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NR222 Health and Wellness

RUA: Health Promotion Project

TOPIC: Early and Middle Childhood

E-BOOK: Potter, P.A., Perry, A. G., Stockert, P. & Hall, A. (2021). Fundamentals of Nursing (10th ed.). Elsevier.

Required Uniform Assignment: Health Promotion Paper Guidelines

Purpose

This assignment allows the learner to apply knowledge gained about health promotion concepts and strategies, enhance written communication skills, and demonstrate a beginning understanding of cultural competency.

Course outcomes:

This assignment enables the student to meet the following course outcomes:

1. Discuss the professional nurse’s role in health promotion activities. (PO 1 and2)

3.Discuss health promotion, illness prevention, health maintenance, health restoration, and rehabilitation in relation to the nurse’s role in working with various populations. (PO 1,2, and 8)

Preparing the assignment

Follow these guidelines when completing this assignment. Speak with your faculty member if you have questions.

1)Identify a health problem or need for health promotion for a particular stage in the life span of a population from a specific culture in your area.

2)Choose one of the Leading Health Indicators (LHI) priorities from Healthy People 2020:

https://www.healthypeople.gov/2020/Leading-Health-Indicators

APA, formatting, or grammar assistance, visit the APA Citation & Writing page located at

https://library.chamberlain.edu/APA.

8)Include the following sections (detailed criteria listed below and in the Grading Rubric):

a.Introduction and Conclusion

•Introduction establishes the purpose of the paper and describes why the topic is important to health promotion in the target population in your area.

•Introduction stimulates the reader’s interest.

•Conclusion includes the main ideas from the body of the paper.

•Conclusion includes the major support points from the body of the paper.

Relate Topic to Target Population

•Describes the topic and target cultural population.

•Includes statistics to support the significance of the topic.

•Explains how the project relates to the selected Healthy People 2020 topic area.

•Applies health promotion concepts.

Summary of Articles

–

•A minimum of three (3) scholarly articles, from the last 5 years, are used as sources.

•Articles meet the criteria of being from scholarly journals and include health promotion and wellness content.

•At least one article is related to the chosen cultural group.

•Summarizes all key points and findings from the articles.

•Includes statistics to support the significance of the topic.

7.Identify health promotion strategies throughout the lifespan. (PO 1,2, and 4)

Required Uniform Assignment:

Health Promotion Paper Guidelines NR222Health Promotion Project Guidelines V4Revised:

•Discusses how information from the articles is used in the Health Promotion Project, including specific examples.

Health Promotion Discussion

•Describes approaches to educate the target population about the topic.

•The approaches are appropriate for the cultural target population.

•Identifies specific ways to promote lifestyle changes within the target population.

•Applies health promotion strategies.

APA Style and Organization

•TurnItIn is used prior to submitting a paper for grading.

•Revisions are made based on the TurnItIn originality report.

•References are submitted with the assignment.

•Uses current APA format and is free of errors.

•Grammar and mechanics are free of errors.

•Paper is 3-4 pages, excluding title and reference pages.

•Information is organized around required components and flows in a logical sequence.

Required criteria

1.Introduction establishes the purpose of the paper and describes why topics important to health promotion in the target population in your area.

2.Introduction stimulates the reader’s interest.

3.Conclusion includes the main ideas from the body of the paper.

4.Conclusion includes the major support points from the body of the paper.

Relate Topic to Target Population

1. Describes the topic and target cultural population.

2.Includes statistics to support the significance of the topic.

3.Explains how the project relates to the selected Healthy People 2020 topic area.

4.Applies health promotion concepts.

Summary of Articles

1.A minimum of three (3) scholarly articles, from the last 5 years, are used as sources.

2.Articles meet the criteria of being from scholarly journals and include health promotion and wellness content.

3.At least one article is related to the chosen cultural group.

4.Summarizes all key points and findings from the articles.

5.Includes statistics to support the significance of the topic.

6.Discusses how information from the articles is used in the Health Promotion Project, including specific examples.

Health Promotion Discussion

1. Describes approaches to educate the target population about the topic.

2.The approaches are appropriate for the cultural target population.

3.Identifies specific ways to promote lifestyle changes within the target population.

4.Applies health promotion strategies.

APA Style and Organization

1.TurnItIn is used prior to submitting the paper for grading.

2.Revisions are made based on the TurnItIn originality report.

3.References are submitted with the assignment.

4.Uses current APA format and is free of errors.

5.Grammar and mechanics are free of errors.

6.Paper is 3-4pages, excluding title and reference pages.

7.Information is organized around required components and flows in a logical sequence.

119© NAPICU 2016

Journal of Ps

chiatric
Intensive Care

Journal of Psychiatric Intensive Care, 12 (2): 119–127
doi:10.20299/jpi.2016.009
Received 15 July 2015 | Accepted 28 January 2016
© NAPICU 2016

REVIEW ARTICLE

The use of a token economy for

behaviour and symptom management

in adult psychiatric inpatients: a critical

review of the literature

Krista Glowacki, Grace Warner, Cathy White

School of Occupational Therapy, Dalhousie University, Canada
Correspondence to: Krista Glowacki, School of Occupational Therapy, Forrest
Building, PO Box 15000 Halifax, Nova Scotia, B3H 4R2, Canada;
krista.glowacki@dal.ca

Background: A token economy is a behavioural modification and reward
based intervention in which tokens are given for predefined terms. This
review aims to answer the question: What is the effectiveness of the use of
a token economy for the reduction of negative behaviours and symptoms
in adult psychiatric inpatients?
Method: A systematic review of studies using a token economy for adults
with mental illness, within an inpatient setting was undertaken for the
period 1999–2013. References cited in relevant literature were also
examined

Results: The Oxford CEBM Levels of evidence was used to determine
quality. Grade A and B recommended studies were included in the review.
A total of seven studies were included in the analysis. All of the studies
showed the effectiveness of a token economy for reducing negative
behaviours and symptoms in the short-term.
Conclusions: The use of a token economy, on the basis of reward and
encouragement, should be considered within inpatient psychiatric settings.
The literature shows the effectiveness on behavioural changes in reduction
of violence and aggression. The literature on negative symptom reduction
is scarce and cannot be generalised. There is no evidence to support the
transfer outside of an inpatient/secure setting.

Key words: token economy; psychiatric inpatient; symptom manage-
ment; behaviour management

Financial support: This research received no specific grant from any funding agency,
commercial or not-for-profit sectors.
Declaration of interest: None.

120 © NAPICU 2016

GLOWACKI ET AL.

Introduction

With the shift toward community-based mental health
care, inpatient psychiatry units are seeing an increase in
acuity of the patients who come through their doors (Bow-
ers, 2005). Common reasons for admission include danger
to self or others, severe mental disorder such as psychosis,
and extreme behaviours such as agitation, mania,
unpredictability, confusion, disorientation, emotional
lability, distress/tears, acting out and delusions (Bowers,
2005). Patients may exhibit negative symptoms such as
slow and superficial responses, social withdrawal, and
lack of energy (Hopko et al. 2003; Gholipour et al. 2012),
or negative behaviours, including agitation and aggres-
sion particularly toward staff members (Lepage et al.
2003; Park & Lee, 2012). Thus, the creation of a safe and
secure environment becomes paramoun

As Bowers (2005) discussed, ongoing risk assessment
and monitoring and observation of the patients are routine
aspects of the care, which may lead to the need to emplo

skills in negotiation, persuasion, coaxing, distraction and
de-escalation. When patients do escalate, disrupting the
milieu and placing themselves and/or others at risk, be-
haviour management strategies such as exerting physical
control, restraints and coercive use of medications may be
employed to mediate the behaviour. One approach to
behaviour modification that has received limited recent
attention in the literature is the use of a token econom

Background

A token economy, developed for use within inpatient
psychiatry settings, is a behaviour modification interven-
tion that can be used to shape behaviours including acquir-
ing new skills, reducing undesired behaviours, increasing
treatment compliance, and improving overall manage-
ment of patients on psychiatry units (LePage et al. 2003;
McMonagle & Sultana, 2000). This intervention is based
on operant conditioning. Patients can earn ‘tokens’ which
have no innate value, and can exchange them for some-
thing that does have value to them, such as goods, services
or privileges in the facility when they exhibit a desired
behaviour (Seegert, 2003; McMonagle & Sultana, 2000).
The first principle of the token economy is the law of cause
and effect based on the idea that reinforcement is the most
effective means in changing behaviour. The second princi-
ple is the law of contiguity association, in that two events
will be associated with one another if they happen together
(Dickerson et al. 2005; McMonagle & Sultana, 2000). In
the original economy, both reward and punishment tech-
niques could be implemented (Kreyenbuhl et al. 2010).
Punishment is now viewed as inappropriate within a
healthcare setting, causing the decline of this intervention.
Punishment is considered a negative consequence, includ-

ing the removal of tokens. There are common mis-
conceptions about all token economies, including the
belief that the intervention is abusive, it does not foster
individual treatment, and does not generalise. These mis-
conceptions prevail among health care practitioners and
further contribute to its lack of use (LePage et al. 2003).

A token economy can facilitate improvement in behav-
iour and function. It is an economically friendly
intervention, and can be beneficial in facilities with lim-
ited resources (LePage, 1999; Seegert, 2003; Coelho et al.
2008; Comaty et al. 2001; McMonagle & Sultana, 2000;
Kreyenbuhl et al. 2010). It is relatively simple in its overall
conceptualisation for those involved, and is beneficial for
reducing challenging or disruptive behaviours (LePage,
1999; Coelho et al. 2008). Token economies can be used to
increase functioning and to foster recovery, a key focus of
today’s mental health care (Hassell, 2009).

A systematic review of the use of token economies was
published in 2000, analysing literature up to 1999
(McMonagle & Sultana, 2000). McMonagle & Sultana
(2000) concluded by recommending the token economy
as a cost-effective alternative to psychosocial interven-
tions in institutions with financial struggles. The article
also recommends further in-depth research in a controlled
setting using randomised trials to further explore effec-
tiveness. This systematic review of the literature examines
current research (1999–2013) on the use of a current token
economy in adult inpatient psychiatric settings. The ques-
tion guiding the review is: What is the effectiveness of the
use of a token economy for the reduction of negative
behaviours and symptoms in adult psychiatric inpatients?

Method

Inclusion criteria

Types of studies. Peer reviewed articles including:
randomised controlled trials, prospective cohort studies,
retrospective cohort studies and pre–post design.

Types of participants. Adults ages 18 and older admitted
to a psychiatric facility as an inpatient in a forensic, acute,
or rehabilitation unit, with a mental health disorder as
identified in the Diagnostic Statistical Manual of Mental
Disorder, 5th Edition (DSMV).

Types of interventions. Intervention included a token
economy in which tokens or vouchers are given as rewards
for behaviour specified prior to entering the programme/
economy. Rewards may be given for positive behaviour or
abstinence of negative behaviour. The goal is to achieve
behavioural change by means of use of non-monetary and
non-consumable tokens, which can be exchanged for a
variety of goods, privileges or services in the facility.

121© NAPICU 2016

A TOKEN ECONOMY

Types of outcome measures. To determine if the therapy is
effective, there must be a reduction in one of the two
identified outcomes after the implementation of the inter-
vention. The identified outcomes are negative behaviours
or negative symptoms. Negative behaviours include: vio-
lence, aggression, and drug abuse. Negative symptoms
include: flat affect, lack of pleasure in life, lack of partici-
pation, lack of ability to begin and sustain activities, and
lack of socialisation and interaction with others. Out-
comes can be measured by observation data, frequency
data, incident reports, patient charts, group participation
numbers/percentages and number of positive urine sam-
ples. Statistical information was extracted from each study
inclusive of average test scores and standard deviation,
statistical significance and effect size in changes or differ-
ences.

Search strategy

Electronic searches were undertaken, limiting results to
the English language and publication in the period 1999–
2013 (due to the McMonagle & Sultana (2000) review
including research prior to 1999). The databases CINAHL,
EMBASE, OTseeker, PubMed, PsycInfo and Google
Scholar were used. The search terms used in CINAHL
(EBSCOhost) were: (1) “token economy” OR (tokens OR
vouchers) and psychiatric OR (mental* N2 (health OR ill*

OR disorder*)) and inpatient* OR hospital* OR ward*
OR unit OR patient* OR forensic*; (2) “token economy”
OR tokens OR vouchers and psychiatric OR mental*
NEAR/2 (health OR ill* OR disorder*) and inpatient* OR
hospital* OR ward* OR unit OR patient* OR forensic* and
behavi* OR violen* OR aggressi* OR negative; (3) “To-
ken economy” and adult; (4) “Token economy” and
psychiatric OR (mental* N2 (health OR ill* OR disor-
der*)); (5) Voucher-based and mental health. Other similar
search terms were used in the other databases. An exami-
nation of references cited in relevant literature was also
undertaken.

Exclusion criteria

Research done before 1999, participants under the age of
18, outpatient settings, and diagnoses not in the DSMV
were excluded. Specific study types not included were:
systematic reviews, open forum blogs, hospital unit re-
views and descriptive articles of intervention without a
measureable outcome (see Fig. 1).

Data extraction & quality review

Articles were identified through electronic searches and
abstracts were reviewed. Those that did not meet the
inclusion criteria were then excluded. Of the abstract
reviews, 20 articles were identified and the full manuscripts

Identified through

searching database:

n = 342

Identified through

examination of

references:

n = 3

Excluded after

abstract review:

n = 325

Full-text articles assessed

for eligibility:

n = 20

Included after

manuscript review:

n = 7

Excluded after manuscript review: n = 13

Reasons: Population not inpatients: n = 4

Study design: n = 7

Outcome measured not negative behaviour change: n = 1

Full text not accessible: n = 1

Fig. 1. Articles included and excluded.

122 © NAPICU 2016

GLOWACKI ET AL.

of the papers were read and assessed for quality and
eligibility. The Oxford Centre for Evidence-Based Medi-
cine Levels of Evidence was used to determine quality,
and only grade A and B studies were included in the review
(OCEBM, 2009). Grade A studies are considered the
highest quality and grade B studies are the second highest
quality. After the full manuscript reviews, 13 were ex-
cluded, leaving 7 studies to be included in the systematic
review. Figure 1 indicates reasons why studies were ex-
cluded.

Results

Data were extracted from seven studies and compared to
determine the effectiveness of a token economy (Table 1).
Each study included a rewards and incentive based token
economy for adults within an inpatient psychiatry setting.
Of the seven studies, three were randomised controlled
trials, one was a prospective cohort, two were pre–post
designs and one was a retrospective cohort. All of these
studies were categorised using the OCEBM (2009) to
determine study quality.

The studies classified as grade A of the OCEBM (2009)
were the three randomised controlled trials (Hopko et al.
2003; Gholipour et al. 2012; Park & Lee, 2012).
Randomisation methods were difficult to assess as entire
inpatient units were used. Two of the studies looked only at
male units and were done outside of North America
(Gholipour et al. 2012; Park & Lee, 2012), and in one, all
males on the unit were diagnosed with schizophrenia
(Gholipour et al. 2012). Thus, cultural and gender differ-
ences should be considered and the results be used with
caution to generalise to North American culture and prac-
tice, and to mixed units. Two of the studies had small
sample sizes (Hopko et al. 2003; Gholipour et al. 2012).
The next grade of studies, level B of the OCEBM (2009),
were pre–post designs and prospective cohorts (LePage,
1999; Comaty et al. 2001; LePage et al. 2003). Two of the
studies only analysed one unit of a hospital, limiting the
generalisation, and there was no control group as all patients
in the unit participated in the token economy (LePage,
1999; LePage et al. 2003). Lastly, a retrospective study,
also grade B of the OCEBM (2009) was used (Hassell,
2009). This included an analysis of medical records and no
power analysis was used to determine if sample size was
adequate. In the same study various healthcare profession-
als implemented the token economy and no information
was given on inter-relater reliability or training. It should
also be noted that in all of the studies the intervention was
combined with individualised pharmacological treatment.

The effect of interventions on outcomes

The effectiveness of the intervention being analysed will
be reported as a narrative synthesis. This part will be

separated into two sections. The first will describe the
effectiveness of the intervention on negative behaviours,
and the second will describe the effectiveness on negative
symptoms.

Behaviour. Behavioural change was an outcome meas-
ured in five of the studies (LePage, 1999; Comaty et al.
2001; LePage et al. 2003; Hassell, 2009; Park & Lee,
2012). These studies included violent and aggressive be-
haviour in a physical or non-physical manner that could
harm or threaten other individuals or themselves, mainly
reported as ‘incidents’. All of the studies’ findings support
the efficacy of the token economy for reducing negative
behaviours and unit incidents related to these behaviours
on inpatient psychiatric units. It should be noted that one
study did not have a control, so improvements in behav-
iour and function cannot be attributed to the token economy
alone (Hassell, 2009). Further, one study and its results
provides data to support the positive long-term impact a
token economy can have on the safety and function of an
acute care unit (LePage et al. 2003).

Negative symptoms. The effect of the intervention on
negative symptoms was examined in two studies (Hopko
et al. 2003; Gholipour et al. 2012). The findings from both
studies support the efficacy of the token economy for
negative symptom reduction in an inpatient setting. How-
ever, the study by Hopko et al. (2003) only included
inpatients diagnosed with depression, and the study by
Gholipour et al. (2012) only included males with schizo-
phrenia. See Table 1 for a summary of the outcomes,
results, and the statistical data from each study.

Discussion

This systematic review supports the efficacy of a token
economy for reducing negative behaviours in adults with
mental health illness in an inpatient psychiatry setting. All
five of the studies analysing behavioural change showed
statistical significance in the reduction of negative behav-
iours. While the literature reviewed on the efficacy of the
economy for reducing negative symptoms supported the
use of the intervention, the number of studies was limited,
providing insufficient evidence to support its use. Further,
the symptom reduction studies only targeted one diagno-
sis, not representative of most psychiatric inpatient units.
The research on symptom reduction alone is scarce, and
this outcome measure needs to be explored further. All of
the studies looked at the effects within an inpatient setting,
and the regime of hospital units is important to con-
sider. This includes structure, schedules, expectations and
staff. None of the studies were able to look at the direct
effects on behaviour or symptoms outside of an inpatient
setting, so this is an important caution if considering use of

123© NAPICU 2016

A TOKEN ECONOMY
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IP
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p
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=

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7
.

C
o
n
tin

u
e
d

124 © NAPICU 2016

GLOWACKI ET AL.

Ta
b

le
1

.
C

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tin
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125© NAPICU 2016

A TOKEN ECONOMY

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GLOWACKI ET AL.

this intervention in a community setting. Comaty et al.
(2001) looked at a three-year follow-up after discharge
and re-hospitalisation rates, but the data was not conclu-
sive; thus the authors were unable to say whether a longer
stay in the community was a result of the token economy
itself.

Using a token economy may be a means of reducing
violence and aggression on inpatient units. Improved safety
in inpatient units for staff and patients may allow healthcare
practitioners to focus their attention on treatment and
rehabilitation, and less on control of the unit. Behavioural
focus could be less on the reduction of negative behav-
iours, and more on the promotion of positive behaviour for
rehabilitation and recovery. Further, reduction in negative
symptoms may also increase participation and collabora-
tion of patients toward rehabilitation goals.

Healthcare practitioners should be cautious in using a
token economy. The token economies used in the studies
of this paper varied in rewards, desired behaviour and
structure. In saying this, the general concept of each
economy was the same, earning tokens for positive behav-
iour towards rehabilitation that can be accumulated for
pre-determined rewards. The economy has potential for
abuse if implemented improperly, so programmes should
limit punishment and response costs for behaviour. This is
inclusive of the removal of tokens for negative behaviour.
Based on a recovery-oriented, patient-centred approach,
the following recommendations derive from the literature:

1. Participants in the programme should be given the
option of enrolling at admission, and participation
should stay voluntary throughout (LePage et al. 2003;
Park & Lee, 2012).

2. Staff and patients involved in the token economy
should collaborate to pre-determine rewards (Chiou
et al. 2006; Dunn et al. 2008; Park & Lee, 2012).
Rewards should also be individualised (Park & Lee,
2012).

3. Thorough staff training should be done to ensure
consistency in programme implementation (LePage
1999; LePage et al. 2003).

4. The token/voucher should be given immediately,
thereby verifying positive behaviour (Chiou, et al.
2006; LePage et al. 2003).

5. The economy should be used in congruence with
individualised treatment programmes (LePage, 1999;
Gholipour et al. 2012; Park & Lee, 2012).

It is important to identify the limitations to this literature
review. A small number of studies were analysed, as
there are limited recent research studies on this interven-
tion. The quality is also limited by the fact that only
three studies were randomised controlled trials. Further,
this was a brief review of the literature available. The

research was only analysed by one person, and only
English studies were used.

Areas for future research have been identified from this
review. The first is using a date after hospital discharge to
focus on psychosocial outcomes of participants and their
functioning in society outside of an institutional environ-
ment. Usually hospitalisation is temporary, and it is
important to find a transferable intervention for commu-
nity care and living. Further, multiple units in one hospital,
or comparison of multiple hospital studies could be done
with comparison of control and experimental groups.
Research should also be done on symptom reduction for a
wider range of diagnoses within a hospital or inpatient
unit. Research could also be done on the comparison of
different types of rewards within the economies.

Conclusions

The findings of this literature review support the efficacy
of a token economy for reducing negative behaviours in an
inpatient psychiatric setting. This intervention should be
considered by healthcare professionals working in an
inpatient setting for reduction of negative behaviours, or
increased safety of the units. When implementing a token
economy, the recommendations made on adapting the
economy based on a recovery-oriented patient-centred
practice should also be considered. Few studies were done
on the efficacy of the economy for reducing negative
symptoms, but all that were done determined that the token
economy was effective in symptom reduction. The use of a
token economy for symptom reduction should be used
with caution until further research is done on the topic.

Since the overall number of research studies was lim-
ited, the findings identify the need for further research on
this intervention and its effects on reducing negative be-
haviours and symptoms. While more research is needed,
the current findings should encourage healthcare practi-
tioners to consider the use of a rewards-based token
economy as a treatment intervention in an inpatient psy-
chiatry setting.

Acknowledgements

School of Occupational Therapy at Dalhousie University.
The Waterford Hospital in St. John’s Newfoundland, where
the research first started based on a clinical need.

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Reproduced with permission of copyright owner. Further reproduction
prohibited without permission.

Received: 17 May 2016 Revised: 29 July 2016 Accepted: 13 September 2016

I 10.1002/hup.2557

R E S E A R C H A R T I C L E

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

1 Hospital Alejandro Korn, Melchor Romero, La

Plata, Argentina

2 Clinica City Bell, La Plata, Argentina

3 Departamento de Docencia e Investigacion,

Hospital Jose T Borda, CABA, Argentina

4 Hospital Jose T. Borda, CABA, Argentina

5 ADINEU, CABA, Argentina

6 Department 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

Hum Psychopharmacol Clin Exp 2016; 1–7

Abstract

Objective The aim of this real‐world study was to evaluate the effect of agomelatine on anhe-

donia 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 (General-

ized 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 life-

time (Sadock & Sadock, 2009). The World Health Organization esti-

mated 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 evi-

dence 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). Anhe-

donia has been considered crucial for the diagnosis of depression

wileyonlinelibrary.com/jo

(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 recep-

tors (Audinot et al., 2003, Millan et al., 2003, De Berardis et al., 2013b).

These receptors act in synergy increasing dopamine and norepinephrine

2 GARGOLOFF ET AL.

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 condi-

tions, 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 participa-

tion in the study, and the protocol was approved by a local ethic com-

mittee and conducted in accordance with the principles of good clinical

practice.

All planned procedures relating to this noninterventional/observa-

tional 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 Edi-

tion, 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 evaluation 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 Improve-

ment (CGI‐I) were administered by the physician and constitute a gen-

eral measure of the patient’s psychopathological state before and after

treatment implementation (Guy, 1976).

Each physician managed his patients according to their usual clini-

cal practice and recorded the visit follow‐up by using the electronic

medical report form provided. Safety evaluations 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. Corre-

lation 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

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.

GARGOLOFF ET AL. 3

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 somno-

lence, 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

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

FIGURE 3 Response and remission rate

4 GARGOLOFF ET AL.

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 antidepres-

sant (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

TABLE 2 Assessment in MDE patients with first MDE and with recurrent

First

MDE

Baseline Week 1 Week 4 Wee

SHAPS 9.9 ± 3.9 8.2 ± 4.4 6.0 ± 5.0* 4.1 ±

QIDS‐SR‐16 15.0 ± 5.1 11.9 ± 6.4* 8.8 ± 7.1* 6.1 ±

GAD‐7 13.0 ± 4.8 10.8 ± 4.8* 8.0 ± 5.2* 6.2 ±

CGI‐S 4.5 ± 0.7 4.2 ± 0.9 3.8 ± 1.1* 3.5 ±

CGI‐I — 2.8 ± 0.8 2.5 ± 1.0 2.0 ±

Note. CGI‐I = Clinical Global Impression of Improvement; CGI‐S = Clinical Global
MDE = major depressive episode; QIDS‐SR‐16 = Quick Inventory of Depressive
Scale.

Results are expressed as mean ± SD, analysis of variance for repeated measure

*Significant differences with baseline.

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 signif-

icant changes in body weight, blood pressure, or heart rate.

4 | DISCUSSION

To our knowledge, this is the first study in Argentina evaluating anhe-

donia in depression and the effect of an antidepressant treatment as

the primary endpoint. The main finding of this real‐world, observa-

tional, 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 stud-

ies (Stein, Picarel‐Blanchot, & Kennedy, 2013, Taylor et al., 2014; De

Berardis et al., 2013b; Di Giannantonio and Martinotti, 2012), and pos-

itive 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 treat-

ments. 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 anti-

depressants inhibitors of CYP 1A2 in the market in Argentina at the

time the study was performed. A possible explanation lies in the phar-

macology 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

MDE

Recurrent MDE

k 8 Baseline Week 1 Week 4 Week 8

4.9* 7.4 ± 4.5 6.2 ± 4.5 6.2 ± 3.8* 4.1 ± 4.3*

6.2* 16.0 ± 4.2 11.0 ± 5.8* 8.0 ± 5.9* 6.9 ± 5.5*

4.9* 14.7 ± 4.1 11.3 ± 4.6* 8.6 ± 5.1* 8.3 ± 5.3*

1.4* 4.4 ± 0.7 3.9 ± 0.9* 3.3 ± 1.1* 3.0 ± 1.2*

1.0 — 2.9 ± 0.9 2.3 ± 1.0 2.0 ± 1.4

Impression of Severity; GAD‐7 = Generalized Anxiety Disorder 7‐item scale;
Symptomatology 16‐item Self‐Report; SHAPS = Snaith–Hamilton Pleasure

(LOCF), p < 0.05.

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 Anx-
iety 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

areas, namely, prefrontal cortex without influence in extracellular sero-

tonin levels (Millan et al 2003). Enhancement of dopaminergic and nor-

adrenergic 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 coadministra-

tions 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 pro-

posed in other studies (Martinotti, Orsolini, et al., 2016a).

These results are consistent with a significant number of other tri-

als, but with the relevant parameter of the real‐life setting. Daily clini-

cal 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 bet-

ter 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 inter-

esting insights into the differences between randomized clinical trials

management and routine care management, and the potential implica-

tions 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 com-

parison 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 anhe-

donia is specific and not due to the remission in depression because

improvement in anhedonia appears earlier than the efficacy on depres-

sion 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 improve-

ment 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 anal-

ysis, 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 effi-

cacy of agomelatine in depression and in anxiety within depression. The

efficacy of available antidepressants in anhedonia has been poorly eval-

uated 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

6 GARGOLOFF ET AL.

agomelatine in this important symptom deserve to be confirmed in larger

real‐life studies, they offer a very important property to this novel anti-

depressant 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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