Home The Pros and Cons of Addiction

The Pros and Cons of Addiction

Addictions come in many forms and almost always involve a complex three-way interaction between the person, the object of the addiction (e.g., drugs, gambling, chocolate), and the societal context of the addiction. This complex interaction raises a controversial social question: Is addiction always a bad thing? Although there is often a significant amount of social stigma attached to addictions, and popular media often focuses on the treatment and prevention of addiction, there may also be associated positive qualities of addictive substances and behaviors.

Initial post will be written on a specific substance that has addictive potential (e.g., alcohol, cocaine, ibogaine, marijuana, ayahuasca, MDMA) of your choice.

For this discussion, you must explain both the positive and negative potential of addiction to your chosen substance or behavior. Therefore, you must choose a substance or behavior that presents both positive and negative potential outcomes.

Research your substance or behavior providing at least two peer-reviewed resources to support any claims made. In your post, construct clear and concise arguments using evidence-based psychological concepts and theories to create a brief scenario or example of a situation in which your chosen addiction provides both positive and negative potential outcomes for a subject. Integrate concepts developed from different content domains to support your arguments. Evaluate and comment on the reliability and generalizability of the specific articles and research findings you have chosen to support your arguments. Explain how the APA’s Ethical Principles and Code of Conduct might be used to guide your decisions as a psychology professional if you were assigned to consult with the subject in the situation you have created.

https://www.apa.org/ethics/code/index

A damage/benefit evaluation of addictive product useadd_3675 441..450

Catherine Bourgain1,2, Bruno Falissard1,2, Lisa Blecha1,2,3, Amine Benyamina1,2,3,
Laurent Karila1,2,3 & Michel Reynaud1,2,3

INSERM, Paris, France,1 Université Paris Sud and Université Paris Descartes, Villejuif, France2 and Hôpital Paul Brousse, Villejuif, France3

ABSTRACT

Aims To obtain damage/benefit assessments of eight commonly used addictive products and one addictive behaviour
from French addiction experts and link these to overall evaluations. Design and setting Criteria-based evaluation by
experts in addiction. Specific statistical modelling to estimate the relative contribution of various criteria to formulating
expert general opinion on products. Participants Forty-eight French experts in addiction. Measurements Twelve
criteria covering the whole spectrum of damages and benefits to users and to society evaluated using visual analogue
scales (VAS). Direct measure of expert overall subjective opinions on products from user and from social perspectives.
Findings Damage scoring identified alcohol (damage score = 48.1), heroin (damage score = 44.9) and cocaine
(damage score = 38.5) as the most harmful products to users and to society; gambling was considered the least harmful
(score = 22.5), replicating previous results. Damage scoring correlated poorly with legal status or with overall subjec-
tive expert opinions of products. Benefit perception scores indicated alcohol as a clear outlier (benefit score = 45.5)
followed by tobacco (benefit score = 34.3) and cannabis (benefit score = 31.1). Statistical modelling suggested that
experts attributed 10 times more importance to benefit perception than to damages when making their subjective
opinion from a user perspective and two times more importance to benefit perception than to damages in formulating
their opinion from a social perspective. Conclusions The perceived benefits of addictive products appear to have a
major impact on the opinion of those products expressed by a number of French addiction experts.

Keywords Criteria-based evaluation, damage evaluation, perceived benefit evaluation, subjective opinion.

Correspondence to: Michel Reynaud, Department of Psychiatry and Addictology, University Paris SUD, Paul Brousse Hospital, 12/14 Avenue Paul
Vaillant Couturier, F-94804 Villejuif, France. E-mail: michel.reynaud@pbr.aphp.fr
Submitted 4 April 2011; initial review completed 31 May 2011; final version accepted 26 September 2011

INTRODUCTION

A number of studies have been conducted recently to
assess harm comparatively for different addictive pro-
ducts [1–4]. All these studies show that the measure of
product harm to users and to society is rarely predictive of
its legal status. Otherwise, alcohol and tobacco would
be illegal.

One explanation for this discrepancy is that public
policies are not based on up-to-date scientific facts on
drugs. Efforts should thus be made to collect scientific
data on drug harms and better inform politicians.
However, a complementary explanation could be that
perceived benefits to society and to users deeply influence
political decisions. If this hypothesis is valid, then restrict-

ing the evaluation of addictive product use to damages
severely limits its relevance for policy makers.

Evaluating benefits is not an easy task. For most eco-
nomic and social benefits facts do exist [5–8], but cultural
benefits and user benefits are subjective items. Ideology
[9], history, culture and personal experiences [1], as well
as pressures from organized lobbies, all have an influence
on an individual’s perception of benefits. The issue is
whether reliable and reproducible measures of benefit
perception are possible.

Discussing ‘benefits associated with product con-
sumption’ when considering drugs with very deleterious
effects could sound counterintuitive or even shocking to
therapists. Damage/benefit analyses have been carried
out for some addictive products, in the form of both

Funding: Inserm/University Paris SUD funded the regular salaries of all investigators.

RESEARCH REPORT doi:10.1111/j.1360-0443.2011.03675.x

individual analysis [10–13] and comparative analysis,
but these only considered user-perceived benefits [1]. To
our knowledge, the current study presents the first simul-
taneous damage/benefit assessment of commonly used
drugs and addictive behaviours. Following work by Nutt
et al. [2,3], we based our study on the medical and scien-
tific knowledge of experts on addictive products, asking
them to evaluate all products simultaneously without
considering their legal status. To clarify further the
general perception of experts on addictive products, these
criteria-based measures were complemented with an
assessment of their global subjective opinions on addic-
tive products. Crossing these two classes of measures
shed an interesting light on the making of expert general
opinion.

METHOD

Study design

We focused on eight commonly used addictive products:
alcohol, tobacco, cannabis, cocaine, heroin, amphet-
amine, ecstasy and other synthetic drugs (with the excep-
tion of amphetamine and ecstasy). Products rarely used
in France, such as methamphetamine, were not included.
Instead, we added gambling, a common addictive behav-
iour, proposed recently for inclusion among addictions
in the future DSM-5. To simplify this text, we will refer to
gambling as a ‘product’ in what follows.

Our study design is based on previous work by Nutt
et al. [2,3], with appropriate adaptations implemented
to deal with the joint evaluation of damages and bene-
fits. First, to facilitate the simultaneous evaluation of
damages and benefits, the procedure for damage assess-
ment was simplified. Secondly, the inevitable heterogene-
ity of benefit perception among experts was buffered by
querying a substantial number of experts. Thirdly, the
protocol did not include consensus stages, as we believed
that such stages would be much more complicated to
build for benefits than for damages.

Our ad hoc methodology is based on several precise
criteria for both damage and benefit evaluation. Whereas
Nutt et al. considered, respectively, nine [2] and 16 [3]
criteria for damage assessment, we defined six criteria
for damage assessment covering the entire spectrum
of potential product effects. Three criteria described
damages to product users (‘user damages’) and three
others described damages at the societal level (‘social
damages’). Six criteria covering the entire spectrum of
potential beneficial product effects were constructed and
subdivided into three criteria for benefits associated with
product consumption (‘user benefits’) and three criteria
for benefits to society (‘social benefits’). Table 1 shows
the descriptions of these 12 criteria as presented to
evaluators.

The authors defined these criteria with the help of
physicians from the Department of Psychiatry and
Addictology of Paul Brousse Hospital (Villejuif, France) to
ensure expertise on all nine products. All criteria were
then validated by the executive committee of the French
Federation on Addiction (FFA), a society that includes
most professional French associations involved in addic-
tions care (including hospitals, medico-social centres,
universities, harm reduction, general practitioners and
patient self-help groups).

Criteria were designed such that each criterion consti-
tuted a category deemed to have an equivalent contribu-
tion to global damages (or benefits). In this way, fixing
an equal number of criteria for damages to users and
damages to society meant that if a simple sum of criteria
were performed to obtain a global damage measurement,
that measurement would correspond to a 50–50%
weighting of user and social dimensions, respectively.
This choice is similar to that made by the expert consen-
sus group of Nutt et al. [3], which chose a 54.2% weight
for social damage criteria and a 45.8% weight for user
damage criteria.

We sampled a significantly larger group of experts
than the 15 experts gathered by Nutt et al. [2,3]. Recruit-
ment took place at an FFA board meeting in May 2010.
Forty-eight experts (mean age = 48 years, 60% men,
49% psychiatrists, 77% physicians and 21% other
medico-social professions) participated in the study. This
group is representative of the FFA board members
and therefore constitutes a relevant expert panel on
addictions.

Two weeks in advance of the FFA board meeting all
meeting participants received a list of publications in
high-impact journals and important reports for each
product, validated by the criteria expert group and avail-
able on our website, along with a presentation of our
study. The evaluation questionnaire was presented
orally during the meeting. For each of the 12 criteria for
the nine products, the questionnaire included a visual
analogue scale (VAS) graduated from 0 (‘no damage’ or
‘no benefit’) to 10 (‘extreme and frequent damage’ or
‘extreme benefit’). The comparative perspective between
products in the scoring was fostered through a concomi-
tant evaluation of each criterion for the nine products,
using similar VAS.

Each expert was instructed to complete the question-
naire individually—there was no consensus stage. The
larger size of the expert sample recruited by this simple
procedure opened the way for interesting statistical
analyses of the evaluations and meaningful interpreta-
tions of summary statistics. However, not including a
consensus stage has an important drawback. It impedes a
decision-making analysis or the development of alterna-
tive methods able to elucidate how different criteria

442 Catherine Bourgain et al.

should be weighted for global evaluation. We mentioned
above that our criteria for damages and benefits were con-
structed by our experts with a particular concern for the
relative importance of the various categories. For further
reflection, two complementary questions were included
in the questionnaire for each product. One pointed to the
user dimension—‘Do you think that it is preferable to live
and consume the product?’—with answers ‘yes, I prefer
to live and consume the product’ or ‘no, I prefer to live and
not consume the product’. The other pointed to the social
dimension—‘Do you think that it is preferable to live in a
society where the product is consumed?’—with answers

‘yes, I prefer to live in a society where the product is
consumed’ or ‘no, I prefer to live in a society where the
product is not consumed’. These questions had two objec-
tives. First, they correspond to the ‘expert overall subjec-
tive opinion from a user perspective’ and ‘expert overall
subjective opinion from a social perspective’. Thus, they
allow quantitative descriptions of these items. Secondly,
crossing these global opinions with the criteria-based
scoring via statistical modelling (see below) revealed the
weights that our experts associated implicitly with the
different damage and benefit criteria when formulating
their opinions.

Table 1 Evaluation criteria and their definition.

User damages or benefits Social damages or benefits

Damages Acute health damages. These include all immediate
effects, for example: respiratory failure, cardiovascular
disease, overdose, coma, traffic accidents, acute
behaviour disorders, violence, acute psychotic
disorders, etc.

Health and social costs. These include, for example,
direct health expenditures related to care and
hospitalization, indirect welfare expenditures related
to invalidity and sick leave and expenditures linked to
welfare benefits and permanent disability. Public
health and social expenditures are associated with the
frequency of consumption and the hazards of these
products

Chronic health damage. For example: cancer, chronic
cardiovascular disease, lung disease, cirrhosis, chronic
psychosis, chronic cognitive disorders, dementias,
hepatitis, human immunology virus (HIV)

Legal costs. These may be linked with violence and
antisocial behaviours caused by the use of these
products related to the fight against trafficking and
the parallel economy from illicit substances, etc.
These costs may also include importation duties,
cost of police and legal fees as well as the cost of
incarceration

Dependence. This dimension takes into account
elements of both physical dependence and psychical
dependence, especially loss of control, cravings, and
the compulsive needs it causes

Social consequences of dysfunctional behaviour. Social
dysfunction, related to accidental or intentional
damages caused to others, material damages (family
or social violence); consequences to family
functioning, caused by the effects of the product,
or to the modified motivations of its consumers which
distances them from their family in favour of the
activities linked to the products are evaluated

Benefits Hedonistic benefits. Here, the intensity of the pleasure
obtained and the intensity or the uniqueness of the
sensations procured is evaluated

Economic benefits. The economic importance (in the
legal economy) of production, sales, distribution,
commercialization, promotion and consumption of
the product is evaluated. NB: The benefits to the
society are evaluated taking into account the
percentage of consumers

Identity benefits. Using the product enables the
consumer to integrate certain environments and
social codes that reinforce his identity. The potential
for socialization, related to the collective and cultural
value of its use, is to be evaluated

Social benefits. The importance of the product’s
consumption in maintaining social balance, especially
among social groups who compete for its production
and distribution is evaluated. NB: The benefits to
society are evaluated taking into account the
percentage of consumers

Auto-therapeutic benefits. Product use enables the
consumer to soothe internal suffering and tension,
especially those generated by relations with others.
Eventual health benefits from these substances
(cardiovascular benefits from wine (French paradox),
nicotine and neurones, etc.) are to be integrated

Cultural benefits. The product’s place among the various
cultures and microcultures, its festive or convivial
value, its integration into social rituals is evaluated.
NB: These benefits are evaluated taking into account
the percentage of its consumers

Damages/benefits evaluation of addictive products 443

Analyses of VAS scores and expert general opinion

For each criterion and each product, we used the mean
values of VAS scores for the entire expert sample as
summary statistics. This choice was validated by the
homogeneity of the mean VAS scores across subgroups of
experts (male experts, female experts, physicians, etc.).

We calculated an overall damage score for each
product by summing the mean VAS scores for all six
damage criteria. As discussed previously, this measure-
ment gives equal importance to all six criteria. A similar
overall benefit score was computed for each product, with
an equal relative weight for all six criteria.

To produce an initial approximation, we calculated a
damage/benefit balance for each product by subtracting
the overall benefit score from the overall damage score, a
positive balance reflecting an excess of damages over ben-
efits. In this raw computation, damages and benefits are
supposed to have the same importance: one unit of harm
is deemed equivalent to one unit of benefit.

To test the validity of this hypothesis and to refine the
damage/benefit balance computation, we analysed the
expert overall opinions on products. Subjective opinions
on product consumption from both a user and a social
perspective were first described as proportions of ‘yes’
answers from experts.

Secondly, we designed a specific statistical analysis to
cross the information on the overall opinions of experts
with their criteria-based evaluation of damages and ben-
efits. The main goal of this analysis was to estimate the
weights assigned implicitly to the different damage and
benefit criteria by the experts when making their overall
opinions on products.

We built a model in which the opinion is the variable
to be explained and the criteria-based evaluations of
damages and benefits are the possible explanatory vari-
ables. We hypothesized that the opinions could be mod-
elled correctly by a linear combination of damage and
benefit criteria. Because the opinion is a binary outcome
(yes/no), logistic modelling was the natural regression
framework to be applied. With this model, the estimation
of a regression coefficient for an explanatory variable
directly represents its relative importance in the making of
expert opinions. Damages and benefits are rescaled. Esti-
mations of regression coefficients are the weights implic-
itly assigned by experts to the damage and benefit criteria.

As the overall opinions of experts from a user and
from a social perspective were collected separately, two
separate sets of regressions were performed. In the first
set, the opinion from a user perspective was regressed on
the three user criteria for damages and the three user
criteria for benefits. In the second set, the opinion from a
social perspective was regressed on the three social crite-
ria for damages and the three social criteria for benefits.

The validity of all the regressions performed was checked
by controlling that, for all regression coefficients bi, the
ratio s(bi)/bi was below 30.

To ensure a robust estimation of the regression
parameters, the making of expert opinions was analysed
jointly for all products.

Three models were applied successively and separately
to the two regression sets. Under the most general model
(model 1), all six criteria used to regress the opinion had
an independent regression coefficient. Thus, the weight
assigned to each criterion could differ. Under the inter-
mediate model (model 2), a single regression coefficient
was estimated for all damage criteria and another for all
benefit criteria. Benefits and damages criteria could thus
contribute unequally to the making of expert subjective
opinion, but all benefit criteria were forced to have the
same weight and all damage criteria were forced to have
the same weight. Under the simplest model (model 3), a
single regression coefficient was applied to all criteria. In
this final case, all benefit and damage criteria were forced
to have the same weight, which corresponded strictly to
the raw damage/benefit balance proposed above.

All three models provided relative weights for each
criterion but model 1 had more parameters than model 2
and model 2 had more parameters than model 3. To iden-
tify the most parsimonious model, i.e. the model with the
smallest number of parameters and the best capacity
to explain the overall subjective opinions, we used the
Akaike information criterion (AIC) [14]. This criterion,
derived from the maximum likelihood computation, was
computed for each model. The most parsimonious model
was then identified as the one with the minimum AIC
value. We chose this criterion because, statistically speak-
ing, it is a valid way to identify the most parsimonious
model even when outcomes of the regression are non-
independent. This is the case in our study, as opinions on
all products were analysed jointly and the opinions of a
given expert on different products may be correlated.

Finally, the relative weights estimated from the most
parsimonious model were used to refine the damage/
benefit balance for each product. Instead of simply sub-
tracting the overall benefit score from the overall damage
score, the ‘overall weighted damage–benefit balance’ was
computed by summing the damage criteria scores, each
one multiplied by the corresponding estimated weight,
and subtracting the benefit criteria scores, each one
multiplied by the corresponding estimated weight.

All analyses were performed using R software for
statistical analyses [15].

RESULTS

Figure 1 shows the nine products ranked by their overall
damage scores with the relative contribution of all six

444 Catherine Bourgain et al.

criteria. According to both individual and social criteria,
alcohol is the most harmful product, followed by heroin
and cocaine. If tobacco, cannabis, amphetamine, ecstasy
and other synthetic drugs show similar overall damage
scores, tobacco is characterized by relatively greater
damage to users over damage to society. Gambling is a
clear outlier, with less damage to users and to society. The
correlation between this overall damage score and the
total harm score proposed by Nutt et al. [3] for the seven
products in common (alcohol, tobacco, heroin, cocaine,
cannabis, amphetamine, ecstasy) is remarkably high
(r2 = 0.95). This is all the more interesting because the
Nutt et al. harm score computation involved an explicit
differential weighting of criteria, whereas our score
embeds the relative importance of criteria in those crite-
ria’s definitions. We consider this result as a first valida-

tion of our damage grid. Furthermore, similarly to Nutt
et al. [2,3], the correlation between our overall damage
score and the legal status of products is very poor.

Interestingly, the correlations between the overall
damage scores and the overall subjective opinions
expressed by experts on the products from both a user and
a social perspective are also poor (see Table 2). With 75%
of experts preferring the possibility of a product’s con-
sumption and 92% of experts preferring to live in a
society where its consumption is possible, alcohol ranked
first in terms of overall positive opinions although it was
considered to be the most harmful product. Conversely,
gambling was the ‘product’ with the smallest damage
score but only 29% of the experts chose the possibility to
gamble and 52% preferred to live in a society where gam-
bling is possible. We note that for all products, experts

Figure 1 Products ordered by decreasing overall damages. Contributions to the overall score of each six damage criteria. The three user
criteria are clustered at the top shown in blue; the three social criteria at the bottom shown in red

Table 2 Expert general subjective opinion on the products. Proportions of experts preferring to live and consume the product and
proportions of experts preferring to live in a society where the product is consumed.

Alcohol Gambling Cannabis Tobacco Amphetamines Ecstasy
Synthetic
drugs Cocaine Heroin

Prefer to live and consume the product 75% 29% 23% 13% 10% 8% 11% 8% 15%
Prefer to live in society where the

product is consumed
82% 58% 42% 38% 27% 24% 24% 22% 20%

Damages/benefits evaluation of addictive products 445

were more tolerant to product use when considering
the social perspective than when considering the user
perspective.

These results confirm that, even for experts, the
overall damage score is not a sufficient explanatory vari-
able for their subjective opinion on products. This rein-
forces the idea of benefit perception measurements.

Figure 2 shows the nine products ranked by their
overall benefit scores with the relative contribution of
all six criteria. Alcohol stands as a clear outlier with
the highest individual and social benefits, followed by
tobacco. Cannabis ranked third, with an overall benefit
score greater than that of gambling.

In an initial approximation, damages and benefits
were pooled in the raw balance in which all criteria con-
tribute equally to the global balance (damage criteria are
counted positively and benefit criteria are counted nega-
tively). Using this approach, gambling and tobacco are
the only two products with a negative balance, meaning
that benefits are estimated to be higher than damages.
The balance for cannabis is more favourable than for
alcohol, although both are positive. The balance is clearly
positive for all other products (see Fig. 3).

To test the robustness of this raw approach to
damage/benefit balance assessment, we applied ad hoc
statistical modelling in which expert overall subjective

opinions were regressed on damage and benefit VAS
score evaluations. The results, presented in Table 3, show
that the model that best explains expert preference
formulations is model 2 for both user preference (smaller
AIC of all three models) and social preference (equal
AIC for models 2 and 1 but model 2 is preferable as it is
more parsimonious). This means that using the raw
damage/benefit balance to summarize the criteria-based
evaluation of experts (i.e. model 3) is not the best way
to predict the general subjective opinions expressed by
experts. Interestingly, however, assigning equal weights
to all damage criteria, on one hand, and equal weights to
all benefit criteria, on the other hand, is a more parsimo-
nious model of subjective opinion than considering each
criterion separately. This result reinforces the robustness
of the relative weighting embedded in our damage crite-
ria definition, already indicated by the comparison with
Nutt et al. [3]. Figure 4 presents the weights for damage
and benefit criteria, estimated using models 2 and 1.
From this analysis we estimate that, globally, experts give
10 times more importance to benefits than to damages
when making their subjective opinion from a user
perspective. Although it is less parsimonious, model 1
proposes interesting estimations of the relative impacts
of the different criteria evaluated. The two criteria iden-
tified as having the greatest impact on subjective

Figure 2 Products ordered by decreasing overall benefits. Contributions to the overall score of each six benefit criteria. The three user
criteria are clustered at the top shown in blue; the three social criteria at the bottom shown in red

446 Catherine Bourgain et al.

opinion-making are ‘identity benefits’ and ‘auto-
therapeutic benefits’.

The evaluations of benefit criteria also have a more
decisive impact on the general subjective opinion from a
social perspective than the evaluations of damage crite-
ria, but the differential is more balanced (weights for ben-
efits are 1.67 those for damages). Three criteria appear to
be underweighted under model 3: social consequences,
legal costs and economic benefits.

Finally, Fig. 5 presents the overall weighted damage–
benefit balance, calculated using the weights estimated
under model 2. In this representation, the correlation
with legal status is notable. All legal products are on the
right side of the scale; all illegal products are on the
left. Note that gambling and cannabis have very similar

profiles. Both have a balance less favourable than that
of tobacco, although the expert subjective opinions on
these two products were positive more frequently than
for tobacco. This can be explained by experts’ opinions
associating low economic benefits with cannabis and
relatively small benefits to users with gambling.

DISCUSSION

The results from this damage/benefit analysis are inter-
esting from several perspectives.

First, we identified alcohol, heroin, cocaine and
tobacco as the most harmful addictive products. This
result correlates strongly with the expert consensus-
based measures of harm proposed by Nutt et al. [3]. The

Figure 3 Overall unweighted damage–benefit balance

Table 3 Comparison of models linking expert general subjective opinion and criteria-based evaluation of damages and benefits.

Weighting scheme applied to the damage/benefit criteria

Subjective opinion from
a user perspective

Subjective opinion from
a social perspective

n AIC n AIC

Equal weight for all criteria; univariate model 3 1 440 1 476
Equal weight for damage criteria/equal weight for benefit

criteria; bivariate model 2
2 427 2 472

Independent weight for all criteria; multivariate model 1 6 422 6 472

Akaike’s information criterion (AIC) and number of parameters (n) are presented for the three models studied, processing the subjective opinions
separately both from a user perspective and a social perspective.

Damages/benefits evaluation of addictive products 447

User Preference

Social Preference

Damage criteria
–0.0107

[–0.05;+0.03]

Bivariate model 2

Multivariate model 3

Acute health
damages
–0.0207

[–0.13;+0.09]

Chronic health
damages
–0.0079

[–0.12;+0.14]

Hedonist
benefits
0.0136

[–0.12;+0.15]

Auto-therapeutic
benefits
0.130

[0.01;+0.25]

Identity
benefits
0.147

[0.03;+0.26]

Dependence

–0.0109
[–0.14;+0.11]

Health and
social costs

–0.182
[–0.29;–0.07]

Legal
costs

–0.049
[–0.16;+0.06]

Economic
benefits
0.083

[0.01;0.17]

Cultural
benefits
0.127

[0.03;0.22]

Social
benefits
0.170

[0.06;0.27]

Social
consequences

–0.0023
[–0.10;+0.10]

Benefit criteria
0.113

[0.06–0.166]

Damage criteria
–0.0624

[–0.097;–0.027]

Benefit criteria
0.1

[0.075–0.137]

Figure 4 Estimation of weights associated
with damage and benefit criteria in expert
subjective opinion-making and correspond-
ing confidence intervals. (a) Analysis of
expert opinion from a user perspective and
(b) from a social perspective. Estimation
obtained with the bivariate model
2—upper part of (a) and (b) and the mul-
tivariate model 1—lower part of (a) and
(b)

Figure 5 Overall weighted damage–benefit balance

448 Catherine Bourgain et al.

similarity in harm assessment obtained using two rela-
tively different study designs in two different countries
certainly strengthens the value of these evaluations. It
also validates our criteria definitions and our direct and
larger expert-sample based evaluation procedure, at least
for the seven commonly used products included in the
two studies.

Secondly, our analysis of subjective opinion-making
suggests that the perceived benefits from a user perspec-
tive are particularly important. This result is all the more
interesting because most experts queried in our study
were therapists. In other words, having an outstanding
knowledge of harm to users did not prevent these experts
from considering benefits first. From an evolutionist per-
spective, this result is not surprising. If the use of psycho-
active products is present in every culture and every era,
this is because of the pleasure obtained, the positive emo-
tional states created, the stimulating and therapeutic
effects against stress, pain, suffering or negative symp-
toms associated with psychiatric disorders [16]. Recent
neurobiological data also support this perspective
[17–20]. Psychoactive products modify and modulate
the fundamental mesocorticolimbic network involved in
pleasure, motivation or regulation of emotions.

Thirdly, as noted by others [1–3], our data show that
the correlation between level of harms and drug legisla-
tion is poor, yet our systematic damage/benefit approach
shed an interesting light on this discrepancy. The esti-
mated damage/benefit weighted balance clusters the
products into three categories: alcohol and tobacco
appear at the most favourable end of the scale, gambling
and cannabis cluster in the middle and all other illegal
products are grouped at the least favourable end of the
scale. This clustering reflects the particular status of
alcohol and tobacco. The harmfulness of alcohol is out-
weighed completely by the high perceived benefits associ-
ated with this product. A similar mechanism is observed
for tobacco. At the other end of the scale, perceived
benefits for heroin, cocaine, ecstasy, amphetamines and
other synthetic drugs are notably weaker. Their buffering
effect on damages is less marked. Cannabis is the product
for which the legal status appears the most questionable
from our study. With high perceived benefits and moder-
ate damages, cannabis has a weighted balance equivalent
to gambling.

This correlation between legal status and the damage/
benefit weighted balance should, however, be considered
with caution. By construction, benefits to society (in par-
ticular economic and social benefits) are highly depen-
dent on the legal status of the products. Taxes cannot be
applied to illegal products. Note that legality also influ-
ences the evaluations of damages to society. The fight
against trafficking and the parallel economy from illicit
substances represents substantial legal costs. Our mea-

surements and results should thus be taken for what they
are: evaluations and analyses within in a specific legal
context.

The present results are based on evaluations by
experts in addiction. If their expertise on damages is
expected to be strong enough to provide objective analy-
sis, the situation is necessarily different for benefits.
Frequent exchanges with product users, empathy and
personal experiences of direct consumption of some
products influence experts’ knowledge but do not provide
objective analysis. At best, their evaluation reflects accu-
rately the perception of benefits among French experts in
addiction. However, when designing the present study, we
hypothesized that the subjectivity inherent in measuring
benefits should not prevent their analysis. As our study
illustrates, benefits have significant importance in
opinion making, even among damage experts, thus
strengthening our hypothesis. The goal here is not to
collect objective facts on benefits. We know that such
perceptions are complex and influenced by personal
history, culture, experiences and efficacy of certain pow-
erful lobbies. Rather, we think that, as for damages, a
precise understanding of benefit perception could help
to improve public policies in addiction. Consequently,
similar studies should be conducted in the general
population or in specific groups targeted for public health
campaigns. The methodology developed in this paper
could be fruitful for evaluating damage/benefit balances
in the general public and among policy makers.

Declarations of interest

None.

Acknowledgements

The authors are grateful to all the experts who partici-
pated in the study, to the Board of Fédération Française
d’Addictologie and to Dr Gisèle Gilkes-Dumas for her help
in collecting data. Mrs Nathalie Da Cunha assisted with
some of the data management.

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450 Catherine Bourgain et al.

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Users should refer to the original published version of the material.

Cultural and religious considerations in pediatric
palliative care

LORI WIENER, PH.D.,1 DENICE GRADY MCCONNELL, M.A., M.S.W.,2

LAUREN LATELLA, BS.,1,3 AND ERICA LUDI, BS.4
1Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
2Adams Hanover Counseling Services, Inc., Hanover, Pennsylvania
3Cornell University, Ithaca, NY
4National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland

(RECEIVED August 12, 2011; ACCEPTED August 15, 2011)

ABSTRACT

Objective: A growing multicultural society presents healthcare providers with a difficult task of
providing appropriate care for individuals who have different life experiences, beliefs, value
systems, religions, languages, and notions of healthcare. This is especially vital when end-of-life
care is needed during childhood. There is a dearth of literature addressing cultural
considerations in the pediatric palliative care field. As members of a specific culture often do not
ascribe to the same religious traditions, the purpose of this article was to explore and review how
culture and religion informs and shapes pediatric palliative care

Method: Comprehensive literature searches were completed through an online search of nine
databases for articles published between 1980 and 2011: PsychINFO, MEDLINEw, Journal of
Citation Reports-Science Edition, Embase, Scopus, CINAHLw, Social Sciences Citation Index
(SSCI), EBSCO, and Ovid. Key terms included: culture, transcultural, spiritual, international,
ethnic, customs or religion AND end-of-life, palliative care, death, dying, cancer, or hospice, and
children, pediatrics, or pediatric oncology. Reference lists in the retrieved articles were
examined for additional studies that fit the inclusion criteria, and relevant articles were
included for review. In addition, web-based searches of specific journals were conducted. These
included, but were not limited to: Qualitative Health Research, Psycho-Oncology, Journal of
Psychosocial Oncology, Journal of Pediatric Psychology, Journal of Pediatric Health Care,
Journal of Pediatric Oncology Nursing, Omega, Social Work in Health Care, and Journal of
Palliative Medicine.

Results: Thirty-seven articles met eligibility criteria. From these, seven distinct themes
emerged that have implications for pediatric palliative care. These include the role of culture in
decision-making, faith and the involvement of clergy, communication (spoken and unspoken
language), communicating to children about death (truth telling), the meaning of pain and
suffering, the meaning of death and dying, and location of end-of-life care.

Significance of results: The review of the literature provides insight into the influence of
religion and how culture informs lifestyle and shapes the experiences of illness, pain, and end-
of-life care. Recommendations for providing culturally sensitive end-of-life care are offered
through the framework outlined in the Initiative for Pediatric Palliative Care Quality
Improvement Project of 2002. Cultural traditions are dynamic, never static, and cannot be
generalized to all families. Guidelines to aid in approaches to palliative care are provided, and
providers are encouraged to define these important differences for each family under their care.

KEYWORDS: Culture, Pediatric palliative care, Religion, Spirituality, Children, Ethnicity

Address correspondence and reprint requests to: Lori Wiener,
National Cancer Institute, National Institutes of Health, 10
Center Drive, Pediatric Clinic, 1-6466, Bethesda, MD 20892.
E-mail: wienerl@mail.nih.gov

Palliative and Supportive Care (2013), 11,

– 67.
# Cambridge University Press, 2012 1478-9515/12 $20.00
doi:10.1017/S1478951511001027

INTRODUCTION

A growing multicultural society presents healthcare
providers with a difficult task of providing appropri-
ate care for individuals who have different life experi-
ences, beliefs, value systems, religions, languages,
and notions of healthcare. Cultural practices and
spiritual beliefs are the foundations on which many
lives are based, and quality care requires medical
providers to be both culturally sensitive and cultu-
rally competent. This is especially vital during the
vulnerable period of end-of-life during childhood
(Levetown, 1998; Contro et al., 2010). Although re-
search has been growing in the palliative care field,
the majority of literature on pediatric palliative care
focuses on epidemiology, parental decision-making
factors, models of care, ethical and legal consider-
ations, symptom management, and ways of providing
total care for the family (Gilmer, 2002; Tomlinson
et al., 2006; Moody et al., 2011). Children with life-
limiting and life-threatening illnesses that lead to
death deserve a cultural reappraisal of how we care
for them when the aim of care has shifted from cura-
tive to simply offering the best possible “health” and
“quality of life” (Benini et al., 2008).

Beginning with brief overviews of cultural compe-
tence and pediatric palliative care, this article re-
views the relevant literature, describes the
influence that culture and religion can have on end-
of-life pediatric care, and highlights the importance
of integrating culture with death and dying tra-
ditions. Recommendations for providing culturally
sensitive end-of-life care are offered through the fra-
mework outlined in the Initiative for Pediatric Pallia-
tive Care Quality Improvement Project of 2002.
These include the following areas of improving
pediatric palliative care: maximize family involve-
ment, involve children in decision making, minimize
pain, provide emotional and spiritual support to fa-
milies, facilitate access to needs, enhance continuity
of care, and offer bereavement support (Solomon
et al., 2002).

Cultural Competence

The concept of cultural competence and its necessity
in treatment of diverse patients and families has
flourished within the last decade. Research shows
that cultural competence is more than accumulated
knowledge of cultural practices; it encompasses a
need for medical practitioners to consider their own
constructs of bias and belief (Surbone, 2008; Kuma-
gai & Lypson, 2009). Cultural competence must be
considered in context of the diverse personal, medical
and practitioner cultures that abound in clinical set-
tings (Taylor, 2003). Moreover, cultural practices can-
not be taken out of patient context. It is easy to

oversimplify cultural or religious practices. Social
factors, such as class and literacy, differentiate indi-
viduals within cultural norms (Taylor, 2003). Like-
wise, practitioners must be aware of the contrary
effect of perpetuating rigid stereotypes about what
members of a particular ‘‘culture’’ believe, do, or
want, and how that translates to provision of care.
The modern view of cultural competence emphasizes
its fluidity: a process that bridges care and patient
need as a vital link in communication with patients
and families during tragic circumstances.

Pediatric Palliative Care

Palliative care is aimed at improving the quality of
life for patients and their families who are confronted
with life-threatening illness by providing support
and care for pain, physical symptoms, psychological
and social stress, and spirituality. Pediatric palliative
care encompasses the same goals as adult palliative
care, but focuses specifically on serving the unique
needs of the child and family (Anghelescu et al.,
2006). During youth, life-threatening illness is
shaped by the child’s developmental context, which
includes not only physical transitions but also
psychological, emotional, and spiritual changes. For
example, pediatric palliative care in the neonatal
unit is fundamentally different from the pediatric
palliative care appropriate with an adolescent, whose
complexity of thought allows greater reflection re-
garding his or her beliefs and wishes about death
(Himelstein et al., 2004). A particular challenge
specific to pediatric palliative services is that end-
of-life care for a child seems inherently unnatural
in the mind of many parents and doctors, who often
struggle to accept that nothing more can be done
for a child. It is not unheard of for children with leu-
kemia to receive “a third or fourth bone marrow
transplantation in an attempt to induce a short-
term remission or to maintain some quality of life,
but with no hope of cure” (Himelstein et al., 2004,
p. 1758), something typically outside the standard
of medical care for an adult patient. Discrepancies
in treatment goals between staff and family and
lack of understanding of the concept of palliative
care can also delay the introduction of pediatric pal-
liative care services, and may prolong physical pain
in children, as well as emotional and psychological
suffering in their parents and treatment team (Koe-
nig & Davies, 2002; Anghelescu et al., 2006; Mack
& Wolfe, 2006; Davies et al., 2008).

Dealing with the potential loss of one’s child is a
catastrophic experience across cultures (De Trill &
Kovalcik, 1997); however, the literature suggests
that cultural influences may further complicate the
appropriate integration of pediatric palliative care.

Wiener et al.48

A study conducted by Davies et al. (2008) found that
nearly 40% of healthcare providers identified cul-
tural differences as a frequently occurring barrier
to adequate pediatric palliative care. For example,
Latino parents tend to have an overarching belief
that every effort should be made to save the child, a
notion found to make parents hesitate to institute
palliative care, regardless of illness severity (Thibo-
deaux & Deatrick, 2007). Sandoval (2003) found
that African-American individuals with strong ties
to Christianity might be hesitant to discontinue
life-prolonging treatments because of a belief in di-
vine rescue (Sandoval, 2003). In such circumstances,
by accepting palliative care, parents may feel that
their child is not being provided with the best poss-
ible care. Moreover, such interpretation can lead to
a preference for life-prolonging treatments over in-
terventions designed to reduce suffering and to pro-
vide comfort and suppor

The underutilization of palliative care services
among ethnic minorities, specifically Latino, Indian,
Native and African-Americans, has been well descri-
bed and often attributed to factors such as lack of the
family’s familiarity with hospice and palliative care
services, language barriers, religious differences, dif-
ficulties in accessing insurance, distrust of the
healthcare services, discomfort with introducing
additional healthcare with professionals not of one’s
ethnic or cultural background into the home,
physicians’ discomfort, or a combination of factors
(Greiner et al., 2003; Lyke & Colon, 2004; Hardy
et al., 2011). However, there is a clear dearth of litera-
ture addressing cultural considerations in the pedi-
atric palliative care field. Moreover, members of a
specific culture often do not ascribe to the same reli-
gious traditions. This article sought to explore and
address the influence of religion in pediatric pallia-
tive care, with emphasis on how culture informs life-
style and shapes the universal experiences of illness,
pain, and death.

SEARCH METHODS

Literature reviewed for this article was identified
through an online search of nine databases (Psy-
chINFOw, MEDLINEw, Journal of Citation Reports-
Science Edition, Embase, Scopus, CINAHLw, Social
Sciences Citation Index (SSCI), EBSCO,and Ovid)
for articles published between 1980 and 2011. Key
terms: culture, transcultural, spiritual, inter-
national, ethnic, custom or religion and end-of-life,
palliative care, death, dying, cancer, or hospice, and
children, pediatrics, or pediatric oncology were com-
bined. Reference lists in the retrieved articles were
examined for additional studies that fit the inclusion
criteria, and those relevant articles were also inclu-

ded for review. In addition, web-based searches of
specific journals were conducted. These included,
but were not limited to: Qualitative Health Research,
Psycho-Oncology, Journal of Psychosocial Oncology,
Journal of Pediatric Psychology, Journal of Pediatric
Health Care, Journal of Pediatric Oncology Nursing,
Omega, Social Work in Health Care, and Journal of
Palliative Medicine. Studies were excluded if they fo-
cused on adjustment of children with serious illness
rather than on cultural issues, or were not published
in English.

Considering the limited number of published re-
ports in the area of culture and pediatric palliative
care, both qualitative and quantitative studies were
included. Reference lists from retrieved articles and
review articles were also searched for relevant
studies. Two psychology students, a master’s level so-
cial worker, and a scientific librarian conducted the
search. Two separate reviewers with pediatric
psychosocial oncology experience examined the
full-text articles against the predetermined in-
clusion/exclusion criteria. Many other studies and
resources provided important insights into cultural
and religious beliefs that have applicability in end-
of-life care, and are included in the references. Tables
were constructed using categories such as demo-
graphic and cultural characteristics, followed by the
creation of codes in order to perform a thematic
analysis of the findings of each article. Once codes
were independently grouped together in broad
themes, consensus was obtained between the author
(L.W.) and reviewers.

RESULTS

Out of 93 articles identified through the literature
searches, 37 met inclusion criteria: Crom, 1995; De
Trill & Kovalcik, 1997; Flores et al., 1998, 2000; Leve-
town, 1998; Cantro et al., 2002; Crawley et al., 2002;
Koenig & Davies, 2002; Solomon et al., 2002; Field &
Behrman, 2003; Mazanec & Tyler, 2003; Himelstein
et al., 2004; Kato et al., 2004; Munet-Vilaro, 2004;
Owens & Randhawa, 2004; Kemp, 2005; Abbe et al.,
2006; Anghelescu et al., 2006; Campbell, 2006; Lobar
et al., 2006; Mack et al., 2006; Meyer et al., 2006; Tom-
linson et al., 2006; Kobler et al., 2007; Thibodeaux
et al., 2007; Benini et al., 2008; Davies et al., 2008;
Jacob et al., 2008; Kongnetiman et al., 2008; Surbone,
2008; Dell, 2009; Cantro et al., 2010; Gupta et al.,
2010; Hatano et al., 2011; Moody et al., 2011). From
these, seven distinct themes emerged that have impli-
cations for pediatric palliative care. These include the
role of culture in decision making, faith and the invol-
vement of clergy, communication (spoken and unspo-
ken language), communicating to children about
death (truth telling), the meaning of pain and

Pediatric palliative care: Influence of culture and religion 49

suffering, the meaning of death and dying, and
location of end-of-life care.

The Role of Culture in Decision Making

Appreciation of cultural norms and customs is criti-
cal as it pertains to family decision makers and those
who learn about the diagnosis or prognosis. For
many cultures, family can be defined as not only im-
mediate family members but also extended family
and community members. For example, Olsen et al.
(2007) report that Native American individuals
may want information shared with community lea-
ders so that they can help in decision making for
the child. Mazanec and Tyler (2003) found that
many African-American families prefer that conver-
sations be initiated with the eldest member of the fa-
mily, typically the male. Similar traditions of
respecting the opinions of elders exist in Russian cul-
ture (Lipson et al., 1997; Matthews et al., 2006).
Other studies found that Latino and Asian families
when assessing the spiritual care needs of Latino
and Asian families, other studies found that the
family may stipulate that information be conveyed
without the child present (Mazanec & Tyler, 2003;
Brolley et al., 2007; Cardenas et al., 2007).

Child-rearing practices in different cultures may
also play a role in decision making. Some cultures
emphasize autonomy and independence, whereas
others encourage boundary melding. For example,
Japanese child rearing practices seem to blur bound-
aries between mother and child (Seiko, 1989; De Trill
& Kovalcik, 1997). Other cultures emphasize living
in harmony with one’s environment rather than at-
tempting to control it, which may lead to a more pas-
sive approach to illness and decision making. Illness
may also have a different meaning depending upon
which member of the family is ill. This is more preva-
lent for some traditional cultures that seem to pre-
sent a strong desire to have male children to
sustain the family line (Namboze, 1983).

Gender often plays a role in decision making. In
both Asian and Latino families, the mother is typi-
cally regarded as the primary caregiver; therefore,
decisions will often be placed in her hands (Himel-
stein et al., 2004; Phan & Tran, 2007). However,
when possible, Latino women will seek the per-
mission of the child’s father before deciding to seek,
continue, or discontinue treatment. This is a reflec-
tion of familismo, a term used to describe the power
and strength of the family in Latino culture. Famil-
ismo is characterized by interdependence, affiliation,
and cooperation (Cardenas et al., 2007). However,
these traditional role assumptions are challenged
when language becomes a barrier. The normative
hierarchical family structure is often waived based

on the individual who speaks the best English, which
often leads to a child or adolescent becoming the fa-
mily spokesperson (Campbell, 2006). When the ill
child is placed in a role of authority as translator of
medical information for parents, conflict can ensue
when treatment decisions need to be made (DeTrill
& Kovalcik, 1997).

Faith and the Involvement of Clergy

Parents of children receiving palliative care have no-
ted that faith is central to their efforts to provide gui-
dance, make sense of their situation, grant
permission around end-of-life decision making, and
to better cope (Meyer et al., 2006). Table 1 provides
an overview of major faith traditions, beliefs, and
practices at the end of life. Most families who are re-
ligious have certain customs around end-of-life care
that they would like to have respected. Catholic La-
tino families will likely want a priest at the child’s
bedside to complete death rituals (e.g., reading of
last rites) (Lee et al., 2007). Buddhists may wish to
have a monk chant. However, the intention of this
Table is not to be an algorithm, but rather a guide fa-
milies of diverse faiths.

Whereas a guide for families of diverse faiths and
religious traditions are important across cultures,
the involvement of pastoral workers in pediatric
palliative care is not universal. For example, Vietna-
mese families visited by the hospital chaplain often
interpret this as a symbol of the child’s impending
death (Phan & Tran, 2007). Latino families may not
want mental health workers involved in the grief pro-
cess because they believe it signifies their grief as
pathological (Cardenas et al., 2007). Overall knowl-
edge of cultural differences is important, but it is vi-
tal that healthcare practitioners understand that
such practices differ among people from the same
heritage. For example, whereas most Vietnamese
are Buddhist, they may have other religious affilia-
tions such as Catholic, Evangelical Protestant, and
Chinese Confucianism, and each religion may have
a different practice. Asking family members about
their preferences and rituals will help providers un-
derstand their particular needs and desires and re-
duce the likelihood of stereotyping.

Communication: Spoken and Unspoken
Language

Communication is a means by which people connect
(Andrews, 2003), and verbal communication entails
language, which can be a critical barrier in facilitat-
ing meaningful and deep communications that are
foundational to pediatric palliative care (Kemp,
2005). Breakdowns in communication can lead to im-
proper diagnosis, inadequate pain management,

Wiener et al.50

Table 1. Major faith traditions, beliefs and practices regarding illness, dying and deatha

Buddhismb Catholicismc Hinduismd Islame
Jehovah’s
Witnessf Judaismg Mormonismh Protestantismi

7th Day
Adventist

Illness/death
rites or
rituals

Family presence
is important.

May chant
mantras as
infant/child
becomes
seriously ill.

The child’s body
should not be
touched after
death.

Family may
take the body
home to
prepare it for
burial.

The body should
not be moved
for 8 hours
after death.

Sacrament of
the sick
with
anointing of
oil,
communion,
and final
blessing by
priest.

Ideal to be
surrounded
by family and
friends who
sing sacred
hymns and
say prayers or
chant the
dying
person’s
mantra.

When death is
near, the
family
spiritual
leader is
asked to
conduct final
rites.

The body should
be as close to
the ground as
possible to
help the soul
absorb into
the ground.

Body is washed
3 times.

Muslim, burial
performed
within 24
hours.

Cremation
forbidden.

Prayer;
reading
Bible.

Prayers for the
sick.

No cremation.
Living person

always with
body after
death.

Burial as soon
after death as
possible.

Laying on of
hands,
prayer,
anointing
with oil.

Allow the ill to
express
sadness at
life being cut
short.

Variable; may
include prayer,
anointing body
with oil,
communion,
laying on of
hands, final
blessing.

Family presence
may be
important.

Prayer,
anointing
with oil

Autopsy According to
individual
situation.

No
restrictions.

If required by
law.

Limited to
medical and
legal
reasons.

If required
by law.

If required by law. No intrinsic
objection.

No restrictions. No restrictions.

Existence of
Heaven

There are
numerous
heavens,
hierarchically
arranged and
inhabited by
joyous beings
known as
“gods” and
“demi-gods”.

“Heaven” is a
condition
rather than
a place;
provides
eternal
fullness of
life.
Supreme
happiness
flows from
intimacy
with God.

Heaven is a
place similar
to life on
earth, but
without
sickness, old
age, death. A
soul enjoys
the rewards
of his or her
good deeds.

Heaven is
described as
a “garden”
having
several
layers with
the highest
being
directly
under God’s
throne.
Souls are
content.

Some people
will go to
heaven to
rule with
God and
Jesus. The
remainder
of the
righteous
will enjoy
paradise
on earth.

Heaven is a place
where anxiety
and travail are
ended. Quiet,
peaceful,
intellectual
activity takes
place and the
mysteries of
life are solved.

There are 3
“degrees of
glory”; all are
places of
continuing
growth and
progress.
Those who
attain the
highest level
will live with
God, Christ
and their
own families.

Varies. Some
believe Heaven
is a place with
streets of gold,
or a place to be
in the presence
of God,
whereas others
believe Heaven
is a condition
of eternal
happiness and
fulfillment.

Heaven is being
in the
presence of
God. It is the
dwelling
place of God
and will
ultimately be
located on
the renewed
earth.

Continued

P
ed

ia
tric

p
a

llia
tiv

e
ca

re:
In

fl
u

n
ce

o
f

cu
ltu

re
a

n
d

relig
io

n
5
1

underutilization of prescription medications, and dif-
ficulty in obtaining informed consent between Latino
patients and their medical providers (Crom, 1995;
Flores & Vega, 1998; Flores, et al., 1998, 2000) as
well as in other cultures. Families can experience ad-
ditional despair when language barriers result in an
inability to acquire complete information about their
child’s health status or a physician’s recommended
interventions (Contro et al., 2002). This emphasizes
the need for trained medical interpreters to be used
to mediate communication between family and
healthcare professionals (Field & Behrman, 2003;
Randhawa et al., 2003). The choice of words, too,
can create barriers to successful communication.
For example, Native American, Filipino, Chinese,
and Bosnian cultures emphasize that once words
are spoken out loud, they may become a reality (Sea-
right & Gafford, 2005). Therefore, reluctance for
parents to talk about end-of-life care may be based
on the belief that acknowledgement of their child’s
impending mortality may be self fulfilling (Liu
et al., 1999). In addition to the spoken word, other
nonverbal cultural variations may impede accurate
communication. Nodding the head in many Asian
and Latino communities simply indicates listening,
not agreement to what a healthcare professional is
saying (Phan & Tran, 2007). Direct eye contact may
be interpreted as aggressive or hostile in the Chinese
and African American communities (Campbell, 2006).
In Latino communities, direct eye contact can be
viewed as a means of transferring illness via mal
ojo, or evil eye (Lipson et al., 1997). A similar view is
prevalent in both Native American and Vietnamese
communities (Olsen et al., 2007; Phan & Tran, 2007).

In the United States, communicating difficult in-
formation is often accompanied by gestures such as
touching the arm or hand, which are often used to
convey warmth, empathy, or reassurance. However,
gestures can be interpreted differently by other cul-
tures and are imbued with great cultural significance
and meaning. Some cultures are more tactile than
others (Giger & Davidhizar, 2004). Touching a child’s
head, a common means of showing affection in
European-American culture, can be viewed as disres-
pectful. For example, Native Americans have many
traditions around the head and the hair, and prefer
that no one touch their head unless absolutely
necessary. Native Americans also prefer to have
medical examinations conducted from the feet up
rather than from the head down to demonstrate
that the most important part of the body is attended
to last (Olsen et al., 2007). More recent Vietnamese
immigrants may have concerns about touching the
patient’s head (Phan & Tran, 2007). If this is an
area of concern, head touching or patting as means
of building rapport should not be used with theT

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Wiener et al.52

child. Religious doctrine, too, must be respected. In
the Orthodox Jewish traditions, touching a parent
of the opposite sex, even if the intent is to show com-
passion, is prohibited. Similar views may be shared
by individuals of Islamic faith (Campbell, 2006).

Communication with Children about Death:
Truth Telling

Communication with patients and families in pallia-
tive care is influenced by many factors beyond the
child’s age, especially regarding the cultural dimen-
sions of truth telling (Hatano et al., 2011). If a parent
opposes disclosure of a terminal illness (especially
when the child is an adolescent), conflict between
the healthcare team and family can occur, even
when cultural norms are followed. Western psychoso-
cial care recommends that parents should be commit-
ted to truthfulness beginning at the child’s initial
diagnosis and encourages open, age-appropriate
communication with children (Matthews et al.,
2006). Reluctance to discuss death can represent
parents’ own pain and inability to accept the cer-
tainty of their child’s end of life. Families may decide
not to discuss death even if their child may anticipate
not surviving the illness, and nondisclosure can inter-
fere with preparation for dying (Davies et al., 2008).

There are many cultures where nondisclosure of
life-threatening diagnoses to a child is acceptable
(Elwynet al., 1998). Chinese, Korean, and Russian-
American families often choose not to convey a death
diagnosis to the child for fear that this will damage
his or her hope, causing a poorer prognosis (Brolley
et al., 2007; University of Washington Medical Cen-
ter, 2007; Song & Ahn, 2007). Parental decisions
about whether to inform a child about impending
death may also depend upon whether they believe
the emotional burden associated with this knowledge
may be harmful to their child or may expedite the
child’s death (Woo, 1999; Payne & Chapman, 2005;
Gupta et al., 2010).

Lack of communication can lead to emotional dis-
tance at a time when closeness is most needed. If
the family is comfortable with their child participat-
ing in his or her end-of-life care, documents that ad-
dress advance care planning may be useful to
initiate such conversations (Wiener et al., 2008).
Most hospice programs require an advance directive
(AD) prior to services being provided. However, re-
search shows that non-white adults, particularly
Asians, Hispanics, African-Americans, and Mexi-
can-Americans, have lower rates of completing writ-
ten ADs than other ethnic groups. Factors that
elucidate this claim include distrust of the healthcare
system, varying cultural perspectives on death and
suffering, the role of family dynamics (Baker, 2002;

Perkins et al., 2002; Searight & Gafford, 2005), an
aversion to signing legally binding documents (Kit-
zes & Berger, 2004), or a view that discussions about
advance directives is disrespectful and can bring bad
luck (Orona et al., 1994). No research was found that
examined cross-cultural similarities and differences
pertaining to parental attitudes toward advance
care planning for one’s child. Parents, however, often
have strong wishes about their child’s end-of-life care
but may express them at different times to different
people — or not at all. Diligently learning about the
child’s and family’s wishes, some of which may be roo-
ted in ethnic culture, is paramount to avoiding com-
munication pitfalls (Perkins, et al., 2002). For
example, appointing a specific family member to be
in charge of end-of-life decision making may lead to
extended family conflict for many Latinos, who find
a consensually oriented decision-making approach
more acceptable (Morrison et al., 1998). Alterna-
tively, presenting issues in hypothetical terms to de-
termine level of comfort (Srivastava, 2007) may be
less threatening to those who find direct conversa-
tions about death disrespectful or unacceptable.

Meaning of Pain and Suffering

Regardless of whether a family chooses to discuss im-
pending death with their child, the management of
their child’s pain and suffering is a critical issue for
all parents. In a landmark study designed to gain
greater understanding and insight into the symp-
toms experienced by children at the end of life, Wolfe
et al. (2000) found that 89% of parents believed their
children suffered “a lot” or “a great deal” from at least
one symptom in the last month of life. In other
studies, inadequate assessment of pain was found
to be a barrier to effective pain treatment in children
from diverse ethnic backgrounds (Flores & Vega,
1998; Abbe et al., 2006; Ljungman et al., 2006; Jacob
et al., 2008). Specifically, language and cultural bar-
riers make pain assessment and treatment particu-
larly challenging for clinicians. Anderson and
colleagues (2000) discovered minorities in the United
States to be at greater risk for unmanaged pain be-
cause of a lack of medical insurance, poor access to
appropriate preventive care, delay in reporting
symptoms, cultural beliefs, distrust of medicine,
and other factors associated with physician judg-
ment. It is possible that these barriers exist for famil-
ies considering pediatric palliative care and pain
management.

The perception and experience of physical pain
and the meaning pain has to one’s existence varies
by culture (Davidhizar & Bartlett, 2000). In the Chi-
nese culture, pain has been understood as a result of
blocked Qi. To resolve the pain, the blockage must be

Pediatric palliative care: Influence of culture and religion 53

removed and the patient must return to a state of
harmony with the universe (Chen et al., 2008). La-
tino individuals have been noted to interpret pain
and suffering as a form of punishment from a spiri-
tual power — with the sick individual needing to
endure pain to be granted entrance to heaven (David-
hizar & Giger, 2004) and as a test of their personal
fortitude (Munet-Vilaro, 2004). Other countries
such as India, Bangladesh, Nepal, Pakistan, and oth-
ers in South Asia were found to share similar views of
reincarnation pain (Matthews et al., 2006). For the
reasons mentioned, individuals from these cultures
may be more likely to under report pain or feel they
have to endure it. Whether these findings hold true
for children as well as adults is not known.

Culture can also influence the request for medi-
cations or treatments to assist in ameliorating
pain (Post et al., 1996). Chinese, Korean, Vietna-
mese, and Native Americans have been reported to
view asking for assistance with pain as a sign of dis-
respect (Burhansstipanov & Hollow, 2001; Gunnars-
dottir et al., 2002). Campbell (2006) found that
Vietnamese individuals often find it rude to say no
to a doctor, therefore increasing the likelihood that
they will not contradict doctor’s orders if the
amount of pain medication is insufficient. Within
this cultural frame of mind, medical professionals
are viewed as experts in their respective areas and
are not to be corrected. If the patient explained
that more medication might be necessary, the pain
could be more adequately controlled (Dell, 2009). Al-
ternatively, cultures that value self-control and stoi-
cism in the face of pain further decrease the
likelihood of voicing complaints of unmanaged
pain (Brolley et al., 2007). Research conducted on
pain perception in Native Americans found that
this population will often not report pain, or will
do so through metaphors or storytelling, making
pain management challenging. For example, one
Native American patient told a long, detailed story
about the pain of one of his tribesman, when the
pain was actually his own (Olsen et al., 2007). Chil-
dren raised within these cultural norms may adopt
similar styles to describe or attribute their pain or
the need for pain management.

Choice of treatment at the end of life may also re-
flect cultural differences that are incongruous or sup-
plemental with the medical treatment provided in
the hospital or as recommended by hospice providers.
Latino individuals with indigenous roots may engage
in healing rituals that seek to remove evil spirits
from the body of the sick individual (Mazanec &
Tyler, 2003). Some practices commonly described in
the literature include the use of amulets, herbs, or
natural remedies. Chinese Americans may incorpor-
ate special cloths or amulets into treatment and may

give the sick individual special foods in an attempt to
restore balance in metaphysical energies (Mazanec &
Tyler, 2003). Asian, Native American, and Latino in-
dividuals may choose to augment Western medical
treatments with specific herbs deemed beneficial
for their child, such as ginseng, an herb often used
by Korean families (Brolley et al., 2007; Song &
Ahn, 2007). Vietnamese families may use a practice
known as cao gio (coin rubbing) or bat gio (skin pinch-
ing) as a means of removing noxious elements from
the body (Campbell, 2006). Native Americans might
seek treatment in a sweat lodge prior to and in con-
junction with hospital-based treatment as a means
of purifying the body of toxins introduced by Euro-
pean-Americans. This act is thought to repair phys-
ical and spiritual damage to an individual.
Alternative medicine, such as massage, acupunc-
ture, or moxibuxtion1 might also be viewed as front-
line treatments across cultures (Campbell, 2006).
Moreover, many ethnic minorities in the United
States will often seek medical help from traditional
healers before using standard medical hospitals or
outpatient settings (Cardenas et al., 2007). Different
customs and traditions related to cause of illness and
proper treatment can significantly impact the degree
to which families will seek out and follow through
with treatment. Research is lacking but it has been
suggested that less acculturated families may also
have less access to health insurance (Flores & Vega,
1998). Consequently, it is possible that minority chil-
dren might initially present with greater severity of
disease than individuals who are more acculturated
to United States societ

Meaning of Illness, Dying and Death

A common existential or spiritual issue often grap-
pled with by children and young adults living with
a life-threatening illness is the search for the mean-
ing of pain, illness, suffering, and death. This mean-
ing is not static across cultures. Native American
children and families, for example, typically have a
holistic view of both health and sickness (Olsen
et al., 2007). Believing in a delicate balance between
nature, spirituality, people, and the greater commu-
nity, any balance disruption can lead to illness and/
or death (Olsen et al., 2007). In Chinese, Korean,
and Vietnamese cultures, illness and death are
viewed as a natural part of life (Brolley et al.,
2007; Phan & Tran, 2007; Song & Ahn, 2007), and

1Moxibuxtion is a traditional Chinese medical technique that
involves the burning of mugwort, a small spongy herb. This is
thought to accelerate healing in the sick individual (Mazanec &
Tyler, 2003).

Wiener et al.54

illness may occur when there is an imbalance in
competing energies within the body (Matthews
et al., 2006). These energies include, but are not lim-
ited to, hot and cold and light and dark (Brolley et al.,
2007).

Vietnamese families describe illness as a conflict
between the body and nature (Phan & Tran, 2007).
Many Asian individuals of Buddhist, Confucian, or
Hindu faiths may attribute illness and suffering to
bad karma (Brolley et al., 2007) and view suffering
as a mechanism for atoning for sins committed in a
former life. Avoidance of suffering will only transfer
pain to the next life (Mazanec & Tyler, 2003). South
Asian communities also often attribute illness and
suffering to sins committed in a previous life (Mat-
thews et al., 2006). For this reason, individuals
within these communities who are critically ill may
be stigmatized rather than treated empathetically;
they are seen as deserving the affliction from which
they are suffering (Chaturvedi, 2008). Muslims be-
lieve that illness can result from bad actions, in this
or past lives, and that illness washes away a person’s
sins (Minarik, 1996). Korean and Russian individ-
uals sometimes view illness as arising from interfa-
milial or peer conflict (Brolley et al., 2007; Song &
Ahn, 2007). Latino families will often interpret death
as something both natural and uncontrollable, and
believe that one’s fate is often left in the hands of
God (Cardenas et al., 2007). Actions taken at the
end of life may be associated with later bereavement
reactions. For example, people in the Chinese culture
who believe a “bad death” is a curse may be over-
whelmed with guilt if they have been unable to facili-
tate what they believe to be a “good death” for their
child (Xu, 2007).

Himelstein et al. (2004) recommends conducting
spiritual assessments with the child and family as
an essential element of pediatric palliative care.
This includes assessing the child’s hopes, dreams,
and values as reported by the child, beliefs about
the meaning of life and death, and opinion on the
role of prayer and ritual in times of illness. In ad-
dition, conversations around past experiences with
death or other traumatic events are often useful in
determining the child’s view of what occurs to some-
one following both physical and metaphysical death
(Himelstein et al., 2004). Gently probing spiritual va-
lues surrounding pain and suffering can also facili-
tate appropriate spiritual care for a child and
family. If, for example, one learns that the child is ex-
periencing spiritual distress because his or her pain
cannot be overcome with meditation, then counseling
from a spiritual advisor might improve quality of care
and communication (Whitman, 2007; Thrane, 2010).
Family members may benefit from being asked if
there are times that they would like a minister or

other spiritual leader present as such support can re-
duce distress and suffering throughout the trajectory
of the child’s illness and death (Braun & Nichols,
1997).

Location of End-of-Life Care

The meaning and purpose sought in both life and
death, including rituals and customs, might be
linked to a specific desired setting for end-of-life
care. Religious practices post-death are broadly ad-
dressed in Table 1. Limited literature is available
on cultural differences pertaining to whether one’s fi-
nal days are best spent at home or in a medical facil-
ity. Some Chinese individuals believe that death in
the home is a sign of bad luck, whereas other Chinese
individuals fear that if an individual dies while in the
hospital, his or her soul will be lost (Mazanec & Tyler,
2003). Both Latino and Filipino families may prefer
that the child die at home. Many Filipino families
prefer that every family member possible say a per-
sonal goodbye to the child, which calls for sensitivity
by hospice or hospital workers and may impact on
home-based or hospital-based palliative care (Maza-
nec & Tyler, 2003). Moreover, if any stigma exists
around the child’s illness, families might ask that
hospice workers be discreet in arrival and departure
from the home so as not to draw attention to the
family (Chaturvedi, 2008).

Indian families may prefer that end-of-life care
focus on symptom management and control of the
child’s pain. They may not see a need to involve
the palliative care team in addressing the spiritual
or holistic needs of the child (Owens & Randhawa,
2004). Many Indian families will also designate cer-
tain rooms in their home for specific activities,
which may impact home care. Healthcare pro-
fessionals will be expected to spend their time not
in the child’s sick room but rather in a room desig-
nated for greeting and hosting guests.

When death occurs, cultural differences in ex-
pressions of grief may be observed. In Latino cul-
ture, the grief process may be displayed very
publicly. Family members often wail at the bedside
of the sick individual, both before and after death
(Cardenas et al., 2007). Such conduct is not permit-
ted in Islam, which holds that believers are to face
bereavement like all the other trials of life, with
patience, and wailing could indicate discontent
with Islam (al-Jawziyyah, 1997). Beliefs and tra-
ditions may also mandate how the body should be
cleaned, prepared, and cared for following a child’s
death. Such traditions may also include who tou-
ches the body last, whether someone needs to stay
with the body until burial, and rituals of giving for-
giveness for any harm or discomfort caused during

Pediatric palliative care: Influence of culture and religion 55

his/her lifetime. Families may have strong feelings
about issues such as autopsy and organ donation. It
is critically important that each family be asked
about their own traditions and beliefs so that
whenever possible, arrangements can be made to
respectfully accommodate families (Kobler et al.,
2007).

CLINICAL IMPLICATIONS AND FUTURE
DIRECTIONS

Models of pediatric palliative care call for a family-
centered approach and early integration of palliative
care to enhance the quality of life for the child and fa-
mily members (Wolfe et al., 2000). A family-centered
approach is also appropriate cross-culturally, as it
aligns with collectivist traditions and is sensitive to
structural differences in family roles and values. As
the patient population in the United States becomes
increasingly multicultural, a nascent body of evi-
dence supports cross-cultural training, the use of
cross-cultural principles, and the appreciation of
the needs of immigrant patients and families. The In-
stitute of Medicine has published two reports under-
lining the necessity for cross-cultural training
(Institute of Medicine, 2001, 2011). In 2002, the In-
itiative for Pediatric Palliative Care (IPPC) under-
took a quality improvement project designed to help
improve both access to and utilization of pediatric
palliative care. The IPPC group specifically highligh-
ted the exigency of providing care that is culturally
sensitive, but specific directives on how to accomplish
this were not provided. Table 2 provides information
on how to provide culturally sensitive care within the
pediatric palliative setting by synthesizing IPPC’s
framework. Considerations for tailoring these sug-
gestions to align with best practices for cultural com-
petency and sensitivity within different ethnic
populations are reviewed in Table 3.

There are now a plethora of online resources to as-
sist in implementing cultural competence (see Uni-
versity of Washington Medical Center’s Culture
Cluesw; Ethnomed; Health Resources Service Ad-
ministration (HRSA) Cultural Competence Resour-
ces for Health Care Providers). The trouble now is
not availability of resources, but creating a balance
of cultural education with individual conversations.
Concepts of culture should not be used to predict in-
dividual behavior, as this can lead to stereotyping
(Crawley et al., 2002). Future research regarding cul-
turally based preferences in pediatric palliative care
will help physicians improve working models of pal-
liative care to ensure the best quality of life and
end-of-life care for the child and family faced with a
life-threatening illness.

Study Limitations and Future Research
Directions

Several limitations to this review of cultural
considerations in pediatric palliative care are impor-
tant to note. The influx of immigrants into the United
States makes it impossible to document all cross-
cultural differences, especially as ethnic communities
represent many different national origins, cultures,
languages, and traditions. Therefore, research lags
behind real time. Most current literature addresses
cultural differences from an informative angle, provid-
ing a survey of practices and beliefs unique to ethnic
groups. Group and individual viewpoints within cul-
tural differences are not well explored. Some areas of
needed study include practitioner bias, results of
cross-cultural training, and healthcare system hand-
ling of cultural practices that may bump into Western
ways of medical services delivery. Also, future studies
should address a systems perspective in cultural
differences, training, practitioner accommodation,
and patient and family responses pertaining to a
child’s death in particular. Additionally, few empiri-
cally based studies concerning cultural variances
within pediatric palliative care have been published,
and most of these concern adult cohorts. The pediatric
data available are primarily descriptive or based on
parent report. Finally, the studies identified through
this search were limited by great variability in terms
of sample size, study setting, patient demographics,
and measurements used. These weaknesses in the lit-
erature limit conclusions and extrapolation. It is
hoped that the current review will inspire both new
and seasoned researchers to investigate best practices
in diverse nations to promote excellent care for chil-
dren at the end of life. The authors hoped to learn
about the appropriateness for members of a health-
care team to attend funerals in different faith and cul-
tural communities. Such information was not found in
this search. This would be another important area of
exploration in future studies.

CONCLUSIONS

A number of potential barriers to Western ideas of ap-
propriate pediatric palliative care emerged from the
literature. These cultural barriers may not be mani-
fested overtly by patients or their families, but can re-
sult in the misinterpretation of medical information
(De Trill & Kovalcik, 1997) and care options at the
end of life. Palliative care commands knowledge
and respect of individual value systems, beliefs, fa-
mily structure, religion, ethnic roots, and cultural
norms, as well as group cultural practices. Under-
standing ethnic variations is only a start, not an
end, to the needed exploration (Perkins et al.,

Wiener et al.56

Table 2. Synthesizing IPPC’s framework to provide culturally sensitive pediatric palliative care

Content areas Recommendations Cultural examples

Maximize family involvement in
decision making and care planning,
allowing comfort for individual
family members.

Family structure and roles differ cross-
culturally. Family beliefs differ
within a cultural/spiritual
community. Avoid stereotypes.
It is important to initially assess
families’ religious beliefs, rituals, and
dietary practices to avoid future
conflict.
Talk with parents or designated
decision makers about their
perceived and desired role in caring
for the ill child. Ask about their
perceptions and fears regarding the
disease and outcome (De Trill &
Kovalcik, 1997).

Native Americans may want
information shared with
community leaders to help in the
decision-making process (Olsen
et al., 2007).
Asian and Latino families often
place decisions in the mother’s
hands, as she is typically the
primary caregiver (Himelstein
et al., 2004).
When possible, women from Latino
cultures will seek permission of the
child’s father; relates to familismo –
concept of the strength of family
(Cardenas et al., 2007).
Traditionally, the eldest male in
Vietnamese families makes
decisions (Lee et al., 2007).
In Russian culture, the entire
family makes decisions – the
patient and the person closest to the
patient have the most influence
(Milshteyn & Petrov, 2007).

Inform and involve children with life-
threatening illnesses in decisions
about their care as fully as possible,
given their developmental abilities
and desires.

To avoid conflict between the healthcare
providers and the family, honest and
open communication to children
should occur with caregiver consent.
The child’s age, awareness of his/her
fate and lack of communication can
interfere with end-of-life care (Davies
et al., 2008).

Chinese, Korean, and Russian-
Americans normally decide not to
convey the diagnosis to the child
(Brolley et al., 2007; Song & Ahn,
2007 University of Washington
Medical Center, 2007).
Latino families prefer to hear the
diagnosis first so they can relay the
information to the child (Lipson
et al., 1997; Sandoval, 2003).

Reduce pain and distressful symptoms
for children with life-threatening
illnesses.

Many cultures have different
interpretations of enduring pain and
relief of pain.
Assess family attitudes and beliefs in
order to reduce pain and distress.
Ask how pain and suffering have
been managed in the past and
whether strong beliefs exist
pertaining to treatment.
Great care should be taken in
discussing any medical condition to
assure understanding.
May receive a more accurate picture
of suffering by asking about changes
in functioning rather than a
description of pain.

Chinese families may incorporate
special cloths into treatment
(Mazanec & Tyler, 2003).
Asian-Americans may request or
stop using pain medications
because of fear of side effects, a
belief that pain will be a burden to
family members, and “deeply-rooted
values and beliefs of stoicism and
fatalism which inhibit pain
expression” (Dhingra, 2008, p. 29).
Asian, Native American, and Latino
families may augment Western
medicine with specific herbs
(Mazanec & Tyler, 2003; Brolley
et al., 2007) whereas other ethnic
minorities may seek medical
attention from traditional healers
(Cardenas et al., 2007; Olsen et al.,
2007; Phan & Tran, 2007).
Nodding the head indicates the
person is listening; it does not
signify agreement (such as pain is
under control).
Vietnamese families may take part
in “cao gio” (coin rubbing) or “bat
gio” (skin pinching) to remove
noxious elements from the child’s

Continued

Pediatric palliative care: Influence of culture and religion 57

Table 2. Continued

Content areas Recommendations Cultural examples

body (Campbell, 2006; Phan &
Tran, 2007).
Latino and Filipino individuals may
wail at the patient’s bedside to
indicate their respect (Mazanec &
Tyler, 2003).
Morphine may be feared and seen
as a sign of hopelessness in Russian
and Indian cultures (Milshteyn &
Petrov, 2007).

Provide emotional and spiritual
support to children and families as
they cope with the multiple losses
associated with life-threatening
conditions.

In some cultures, emotional well-being
may be considered a family issue and
incorporation of mental health
services can be misinterpreted as an
implication of mental illness.
Mental health workers should be
careful when discussing their role
and services – limit psychological
terminology when possible.
Because of some cultural differences,
documented religion might not
address spiritual beliefs or traditions.
Spiritual assessments are essential
in pediatric palliative care.
The term “palliative” can be
perceived in many cultures as giving
up hope; time and consideration are
needed when introducing the
concept.

Korean families believe that mental
illness is shameful and stigmatizing
(Brolley et al., 2007).
Latino families see mental illness as
a sign of weakness (Cardenas et al.,
2007).
It is always helpful to ask whether
there is anything that the family
would like to share about their
faith, their child’s emotional well-
being, or beliefs about illness that
can help provide the best care
possible.
Psychological problems can be
presented as vague physical
complaints. Symptoms of
depression may be expressed as a
cultural metaphor such as having
“heart problems,” “being out of
harmony,” or having problems with
social or physical universe.

Facilitate continuity of care across
settings, both within and outside the
hospital. Offer bereavement support
to the child and the family before and
after a child’s death.

Ethnic minorities under-utilize hospice
services (Mazanec & Tyler, 2003;
Sandoval, 2003).
Hospice workers should be sensitive
to cultural practices when taking care
of children within a family home.
Inquire about personal family
traditions.
Family practices may conflict with
healthcare policies.
Ask before incorporating spiritual
care prior to death. Such visits can be
viewed negatively by some cultures.
Both spiritual and psychosocial
providers should adequately explain
their role and purpose for visiting.
Appropriate communication methods
are vital for home-based and hospital
based healthcare professionals. Ask if
and how the family would like to be
contacted.

Nearly all Japanese children with
cancer will die in a hospital (Kato
et al., 2004).
Some Chinese-Americans believe
that death at home is bad luck,
whereas others fear that death in a
hospital means they may lose their
soul (Mazanec & Tyler, 2003).
Filipino families want every family
member to say a personal goodbye
to the dying person (Mazanec &
Tyler, 2003).
Latino families may want to stay
with the body until burial (Kobler
et al., 2007).
Some Latino families believe that
the child’s spirit is lost if the child
dies in the hospital. They may also
want to light candles for 24 hours or
display pictures of saints to honor
the child (Cardenas et al., 2007).
Vietnamese families who are seen
by a chaplain believe that the
chaplain’s presence is a sign of
finality (Campbell, 2006).
Catholic Latino families may want a
priest to be present at the bedside to
complete death rituals (Cardenas
et al., 2007; Phan & Tran, 2007).

IPPC, Initiative for Pediatric Palliative Care.

Wiener et al.58

Table 3. Ethnicity and cultural considerations at end of life

Ethnicity
Family structure/ Role of

family

Communication
considerations

Meaning of illness,
suffering, and death

Healing practices and
rituals

Considerations for palliative/
end of life care

Chinese
(Lipson et al., 1996;

Mazanec & Tyler,
2003; Payne &
Chapman, 2005;
Campbell, 2006;
Brolley

et al., 2007)

Loyalty to family and devotion
to traditions emphasized.

When possible, engage the
whole family in discussions
that involve decisions and
education about care.

May be reluctant to say “no”
to a doctor or healthcare
provider because it may be
considered disrespectful or
cause disharmony.

Direct eye contact may be
interpreted as hostile or
rude, specifically with
women.

A slight bow demonstrates
respect for authority
figures.

Patient and family may nod,
say “yes” or offer other
affirmative vocalizations,
but this often conveys that
they heard what the staff
member is saying, not
necessarily agreement,
approval or
understanding.

Illness and death often
viewed as a natural part
of life.

Health is the result of
balancing competing
energies: hot and cold,
light and dark.

May incorporate special
cloths or amulets.

May consume special foods
and herbs that restore
yin/yang balance.

Patients may seek
traditional Chinese
therapies such as
massage, acupuncture,
and moxibuxtion
(traditional Chinese
medicine technique that
involves the burning of
mugwort, a small,
spongy herb, to facilitate
healing).

There is no one monolithic
Chinese culture. Rituals
will depend upon religion
(Buddhism, Confucianism,
Taoism, Christianity).

Some believe that death in the
home is a sign of bad luck.

Some believe that if a person
were to die in the hospital,
his/her soul would get lost.

Typically will not want organ
donation or autopsy to be
performed.

Japanese
(Long, 2004; Pierce,

2007; Kongnetiman
et al., 2008)

Family members collectively
make the decision regarding
medical treatment

Patient and family may use
nonverbal, subtle, and
indirect communication.

Families prefer to be told the
diagnosis directly first to
decide whether or not to
tell the patient.

Death is viewed as natural,
inevitable and not the
final aspect of life. Beliefs
of reincarnation may be
present.

Families may not
acknowledge that death is
caused by cancer because
cancer is stigmatized in
Japanese culture.

May perform Reiki – a
Japanese method of
reducing stress and
promoting relaxation as
a healing mechanism.
Other healing methods
may include acupuncture
and moxibuxtion.

The prayer of “pillow sutra”
may be recited before
moving the body.

May refer to die at home
rather than in a hospital.
Family members may
gather around the
bedside and have a
minister perform special
chants.

May prefer cremation instead
of burial.

Belief that the body should be
whole to be properly
reincarnated. May not
want organ donation.

Korean Mothers are exclusive
caregivers, but the oldest

It is respectful to give a slight
bow when you greet

If Buddhist or Confucian,
illness and death are seen

May seek help from a
hanui, or traditional

The patient will often trust
family to make medical

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Table 3. Continued

Ethnicity Family structure/ Role of
family

Communication
considerations
Meaning of illness,
suffering, and death
Healing practices and
rituals
Considerations for palliative/
end of life care

(Murphy, 1995; Song &
Ahn, 2007)

male is typically the
spokesperson

someone.
Sustained eye contact is

uncommon. Men and men
may shake hands, but
women and men and
women and women do not.

Self-control is often of high
priority; patient may not
express pain verbally.

as a natural part of life.
Symptoms may be result of

bad karma
Illness can result from

conflict in family and peer
relationships.

Health is the result of
balancing competing
energies: hot and cold,
light and dark.

healer, who often uses
herbs. Ginseng is
especially common.

decisions for him/her, and
see no need for an advanced
directive.

May view Western medicine
as too strong, and as a
result may alter how much
medicine is taken (only
taking half, stopping
medication before told).

Vietnamese
(Lee et al., 2007;
Phan & Tran, 2007)

The women in the family are
the primary providers.

The family spokesperson
may be the person with the
best English.

Family and patient may nod
or say yes to demonstrate
that they hear you, not as a
sign of assent or
understanding.

Often seen as disrespectful to
say no to a doctor as they
are the expert.

May avoid eye contact as sign
of respect.

May not request medicine for
pain, even when needed.

Illness may be explained as
imbalance between the
body and nature, the
result of germs, or the
result of a behavioral
cause.

May utilize coin rubbing (ao
gio) or skin pinching (bat
gio) to aid in removal of
unwanted elements in
the body.

Visit from a hospital chaplain
may be viewed as signifying
impending death. These
visits should be explained
thoroughly before
occurring.

Filipino
(Mazanec & Tyler,

2003; Kemp &
Rasbridge, 2004;

Lobar et al., 2006;
Diversicare, 2009)

In the Philippines, family may
be an extended multi-
generational household.

Philippine community persons
should be contacted when
family is not available.

Communication should be
directed toward the head
of the family, and should
not take place while
patient is present.

On first encounter, use Mr.
Mrs., Miss or professional
title.

Sometimes discussing end-
of-life preferences is
avoided as it is thought it
may hasten death

Most (90%) are Catholic;
will often utilize
“sacrament of the sick.”

Use of rosary beads and
frequent use of rosary
beads and prayer at
bedside.

Individuals will likely prefer
to die at home.

Family may prefer to clean
body after death.

Each family member may
wish to personally say
goodbye.

Typically do not want organ
donation, autopsy or
cremation.

Loud demonstrations
involving crying and
wailing show respect,
importance, and love for
the deceased.

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Table 3. Continued
Ethnicity Family structure/ Role of
family
Communication
considerations
Meaning of illness,
suffering, and death
Healing practices and
rituals
Considerations for palliative/
end of life care

South Asian:
India, Bangladesh,

Nepal, Pakistan,
Maldives, Sri Lanka

(Laungani, 1996;
Minarik, 1996;
Moazam, 2000;
Periyakoil et al.,
2011)

While the decision maker is
typically the family
patriarch, the family is
actively involved and death
is viewed as a family and
communal process. Rituals
are very important.

Communication is enhanced
when providers ask
specific questions such as
How do you think your
child’s sickness should be
treated? What alternative
therapies are you using
currently? How do want us
to help you? Who do you
turn to for help? Who
should be involved in
decision making?

Close knit family is common
structure.

Family members and
physicians may share
decision-making duties.

Cancer (and other chronic or
terminal illnesses) is
often attributed to sins
committed in a past life.
Because of this, there is
often stigma associated
with serious illness, and
sometimes even social
isolation of the family.

May feel that the illness is
washing away her/his
sins and would resolve
once the sins are washed
away or by doing certain
religious rituals. Illness
should not be capitalized.

Many South Asians are
Hindu, and may request
such rituals as:

Putting patient on the
ground instead of in a
bed

Pouring holy water into the
mouth or onto the bed of
patient

Health professionals within
the home should be
cognizant of the spatial
culture. Certain rooms are
often delegated for specific
activities, such as greeting
or caring for the sick.

Moslem death rituals may
include ceremonial
washing of the body with
holy waters, directional
positioning of the body
toward the Holy Land of
Mecca, and recitation of the
Holy Koran by loved ones.

May be different preferences for
care of the remains of their
child. Ask about preferred
rites and rituals in a
sensitive and gentle manner.

Latino
(Mazanec & Tyler,

2003; Sandoval,
2003; Davidhizar &
Giger, 2004;
Cardenas et al.,
2007; Tellez-Giron,
2007)

Mother determines when a
person needs care, but the
permission to seek/
continue/ discontinue care
comes from the father.
Usually spokesperson is
typically the father or oldest
male.

Although a male often speaks
for the household, decisions
are typically made as a
family.

Familismo is a term used to
describe the power and
strength of the family in
Latino culture, and is
characterized by
interdependence, affiliation,
and cooperation.

The family is a source of
emotional support and there
is a high degree of intimacy
between all family members.
Patients will likely want to
be near to and be able to see
their family as much as
possible.

Nodding often used to signify
respect, and should not be
taken as a sign of assent.

Eye contact may be avoided
by some Latino groups as a
sign of respect, or because
of the belief in evil eye.

Personalismo: Having
informal conversations
with all family members,
and not just addressing
the patient and his or her
parent can build trust.
Mutual respect must be
demonstrated.

Respeto is highly valued in
terms of familial
hierarchy. Should address
older individuals using
Señor or Señora.

Pain often viewed as a form
of punishment. The
suffering of pain must be
endured if the individual
is to enter heaven.

Illness may be seen as the
result of an imbalance
(between external and
internal causes, hot and
cold, natural and
supernatural).

May believe that the patient
was specially selected for
suffering.

Belief in espiritismo: good
and evil spirits affect
health and well-being.

Some believe that illness can
be explained by mal ojo,
or evil eye. For example, if
people admire a child
without touching them,
child can become ill.

Death viewed as a natural
end to the life process,
and something that is
completely out of one’s
control (in hands of God).

Wailing at bedside of sick
individual is common
and seen as sign of
respect.

May seek care from
curanderos (folk
healers).

Often use amulets or
rosaries when praying
for sick individual, and
may display pictures of
saints in hospital room.

May ask to have candles lit
at all times while the
individual is in the
hospital. May have
concern that the spirit
will get lost in the
hospital room.

After death, often offer
daily masses and light
candles in honor of the
deceased.

Many Latinos will not want to
stop life prolonging
treatments, regardless of
the severity of the illness of
the child/individual.

Jerarquimo may influence the
family’s belief that there is a
medical cure for the patient.

Do not typically utilize
hospice services, perhaps
due to unfamiliarity with
system, language barriers,
or distrust of healthcare
system.

Would greatly benefit from
increased education
regarding hospice.

Prefer for individual to die at
home (death in hospital
could indicate loss of soul).

Those who are Catholic (90%)
will often want to have a
priest or clergy member say
the last rites when death is
near.

Often prefer to cleanse the
body by themselves after
death, as a sign of respect
for life and death.

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Typically do not want organ
donation or autopsy to be
performed.

Grieving is considered normal
and natural, and wailing is
common. May be hesitant
to involve mental health as
this connotes grieving is a
sign of mental illness.

Native American
(Campbell, 2006; Olsen

et al., 2007)

Family unit includes not just
immediate and extended
family, but also community
leaders.

Direct eye contact may be
interpreted as hostile,
rude or dangerous to the
soul.

Pain will either not be
expressed or may be
expressed through
storytelling rituals.
Storytelling is also used as
a way to build trust and
relationships with people.

Silence is highly valued.

Often view health and
illness as holistic in
nature. People,
community, nature and
spirituality are all
connected, as are
physical, spiritual,
emotional and mental
health.

People become sick when
there is a disruption in
the balance of these
forces.

May want to seek
traditional healers for
help in restoring
harmony of sources of
life.

Herbal remedies may be
used in conjunction with
healing ceremonies.

May use sweat lodges

May be hesitant to sign
advance directives or other
end of life documents
because of general mistrust
of signed documents
(history of misuse of
written treaties and
documents with Native
Americans by the U.S.
government and other
majority entities).

African- American
(Mazanec & Tyler,

2003; Sandoval,
2003; Campbell,
2006; Mitchem,
2007)

Place large importance on
family.

Conversation should be
initiated with the eldest
member of the family.

Likely to see public displays
of emotion from the family.

Direct eye contact may be
interpreted as hostile or
rude.

In African-American folk
healing, human life is
understood relationally.
Illness is derived from
germs and from
situations that break
connections with others.
Death is not a formal
break with life because
the spirit/soul continues
and may be able to
interact from the next
plane of existence.

Story and action are
intertwined in healing.
The healer or
“rootworker” is
important as this person
can orchestrate the
natural, spiritual, and
relational aspects of life.

Rely on healthcare team for
help with cleaning and
preparation of body.

May refuse to stop life
prolonging treatments
because of a belief in divine
rescue. This signifies that
an all-powerful God can
bring about miraculous
interventions and is
derived from the Old
Testament.

Do not typically complete
advance directives, in part
because of belief that this
limits access to appropriate
medical care.

Often will prefer a life-
prolonging treatment to a
pain-reducing one. May see
palliative care as an effort
on the part of medical
providers to deny them the
best treatment possible.

Caribbean-American
(Lipson et al., 1997;

Fernandez Olmos &

Men hold a position of authority
whereas women are seen as
the nurturers and tend to the

Families may be more
expressive or

Healing practices often
originated in spiritual
practices.

Those who require balance
due to illness may seek
out the help of a priest of

Close relatives will likely
want to be present at the
time of the patient’s death

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Paravisini-Gebert,
2003)

family.
Children are to be respectful of

elders.

demonstrative than the
average family.

Sickness and death are not
always attributable to
natural causes – a curse
can cut lives short.

Afro-Cuban therapies are
often plant based and
herbs are used for
spiritual cleansing.

Ocha.
Prayer and hymn-singing

at the patient’s bedside
may occur.

Some Caribbean-
Americans may use
voodoo practices in
addition to following
Catholic traditions.

Those who practice Voodoo
will have rituals that
evolve around spirits
that represent a fusion of
African and Creole gods,
the spirits of deified
ancestors, and Catholic
saints.

and efforts to bring the
family together are
important.

Patient and family may desire
that, if the patient is of age,
he or she have holy
communion before his or
her death.

Older generations may
believe that the body needs
to be intact for it to pass
into the afterlife, thus may
object to either autopsy or
organ donation.

Burial is most common, and
funerals are very
important. Home is usually
kept open for a week to
welcome mourners.

Russian- American
(Milshteyn & Petrov,

2007; University of
Washington Medical
Center, 2007).

The parent or the eldest child
typically makes decisions.

The patient is often not told
of prognosis as there is a
belief that this will only
worsen his or her
condition.

Often prefer that the doctor,
rather than a nurse or
other staff member,
communicate diagnosis
and treatment
considerations.

Family members often want
to have long conversations
with the doctor regarding
the patient, and prefer
these conversations be
held in a private room.

Family members may appear
cheerful with patient to
avoid causing further
distress to patient.

Illness may be attributed to
environmental causes,
including familial stress
and conflict.

For many Russians, and
specifically Russian Jews,
nutrition is extremely
important to health. If a
patient can eat it is seen
as a very positive sign.

Family is very important,
and usually at least one
family member will
always be at the bedside
of the patient.

Laying of the hands often
used.

Religious icons may be
brought to the hospital
room.

The earth is considered
sacred, and therefore soil
might be brought into the
room in jars or pots.

Often will not grieve in front
of the dying individual;
however it is acceptable for
the patient to express their
pain and grief openly.

Providing a patient with
morphine may be
interpreted to mean that
the patient’s case is
hopeless/terminal.

Autopsy is acceptable, but
organ donation often is not.

Typically will not want to sign
an advance directive or
durable power of attorney
document.

All relatives and friends are
expected to visit the patient
if death is judged to be close.

Often prefer a priest, rabbi, or
other religious figure to be
present at the death.

Family may either close the
eyes and mouth of patient
after death or place coins on
their eyes.

If the child dies in the
hospital, may request the
body to be brought by the

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2002). Beliefs and practices vary along the spectrum
of education and Western acculturation. Moreover,
families may not be able to perform traditional ri-
tuals or customs within Western cultures, and feel
they must conform to practices that differ greatly
from their own fundamental beliefs, values, and
practices (Laungani, 1996). At the end of a child’s
life, the focus needs to be on quality as defined by
the family, not the provider. Supporting parents so
that they can fulfill their traditional role as care-
givers, protectors, decision makers, providers of
love and physical tenderness, and instillers of faith
(Meyer et al., 2006) requires an individualized ap-
proach to end-of-life care. Respecting beliefs, cus-
toms, and traditions with a focus on preserving the
integrity and sanctity of the parent – child relation-
ship is of utmost importance in pediatric palliative
care.

ACKNOWLEDGMENTS

We gratefully acknowledge Laurie Steffen and Brie Kohrt
for their early literature searches and preliminary review
of the literature. We are also most appreciative of the
time and effort given to this article by Nia Billing, who
helped format the references for the manuscript, and Ha-
ven Battles for her critical review of the manuscript. This
research was supported by the Center for Cancer Research,
National Cancer Institute and the National Institute of
Mental Health. The opinions expressed in the article are
the views of the authors and do not necessarily reflect the
views of the Department of Health and Human Services
or the United States government.

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Pediatric palliative care: Influence of culture and religion 67

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

Alcohol & Alcoholism Vol. 43, No. 1, pp. 15 – 24, 2008
Advance Access publication 12 October 2007

doi:10.1093/alcalc/agm145

SEROTONERGIC ANTI-DEPRESSANTS AND ETHANOL WITHDRAWAL
SYNDROME: A REVIEW

I. TAYFUN UZBAY*

Gulhane Military Medical Academy, Department of Medical Pharmacology, Psychopharmacology Research Unit, Etlik 06018 Ankara, Turkey

(Received 24 July 2007; in revised form 24 August 2007; accepted 3 September 2007;
advance access publication 12 October 2007)

Abstract — Aim: To review laboratory findings on the effects of anti-depressant agents that interact with the serotonergic
system on signs of ethanol withdrawal syndrome in rats. Method: Adult Wistar rats received a modified liquid diet to produce
ethanol dependence. Signs of ethanol withdrawal, locomotor hyperactivity, stereotyped behaviour, tremor, wet dog shakes, agitation,
and audiogenic seizures, were evaluated for the first 6 h of ethanol withdrawal. The effects of the anti-depressants fluoxetine,
venlafaxine, escitalopram, tianeptine, and extract of Hypericum perforatum (St. John’s wort) (HPE) were examined. Results: Some
beneficial effects of fluoxetine, tianeptine, HPE, escitalopram and venlafaxine on ethanol withdrawal signs were observed, ranked as
follows: fluoxetine = tianeptine > HPE > escitalopram > venlafaxine. Conclusions: Tianeptine and fluoxetine seem to be potent
pharmacologically active agents on ethanol withdrawal syndrome in rats. Thus, these anti-depressants may be useful in treatment of
ethanol withdrawal syndrome in patients with alcoholism. In addition to serotonergic effects, interactions with nitrergic, glutamatergic,
and adenosinergic systems may also provide a significant contribution to the beneficial effects of these drugs on ethanol withdrawal
syndrome.

INTRODUCTION

Ethanol abuse and dependence remain among the most com-
mon substance abuse problems worldwide. The discontinua-
tion of chronic administration of ethanol is associated with
excitatory withdrawal signs called ethanol withdrawal syn-
drome. Ethanol withdrawal syndrome is the most impor-
tant evidence, which indicates the development of a phys-
ical dependence to ethanol (O’Brien, 1996). Although the
signs of ethanol withdrawal syndrome in humans (Thompson,
1978) and rodents (Majchrowicz, 1975; Uzbay and Kayaalp,
1995; Uzbay et al ., 1997) have been well described, the
mechanisms underlying physical dependence to ethanol and
ethanol withdrawal syndrome are poorly understood. Among
the numerous neurotransmitter systems implicated in the phar-
macological effects of ethanol, the serotonergic system has
received particular attention. Serotonergic system has been
shown to play an important role in the regulation of ethanol
intake, preference, and dependence via central mechanisms
(Roy et al ., 1987; Rezvani et al ., 1990; Ferreria and Soares-
DaSilva, 1991; McBride et al ., 1991; Sellers et al ., 1992;
Wallis et al ., 1993; LeMarquand et al ., 1994; Uzbay et al .,
1998, 2000).

Depression is an important psychiatric disorder that affects
individuals’ quality of life and social relations directly.
Depression is characterized by emotional symptoms such as
hopelessness, apathy, loss of self-confidence, sense of guilt,
indecisiveness, and amotivation, as well as biological symp-
toms like psychomotor retardation, loss of libido, sleep dis-
turbances, and loss of appetite. When the symptoms are very
severe, major depression is considered. The prevalence of
major depression is approximately 9% both in the United

*Author to whom correspondence should be addressed at: Gulhane Military
Medical Academy, Faculty of Medicine, Department of Medical Pharma-
cology, Psychopharmacology Research Unit, Etlik 06018 Ankara, Turkey.
Tel: +312-304 4764; Fax: +312-304 2010;
E-mail: tuzbay@gata.edu.tr; uzbayt@yahoo.com

States and Europe (Fichter et al ., 1996; Lepine et al ., 1997).
A decrease in serotonergic activity is associated with depres-
sion. In experimental studies, a decrease in brain serotonergic
activity due to social isolation is known for decades (Garat-
tini et al ., 1967). Specifically, rodents show hyperactive and
aggressive behaviour during long-term social isolation, which
can be blocked with anti-depressant treatment (Garzon and
del Rio, 1981). These social isolation forms based on sero-
tonin deficiency are used as experimental depression model
in rodents (Leonard, 1998). On the other hand, selective sero-
tonin re-uptake inhibitors (SSRIs) and some post-synaptic
receptor agonists, which increase serotonergic activity in the
synaptic space, are used widely and effectively to treat depres-
sion (Cowen, 1998; Vaswani et al ., 2003).

Alcoholism and depression are often associated in psy-
chiatric patients. Many alcoholic patients have symptoms
of depression (Weissman and Myers, 1980; Miguel-Hidalgo
and Rajkowska, 2003). A positive association between high
ethanol intake and a depression-like status has been suggested
also in genetically selected ethanol-preferring AA rats (Kiian-
maa et al ., 1991) and in fawn-hooded rats (Overstreet et al .,
1992). Previous studies from our laboratory also indicated
a significant decrease in striatal serotonin levels of rats dur-
ing early ethanol withdrawal (Uzbay et al ., 1998) and chronic
ethanol consumption (Uzbay et al ., 2000). These observations
imply that there might be a correlation between decreased
serotonergic activity and ethanol dependence. Thus, drugs that
increase serotonergic activity in synapses could be useful in
treatment of ethanol withdrawal or dependence. Furthermore,
some anti-depressant drugs are in general use for patients
with ethanol dependence. They are mainly indicated in the
treatment of ethanol withdrawal and combined psychiatric
disorders (Miller, 1995; Favre et al ., 1997; Myrick et al .,
2001). Although effects of some serotonergic anti-depressants
on ethanol intake and/or ethanol abuse have been investigated
in several studies, data relating to the action of anti-depressant
drugs during ethanol withdrawal period are very limited.

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16 I. T. UZBAY

An ethanol-dependent rat model was developed in our
Psychopharmacology Research Unit by a modified liquid diet
technique in 1995 (Uzbay and Kayaalp, 1995). Numerous
experimental studies were, and are being performed in our
laboratory to understand the mechanism and etiology of
alcoholism. Some of these were involved in the effects of
anti-depressant drugs on ethanol withdrawal syndrome in rats.
In this review, it was aimed to analyse the results obtained
from ethanol-dependent rat models treated with various anti-
depressant drugs that interact with the serotonergic system via
different mechanisms. A relationship between the drug effects
and the signs of ethanol withdrawal has also been evaluated
and discussed.

ETHANOL-DEPENDENT RAT MODEL BY THE
MODIFIED LIQUID DIET

Subjects and laboratory
Procedure in all studies was in accordance with the Guide
for the Care and Use of Laboratory Animals as adopted
by the National Institutes of Health (USA). Adult Wistar
rats (182 – 339 g in weight at the beginning of the exper-
iments) were subjects. They were housed in a quiet and
temperature- and humidity-controlled room (22 ± 3◦C and
65 ± 5%, respectively), in which a 12-h light/dark cycle was
maintained (07:00 – 19:00 light).

Chronic ethanol administration to rats
For chronic ethanol administration, the rats were housed
individually and ethanol was administered in the modified
liquid diet as previously described (Uzbay and Kayaalp,
1995). The rats received a modified liquid diet with or without
ethanol ad libitum. No extra chow or water was supplied. The
composition of the modified liquid diet with ethanol was: cow
milk 925 ml (Mis Süt, Turkey), 25 – 75 ml ethanol (96.5%
ethyl alcohol; Tekel, Turkish State Monopoly), vitamin A
5000 IU (Akpa İlaç Sanayi, Turkey) and sucrose 17 g (Uzbay
and Kayaalp, 1995). This mixture supplied 1000.7 kcal/l.

At the beginning of the study, rats were given the modified
liquid diet without ethanol for 7 days. Then, liquid diet
with 2.4% ethanol was administered for 3 days. The ethanol
concentration was increased to 4.8% for the following 4 days
and finally to 7.2% for another 21 days. Liquid diet was
prepared on a daily basis and presented at the same time
each day. The weight of the rats was recorded every day,
and daily ethanol intake was measured and expressed as
g/kg/day. Control rats were pair fed with an isocaloric liquid
diet containing of sucrose as a caloric substitute to ethanol.

Drugs used and dose regimens in the studies
Fluoxetine (2.5 – 10 mg/kg, Sigma Chemical — USA), an
SSRI, venlafaxine (5 – 40 mg/kg, White Company, İstanbul —
Turkey), a serotonin/noradrenalin re-uptake inhibitory agent,
escitalopram (2.5 – 10 mg/kg, Lundbeck — Denmark), a bound-
ing agent at the primary site of pre-synaptic serotonin trans-
porter, tianeptine (5 – 20 mg/kg, Servier Laboratory — France),
a serotonin uptake stimulatory agent, were injected in rats

intraperitoneally. Extract of Hypericum perforatum (HPE)
was prepared by using aerial parts of St John’s wort at
Anadolu University, Department of Pharmacognosy as pre-
viously described (Ozturk et al ., 1996) and injected in rats
intraperitoneally, as well.

Doses of the anti-depressants were selected from our
preliminary experiments and previous studies. Since higher
doses of anti-depressants used in our studies caused sedation
and impairment of motor co-ordination, higher doses were not
tested.

Evaluation of ethanol withdrawal syndrome
At the end of 7.2% ethanol-containing liquid diet adminis-
tration, ethanol was withdrawn from the daily diet. Ethanol-
dependent rats were then assigned to several groups (N =
8 – 10 for each group). Anti-depressants and saline were
injected in the rats 30 min before ethanol withdrawal test-
ing. The rats were then observed for 5 min at the 2nd,
4th and 6th h of the withdrawal period. At each observa-
tion time, the rats were assessed simultaneously for the fol-
lowing behavioural conditions: agitation, tremor, stereotyped
behaviour, wet dog shakes and audiogenic seizures as pre-
viously described (Uzbay and Kayaalp, 1995; Uzbay et al .,
1997).

Ethanol consumption, weight changes and blood ethanol
levels
Daily ethanol consumption of the rats in the control and anti-
depressant treated groups ranged from 10 to 17 g/kg during
exposure to ethanol (7.2%).

No significant weight loss was observed in any of the
studies, as body weights of the rats increased progressively
during the study.

Blood ethanol levels were found higher than 150 mg/dl in
ethanol feeding groups.

EFFECTS OF ANTI-DEPRESSANTS ON ETHANOL
WITHDRAWAL SYNDROME

Fluoxetine
Fluoxetine is an SSRI that exhibits anti-depressant activity
in experimental models (Detke et al ., 1995; Contreras et al .,
2001) and clinical trials (Stokes and Holtz, 1997; Vaswani
et al ., 2003). Fluoxetine increases serotonergic transmission
in synaptic cleft (Stahl, 1996). Studies suggest that SSRIs,
such as zimelidine, citalopram, and fluoxetine, may reduce
ethanol consumption, and that is not thought to be an anti-
depressant effect (Miller, 1995). Limited clinical studies
indicated that fluoxetine reduces the extent of anxiety and
depression during ethanol withdrawal (Romeo et al ., 2000)
and at its anti-depressant doses; it is able to prevent relapses
in patients with alcoholism (Janiri et al ., 1996).

A detailed study reported the effects of fluoxetine on sev-
eral signs of ethanol withdrawal in rats (Uzbay et al ., 2004).
In this study, fluoxetine inhibited withdrawal-induced loco-
motor hyperactivity and attenuated the severity or incidence
of the signs of ethanol withdrawal, such as agitation, increased

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ANTI-DEPRESSANTS AND ETHANOL WITHDRAWAL 17

Table 1. Acute effects of ip administration of fluoxetine on the signs of ethanol withdrawal syndrome in rats

Doses and

Ethanol withdrawal signs

observation
intervals LH Agitation Stereotype Tremors WDS AS

2nd h of EWS
2.5 mg/kg 0 + 0 + + −
5.0 mg/kg + + 0 + + −

10.0 mg/kg 0 + + + + −
4th h of EWS
2.5 mg/kg 0 0 0 + + −
5.0 mg/kg 0 0 0 + 0 −

10.0 mg/kg 0 0 0 0 + −
6th h of EWS a

2.5 mg/kg 0 0 0 + 0 +
5.0 mg/kg + + 0 + 0 +

10.0 mg/kg 0 + 0 + 0 +

(Uzbay et al ., 2004); ip, Intraperitoeal; EWS, Ethanol withdrawal syndrome; LH, Locomotor hyperactivity;
WDS, Wet dog shake; AS, Incidence of audiogenic seizure; −, Not evaluated; 0, Ineffective; +, Statistically
significant attenuation.
a All doses were repeated 30 min before the 6th h of evaluation.

stereotyped behaviour, wet dog shakes, and tremors, dose-
dependently. It also reduced markedly the incidence of audio-
genic seizures (Table 1). Preventive effects of fluoxetine were
seen particularly on agitation, wet dog shakes, tremors, and
audiogenic seizures. Effective doses of fluoxetine did not
cause any significant change in locomotor activities of the
naı̈ve (not ethanol-dependent) rats. Moreover, the inhibitory
effects of fluoxetine on the signs of ethanol withdrawal were
specific and not related to other non-specific effects, such as
sedation and muscle relaxation. These observations clearly
showed that fluoxetine is a pharmacologically active agent on
mechanisms involved in development of physical dependence
on ethanol in rats, and it may have a potential therapeutic
effect in the treatment of ethanol-type dependence.

Escitalopram
Escitalopram is an active enantiomer of citalopram, which is
an SSRI. It has a proven efficacy in the treatment of major
depression, like other SSRIs. It has been shown in non-
clinical and clinical experiments that it has greater efficacy
than equivalent doses of citalopram (Auquier et al ., 2003;
Lepola et al ., 2003; Sánchez et al ., 2004). Unlike classical
SSRIs, it is bound at the primary site of pre-synaptic serotonin
transporter (SERT) with a very high affinity, and it has higher
serotonergic activity than the classical SSRIs (Sánchez et al .,
2004).

In the light of information above, it could be expected
that escitalopram is more effective than the classical SSRIs,
such as fluoxetine on ethanol withdrawal syndrome. Thus,
the effects of escitalopram on ethanol dependence or ethanol
withdrawal have been evaluated in our laboratory (Saglam
et al ., 2006). In contrast to our expectations, in this study,
escitalopram was found to be less effective when compared
to fluoxetine. While fluoxetine had additional preventive
effects on locomotor hyperactivity, agitation, and audiogenic
seizures (Uzbay et al ., 2004), escitalopram was not effective

on these signs of ethanol withdrawal. Its beneficial effects
on ethanol withdrawal syndrome were found to be limited. It
only produced a significant attenuation on tremors (Table 2).
Although it produced some significant decrease on stereo-
typed behaviours and wet dog shakes, these effects were
limited and not dose-dependent (Saglam et al ., 2006). Thus,
results of this study suggest that escitalopram has some lim-
ited beneficial effects on ethanol withdrawal syndrome in rats.
However, it does not have superiority over fluoxetine for treat-
ment of ethanol withdrawal syndrome in rats.

Venlafaxine
Venlafaxine is a bicyclic phenylethylamine derivative which
inhibits pre-synaptic re-uptake of serotonin, noradrenaline,
and, to a lesser extent, dopamine (Holliday and Benfield,
1995). Thus, it increases serotonergic and noradrenergic
transmission in synaptic cleft (Stahl, 1996). Venlafaxine
exhibits an anti-depressant activity in experimental models
and clinical trials (Mitchel and Fletcher, 1993; Holliday and
Benfield, 1995; Dierick, 1997). Anxiety is also a sign of
withdrawal of the drugs that were abused, and produced
physical dependence, such as ethanol in humans (Schuckit,
2000; De Witte et al ., 2003) and rats (Gatch et al ., 2000).
Additionally, several clinical reports have suggested that
venlafaxine has beneficial effects in some kind of anxiety
disorders (Gelenberg et al ., 2000; Ninan, 2000; Gorman,
2003).

Evidence also showed that venlafaxine strongly attenuated
morphine withdrawal in rats (Lu et al ., 2001). However, stud-
ies assessing the effect of venlafaxine on ethanol withdrawal
syndrome or ethanol dependence were limited. Therefore, the
first detailed study investigating the effects of venlafaxine
effects on ethanol withdrawal syndrome were performed in
our laboratory.

In this study, no prominent effect on locomotor hyperac-
tivity, agitation, stereotyped behaviour and wet dog shake

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18 I. T. UZBAY

Table 2. Acute effects of ip administration of escitalopram on the signs of ethanol withdrawal syndrome in rats

Doses and Ethanol withdrawal signs
observation
intervals LH Agitation Stereotype Tremors WDS AS

2nd h of EWS
2.5 mg/kg 0 0 0 0 + −
5.0 mg/kg 0 0 0 + + −

10.0 mg/kg 0 0 0 + 0 −
4th h of EWS

2.5 mg/kg 0 0 0 0 0 −
5.0 mg/kg 0 0 0 0 0 −

10.0 mg/kg 0 0 0 0 0 −
6th h of EWS a

2.5 mg/kg 0 0 0 0 + 0
5.0 mg/kg 0 0 + 0 0 0

10.0 mg/kg 0 0 0 0 0 0

(Saglam et al ., 2006); ip, Intraperitoneal; EWS, Ethanol withdrawal syndrome; LH, Locomotor hyperactivity;
WDS, Wet dog shake; AS, Incidence of audiogenic seizure; −, Not evaluated; 0, Ineffective; +, Statistically
significant attenuation.
a All doses were repeated 30 min before the 6th h of evaluation.

Table 3. Acute effects of ip administration of venlafaxine on the signs of ethanol withdrawal syndrome in
rats

Doses and Ethanol withdrawal signs
observation
intervals LH Agitation Stereotype Tremors WDS AS

2nd h of EWS
5.0 mg/kg 0 0 0 − 0 −

10.0 mg/kg 0 0 0 − 0 −
20.0 mg/kg 0 0 0 − 0 −
40.0 mg/kg 0 0 0 − 0 −
4th h of EWS

5.0 mg/kg 0 0 0 − 0 −
10.0 mg/kg 0 0 0 − 0 −
20.0 mg/kg 0 0 0 − 0 −
40.0 mg/kg 0 0 0 − 0 −
6th h of EWS a

5.0 mg/kg 0 0 0 − 0 0
10.0 mg/kg 0 0 + − 0 0
20.0 mg/kg 0 0 0 − 0 +$
40.0 mg/kg 0 0 0 − 0 0

(Saglam et al ., 2004) ip, Intraperitoneal; EWS, Ethanol withdrawal syndrome; LH, Locomotor hyperactivity;
WDS, Wet dog shake; AS, Incidence of audiogenic seizure; ($, significant prolonged latency); −, Not evaluated;
0, Ineffective; +, Statistically significant attenuation.
a All doses were repeated 30 min before the 6th h of evaluation.

by acute venlafaxine treatment was observed. However, ven-
lafaxine had some limited preventive effects on the audiogenic
seizures. It significantly prolonged the latency of audiogenic
seizures at the dose of 20 mg/kg and reduced the incidence of
the seizures without reaching a statistically significant level
at the dose of 40 mg/kg (Saglam et al ., 2004) (Table 3). As
a result, venlafaxine did not seem to be an agent as effective
as fluoxetine to control ethanol withdrawal syndrome.

Tianeptine

Tianeptine is a tricyclic drug that exhibits anti-depressant
activity in experimental models (Curzon and Datla, 1993) and
clinical trials (Guelfi, 1992; Saiz-Ruiz et al ., 1998). The neu-
rochemical properties of tianeptine vary from those of other
tricyclic and non-tricyclic anti-depressants. It is a unique type
of anti-depressant that produces its effect by enhancing, rather
than inhibiting, serotonin re-uptake (Mennini et al ., 1987).

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ANTI-DEPRESSANTS AND ETHANOL WITHDRAWAL 19

Table 4. Acute effects of ip administration of tianeptine on the signs of ethanol withdrawal syndrome in
rats

Doses and Ethanol withdrawal signs
observation
intervals LH Agitation Stereotype Tremors WDS AS

2nd h of EWS
5.0 mg/kg 0 0 0 0 + −

10.0 mg/kg 0 0 0 + + −
20.0 mg/kg + 0 + + + −
4th h of EWS
5.0 mg/kg 0 0 0 0 0 −

10.0 mg/kg 0 0 0 + 0 −
20.0 mg/kg 0 + + + + −
6th h of EWS a

5.0 mg/kg 0 0 0 + 0 0
10.0 mg/kg 0 + 0 + + +
20.0 mg/kg 0 + + + + +$

(Uzbay et al ., 2006) ip, Intraperitoneal; EWS, Ethanol withdrawal syndrome; LH, Locomotor hyperactivity;
WDS, Wet dog shake; AS, Incidence of audiogenic seizure; ($, significant prolonged latency); −, Not
evaluated; 0, Ineffective; +, Statistically significant attenuation.
a All doses were repeated 30 min before the 6th h of evaluation.

Limited clinical studies indicated that tianeptine has bene-
ficial effects for patients with alcoholism. Malka et al . (1992)
showed that long-term tianeptine treatment results in marked
and consistent improvement in depression and anxiety scores
after alcohol withdrawal. In addition, Favre et al . (1997) sug-
gested that tianeptine prevents alcoholic relapses in patients.

In experimental studies, Daoust et al . (1992) showed that
tianeptine decreases ethanol intake of male Wistar rats without
causing any significant change on either their food intake or
body weight. File et al . (1993) also suggested that tianeptine
is able to reverse the anxiogenic effects of ethanol with-
drawal in the social interaction test in rats. However, ethanol
withdrawal consists of more than anxiety. Other symptoms
such as locomotor hyperactivity, agitation, increased stereo-
typed behaviour and wet dog shakes, tremors, and audiogenic
seizures also appear during ethanol withdrawal in rodents.
In a recent study, Uzbay et al . (2006) reported results from
a detailed study investigating the effects of both acute and
chronic tianeptine treatment on ethanol withdrawal syndrome
in rats. Both acute and chronic administration of tianep-
tine attenuated severity of ethanol withdrawal syndrome
dose-dependently. However, acute tianeptine treatment was
found to be more effective than chronic treatment. While
acute tianeptine treatment was effective on all the signs
of ethanol withdrawal (locomotor hyperactivity, agitation,
increased stereotyped behaviour, wet dog shakes, tremors, and
audiogenic seizures) (Table 4), chronic treatment was inef-
fective on locomotor hyperactivity and agitation. In addition,
chronic tianeptine treatment did not produce any significant
effect on ethanol intake of the rats. Results of this study
indicated that tianeptine may be a potent and pharmacologi-
cally active agent on ethanol withdrawal syndrome in rats. It
may be useful in treatment of ethanol dependence as well as
depression in patients with history of ethanol abuse.

Extract of Hypericum perforatum (HPE, St. John’s wort)

HPE has been usually called St John’s wort, and commonly
used in folk medicine of several European countries. Several
preclinical studies indicate that extract of the common plant
HPE may be useful for treatment of disorders, especially
depression, originating from the central nervous system. Thus,
the anti-depressant-like effect of HPE has been reported in
rodents (Butterweck et al ., 1997; Ozturk, 1997; De Vry et al .,
1999). Several meta-analyses and overviews of randomized
clinical trials also consistently show that HPE displays a
clear anti-depressant action and it has been used for the
treatment of mild to moderate depression (Linde et al ., 1996;
Melchart, 1996; Volz, 1997; Kasper and Dienel, 2002). HPE
has some serotonergic properties reducing 5-HT re-uptake and
inhibiting monoamine oxidase (MAO) activity (Neary and Bu,
1990; Perovic and Muller, 1995; Cott, 1997; Bennett et al .,
1998; Greeson et al ., 2001) like other anti-depressant drugs.

Some experimental studies have been reported involving
the effects of HPE on ethanol abuse and dependence. It was
suggested that HPE inhibits ethanol intake and preference
in several strains of ethanol-preferring rats (De Vry et al .,
1999; Rezvani et al ., 1999; Perfumi et al ., 1999, 2001, 2002)
and mice (Wright et al ., 2003). In a recent report, Perfumi
et al . (2005) showed that HPE significantly reduced ethanol
self-administration, while it did not modify saccharin self-
administration. They also observed that HPE abolished the
increased ethanol intake following ethanol deprivation. Thus,
these results suggested that HPE might be a useful agent in
the treatment of ethanol abuse and dependence.

Although the effects of HPE on ethanol preference and
intake have been investigated in detailed studies, only one
study investigating the effects of HPE on ethanol withdrawal
syndrome was reported (Coskun et al ., 2006). In this study,
HPE blocked both locomotor hyperactivity and stereotyped
behaviours especially at 2nd and 6th h of ethanol with-
drawal. In addition, it attenuated the incidence of tremor in

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20 I. T. UZBAY

Table 5. Acute effects of ip administration of extract of Hypericum perforatum on the signs of ethanol
withdrawal syndrome in rats

Doses and Ethanol withdrawal signs
observation
intervals LH Agitation Stereotype Tremors WDS AS

2nd h of EWS
25.0 mg/kg + − + 0 − −
50.0 mg/kg + − + 0 − −

100.0 mg/kg + − + 0 − −
200.00 mg/kg + − + 0 − −
4th h of EWS

25.0 mg/kg 0 − 0 0 − −
50.0 mg/kg 0 − 0 + − −

100.0 mg/kg + − + + − −
200.00 mg/kg 0 − 0 0 − −
6th h of EWS a

25.0 mg/kg + − + 0 − +$
50.0 mg/kg + − + 0 − +$

100.0 mg/kg + − + 0 − +
200.00 mg/kg + − + 0 − 0

(Coskun et al ., 2006) ip, Intraperitoneal; EWS, Ethanol withdrawal syndrome; LH, Locomotor hyperac-
tivity; WDS, Wet dog shake; AS, Incidence of audiogenic seizure; HPE, Extract of hypericum perforatum
[Yield of HPE were 27.4% (w/v), doses were expressed as dried extract (mg/kg) body weight]; ($, significant
prolonged latency); −, Not evaluated; 0, Ineffective; +, Statistically significant attenuation.
a All doses were repeated 30 min before the 6th h of evaluation.

ethanol-dependent rats at 4th h of ethanol withdrawal. HPE
(100 mg/kg) produced a significant attenuation in the inci-
dence of the audiogenic seizures appearing in 6th h of ethanol
withdrawal. Latency of the audiogenic seizures was also pro-
longed significantly by HPE (25 and 50 mg/kg) treatment
(Table 5). These results imply that HPE may be useful in
the treatment of ethanol withdrawal syndrome.

DISCUSSION AND CONCLUSION

Effects of each anti-depressant on the signs of ethanol with-
drawal during observation terms are shown in Tables 1 – 5.
Their comparative effects were also summarized in Table 6.
As shown in the Tables, treatment of tianeptine, fluoxetine,
HPE, escitalopram, and venlafaxine have some beneficial
effects on the signs of ethanol withdrawal in rats. Effec-
tiveness of the anti-depressants was as follows: fluoxetine =
tianeptine > HPE > escitalopram > venlafaxine. Since any
significant changes on the open field locomotor activities in
naı̈ve groups were not observed, the beneficial effects of the
anti-depressants on ethanol withdrawal syndrome could not
be due to other non-specific effects, such as sedation or mus-
cle relaxation. As shown in Tables 1 – 5, actions of the drugs
are either lost or weakened at the 4t h-h-withdrawal. This may
be related to elimination of single dose of tested drugs. Thus,
second injections were repeated before 6th-h-observations.

Neurochemical findings from clinical (Roy et al ., 1987;
LeMarquand et al ., 1994) and experimental (Murphy et al .,
1987; Uzbay et al ., 1998, 2000) studies suggested significant
changes in central serotonergic neurotransmission in ethanol
dependence. On the other hand, we hypothesized that there

might be a significant association between decreased seroton-
ergic activity and ethanol dependence (Uzbay et al ., 1998,
2000). Our findings indicated some beneficial effects on with-
drawal signs treated by fluoxetine, escitalopram, and HPE to
support this hypothesis.

As venlafaxine inhibits the re-uptake of serotonin more
than noradrenaline, and even more than dopamine in synaptic
cleft (Muth et al ., 1986; Holliday and Benfield, 1995),
serotonergic property of this drug may also be responsible
for its prolonging effects of latency of audiogenic seizures.
Ineffectiveness of venlafaxine on other signs of withdrawal
may be due to its stimulative effects on noradrenalin re-
uptake. Thus, ethanol withdrawal syndrome is especially
characterized by the signs of overactivity of the sympathetic
nervous system (Linnoila et al ., 1987; De Witte et al ., 2003).
Inhibition of noradrenaline re-uptake, besides serotonin, by
venlafaxine and increased noradrenergic activity in synaptic
cleft might mask or prevent its beneficial effects on locomotor
hyperactivity, agitation, stereotyped behaviour, and wet dog
shakes. Some increase in agitation scores by venlafaxine
treatment (Saglam et al ., 2004) also supports this idea. Thus,
signs such as agitation and hyperreflexia, during ethanol
withdrawal are related to increased noradrenergic activity
(Linnoila et al ., 1987).

The beneficial effects of HPE might also be related
to serotonergic mechanisms. HPE has some serotonergic
properties, reducing serotonin re-uptake and inhibiting MAO
activity (Neary and Bu, 1990; Perovic and Muller, 1995;
Calapai et al ., 1999) like other anti-depressant drugs.

Unlike the classical SSRI anti-depressants, escitalopram
is bound at the primary site of SERT with a very high
affinity. In the central nervous system, the concentration
of active serotonin in the synaptic cleft is regulated by

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ANTI-DEPRESSANTS AND ETHANOL WITHDRAWAL 21

Table 6. Comparative effects of anti-depressants on the signs of ethanol withdrawal syndrome in rats

Ethanol withdrawal signs

Drugs LH Agitation Stereotype Tremors WDS AS

Fluoxetine ↓↓ ↓↓ ↓ ↓↓↓ ↓↓↓ ↓↓↓
Tianeptine ↓ ↓↓ ↓↓ ↓↓↓ ↓↓ ↓↓↓
HPE ↓↓↓ − ↓↓↓ ↓ − ↓↓
Escitalopram 0 0 ↓ ↓↓ ↓↓ 0
Venlafaxine 0 0 0 0 0 ↓

LH, Locomotor hyperactivity; WDS, Wet dog shake; AS, Audiogenic seizure; HPE, Extract of
Hypericum perforatum ; −, Not evaluated; 0, Ineffective; ↓, Mild inhibitory effect; ↓↓, Moderate
inhibitory effect; ↓↓↓, High inhibitory effect.

SERT (Tatsumi et al ., 1997; Sanchez et al ., 2004). SERT is
also responsible for termination or modulation of the action
of serotonin released from the pre-synaptic neuron. Thus,
escitalopram has higher serotonergic activity than the classical
SSRIs (Lepola et al ., 2003; Sánchez et al ., 2004) and it
could be expected that escitalopram is more effective than
the classical SSRIs, such as fluoxetine on ethanol withdrawal
syndrome. In contrast to our expectations, Saglam et al .
(2006) found that escitalopram is less effective compared
to fluoxetine. While fluoxetine had additional protective
effects on locomotor hyperactivity, agitation, and audiogenic
seizures (Uzbay et al ., 2004), escitalopram was not effective
on these signs of ethanol withdrawal. These findings imply
that more selective serotonergic activity does not mean more
effectiveness on ethanol withdrawal syndrome. Further studies
are needed to clarify the lower effectiveness of escitalopram
on ethanol withdrawal syndrome.

On the other hand, additional effects of fluoxetine on
nitric oxide (NO) may contribute to its stronger activity on
ethanol withdrawal. Several studies have shown that NO
synthase (NOS) inhibitors cause a prominent attenuation in
the signs of ethanol withdrawal syndrome in rats (Uzbay
and Oglesby, 2001). Wegener et al . (2003) suggested that
local administration of serotonergic anti-depressants, such as
fluoxetine, tianeptine, paroxetine, citalopram, and imipramine,
significantly decrease hippocampal NOS activity in rat brain.
In addition, previous studies indicated that fluoxetine has
some NOS inhibitory effects in humans (Yaron et al ., 1999)
and rats (Luo and Tan, 2001).

Different from SSRIs and other anti-depressants, tianeptine
was shown to enhance serotonin uptake selectively in rat brain
synaptosomes (Mennini et al ., 1987). Thus, this drug can be
described as a serotonin re-uptake enhancer, an atypical anti-
depressant. However, in a recent study from our laboratory, it
was found that tianeptine and fluoxetine, but not venlafaxine,
have similar discriminative stimulus properties in rats (Alici
et al ., 2006). Clinical anti-depressant efficacy of tianeptine
has also been found to be similar to that of SSRIs (Lŏo et al .,
1999; Waintraub et al ., 2000) and other tricyclic-depressants
(Guelfi, 1992; Staner and Mendlewicz, 1993).

Recent studies indicate that anti-depressant effects of this
drug may be attributable to non-serotonergic mechanisms,
including its capacity to buffer excitatory amino acid recep-
tors against stress (Kole et al ., 2002). Tianeptine reverses the
adverse effects of stress on brain morphology and synaptic
plasticity by reducing excessive accumulation of intracellular

calcium, which results from stress-induced excitatory amino
acid activation (McEwen and Magarinos, 2001). It also pre-
vents stress-induced increase in glutamate transporter mRNA
levels in rat hippocampus (Reagan et al ., 2004). On the
other hand, many studies have shown a clear role of exci-
tatory amino acid stimulation in the development of ethanol
dependence (Rossetti and Carboni, 1995; Tsai et al ., 1995;
Hardy et al ., 1999). In addition, blockade of NMDA receptors
markedly reduces ethanol withdrawal signs in rodents (Mor-
riset et al ., 1990; Liljequist, 1991; Thomas et al ., 1997). Fur-
thermore, adenosine A1 agonistic agents have also inhibitory
effect on ethanol withdrawal syndrome in rats (Concas et al .,
1996; Kaplan et al ., 1999) and it has been shown that tianep-
tine has anti-convulsant activity via adenosine A1 receptor
stimulation (Uzbay et al ., 2007). In addition, similar to flu-
oxetine, tianeptine also decreases hippocampal NOS activity
in rats (Wegener et al ., 2003). Glutamatergic, nitrergic, and
adenosinergic mechanisms may be responsible for the promi-
nent beneficial effects of tianeptine on ethanol withdrawal
syndrome.

In the light of the results gained by five anti-depressants
agents, it can be concluded that fluoxetine and tianeptine are
potent and pharmacologically active agents on ethanol with-
drawal syndrome. They may be useful in treatment of ethanol
dependence as well as depression in patients with history
of ethanol abuse. HPE, escitalopram, and venlafaxine also
have limited beneficial effects on some signs of withdrawal.
In addition, anti-depressants did not cause any deteriorating
effect on any of the signs of ethanol withdrawal syndrome.
It implies that anti-depressants could also be used safely in
patients suffering from alcoholism.

Acknowledgements — The author would like to thank Dr Gökhan Göktalay,
Dr Murat Yildirim and Dr Hakan Kayir for their scientific contributions and
valuable comments on the manuscript.

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