacy of agomelatine in the treatment of anhedonia
\namong depressive patients in which specific rating scales have been
\nused to assess these symptoms (Di Giannantonio et al., 2011;
\nMartinotti et al., 2012). In the first, an open\u2010label 8\u2010week study, the
\nprimary endpoints were the effect on depressive and anxiety
\nsymptoms while the effect on anhedonia was a secondary endpoint.
\nIn the second, an open\u2010label 8\u2010week study, the effects of agomelatine
\non anhedonia were compared with venlafaxine XR and anhedonia was
\nevaluated as primary endpoint and significant difference between
\ngroups was observed in favor of agomelatine.
\nThe aim of this study was to evaluate the effect of agomelatine on
\nanhedonia as primary endpoint in outpatients under treatment for
\nmajor depressive episode (MDE) under usual clinical practice conditions, in a real\u2010world setting. Secondary endpoints were changes in
\ndepression and anxiety in MDE patients.
\n2 | METHODS
\nThis study was an open\u2010label, multicenter, 8\u2010week, phase IV trial of
\nagomelatine in outpatients with MDE.
\nAll 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
\npractice.
\nAll planned procedures relating to this noninterventional\/observational study were carried out only as part of the routine of diagnosis and
\ntreatment of usual clinical practice. No intervention was undertaken
\non or with the patient other than that related to usual clinical practice.
\nForty\u2010six psychiatrists from the city of Buenos Aires, Argentina,
\nparticipated in this study.
\nOutpatients aged 25\u201365 years, diagnosed with MDE as defined by
\nthe Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, and treated with agomelatine were included in this
\nstudy. Diagnosis of major depressive disorder was confirmed by the
\nMini International Neuropsychiatric Interview (Sheehan, Lecrubier, &
\nSheehan, 1998). Only patients who provided written informed consent
\nwere included, and each participant was assigned a number by which
\nhe\/she was identified to keep his or her privacy.
\nStudy visit were scheduled for weeks 1, 4, and 8 after treatment
\ninitiation. Only data collected in the respective windows intervals at
\nfollow\u2010up visits (week 1 \u00b1 3 days, week 4 \u00b1 1 week, and week
\n8 \u00b1 2 weeks) after treatment initiation were included.
\nExclusion criteria were represented by hypersensitivity to
\nagomelatine or the excipients, hepatic failure (cirrhosis or active liver
\ndisease), any kind of transaminase abnormalities, concomitant use of
\npotent CYP1A2 isoenzyme inhibitors (e.g., fluvoxamine, ciprofloxacin),
\ndementia, history of bipolar disorder, mania, or hypomania.
\nAgomelatine was administered orally as a 25\u2010mg tablet before
\nsleep. The dose could be increased at the discretion of the physician
\nto 50 mg after 2 weeks of treatment.
\nAnhedonia was evaluated by the Snaith\u2013Hamilton Pleasure Scale
\n(SHAPS), the primary objective of this study (Snaith et al., 1995; Fres\u00e1n
\n& Berlanga, 2013; Franken, Rassin, & Muris, 2007). It is a brief 14\u2010item
\nself\u2010report questionnaire designed to measure hedonic tone and its
\nabsence, anhedonia.
\nDepression was assessed by The Quick Inventory of Depressive
\nSymptomatology 16\u2010item Self\u2010Report (QIDS\u2010SR\u201016), a common self\u2010
\nreporting procedure used to establish inclusion criteria and to measure
\nchanges to the medical treatment (Rush et al., 2003; Trivedi et al.,
\n2004). Response was defined as an improvement of \u226550% in QIDS\u2010
\nSR\u201016 score from baseline, and remission was defined as a QIDS\u2010SR\u2010
\n16 score \u2264 5 at end point (Trivedi et al., 2006).
\nThe Generalized Anxiety Disorder 7\u2010item scale (GAD\u20107) is a self\u2010
\nreporting tool for the Assessment of anxiety disorders and to record
\nchanges in anxiety severity (Spitzer, Kroenke, Williams, & L\u00f6we,
\n2006; Garc\u00eda\u2010Campayo et al., 2010).
\nThe Clinical Global Impression of Severity (CGI\u2010S) and Improvement (CGI\u2010I) were administered by the physician and constitute a general measure of the patient’s psychopathological state before and after
\ntreatment implementation (Guy, 1976).
\nEach physician managed his patients according to their usual clinical practice and recorded the visit follow\u2010up by using the electronic
\nmedical report form provided. Safety Assessments were performed by
\nrecording spontaneously reported adverse events and measurement
\nof aspartate transaminase and alanine transaminase levels according
\nto recommended intervals at baseline and at week 1, 4, and 8 of
\ntreatment.
\nData was expressed as mean \u00b1 SD. Primary and secondary analysis
\nwere performed on the intention\u2010to\u2010treat population, which was
\ndefined as all patients who took at least one dose of agomelatine. Data
\nwere analyzed for normal distribution using the Kolmogorov\u2013Smirnov
\ntest and one\u2010way analysis of variance for repeated measure (Friedman
\ntest) using the last\u2010observation\u2010carried\u2010forward was performed. Correlation was analyzed with Spearman correlation. The difference was
\nconsidered significant if p < 0.05.
\n3 | RESULTS
\nTwo hundred fifty\u2010seven (257) patients were recruited for the study,
\nand data of 143 patients were included in the analysis (81 were
\n2 GARGOLOFF ET AL.
\nexcluded due to unconfirmed start date of treatment and 33 because
\nall visits were outside the recommended intervals; Figure 1).
\nSixteen patients (11.2%) dropped out of treatment: eight patients
\nwere lost to follow up and eight subjects because of adverse events,
\nthree 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
\nof agomelatine was increased from 25 to 50 mg in two patients (1.4%).
\nThe main characteristics of the study population are shown in Table 1.
\nA significant reduction in the severity of anhedonia (SHAPS total
\nscore) was observed (Figure 2), from 8.5 points at baseline to 4.1 at
\nweek 8 (p < 0.001). This improvement was evident from the first week
\n(p < 0.01).
\nA significant decrease in scores on the severity of depression
\n(QIDS\u2010SR\u201016) from 15.5 points at baseline to 6.9 at week
\n8 (p < 0.001) and anxiety (GAD\u20107) from 14.0 points at baseline to 7.3
\nat week 8 (p < 0.001) was found (Figure 2).
\nThe CGI\u2010I score improved from 2.9 in the first week to 2.0 at week
\n8. The CGI\u2010S score improved from 4.5 at baseline to 3.3 at week 8 with
\na statistically significant difference found from the first week of
\ntreatment.
\nIn order to analyze the relation between percentages of changes in
\nSHAPS, QIDS\u2010SR\u201016, and GAD\u20107 scores at week 8 with agomelatine
\ntreatment, Spearman correlation were carried out between these
\nparameters and a significant positive correlation was found in all cases
\n(SHAPS versus QIDS\u2010SR\u201016:r = 0.5532, p < 0.0001; SHAPS versus
\nGAD\u20107:r = 0.5383, p < 0.0001; QIDS\u2010SR\u201016 versus GAD\u20107:
\nr = 0.6513, p < 0.0001).
\nThe proportion of patients achieving the given criteria for
\nresponse (QIDS\u2010SR\u201016 score \u2265 50% of baseline) and remission
\n(QIDS\u2010SR\u201016 score \u2264 5) is shown in Figure 3. Response at week
\n8 was observed in 65.7% of the patients while 49.6% of the patients
\nachieved remission.
\nChange in the QIDS\u2010SR\u201016 was analysed excluding sleep items. A
\nsignificant improvement from the first week was also observed in this
\nanalysis (p < 0.001), demonstrating that the decrease of the total score
\nwas not driven by the decrease of the sleep items.
\nData were analyzed in the subgroup of patients with recurrence
\n(n = 78) or first MDE episode (n = 65). Agomelatine showed a similar
\nand statistically significant (p < 0.05) improvement in SHAPS after
\n4 weeks of treatment. Improvements in QIDS\u2010SR\u201016 and GAD\u20107 were
\nFIGURE 1 Diagram of subject recruited and included
\nTABLE 1 Baseline clinical characteristics of patients (n = 143)
\nAge (years, range) 47.8 \u00b1 11.3 (25\u201365)
\nFemale (%) 64
\nRecurrent MDE (%) 54.5
\nMelancholic MDE (%) 88.8
\nAverage length of current MDE (month) 8.9 \u00b1 23.3
\nConcomitant treatment at baseline with
\nother antidepressant (%)
\n35.7
\nConcomitant treatment at baseline
\n(other psychotropic drug) (%)
\n74.8
\nNote. MDE = major depressive episode.
\nFIGURE 2 Mean change of SHAPS, QIDS\u2010SR\u201016, and GAD\u20107
\nscores. Results are expressed as mean \u00b1 SD, analysis of variance for
\nrepeated measure (LOCF), p < 0.05. * indicates significant differences
\nwith baseline
\nGARGOLOFF ET AL. 3
\nalso similar between both groups and were statistically significant from
\nthe second week of treatment (Table 2).
\nWhen considering the results obtained in monotherapy with
\nagomelatine or with concomitant use of other antidepressants
\n(Table 3), a statistically significant (p < 0.05) SHAPS improvement
\nwas observed from the first week in patients treated with agomelatine
\nonly (n = 92), while in those with concomitant use of other antidepressant (n = 51) the significant improvement was observed from week 4
\n(p < 0.05). An improvement in QIDS\u2010SR\u201016, GAD\u20107, and CGI was also
\nobserved in both groups from the first week of treatment.
\nThe improvements in scores of all the scales evaluated (SHAPS,
\nQIDS\u2010SR\u201016, GAD\u20107, CGI\u2010S, CGI\u2010I) were observed both in patients
\nwith moderate anxiety (GAD\u20107 \u2265 10, n = 116) and in patients with
\nsevere anxiety (GAD\u20107 \u2265 15, n = 69) (data not shown).
\nTaking into account the whole population (n = 257), 27 adverse
\ndrug reactions (ADR) were reported (10.5%). Seventeen corresponded
\nto nonserious ADR: headache (n = 4), insomnia (n = 3), nausea (n = 2),
\nsomnolence (n = 2), epigastralgia (n = 2); two of them were upgraded
\nto serious ADR by the sponsor: dizziness and hypersomnia. Six adverse
\nevents (AE) were informed, and two of them corresponded to an event
\nincluded in the risk management plan (transitory increase of liver
\nenzymes\u2010 < 1.5 ULN). However, both of them were not considered
\nas connected to use of agomelatine.
\nThree cases of lack of efficacy were reported. One pregnancy was
\nreported (with normal, spontaneous delivery, and no abnormalities
\nreported in the child). Two cases of elevation of liver enzimes (GGT)
\nwere reported but both of them were not considered as AE connected
\nto use of agomelatine.
\nAmong the 27 ADR, agomelatine was definitively discontinued in
\nsix cases, the dose was reduced in four subjects, reintroduced in one
\npatient (in which the drug was interrupted by patient’s decision), and
\nmaintained with no change in 16 cases. There were no clinically significant changes in body weight, blood pressure, or heart rate.
\n4 | DISCUSSION
\nTo our knowledge, this is the first study in Argentina evaluating anhedonia in depression and the effect of an antidepressant treatment as
\nthe primary endpoint. The main finding of this real\u2010world, observational, multicenter 8\u2010week study was that agomelatine produced, as
\nearly as the first week following the treatment initiation, a significant
\nimprovement in anhedonia in a population of depressed patients. This
\npositive effect on anhedonia is consistent with previous reports (Di
\nGiannantonio et al., 2011; Martinotti et al., 2012) despite the higher
\nbaseline SHAPS score in our study, which reflects a more severe
\nanhedonic population.
\nAgomelatine improved depressive symptoms measured by the
\nQIDS\u201016 SR and anxiety symptoms as seen with the GAD\u20107, in both
\ncases statistically significant since the first week. The beneficial effects
\nin depression and anxiety symptoms are also in line with previous studies (Stein, Picarel\u2010Blanchot, & Kennedy, 2013, Taylor et al., 2014; De
\nBerardis et al., 2013b; Di Giannantonio and Martinotti, 2012), and positive significant correlations between SHAPS, QIDS\u2010SR\u201016, and GAD\u20107
\nwere found in the total population. However, when the patients in
\nmonotherapy were evaluated, SHAPS improved faster than depression
\nor anxiety scales in comparison to patients with concomitant treatments. Drug\u2013drug interaction appears unlikely to have happened
\nbecause there are no pharmacodynamic interactions known between
\nagomelatine and other antidepressive agents, and there were no antidepressants inhibitors of CYP 1A2 in the market in Argentina at the
\ntime the study was performed. A possible explanation lies in the pharmacology of the antidepressants used in the study: We hypothesize
\nthat the effect of agomelatine in anhedonia is due to its mode of
\naction, by releasing noradrenaline and dopamine in specifically limbic
\nFIGURE 3 Response and remission rate
\nTABLE 2 Assessment in MDE patients with first MDE and with recurrent MDE
\nFirst MDE Recurrent MDE
\nBaseline Week 1 Week 4 (your nursing study bay) Week 8 Baseline Week 1 Week 4 (your nursing study bay) Week 8
\nSHAPS 9.9 \u00b1 3.9 8.2 \u00b1 4.4 6.0 \u00b1 5.0* 4.1 \u00b1 4.9* 7.4 \u00b1 4.5 6.2 \u00b1 4.5 6.2 \u00b1 3.8* 4.1 \u00b1 4.3*
\nQIDS\u2010SR\u201016 15.0 \u00b1 5.1 11.9 \u00b1 6.4* 8.8 \u00b1 7.1* 6.1 \u00b1 6.2* 16.0 \u00b1 4.2 11.0 \u00b1 5.8* 8.0 \u00b1 5.9* 6.9 \u00b1 5.5*
\nGAD\u20107 13.0 \u00b1 4.8 10.8 \u00b1 4.8* 8.0 \u00b1 5.2* 6.2 \u00b1 4.9* 14.7 \u00b1 4.1 11.3 \u00b1 4.6* 8.6 \u00b1 5.1* 8.3 \u00b1 5.3*
\nCGI\u2010S 4.5 \u00b1 0.7 4.2 \u00b1 0.9 3.8 \u00b1 1.1* 3.5 \u00b1 1.4* 4.4 \u00b1 0.7 3.9 \u00b1 0.9* 3.3 \u00b1 1.1* 3.0 \u00b1 1.2*
\nCGI\u2010I \u2014 2.8 \u00b1 0.8 2.5 \u00b1 1.0 2.0 \u00b1 1.0 \u2014 2.9 \u00b1 0.9 2.3 \u00b1 1.0 2.0 \u00b1 1.4
\nNote. CGI\u2010I = Clinical Global Impression of Improvement; CGI\u2010S = Clinical Global Impression of Severity; GAD\u20107 = Generalized Anxiety Disorder 7\u2010item scale;
\nMDE = major depressive episode; QIDS\u2010SR\u201016 = Quick Inventory of Depressive Symptomatology 16\u2010item Self\u2010Report; SHAPS = Snaith\u2013Hamilton Pleasure
\nScale.
\nResults are expressed as mean \u00b1 SD, analysis of variance for repeated measure (LOCF), p < 0.05.
\n*Significant differences with baseline.
\n4 GARGOLOFF ET AL.
\nareas, 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
\ninterest and pleasure (Nutt et al., 2006), while SSRIs increasing the
\nextracellular serotonin levels may dampen the activity of NA and DA
\nneurons (Blier & Briley, 2011). In this study, most of the coadministrations occurred with SSRIs and they may dampen the effect of
\nagomelatine when administered concomitantly to depressed patients.
\nThis peculiar effect of agomelatine on anhedonia may be determined
\nby an interaction with neurotrophic factors, a hypothesis recently proposed in other studies (Martinotti, Orsolini, et al., 2016a).
\nThese results are consistent with a significant number of other trials, but with the relevant parameter of the real\u2010life setting. Daily clinical practice requires a complex interplay between experience and
\njudgment and must draw on data not only from classical randomized
\ncontrolled trials but also from pragmatically designed studies that better reflect real\u2010life clinical practice, as the case of this study run by 46
\npsychiatrists from the city of Buenos Aires. Studies designed to reflect
\na more naturalistic, real\u2010life management approach can provide interesting insights into the differences between randomized clinical trials
\nmanagement and routine care management, and the potential implications of ecology of care on treatment outcomes.
\nAn interesting finding is the significant clinical improvements
\ndetected in anhedonia, depression, and anxiety symptoms observed
\nboth in first episode as in patients with a story of multiple episodes.
\nThis data show and confirm how agomelatine effect is independent
\nfrom the presence of subjects in a drug\u2010naive condition, and may
\nrepresent a good possibility also in patients with a long psychiatric
\nhistory.
\nIn our study, when the items of the QIDS\u2010SR\u201016 were analyzed
\nseparately, an improvement from the first week was still observed
\ndespite of excluding the sleep, suggesting that the score of the QIDS
\nwas not driven by the score of the sleep items. In fact, naturalistic
\nstudies have revealed that the relief of sleep complains with
\nagomelatine had a very low predictive value for treatment response
\n(Gorwood et al., 2013).
\nThe results of agomelatine on anhedonia from this study in comparison to those from large clinical trials in major depressive disorder
\nshould be interpreted with caution, where anhedonia was considered
\nonly as one of the many depressive symptoms and precisely it was
\nnot included as primary or secondary study endpoint. From the mode
\nof action of agomelatine, it could be expected that its effect on anhedonia is specific and not due to the remission in depression because
\nimprovement in anhedonia appears earlier than the efficacy on depression scales in patients treated with monotherapy with agomelatine.
\nThese results confirm those obtained in a previous pilot randomized
\nstudy versus venlafaxine, where both products had similar efficacy in
\nthe decrease of the Hamilton Depression rating scale (HAMD) and
\nHamilton Anxiety rating scale (HAMA) scores over the 8 weeks of
\ntreatment while agomelatine showed a significant greater efficacy than
\nvenlafaxine from the first week of treatment in anhedonia measured
\nby the SHAPS scale (Martinotti et al., 2012).
\nIn contrast, and in line to the mode of action of SSRI, a study with
\nsertraline administered to depressed patients showed that depression
\nand anxiety responded earlier to the antidepressant than the improvement of anhedonia (Boyer, Tassin, Falissart, & Troy, 2000).
\nThe absence of a placebo group, the open design, and the exclusive
\nuse of self\u2010report scales are limitations of the study. However, a high
\nnumber of patients (n = 143) were enrolled and considered for the analysis, with consistent results compared with previous studies (n = 30 in
\neach) (Di Giannantonio et al., 2011; Martinotti et al., 2012). Although
\nthere was a significant number of patients that could not be included in
\nthe analysis for unconfirmed start date of treatment (n = 81), we observed
\nthat this group had similar response compared to included patients in all
\nparameters considered in the study. On the other hand, observational
\nreal\u2010world studies include more heterogeneous populations with a
\nvariety of medical conditions and interventions, as is the case of this
\nstudy, which could reflect more closely the daily clinical practice.
\nIn conclusion, this real\u2010world study confirms the effectiveness of
\nagomelatine in the improvement of anhedonia in a cohort of depressed
\npatients in Argentina and supports the data that demonstrated the efficacy of agomelatine in depression and in anxiety within depression. The
\nefficacy of available antidepressants in anhedonia has been poorly evaluated in the past, even though anhedonia is considered, together with
\ndepressed mood, as one of the two symptoms of depression essentials
\nfor the diagnosis of the disease (DSM IV, 5). Some psychotropic drugs,
\nalso outside the class of antidepressants, have some good potentiality
\nfor this core dimension (Jaehne, Corrigan, Toben, Jawahar, & Baune,
\n2015; Martinotti, Pettorruso, et al., 2016b; Lally et al., 2015), but data
\nare still insufficient to draw any conclusion. Even if the results of
\nTABLE 3 Assessment in MDE patients with or without concomitant use of other antidepressants.
\nWithout concomitant use of other ATD With concomitant use of other ATD
\nBaseline Week 1 Week 4 (your nursing study bay) Week 8 Baseline Week 1 Week 4 (your nursing study bay) Week 8
\nSHAPS 8.5 \u00b1 4.5 6.7 \u00b1 4.5* 4.6 \u00b1 4.5* 3.7 \u00b1 4.5* 8.6 \u00b1 4.4 7.8 \u00b1 4.6 5.6 \u00b1 4.5* 4.8 \u00b1 4.7*
\nQIDS\u2010SR\u201016 14.8 \u00b1 4.5 10.3 \u00b1 5.7* 7.4 \u00b1 5.8* 5.6 \u00b1 5.1* 16.8 \u00b1 4.7 13.4 \u00b1 6.3* 10.1 \u00b1 7.2* 8.2 \u00b1 6.7*
\nGAD\u20107 13.6 \u00b1 4.8 10.7 \u00b1 4.7* 8.3 \u00b1 5.1* 7.1 \u00b1 5.2* 14.6 \u00b1 3.9 11.8 \u00b1 4.6* 8.4 \u00b1 5.3* 7.7 \u00b1 5.5*
\nCGI\u2010S 4.4 \u00b1 0.7 4.0 \u00b1 0.8* 3.6 \u00b1 1.0* 3.3 \u00b1 1.3* 4.5 \u00b1 0.7 4.1 \u00b1 1.0 3.6 \u00b1 1.3* 3.2 \u00b1 1.3*
\nCGI\u2010I \u2014 2.8 \u00b1 0.7 2.4 \u00b1 0.9 1.9 \u00b1 1.1 \u2014 2.9 \u00b1 1.0 2.4 \u00b1 1.2 2.1 \u00b1 1.4
\nNote. ATD = antidepressant; CGI\u2010I = Clinical Global Impression of Improvement; CGI\u2010S = Clinical Global Impression of Severity; GAD\u20107 = Generalized Anxiety Disorder 7\u2010item scale; MDE = major depressive episode; QIDS\u2010SR\u201016 = Quick Inventory of Depressive Symptomatology 16\u2010item Self\u2010Report;
\nSHAPS = Snaith\u2013Hamilton Pleasure Scale.
\nResults are expressed as mean \u00b1 SD, analysis of variance for repeated measure (LOCF), p < 0.05.
\n*Significant differences with baseline.
\nGARGOLOFF ET AL. 5
\nagomelatine in this important symptom deserve to be confirmed in larger
\nreal\u2010life studies, they offer a very important property to this novel antidepressant that can have an impact in the management of depressed
\npatients especially while considering quality of life and remission.
\nCONFLICT OF INTEREST
\nThe authors have declared no conflict of interest.
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\nHow to cite this article: Gargoloff, P. D., Corral, R., Herbst, L.,
\nMarquez, M., Martinotti, G., and Gargoloff, P. R. (2016), Effectiveness of agomelatine on anhedonia in depressed patient: an
\noutpatient, open\u2010label, real\u2010world study, Hum Psychopharmacol
\nClin Exp, doi: 10.1002\/hup.2557
\nGARGOLOFF ET AL. 7<\/p>\n","protected":false},"excerpt":{"rendered":"
RESEARCH ARTICLE Effectiveness of agomelatine on anhedonia in depressed patients: an outpatient, open\u2010label, real\u2010world study Pedro Damian Gargoloff1,2 | Ricardo Corral3 | Luis Herbst4 |\u2026<\/p>\n","protected":false},"author":4,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[7316,7318,7317,7315,7319,7321],"tags":[642,618,8825,576,116,631,19,643,473,633,630,628,450,597,594,626,635,574,622,624,620,621,619,623,617,625,627,634,629,632,644,645,42,66],"class_list":["post-113332","post","type-post","status-publish","format-standard","hentry","category-best-dissertation-writers-uk","category-british-dissertation-writers","category-dissertation-help-online","category-dissertation-writing-services-uk","category-help-with-dissertation-writing","category-uk-dissertation-help","tag-apps-that-write-essays-for-you-free","tag-assignment-writing-services-in-usa","tag-bes","tag-best-dissertation-writing-services","tag-best-essay-writing-service","tag-best-paper-writing-services","tag-best-research-paper-writing-services-in-usa","tag-best-website-to-write-my-essay","tag-cheap-essay-writing-service","tag-cheap-research-paper-writing-service","tag-college-paper-writing-service","tag-dissertation-help-online","tag-dissertation-writing-services","tag-dissertation-writing-services-illegal","tag-dissertation-writing-services-near-me","tag-dissertation-writing-services-usa","tag-essay-writing-service","tag-free-dissertation-writing-services","tag-homework-essay-writer","tag-homework-essay-writer-free","tag-homework-help-global","tag-homework-help-services","tag-homework-help-usa","tag-homework-writing-help","tag-homework-writing-service","tag-legit-research-paper-writing-services","tag-legitimate-dissertation-writing-services","tag-research-paper-writer-online-free","tag-research-paper-writing-services-online","tag-research-paper-writing-websites","tag-write-my-essay-for-me-cheap","tag-write-my-essay-for-me-tik-tok","tag-write-my-essay-free","tag-write-my-paper"],"_links":{"self":[{"href":"https:\/\/www.studyproessays.com\/help\/wp-json\/wp\/v2\/posts\/113332","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.studyproessays.com\/help\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.studyproessays.com\/help\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.studyproessays.com\/help\/wp-json\/wp\/v2\/users\/4"}],"replies":[{"embeddable":true,"href":"https:\/\/www.studyproessays.com\/help\/wp-json\/wp\/v2\/comments?post=113332"}],"version-history":[{"count":0,"href":"https:\/\/www.studyproessays.com\/help\/wp-json\/wp\/v2\/posts\/113332\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.studyproessays.com\/help\/wp-json\/wp\/v2\/media?parent=113332"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.studyproessays.com\/help\/wp-json\/wp\/v2\/categories?post=113332"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.studyproessays.com\/help\/wp-json\/wp\/v2\/tags?post=113332"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}