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The Association of Antidepressant Medication and Body Weight Gain

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Objective: To review the literature and discover which antidepressants are responsible for weight gain and then to discuss the areas with lack of adequate knowledge. Method: An electronic search was conducted through Medline, Pubmed, Cochrane library, and ScienceDirect. Forty nine empirical researches were identified and reviewed. Results: Amitriptyline, clomipramine, and mirtazapine have been associated with more weight gain induction in clinical studies, but not in animal-based studies. All TCAs have been reported to cause weight gain except protriptyline. MAOIs have been associated with weight gain. In SSRI group, citalopram and ecitalopram induce weight, yet mixed results exist for paroxetine and fluoxetine. Researches unanimously reported weight loss effect for bupropion. Some studies suggest contributing factors in the relationship of antidepressants with body weight changes including age, gender, base-line weights and treatment duration. Various results of different treatment durations have been reported in some cases but there are not continuous time-dependent studies for the influences of antidepressants on body weight changes. Conclusion: More studies are required to discover underlying mechanisms and the time-dependent effects of antidepressants on body weight changes.
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1
Review:
The Association of Antidepressant Medication and Body Weight Gain.
Authors
Sara Ranjbar, Faculty of Health and Behavioral Sciences, University of Wollongong, New South Wales, Australia 2522,
Nagesh B. Pai, Graduate School of Medicine, and Illawarra Health and Medical Research Institute, University of Wollongong, NSW
2522, Australia,
Chao Deng, School of Health Sciences, and Illawarra Health and Medical Research Institute, University of Wollongong, NSW 2522,
Australia.
Address for Correspondence
Sara Ranjbar,
Faculty of Health and Behavioral Sciences,
University of Wollongong,
New South Wales, Australia 2522.
E-mail: sr769@uowmail.edu.au
Citation
Ranjbar S, Pai NB, Deng C. The Association of Antidepressant Medication and Body Weight Gain. Online J Health Allied
Scs. 2013;12(1):1. Available at URL: http://www.ojhas.org/issue45/2013-1-1.html
Open Access Archives
http://cogprints.org/view/subjects/OJHAS.html
http://openmed.nic.in/view/subjects/ojhas.html
Submitted: Jan 2, 2013; Accepted: Apr 1, 2013; Published: Apr 15, 2013
Abstract: Objective: To review the literature and discover
which antidepressants are responsible for weight gain and
then to discuss the areas with lack of adequate knowledge.
Method: An electronic search was conducted through
Medline, Pubmed, Cochrane library, and ScienceDirect.
Forty nine empirical researches were identified and reviewed.
Results: Amitriptyline, clomipramine, and mirtazapine have
been associated with more weight gain induction in clinical
studies, but not in animal-based studies. All TCAs have been
reported to cause weight gain except protriptyline. MAOIs
have been associated with weight gain. In SSRI group,
citalopram and ecitalopram induce weight, yet mixed results
exist for paroxetine and fluoxetine. Researches unanimously
reported weight loss effect for bupropion. Some studies
suggest contributing factors in the relationship of
antidepressants with body weight changes including age,
gender, base-line weights and treatment duration. Various
results of different treatment durations have been reported in
some cases but there are not continuous time-dependent
studies for the influences of antidepressants on body weight
changes. Conclusion: More studies are required to discover
underlying mechanisms and the time-dependent effects of
antidepressants on body weight changes.
Key Words: Antidepressants; Body weight; Obesity
Introduction:
Psychotropic drugs have various side effects and body weight
gain is one of the known side effects for a number of
medications in this group. There is extensive empirical
evidence displaying the relationship between antipsychotic
therapy and body weight gain. More precisely second-
generation antipsychotics (SGAs) are known for their
potential to cause significant body weight gain.(1) Yet there
exists a dearth of evidence regarding the effect of
antidepressants upon body weight changes, compared to
antipsychotics and further controversies pertaining to the
effect of antidepressant on weight changes remain.(1)
Depression and obesity are two common health problems in
modern society.(2,3) There are studies suggesting a positive
association between depression and obesity.(4-7) Some
researchers have attempted to establish the underlying
mechanisms for the positive association between obesity and
depression.(4,6,8-11) Wild et al (4), McCarty et al (8), and
Ball et al (9) suggested that women are more prone to
become obese during depression compared to men. Heo et al
(10) found gender, age, and race as contributing factors for
the association of obesity and depression. Social and cultural
factors may also contribute to the weight gain and obesity
occurred in mood disorders.(6) Afari et al (11) investigated
whether shared genetic influences are responsible for the
association between these two conditions and they found a
modest phenotypic association between depression and
obesity. Antidepressant drugs have also been found to be the
potential reasons for weight gain induction in depressed
patients.(5,12,13)
Among antidepressants TCAs (Tricyclic antidepressants),
MAOIs (Monoamine oxidase inhibitors), and mirtazapine are
known to have more problems related to weight gain.(14)
Some patients can also gain weight while taking SSRIs,
particularly paroxetine.(15) The aim of this article is to
undertake a comprehensive review of the literature regarding
the effect of antidepressants upon body weight changes, to
clarify if weight gain occurs frequently on antidepressant
usage and which antidepressants are associated with weight
gain. The available studies will be categorized according to
each antidepressant in order to achieve a general perspective
about the effect of each antidepressant on body weight
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Volume 12, Issue 1; Jan-Apr 2013
2
changes. Finally the areas with deficient knowledge in the
field of antidepressant medication and the weight gain
outcomes will be discussed.
Methodology:
An electronic search was conducted through Medline,
Pubmed, Cochrane library, and Science Direct for the
literature published between January 1973 and August 2012
with two groups of key words: antidepressants, the names of
each particular antidepressant and antidepressant categories
as the first group, and obesity and weight as the key words of
the second group. The articles identified in the search
procedure were reviewed and the reference lists of reviewed
articles were manually searched. References identified as
relevant were retrieved and reviewed. After reviewing all of
the studies, those which did not have any contents about
association between antidepressants and weight changes were
excluded. The remaining articles all concluded the target
content either as the main result or as the secondary result.
Among these articles, forty nine empirical studies were
identified among which some applied mixture of
antidepressants without any discriminations and some used
each particular antidepressant in separate groups. The latter
group which contains more precise results for each specific
antidepressant has been emphasized in the current review.
Results:
Forty nine empirical studies exist among literature regarding
the effect of the antidepressants on body weight changes.
Each antidepressant is discussed separately according to the
relevant literature. Table 1 illustrates the summary of the
results which have been achieved thorough the review.
Amitriptyline
Amitriptyline is the mostly reported antidepressant to cause
weight gain.(12,13,16-22) In a clinical trial 51 depressed
women being treated by amitriptyline were divided into two
groups; one group maintained on amitriptyline for nine
months and another group had the medication withdrawn
after three months. Both groups gained weight during
recovery. Yet the amitriptyline group continued to gain
weight excessively, while the drug withdrawal after nine
months treatment caused weight loss.(16) The result of
another six-week randomized double-blind trial showed
significantly higher body weight gains for taking
amitriptyline than placebo and trazodone (the latter caused
slight weight loss).(17) Pande et al (18) discovered that 100%
of the patients receiving amitriptyline during their treatment
gained weight. Amitriptyline induces remarkable weight gain
in the patients, which is more than the weight gain due to
clomipramine and imipramine administration.(12) Another
study reported modest weight increases (1.7±4.1 Kg) in 22%
of patients being treated with amitriptyline in a double-blind
placebo controlled trial.(20) Berilgen et al (22) found that
amitriptyline causes weight gain and increase in serum leptin
levels and they suggested amitriptyline may cause leptin
resistance. Conversely Hinze-Selch et al (21) did not find
TCAs including amitriptyline to affect plasma leptin levels
while these agents induced weight gain.
Two animal-based experiments using Wistar rats (23) and
OLETF rats (24) failed to mimic body weight gain due to
amitriptyline medication and the study concluded that there
was no linkage between weight gain and amitriptyline
medication in rats.(23, 24) It shows that the available animal
based studies for amitriptyline, could not model
amitriptyline-induced weight gain observed in clinic.
Clomipramine
Clomipramine induces weight gain in human as supported by
two clinical trials.(12, 25) On the contrary, clomipramine
decreased weight gain and food intake in male Wistar rats
maintained on a self-selection regime with separate sources
of protein, fat and carbohydrate (macronutrient self-selection
procedure).(26) During 27 days of this study clomipramine
did not alter protein-rich or fat-rich diet consumption, yet it
decreased energy intake as a result of a decrease in both
carbohydrate-rich diet intake and body weight gain.(26)
Imipramine
Imipramine does not show the same potency to cause weight
increase compared to amitriptyline and clomipramine. A non-
significant weight gain was the result of the majority of the
studies.(27- 29) Mean weights of 2.1 ± 1.5 kg after 6 weeks,
and 4 ± 1.4 kg after 4-6 months were gained in patients
taking imipramine in a controlled trial which both amounts
were less than the weight gain for other TCAs.(12) In an
animal based experimental study weight gain was achieved
and even continued after stopping administering imipramine
to the rats.(30)
Desipramine
Fifty one percent of the patients taking desipramine in a 10-
year lasting clinical trial gained weight (18). Female Sabra
mice also showed a gradual increase in their body weights
while taking desipramine, compared to the placebo-
controlled group of the rats.(31)
Nortriptyline
All of the five available clinical trials for nortriptyline
reported various degrees of weight gain in the patients taking
this medication.(18,21,32-34) A group of researchers
explored the efficacy and tolerability of nortriptyline in 35
children and adolescents suffering from ADHD (Attention
deficit hyperactivity disorder). One of their findings during
their double-blind, placebo-controlled trial was that
nortriptyline caused an average of 5.2 pounds weight gain
through nine weeks of the study.(32) Hinze-Selch et al (21)
found significant weight gains for amitriptyline/ nortiliptyline
in their controlled clinical trial, while they did not report any
increase in plasma leptin levels. In geriatric patients
nortriptyline was not a potent weight gainer as significant
amounts of weight gain (>10 lb) occurred in only 17.2% of
the patients over 30-week period of the study.(34) Twenty
four percent of the patients in the same study showed weight
loss below premorbid level and 20.7% showed no weight
change.(34)
Protriptyline
An average weight loss of 1.75 Ib per week was achieved for
the patients being treated by protriptyline in a clinical trial
investigating the influences of protriptyline on body weight
changes of the patients who had low urinary level of 3-
methoxy-4-hydroxy-phenylglycol.(35)
Maprotyline (Tetracyclic Antidepressant)
As a result of a controlled clinical trial which was
investigating the effects of different antidepressants on body
weight changes maprotyline and amitriptyline induced the
more marked weight gain whereas imipramine and non-
tricyclic antidepressants induced a smaller weight gain.(12)
Maprotyline-treated patients gained a mean weight of 3.2 ±
2.6 kg after 6 weeks and 5.2 ± 4.1 kg after 4-6 months.(12)
Phenelzine and Tranylcypromine
In the only available clinical trial investigating the influence
of phenelzine on body weight changes, weight gain was
achieved for forty six percent of the patients taking this agent
for ten years (18).In the same study tranylcypromine induced
3
the largest increase in the weight (an average of 4.1 ± 2.2 Kg
weight gain in the 73% of the patients) compared to other
included antidepressants consisting of desipramine,
nortriptyline, amitriptyline, and phenelzine.(18)
Moclebomide
The only available trial for the effect of moclebomide on
body weight changes concluded just a non-significant weight
gain as a result of taking this medication during both short-
term (6 weeks), and long-term (18 weeks) treatment.(19)
Fluoxetine
Inconsistent results exist among literature regarding the effect
of fluoxetine on body weight changes. Some researchers
reported weight loss for applying fluoxetine (19, 35- 38), and
some found this agent to inhibit food intake in rats (39).
Conversely other researchers discovered that fluxetine can
provoke weight gain (30,40), or may not cause any changes
in body weight.(24) Michelson et al (41) also searched for the
effect of fluoxetine on body weight changes and detected
both weight loss and weight gain during the acute and
chronic phases of the treatment, respectively. During this
one-year lasting clinical trial with 839 participants of
depressed patients, modest weight loss happened after initial
4 weeks for patients taking fluoxetine.(41) In continuing
phase and after remission of depressive symptoms all patients
gained weight and these were similar in both fluoxetine and
placebo consumed patients. Therefore this can be due to the
remission and not necessarily the medication.(41) Another
study which found counter results for fluoxetine was carried
out according to the baseline weights of the depressed
patients.(42) This study discovered weight loss for
overweight patients as a result of fluoxetine treatment, and
body weight gain for normal weight group.(42)
Fluvoxamine
In a double-blind study, Moon and Jesinger (43) compared
side effects of fluvoxamine and mianserin in 59 depressed
patients. As a result fluvoxaomine did not cause any weight
gain as a side effect while mianserin induced weight gain in
the same study.(43) In another study with 40 participants of
obese women, fluvoxamine caused mean weight loss of 3.1
kg during 12 weeks which was greater but not significantly
different from placebo controlled group.(44)
Correspondingly fluvoxamine does not induce weight gain
and it can even cause weight loss in depressed obese
women.(44)
Paroxetine
Paroxetine is another antidepressant which different results
have been achieved for its influences on body weight
changes. It can cause weight gain as supported by two
randomized clinical trial.(37,45) Benkert et al (41)
investigated the efficacy and tolerability of mirtazapine
versus paroxetine and found that both drugs induced weight
increases after 6 weeks in depressed patients and this effect
was stronger for mirtazapine compared to paroxetine. Body
weight changes of 284 patients with major depressive
disorder who were randomly assigned to double-blind
treatment with fluoxetine, sertraline, and paroxetine were
analyzed in a clinical trial.(37) Significant weight increases
only occurred in paroxetine group during a total of 26 to 32
weeks.(37) Contrarily paroxetine was not found to induce
any statically significant weight increases in depressed
patients during a comparative retrospective study which used
clinical records of double-blind trials.(19) Another study
which concluded paroxetine does not affect body weight is a
clinical trial at which Hinze-Selch et al(21) investigated the
effects of several antidepressants on body weight, plasma
leptin levels, TNF-a, and soluble TNF receptors. The writers
reported that paroxetine did not make any changes in the
mentioned factors including body weight which was similar
to drug-free treatment effects, but opposite to TCAs
treatment which caused increases in body weight and plasma
leptin levels.(21) For animal based studies it is suggested that
paroxetine significantly inhibits pelleted food intake in the
rats.(39)
Citalopram
Wade et al conducted two 12-month trials: (i) a double-blind,
randomized trial of placebo, citalopram, and clomipmmine in
279 patients with panic disorder, and (ii) open trial of
citalopram in 541 depressed patients. In the panic trial,
citalopram-treated patients did not approach statistically
significant weight gain and in the depression trial citalopram
also caused no weight gain or a slight weight gain (<2.5 kg)
in majority of patients.(25) Authors suggested that the
minimal weight increases observed in the depressed patients
may be a result of patients' appetites increasing as their
condition improved.(25) Citalopram was also a cause of non-
significant weight gain in another clinical trial.(46) Among
18 patients who were observed for carbohydrate craving due
to treatment with citalopram (SSRI) in a mood disorder
clinic, eight cases showed a significant increase in
carbohydrate craving together with weight gain shortly after
initiation of treatment.(47)
Escitalopram
During eight-months period of a double-blind clinical trial
patients who were receiving escitalopram gained an average
weight of 1.38 kg which was more than the weight gain in
duloxetine-treated patients.(48) A non-significant weight
gain of 0.14 kg over 6 months was the result of another part-
randomized open trial.(33)
Sertraline
Sertraline can induce a modest weight gain in depressed
patients.(37) Conversely obese patients can lose weight by
taking sertraline particularly those who have low urinary
MHPG (3-methoxy-4-hydroxyphenylglycol).(49)
Meyerowitz and Jaramillo (1994) carried on a clinical trial to
find out the effect of sertraline on the body weight of 23
depressed and overweight patients while measuring their
urinary concentrations of 3-methoxy-4-hydroxyphenylglycol
(MHPG). Results showed that sertraline can cause weight
loss and with an average weight loss of 1.06 lb/week in
patients with low urinary levels of MHPG which was found
to be significantly greater than the average weight loss of
0.42 lb/week in patients with high urinary levels of
MHPG.(49)
Zimelidine
The only available study reported that zimelidine caused no
weight gain and, in many cases, weight loss was
demonstrated with a mean weight change of 0.2 ± 1.8 kg
during one month of applying this antidepressant in a
randomized clinical trial.(50)
Duloxetine
During a double blind controlled trial, duloxetine had
significantly greater incidence of treatment-emergent
abnormal weight gain (> 7% increase in weight from
baseline) compared with placebo.(48) During 10 controlled
clinical trials the effect of duloxetine on body weight of
patients with major depressive disorder was analyzed.(51)
The results of these trials indicated no consistent effect of
Duloxetine on weight as the patients treated with this drug
experienced modest weight loss in acute phase following by a
modest weight gain on longer treatments.(51)
4
Mianserin
In a double-blind, six-week study, Moon, and Jesinger (43)
investigated the effectiveness of mianserin and fluvoxamine
in patients suffering from major depressive episode,
mianserin affected compliance due to weight gain over
longer period.
Mirtazapine
Mirtazapine has been reported in several studies to produce
weight gain in humans.(20,45,46,52) During a double-blind
placebo-controlled study in adult patients with major
depressive disorder, the efficacy of mirtazapine was
compared to amitriptyline. One of the findings of this study
was that measured weight gain was more frequent with
amitriptyline (22% of patients) compared with mirtazapine
(13% of patients).(20) Another comparison was made
between the efficacy and tolerability of mirtazapine versus
paroxetine in 275 depressed outpatients. Patients were
randomly assigned to 6 weeks of treatment with mirtazapine
or paroxetine. The result regarding weight gain showed the
more weight increase in the mirtazapine-treated group
compared to paroxetine-treated group.(45) A multicenter
randomized double-blind trial with the aim of comparing
efficacy and tolerability of mirtazapine and citalopram in
depressed patients yielded that mirtazapine-treated patients
have significantly more increased appetite and body weight
increase (8.8% and 15.3%) than citalopram-treated patients
(1.5% and 4.5%).(46) Laimer et al investigated the influence
of mirtazapine treatment on body weight, body fat mass,
glucose metabolism, lipoprotein profile, and leptin in a group
of seven depressed women compared to seven mentally and
physically healthy female volunteers as a control group.
Results confirmed that mirtazapine significantly increases the
body weight (from a mean of 63.6 ± 13.1 kg to a mean body
weight of 66.6 ± 11.9 kg), body fat mass, and leptin
concentration of the patients.(52) In contrast with human
based studies, there were no direct linkages between the
development of obesity and mirtazapine according to the
animal based controlled study carried on by Jeon, Joe, and
Kee (24) who used OLETF (Otsuka Long-Evans Tokushima
Fatty) rats for their study.
Bupropion
Three randomized clinical trials have investigated the effects
of bupropion on body weight changes. In all of these studies,
researchers concluded that bupropion can induce weight loss
in patients.(53-55) In a randomized double-blind trial, modest
mean weight losses with long-term bupropion SR treatment
was achieved in patients with depression which increased
with increasing baseline body weight.(53) Another
randomized, double-blind, placebo-controlled study
evaluated the efficacy bupropion SR in reducing weight and
depressive symptoms in 422 obese adults with depressive
symptoms. After 26 weeks, the bupropion SR group lost a
greater average amount of weight (4.4 kg: 4.6% of baseline
weight) compared to the placebo (1.7 kg: 1.8% of baseline
weight).(54) The third 48-week double-blind, placebo-
controlled trial showed bupropion SR in conjunction with a
lifestyle intervention program was associated with a dose-
related reduction in body weight.(55)
Trazodone
In a 6-week randomized double-blind research trazodone was
found to cause a slight weight loss in the over-weight
depressed patients. (17)
Discussion:
Significant positive association has been reported between
depression and obesity more markedly among women.(56)
Body weight gain is a known side effect for number of
psychotropic drugs including antidepressants.(57) This
review acknowledges the various and inconsistent effects of
different antidepressants on body weight changes. TCAs and
particularly amitriptyline are well known to cause weight
gain among antidepressants.(18,58,59) Current review has
also revealed that amitriptyline has been repeatedly reported
as a weight gain inducer in clinical studies.(12,13,16- 22) All
TCAs seems to cause weight gain in clinical studies except
protriptyline which caused weight loss when administered to
patients with major depression.(35) SSRI were thought to
induce weight loss rather than weight gain in contrast to
TCAs.(58) As seen among the results, the majority of studies
reported weight loss for fluoxetine-treating patients, yet
weigh gain has been also found for fluoxetine in some
researches. The same inconsistent results apply to paroxetine.
Weight gain has been also achieved in the studies using other
SSRIs including citalopram and ecitalopram. Available
researches for MAOIs reported weight gain for phenelzine
and Tranylcypromine, but not any significant weight changes
for moclebomide. Bupropion is the only antidepressant which
all the studies confirm weight loss induction in depressed
patients being treated with this agent.
Some studies suggested that weight gain can be at least in
parts due to the remission from depression itself and not
necessarily as a result of antidepressant medication.(25, 60)
The fact that losing appetite is one of the important signs of
depression supports this idea. However there are evidences
that antidepressants cause weight gain in patients with other
psychiatric disorders such as ADHD (32) and migraine.(22)
The duration of the treatment is also an important factor that
may affect the results. Number of studies found differences
among short-term and long-term effects of antidepressants on
body weight changes. Michelson et al (41) reported weight
loss for patients taking fluoxetine during the acute phase (4
weeks), and weight gain for the same patients in continuing
phase. Another study comprising of 10 clinical trials
investigating doluxetine effects found also weight loss and
weight gain in acute and chronic treatment phases
respectively, but in non-significant and modest amounts. The
categorization of acute-chronic and short-term, long-term
phases is not the same among different studies considering
the time-dependent effects of antidepressants and it adds
more difficulties for interpreting the results as a general point
of view.
Age is another factor that seems to affect the relationship
between antidepressant medication and body weight gain. As
seen in the study conducted by Corman et al (34)
nortriptyline was not a potent weight gainer in geriatric
patients and it caused even weight loss in some of the
subjects. It is contrary to non-elder patients among whom
nortrptyline shows more potency to induce weight
gain.(18,21,32)
Base line weights of the patients can also impart in the final
results of the weight changes due to antidepressant
medication. This was confirmed in a clinical trial conducted
by Orzack et al (42) who discovered weight gain among
patients with normal weight, but weight loss in overweight
patients when they were treated by fluoxetine.
The inconsistent results for the effects of antidepressants on
body weight changes which have been identified from the
current review can be related to the concurrent psychotropic
medication which happens in co-morbid psychiatric patients.
This phenomenon can also be due to different designs,
sample sizes, and duration of the studies or as a result of
other contributing factors such as genetic vulnerability in
addition to the factors mentioned before.
Obesity and overweight condition may lead to serious health
problems such as cardiovascular diseases. Moreover weight
gain caused by antidepressant drugs is a major reason for
patients’ noncompliance with treatment and poor treatment
5
outcome and fighting weight gain once it has occurred can be
very difficult.(57) Therefore understanding the underlying
mechanisms that contribute to the effect of antidepressants on
body weight changes is important.
The results of animal based studies are not always consistent
with the clinical ones. For instance amitriptyline and
mirtazapine failed to have any direct association with obesity
in rats and in fact it was suggested by Jeon et al (24) that
these two antidepressants may regulate circulating levels of
adiponectin and adiponectin receptor. Amitriptyline has been
also found to be unsuccessful in increasing daily food intake
and body weight of the rats in series of experimental studies
despite applying various dosages, route of administration,
diet composition and palatability.(23) Clomipramine was
chronically administered to male wistar rats exposing to
macronutrient self-selection procedure and it decreased food
consumption and body weight gain (26) while similar to
amitriptyline and miratazpine, clomipramine induces weight
gain in cliniucal studies.(12,25) Interpreting the results of
animal models for producing obesity after antidepressant
medication is challenging when considering the real life
situations for human. Mastronardi et al (30) tried to model
the similar situation of patients experiencing stress/
depression and exposure to short-term antidepressant
medication continuing by high-fat diet consumption in the
rats. For achieving this kind of experiment, repeated restraint
stress (RRS) and short-term antidepressant medication were
applied to the rats following by exposure to high-fat diet for a
long time.(30) Results showed weight gain effects even after
discontinuing the antidepressants consisting of imipramine
and fluoxetine in rats which supported the time-dependent
sensitization phenomenon.(30) In another animal based
experimental study desipramine first provoked weight loss in
the rats following by weight gain in continuing phases of
treatment lasting for more than 3 months.(31)
Many regulatory substances have been known to affect
appetite behavior including neurotransmitters such as
noradrenaline, 5HT, neuropeptides such as cholecystokinin,
corticotropin releasing factor, neuropeptide Y, and opioids
and other hormone-like peptides such as enterostatin,
bombesin, amylin, and leptin (59). TCAs have been reported
to associate with weight gain due to their antagonizing action
on H1 receptors for many years.(61) It has been suggested
that the weight gain induction of citalopram can also be due
to its high affinity to H1 receptors.(61) Some researchers
attempted to find the role of leptin in the association of
antidepressants and obesity.(21, 22) Berilgen et al (22)
discovered that amitriptyline may cause leptin resistance
possibly by different mechanisms and thereby result in
increases in serum leptin levels and BMI. Conversely in
another study amitriptyline did not cause any increases in
leptin levels while inducing weight gain.(21) The underlying
mechanisms for weight gain results of antidepressant
medication is not yet well understood and further studies are
required for investigating the role of neurotransmitters and
other possible contributing factors in the process of gaining
weight due to antidepressant medication. The areas of
controversies such as the opposite results reported in human
versus animals based studies or the different time-dependent
effects of antidepressants on body weight changes need to be
addressed in future studies. More continuous and more
precise time-dependent investigations of the influences of
antidepressants such as what has been done for
antipsychotics (61), can help to clear the role of the treatment
duration in producing weight gain concurrent with
antidepressant medication. Investigating the effects of other
antidepressants which have not been included in previuos
studies such as doxepin, trimipramine, venlafaxine,
nefazodone, and amoxapine is another issue which needs to
be considered in the relevant future studies regarding the
association of antidepressant medication and body weight
changes.
Declaration of interest:
None.
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8
Table 1: Effects of antidepressants on body weight
Name of the
Antidepressant
Design of the Study
Results
Reported Amounts in the Results
References and
the Year of the
Publications
Amitriptyline
Randomized double-blind - 6 weeks
Weight gain
17, 1986
Randomized clinical trial - One month
Weight gain
>10 Ib in 28%; 7-10 lb in 44%; 3-6 Ib in 17%; No change in
11%
13, 1998
Clinical trial
Weight gain
100% of patients (n=5)
18, 1989
Controlled trial
Weight gain
After 6w: 3.2+-3.1 kg; After 4-6m: 6.2+-7.1 kg
12, 1994
Retrospective study of double blind
trials
Weight gain
In both 6week and continuing 18 weeks duration.
19, 1995
Double-blind placebo controlled trial
Weight gain
22% of patients; Mean increase: 1.7 ± 4.1 Kg
20, 1998
Controlled trial
Weight gain
3.5 ± 1.1 kg for amitriptyline/ nortriptyline
21, 2000
Clinical trial
Weight gain and increased leptin level
22, 2005
Animal based experimental study
(Wistar rats)
No change in weight and food intake
23, 1987
Animal based experimental study
(OLETF rats)
No direct linkage with obesity
24, 2008
Clinical trial - 9 months
Weight gain and carbohydrate craving
63, 1973
Imipramine
Clinical trial - 4months (16 weeks)
Weight gain but, not associated with
rapid weight gain
Mean average of 5 lb weight gained in all subjects; 19%: 6-10
lb weight increase; 9%: 11-15 Ib weight increase; 6%: gained >
15 Ib; 6%: 6-10 lb weight loss
27, 1986
Clinical trial - 33 weeks
Not significant changes
Weight changes of: 1.3 ± 5.3 lb for acute phase (9.5 weeks); 3.1
± 7.8 lb for continuing phase (2.3 weeks)
28, 1990
Randomized clinical trial - 8weeks
No significant increase in weight and
appetite
29, 1993
Controlled trial
Weight gain (less than other included
TCAs)
After 6 w: 2.1 ± 1.5 kg; After 4-6 m: 4 ± 1.4 kg
12, 1994
Animal based experimental study (Male
Sprague-Dawley rats)
Weight gain even after discontinuing
the medication
30, 2011
Nortriptyline
Clinical trial
Weight gain
62% of patients gained weight
18, 1989
Double-blind, placebo-controlled trial
Weight gain
Average of 5.2 lb in 9 weeks
32, 2000
Controlled clinical trial
Weight gain
3.5 ± 1.1 kg for amitriptyline/nortriptyline
21, 2000
Part-randomized open-label study
Weight gain
1.82 kg after 6 months
33, 2011
Clinical trial
Weight gain
Overall mean weight gain in 30 weeks: 3.92 ± 10.34
34, 1992
Desipramine
Clinical trial - ten years
Weight gain
51% of patients gained weight
18, 1989
Animal based experimental (Female
Sabra mice)
Weight gain, gradually increase in
chronic treatment
31, 2006
Protriptyline
Clinical trial
Weight loss
Average weight loss: 1.75 lb/w
35, 1992
Clomipramine
Controlled trial - 4-6 months (6w- 4-
6m)
Weight gain
After 6 w: 1.9 ± 3.4 kg; After 4-6m: 6.1 ± 6.3 kg
12, 1994
a double-blind, randomised trial
Weight gain
25, 1999
Animal based experimental, 27 days
(Male Wistar rats)
Decrease food intake and weight
26, 2007
Maprotyline (TeCA)
Controlled trial
Weight gain
After 6 w: 3.2 ± 2.6 kg; After 4-6m: 5.2 ± 4.1kg
12, 1994
Fluoxetine
Clinical trial (6 patients, 9.8 months)
Weight gain
Average weight gain: 20 lb
40, 1991
Clinical trial
Wight loss
Average weight loss of 1.20 lb/w
35, 1992
Double-blind trials
Weight loss
19, 1995
Double-blind parallel study
Weight loss
36, 1996
Randomized clinical trial
Modest but non-significant weight loss
37, 2000
Clinical trial
Weight loss
Mean weight losses: 4th week: 3.24 kg; 8th week: 6.67 kg
38, 2005
Clinical trial
Weight loss
Weight gain
At acute phase (4weeks): Mean absolute weight loss of 0.4 kg;
At continuing phase, mean weight gain of: 26 w: 1.4+-3.2 kg;
38 w: 3.1+-3.8 kg; 50 w: 4.3+-5.3 kg
41, 1999
Clinical Trial
Weight loss; Weight gain
Weight loss in overweight patients; Weight gain in ideal weight
patients
42
Animal based experimental study
(OLETF rats)
No linkage with weight gain
24, 2008
Animal based experimental study (Male
Sprague-Dawley rats)
Weight gain even after discontinuation
30, 2011
Animal based experimental study (Rats)
Inhibiting pelleted food intake
39, 1991
Paroxetine
Randomized clinical trial
Weight gain
45, 2000
Randomized clinical trial
Significant weight increase
37, 2000
Double-blind trials
No change in weight
19, 1995
Controlled clinical trial
No change in weight, and leptin level
21, 2000
Animal based experimental study (Rats)
Inhibiting pelleted food intake
39, 1991
Sertraline
Clinical trial
Weight loss
Average weight loss of: 1.06 lb/week in those with low urinary
MHPG; 0.42 Ib/week in those with high urinary MHPG
49, 1994
Randomized clinical trial
Non-significant (modest) weight
increase.
37, 2000
Citalopram
Clinical trial with 8 patients
Significant weight gain and increasing
carbohydrate craving
47, 1996
Multicenter randomized double blind
trial
Different adverse effects compared to
mirtazapine
Weight gain only in 4.5% of patients
46, 1999
1. Double blind, randomized; 2. Open
trial
no weigh gain or slight weigh gain
Slight weight gain: <2.5 kg
25, 1999
9
Escitalopram
Double blind controlled trial
Weight gain
1.38kg in 8 months
48, 2007
Part-randomized open-label study
Not significant weight change
Average of 0.14 kg weight increase in 6 months
33, 2011
Fluvoxamine
Double blind trial
No weight gain
43, 1991
Double-blind placebo controlled
Weight loss
Overall mean weight loss of 3.1 kg in 12 weeks
44, 1986
Zimelidine
Randomized clinical trial
No weight gain
Mean weight change in one month: 0.2 ± 1.8 kg
50, 1988
Phenelzine
Clinical trial
Weight gain
In 46% of patients
18, 1989
Tranylcypromine
Clinical trial
Weight gain
In 73% of patients (4.1 ± 2.2 Kg)
18, 1989
Moclobemide
Double-blind trial
No changes in w eight
19, 1995
Bupropion
Randomized double-blind trial
Modest weight loss in long-term
53, 2002
Randomized, double-blind, placebo-
controlled
Weight loss
Mean weight loss: 4.4 kg (4.6% of baseline weight) in 26 weeks
54, 2002
Double blind placebo controlled trial
Dose-related reduction in weight
24-week weight loss (% of baseline body weight): 7.2% for SR
300; 10.1% for SR 400;
48-week weight loss: 7.5% for SR 300; 8.6% for SR 400
55, 2002
Trazodone
Randomized double-blind study
Slight weight loss in overweight
patients
17, 1986
Duloxetine
Double blind controlled trial
Weight gain
0.6kg in 8 months
48, 2007
10 controlled clinical trials
No consistent weight change
No significant differences from placebo groups
51, 2006
Mianserin
Double blind trial
Wight gain
43, 1991
Mirtazapine
Double-blind placebo controlled
Weight gain
Average of 1.4 ± 3.1 kg
20, 1998
Multicenter randomized double blind
trial
Different adverse effects compared to
citalopram
15.3% of patients gained weight
46, 1999
Randomized clinical trial
Weight gain
45, 2000
Clinical trial
Weight gain
Weight increased from 63.6 ± 13.1 kg to 66.6 ± 11.9 kg
52, 2006
Animal based experimental study
(OLETF rats)
No linkage with weight gain
24, 2008
... Similar results were achieved in the group of adults studied by Calarge and colleagues [16]. It was observed that in [15][16][17][18][19][20] year olds treated with SSRI's there was a significant increase in all body composition parameters when citalopram and escitalopram were used. No difference were noted in the case of treatment with sertaline and only a slight increase was seen when fluoxetine was used. ...
... Our own studies of women patients show that percentage of adipose tissue was significantly higher in patients treated with SNRI's and NaSSA's compared to the control group. Research suggests that female sex predisposes to increased body weight in diagnosed and pharmacologically treated depression, especially if female patients were treated with NaSSA's (mirtazapine was used) [17]. One study compares patients using mirtazapine and paroxytine (SSRI's). ...
... One study compares patients using mirtazapine and paroxytine (SSRI's). After a six-week treatment period, the results indicate a higher body weight gain in mirtazapine using individuals [17]. A similar relationship was observed in the comparison of mirtazapine with citalopram (SSRI's). ...
... Long-term psychiatric medication use is associated with some undesirable effects, including weight gain [16][17][18][19]. Antidepressants have been associated with weight gain [20]; however, their effect on weight varies [16,21,22]. For example, paroxetine and mirtazapine have been associated with greater risk of weight gain [16,21], whereas bupropion is consistently associated with weight loss [21,22]. ...
... Antidepressants have been associated with weight gain [20]; however, their effect on weight varies [16,21,22]. For example, paroxetine and mirtazapine have been associated with greater risk of weight gain [16,21], whereas bupropion is consistently associated with weight loss [21,22]. The evidence regarding the effect of other Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) on weight is less consistent. ...
... Antidepressants have been associated with weight gain [20]; however, their effect on weight varies [16,21,22]. For example, paroxetine and mirtazapine have been associated with greater risk of weight gain [16,21], whereas bupropion is consistently associated with weight loss [21,22]. The evidence regarding the effect of other Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) on weight is less consistent. ...
Article
Background: Given the high rates of psychiatric comorbidity in bariatric surgery patients, pharmacotherapy is common and could potentially influence weight loss outcomes. Objective: We aimed to identify the impact of psychotropic medication use on percent total weight loss (%TWL) 1 year after bariatric surgery. Methods: In this prospective cohort study, 190 patients were compared based on demographic variables (age, sex, relationship status, employment status), body mass index, %TWL, and psychotropic medication use before and 1 year after bariatric surgery. An analysis of variance test was used as a global test of significance for psychotropic medication comparisons related to %TWL. Significance of post hoc comparisons was calculated with the Tukey's Honestly Significance Difference test. Results: Sixty-one of 190 (32.1%) patients were taking psychiatric medications before surgery; of those, 82% (50/61) continued to take psychiatric medications 1-year after surgery. %TWL did not significantly differ between patients taking no psychiatric medications, one medication, or more than one medication 1 year after surgery (31.4% vs. 29.9% vs. 34.4%, respectively). Among patients taking antidepressants, those taking serotonin-norepinephrine reuptake inhibitors had a significantly higher %TWL than those taking selective serotonin reuptake inhibitors (36.4% vs. 27.8%; P = 0.032). Conclusion: This longitudinal study suggests that psychiatric medication use was not associated with poorer %TWL at 1 year after bariatric surgery. Within class, antidepressant use may have differential effects on weight loss after bariatric surgery and warrants further investigation.
... Long-term psychiatric medication use is associated with some undesirable effects, including weight gain [16][17][18][19]. Antidepressants have been associated with weight gain [20]; however, their effect on weight varies [16,21,22]. For example, paroxetine and mirtazapine have been associated with greater risk of weight gain [16,21], whereas bupropion is consistently associated with weight loss [21,22]. ...
... Antidepressants have been associated with weight gain [20]; however, their effect on weight varies [16,21,22]. For example, paroxetine and mirtazapine have been associated with greater risk of weight gain [16,21], whereas bupropion is consistently associated with weight loss [21,22]. The evidence regarding the effect of other Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) on weight is less consistent. ...
... Antidepressants have been associated with weight gain [20]; however, their effect on weight varies [16,21,22]. For example, paroxetine and mirtazapine have been associated with greater risk of weight gain [16,21], whereas bupropion is consistently associated with weight loss [21,22]. The evidence regarding the effect of other Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) on weight is less consistent. ...
... Escitalopram has a minimal affinity to serotonin, dopamine, and cholinergic receptors, which highly reduce the range of its potential side effects. SSRI-related changes in energy homeostasis and weight gain are often clinically observed [13,14]; however, little is known about stress-related peptidergic neuronal pathways, which could be additional targets for these medications. Although SSRIs often exhibit anxiolytic and sedative properties, their potential direct or indirect effects on stress-related neuropeptides signalling are hitherto completely unknown. ...
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Background: Neuropeptide S (NPS) is a multifunctional regulatory factor that exhibits a potent anxiolytic activity in animal models. However, there are no reports dealing with the potential molecular interactions between the activity of selective serotonin reuptake inhibitors (SSRIs) and NPS signaling, especially in the context of adult neurogenesis and the expression of noncanonical stress-related neuropeptides such as neuromedin U (NMU). The present work therefore focused on immunoexpression of neuromedin U receptor 2 (NMUR2) and doublecortin (DCX) in the rat hippocampus after acute treatment with escitalopram and in combination with selective neuropeptide S receptor (NPSR) blockade. Methods: Studies were carried out on adult, male Sprague-Dawley rats that were divided into five groups: animals injected with saline (control) and experimental individuals treated with escitalopram (at single dose 10 mg/kg daily), escitalopram + SHA-68, a selective NPSR antagonist (at single dose 40 mg/kg), SHA-68 alone, and corresponding vehicle control. All animals were sacrificed under halothane anaesthesia. The whole hippocampi were quickly excised, fixed, and finally sliced for general qualitative immunohistochemical assessment of the NPSR and NMUR2 expression. The number of immature neurons was enumerated using immunofluorescent detection of doublecortin (DCX) expression within the subgranular zone (SGZ). Results: Acute escitalopram administration affects the number of DCX and NMUR2-expressing cells in the adult rat hippocampus. A decreased number of DCX-expressing neuroblasts after treatment with escitalopram was augmented by SHA-68 coadministration. Conclusions: Early pharmacological effects of escitalopram may be at least partly connected with local NPSR-related alterations of neuroblast maturation in the rat hippocampus. Escitalopram may affect neuropeptide and DCX-expression starting even from the first dose. Adult neurogenesis may be regulated via paracrine neuropeptide S and NMU-related signaling.
... Escitalopram has a minimal affinity to serotonin, dopamine, and cholinergic receptors, which highly reduce the range of its potential side effects. SSRI-related changes in energy homeostasis and weight gain are often clinically observed [12,16], however little is known about peptidergic neuronal pathways which could be additional targets for these medications. There is also no findings describing the potential relationships between POMC, kisspeptin, Kiss1R and MCHR1 expressions and SSRI administration in animal models. ...
Article
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Neuropeptides are important, multifunctional regulatory factors of the nervous system, being considered as a novel, atypical sites of antidepressants action. It has already been proven that some of them, such as selective serotonin reuptake inhibitors (SSRI), are able to affect peptidergic pathways in various brain regions. Despite these reports, there is so far no reports regarding the effect of treatment with SSRIs on brain proopiomelanocortin (POMC), kisspeptin, Kiss1R and MCHR1 gene expression. In the current study we examined POMC, kisspeptin, Kiss1R and MCHR1 mRNA expression in the selected brain structures (hypothalamus, hippocampus, amygdala, striatum, cerebellum and brainstem) of rats chronically treated with a 10 mg/kg dose of escitalopram using quantitative Real-Time PCR. Long-term treatment with escitalopram led to the upregulation of MCHR1 expression in the rat amygdala. Kisspeptin mRNA level was also increased in the amygdala, but Kiss1R mRNA expressions were elevated in the hippocampus, hypothalamus and cerebellum. POMC mRNA expressions were in turn decreased in the hippocampus, amygdala, cerebellum and brainstem. These results may support the hypothesis that these neuropeptides may be involved in the site-dependent actions of SSRI antidepressants. This is the first report of the effects of escitalopram on POMC, kisspeptin, Kiss1R and MCHR1 in animal brain. Our findings shed a new light on the pharmacology of SSRIs and may contribute to a better understanding of the alternative, neuropeptide-dependent modes of antidepressant action.
... Finally, experiments controlling the body weight of the rats showed that the treatments did not induced changes in weight compared to the control. Thus, this compound can be proposed as a potential antidepressant agent without affecting locomotor activity and body weight in contrast to other antidepressants [39]. ...
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Background: Magnesium is an essential element related with biochemistry of the brain and different types of depression have been associated with its deficiency. Methods: The structure of a novel magnesium bis(DL-pyroglutamate) (Mg(DL-pGlu)2) was elucidated by X-ray crystallography. Wistar rats were used in the in vivo experiments. The antidepressant-like effect was assessed by the forced swim test (FST) and the antinociceptive activity was evaluated using hot plate test. In both, non-specific effects were evaluated by the open field test. Anti-thyroid activity was examined using Lang's method. Albumin binding behavior was evaluated by 3D fluorescence spectroscopy. Results: For the Mg(DL-pGlu)2 complex (30 mg/kg), the FST test on Wistar rats revealed a decrease of 22% in the immobility time and an increment of 106% in the swimming time. The compound alters neither the locomotor activity nor the body weight after chronic administration. At the same dose, it showed antinociceptive activity, increasing the response latency. It blocks iodination reactions generating a charge transfer complex with iodine hence indicating anti-thyroid activity (Kc = 45366.5 ± 29 M-1). Albumin 3D fluorescence spectroscopy experiments showed intensity increase of peak A and decrease of peak B. Conclusions: The results showed that the new compound produced a lowering of the immobility time and an increment of the swimming ability of the rats. The compound is able to increase the response latency in 70.0%, to capture iodine (anti-thyroid activity) and to interact with albumin through covalent type of interaction of the free NH groups.
... blockade of MAO-B, which will reduce cellular hydrogen peroxide, which is a by-product of dopaminergic breakdown [18], reduced disufide-PKG1α in the VTA and increased sucrose preference in WT mice. This may provide some insight as to why antidepressants including MAO inhibitors can lead to weight gain [45,46]. That deprenyl did not alter food reward in KI mice, shows the effect of altering hydrogen peroxide on food reward was significantly through disulfide-PKG1α. ...
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Genes that are highly conserved in food seeking behaviour, such as protein kinase G (PKG), are of interest because of their potential role in the global obesity epidemic. PKG1α can be activated by binding of cyclic guanosine monophosphate (cGMP) or oxidant-induced interprotein disulfide bond formation between the two subunits of this homodimeric kinase. PKG1α activation by cGMP plays a role in reward and addiction through its actions in the ventral tegmental area (VTA) of the brain. ‘Redox dead’ C42S PKG1α knock-in (KI) mice, which are fully deficient in oxidant-induced disulfide-PKG1α formation, display increased food seeking and reward behaviour compared to wild-type (WT) littermates. Rewarding monoamines such as dopamine, which are released during feeding, are metabolised by monoamine oxidase to generate hydrogen peroxide that was shown to mediate PKG1α oxidation. Indeed, inhibition of monoamine oxidase, which prevents it producing hydrogen peroxide, attenuated PKG1α oxidation and increased sucrose preference in WT, but not KI mice. The deficient reward phenotype of the KI mice was rescued by expressing WT kinase that can form the disulfide state in the VTA using an adeno-associated virus, consistent with PKG1α oxidation providing a break on feeding behaviour. In conclusion, disulfide-PKG1α in VTA neurons acts as a negative regulator of feeding and therefore may provide a novel therapeutic target for obesity.
... Moreover, selective BDNF infusion into the lateral ventricles of the brain decreased food intake and associated excessive weight gain in rat [71]. Conversely, though other studies suggest that BDNF does not play an essential role in the regulation of energy expenditure [72], BDNF-deficient mice show hyperphagia and consequent obesity [73]. Caloric restriction therefore should reduce body weight and hyperglycaemia not only because of the reduced food intake per se, but also the biochemical consequences of the increase in BDNF level. ...
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Recently, most of evidence shows that caloric restriction could induce antidepressant-like effects in animal model of depression. Based on studies of the brain–gut axis, some signal pathways were common between the control of caloric restriction and depression. However, the specific mechanism of the antidepressant-like effects induced by caloric restriction remains unclear. Therefore, in this article, we summarized clinical and experimental studies of caloric restriction on depression. This review may provide a new therapeutic strategy for depression.
... Escitalopram does not bind to serotonin, dopamine (D1 and D2), muscarinic and histamine receptors, which minimize the range of its potential side effects. SSRI-related changes in energy homeostasis and weight gain are often clinically observed [17,18], however little is known about peptidergic neuronal pathways which could be additional targets for these medications. Serotonin neurons located in the midline raphe nuclei send numerous long afferents to almost all brain structures including the hypothalamus, thalamus, hippocampus and neocortex. ...
Article
Background: Spexin (SPX) is a recently discovered neuropeptide that exhibits a large spectrum of central and peripheral regulatory activity, especially when considered as a potent anorexigenic factor. It has already been proven that antidepressants, including selective serotonin reuptake inhibitors (SSRI), can modulate peptidergic signaling in various brain structures. Despite these findings, there is so far no information regarding the influence of treatment with the SSRI antidepressant escitalopram on brain SPX expression. Methods: In this current study we measured SPX mRNA and protein expression in the selected brain structures (hypothalamus, hippocampus and striatum) of rats chronically treated with a 10mg/kg dose of escitalopram using quantitative Real-Time PCR and immunohistochemistry. Results: Strikingly, long-term (4 week) drug treatment led to the downregulation of SPX expression in the rat hypothalamus. This supports the hypothesis that SPX may be involved in the hypothalamic serotonin-dependent actions of SSRI antidepressants and possibly also in the central mechanism of body mass increase. Conversely, SPX expression increased in the hippocampus and striatum. Conclusions: This is the first report of the effects of a neuropsychiatric medication on SPX expression in animal brain. Our findings shed a new light on the pharmacology of antidepressants and may contribute to a better understanding of the alternative mechanisms responsible for antidepressant action.
Article
Background: Newly identified multifunctional peptidergic modulators of stress responses: neuromedin U (NMU) and neuropeptide S (NPS) are involved in the wide spectrum of brain functions. However, there are no reports dealing with potential molecular relationships between the action of diverse anxiolytic or antidepressant drugs and NMU and NPS signaling in the brain. The present work was therefore focused on local expression of the aforementioned stress-related neuropeptides in the rat brain after long-term treatment with escitalopram and clonazepam. Methods: Studies were carried out on adult, male Sprague-Dawley rats that were divided into 3 groups: animals injected with saline (control) and experimental individuals treated with escitalopram (at single dose 5 mg/kg daily), and clonazepam (at single dose 0.5 mg/kg). All individuals were sacrificed under anaesthesia and the whole brain excised. Total mRNA was isolated from homogenized samples of amygdala, hippocampus, hypothalamus, thalamus, cerebellum and brainstem. Real time-PCR method was used for estimation of related NPS, NPS receptor (NPSR), NMU, NMU and receptor 2 (NMUR2) mRNA expression. The whole brains were also sliced for general immunohistochemical assessment of the neuropeptides expression. Results: Chronic administration of clonazepam resulted in an increase of NMU mRNA expression and formation of NMU-expressing fibers in the amygdala, while escitalopram produced a significant decrease in NPSR mRNA level in hypothalamus. Long-term escitalopram administration affects the local expression of examined neuropeptides mRNA in a varied manner depending on the brain structure. Conclusions: Pharmacological effects of escitalopram may be connected with local at least partially NPSR-related alterations in the NPS/NMU/NMUR2 gene expression at the level selected rat brain regions. A novel alternative mode of SSRI action can be therefore cautiously proposed.
Article
Weight gain is a common complaint of patients receiving antidepressant drug treatment. The antidepressant sertraline, a selective serotonin uptake inhibitor, has been reported to promote weight loss. In this study, measurement of urinary concentrations of 3-methoxy-4-hydroxyphenylglycol (MHPG) was used to help classify the response of patients who were depressed and overweight to treatment with sertraline. The authors found a significant difference between the average weight loss of 1.06 lb/week in patients with a low urinary MHPG and the average weight loss of 0.42 lb/week in those with a high urinary MHPG. During this study, the maximum weight loss by a patient was 69 pounds over 36 weeks.
Article
Weight gain is a common complaint of patients receiving antidepressant drug treatment. Fluoxetine, an antidepressant that is a selective serotonin uptake inhibitor, as well as protriptyline, an antidepressant that has effects on the reuptake inhibition of norepinephrine, both have been reported to help effectuate weight loss. In this study, 3-methoxy-4-hydroxy-phenylglycol (MHPG) was used to help classify patients for choosing the most appropriate antidepressant. Patients with a high MHPG were placed on fluoxetine, whereas those with a low MHPG received protriptyline. The authors found that depressed patients receiving these antidepressants could actually lose weight during the course of the treatment process. There was no significant difference between the average weight loss of 1.20 lb/wk on fluoxetine and the average weight loss of 1.75 lb/wk on protriptyline.