Received: 11 June 2019 Revised: 30 July 2019 Accepted: 31 July 2019

DOI: 10.1111/obr.12934

REVIEW

Effects of antidepressant and antipsychotic use on weight gain:

A systematic review

Lucia Alonso‐Pedrero1,2 | Maira Bes‐Rastrollo2,3,4 | Amelia Marti1,2,3

1
Department of Nutrition, Food Science and
Physiology, University of Navarra, Pamplona, Summary
Spain Weight gain is an adverse effect of antidepressants and antipsychotics. This side
2
IdiSNA, Navarra Institute for Health
effect can lead to numerous comorbidities and reduces life expectancy. The use of
Research, Pamplona, Spain
3
Centro de Investigación Biomédica en Red
these drugs is increasing worldwide, and the weight gain produced by them repre-
Área de Fisiopatología de la Obesidad y la sents a common clinical challenge. The goal of this systematic review was to evaluate
Nutrición (CIBERobn), Instituto de Salud Carlos
III, Madrid, Spain
the potential association of antidepressant and antipsychotic therapy with body
4
Department of Preventive Medicine and weight gain in cohort studies. A search of cohort studies investigating the association
Public Health, University of Navarra, between weight gain and the use of antidepressants and antipsychotics in individuals
Pamplona, Spain
was conducted through the PubMed database from 1 January 2008 to 31 January
Correspondence 2019 following the PRISMA statement. We found 27 independent eligible cohort
Amelia Marti, Department of Nutrition, Food
Science and Physiology, University of Navarra, studies that included children (2‐18 years old) and adult (18‐103 years old) subjects.
Irunlarrea 1, 31008 Pamplona, Navarra, Spain. Most of the included studies showed a 5% weight gain in individuals using antide-
Email: amarti@unav.es
pressant therapy. However, Quetiapine, Haloperidol, Trifluoperazine, Risperidone,
Funding information Aripiprazole, Olanzapine, and Clozapine increased body weight ≥7% from baseline,
Asociación de Amigos de la Universidad de
Navarra which is considered a clinically significant result. Weight loss was found in individuals
treated with Bupropion. Further cohort studies with higher sample sizes and longer
durations of treatment are needed to confirm our observations.

K E Y W OR D S

antidepressant, antipsychotic, drug, weight gain, mental disorders

1 | B A CKG R O U N D disorders, schizophrenia and other psychosis, dementia, and develop-

During the last decade, the prevalence of mental disorders has
increased, comprising of 22.8% the global disease burden1 and causing
significant effects on people's health with negative socio‐economic
consequences.2 There are 350 million people affected by mental dis-
orders around the world3. The disorders include depression, bipolar
ABBREVIATIONS: ASD, autism spectrum disorder; WHO, World Health Organization; FDA,
Food and Drug Administration; TCAs, tricyclic antidepressants; SSRIs, selective serotonin
reuptake inhibitors; SGAs, second‐generation antipsychotics; FGAs, first‐generation
antipsychotics; PRISMA, Preferred Reporting Item for Systematic Review and Meta‐
analysis; BMI, body mass index; AHRQ, Agency for Healthcare Research and Quality;
SNRIs, serotonin‐noradrenaline reuptake inhibitors; hSERT, serotonin reuptake transporter
antidepressants with a high level of binding affinity; HDL, high density lipoprotein; BMI‐
SDS, body mass index standard deviation score; MAOIs, monoamine oxidase inhibitors; ce,
chlorpromazine equivalents; WHR, waist‐to‐hip ratio.
mental disorders (autism spectrum disorder [ASD]). The World Health
Organization (WHO) indicates that mental disorders affect people
from any age, social condition, or country.4
Depression is the most common mental disorder. This disease may
produce mental distress and also influences simple daily tasks affect-
ing family and work relationships.2 Moreover, depression is considered
as the main cause of disability, contributing to a high morbidity and
mortality.2 In the worst‐case scenario, depression can lead to suicide,
which nowadays is considered the second leading cause of death
among people 15 to 29 years old.4 When talking about this disease,
the WHO gives special attention to the three most affected popula-
tion groups nowadays, which are young people from 15 to 24, women
in childbearing age (especially after child birth), and people over 60
years old. The WHO estimates that the number of people affected

Obesity Reviews. 2019;1–11. wileyonlinelibrary.com/journal/obr © 2019 World Obesity Federation 1

2 ALONSO‐PEDRERO
by depression has increased2 by 18.4% between 2005 and 2015.
Depression in 2015 globally affected 322 million people worldwide,
which represents 4.4% of the global population. Specifically, 2.9%
and 5.8% of the population is affected by depression in the Pacific
region and the American region, respectively2. In Europe, the country
with the highest prevalence is Norway (7.4%), followed by the
Netherlands2 (6.4%). Spain had a lower prevalence, with 5.1% of the
2
population affected by depression in 2015.
Weight gain is widely known as an adverse effect associated with
the use of antidepressants and antipsychotics that occurs in individ-
uals affected by depression, bipolar disorders, schizophrenia, demen-
5
tia, and ASD. Metabolic conditions often worsen in individuals using
antidepressants or antipsychotics.6 As a consequence of higher inci-
dence of mental disorders, the US Food and Drug Administration
(FDA) advises about the side effects of these types of medications.
Obesity, diabetes mellitus, and metabolic syndrome are indepen-
dent cardiovascular risk factors that take the lives of 17.7 million peo-
ple every year, which corresponds to 31% of all global deaths.7 The
fact that psychotropic drugs contribute to weight gain, obesity, diabe-
tes mellitus, dyslipidemia, and metabolic syndrome leads to medication
nonadherence, contributing to backsliding and hospitalization.3 Mental
disorders associated with overweight or obesity are more frequent in
women than in men.8,9
Antidepressants are increasingly being prescribed in individuals
affected by depression. Statistics show that antidepressants were pre-
scribed in 23% of 1.5 million subjects in the primary care population at
least once10 between 1995 and 2011. Amitriptyline, Mirtazapine, and
Nortriptyline, which are tricyclic antidepressants (TCAs), were associ-
ated with weight gain in short‐term treatments (4‐12 wk), increasing
weight over +1.52, +1.74, and +2 kg, respectively.11 Interestingly, Par-
oxetine (+2.73 kg), Citalopram (+1.69 kg), and selective serotonin
reuptake inhibitors (SSRIs) were also associated with weight gain in
medium‐ and long‐term treatments (from 3 mo to 18 y of follow‐up).11
Antipsychotics, which are also known as neuroleptics or tranquil-
izers, are the main medication used to treat psychotic (schizophrenia)
and bipolar disorders, but they are also used to treat dementia and
ASD. Antipsychotics are commonly related to weight gain. An increase
in weight has been reported in 40% to 80% of the individuals treated
with second‐generation antipsychotics (SGAs) and first‐generation
11
antipsychotics (FGAs). SGAs and FGAs differ from one another in
their pharmacodynamic characteristics. FGAs are also known as typical
antipsychotics, dopamine antagonists, neuroleptics, and classic anti-
psychotics. They reduce dopaminergic neurotransmission in the four
dopamine pathways by blocking D2 receptors.12 SGAs have a high
affinity for 5‐HT2A receptor because they are dopamine‐serotonin
antagonists; thus, they are able to reduce psychotic symptoms.13 Spe-
cifically, a clinical balance between FGAs and SGAs should be reached
because FGA treatment has toxic side effects compared with SGAs.
Numerous studies have associated antidepressant and antipsy-
chotic treatments with weight gain;11,14-17 however, there are few psy-
chotropic drugs—Bupropion—linked to weight loss.14 Therefore, the
present study was designed to evaluate the association between anti-
depressant and antipsychotic therapy and weight gain in cohort studies.
ET AL.
2 | METHODS
A systematic review methodology was performed based on the
Preferred Reporting Item for Systematic Review and Meta‐analysis
(PRISMA) statement recommendation.18 The primary search strategy
was carried out through the PubMed database using the terms
“drug(s),” “antidepressant(s),” and “antipsychotic(s)” hedge with the
following combination of keywords filtering for title: “weight gain,”
“BMI,” “body weight,” and “overweight” all of them followed by the
term “cohort study” in all fields. Thus, only cohort studies were
included. Seven additional published reports were obtained by
cross‐matching references of the selected articles. The selected lan-
guages of the articles were English and Spanish. Only human studies
were included.
From 71 articles that were initially screened though the PubMed
database, 33 articles were reviewed in greater detail, six were excluded,
and 27 cohort studies were chosen (Figure 1). We included studies that
examine antidepressants and antipsychotics associated with weight in
cohort studies for human subjects in the last 10 years (from 2008 to Jan-
uary 2019). Studies were included according to the following eligibility
criteria: cohort (prospective and retrospective) studies; pediatric (from
2 to 18 y) or adults (≥18 y) participants. We excluded articles related
to mechanisms associated with antipsychotic‐induced weight gain,
genes associated with antipsychotic‐induced weight gain, and those
that showed any strategy to lose weight in individuals treated with anti-
psychotics. Any articles describing drugs different from antipsychotics
or antidepressants, articles not associating weight gain and drugs, let-
ters to the editor reviewing other studies, articles assessing heritability
estimates of antipsychotic‐induced weight gain, and cross‐sectional
studies and reviews were also excluded.
Two investigators independently selected the studies, reviewed
the main reports, extracted the relevant information for the included
cohort studies (Table S1) and assessed the association between
weight gain and drugs. As the identified studies involved different
populations, drugs, and dosages, no quantitative meta‐analyses were
done.
Table 1 shows a summary of the main antidepressants and antipsy-
chotics mentioned in this review and specifies the weight change and
the dosage of each drug at different follow‐up in different studies.
Table S2 shows a summary of a positive or a negative association of
antidepressant or antipsychotics with weight gain.
2.1 | Quality of evidence assessment
In an attempt to grade the evidence of the studies included in this
review, Newcastle‐Ottawa Quality Assessment for Cohort studies
(Table 2) was used.21 Thresholds were followed in order to convert
the Newcastle‐Ottawa scale to Agency for Healthcare Research and
Quality (AHRQ) standards (good, fair, and poor) (Table S 1). In general,
a good study meets the criteria of selection, comparability, and out-
come for its study design, a fair study does not meet all the criteria
for its study design, and a poor study contains a fatal flow.
ALONSO‐PEDRERO ET AL.
FIGURE 1 Flowchart of the study selection
3 | RESULTS
Twenty‐seven articles were selected according to the inclusion criteria
for this systematic review (Figure 1). In those research articles, the link
between weight gain and the use of antidepressants and antipsy-
chotics in children and adults from cohort studies was investigated.
All but one of the selected articles were written in English; the remain-
ing one was written in Spanish. The sample sizes of the studies ranged
from 20 to 314 449 subjects (mean sample size = 17 005). The esti-
mated mean duration of treatment was 3.45 years. Table S1 summa-
rizes the main characteristics of the 27 included articles. In these
cohort studies, half individuals were women and half were men. Ages
ranged from 2 to 18 years old in paediatric populations and from 18 to
103 years in adult populations.
Only cohort studies were included in this review because these
types of studies allow the direct establishment of the incidence
(weight gain in this case) and enable causality, as well as the tempo-
rary relationship between the exposure and the outcome, the quan-
tification of the risk, and the study of more than one outcome
derived from the exposure. Fourteen prospective and thirteen retro-
spective studies were included, all of them conducted in both sexes.
Retrospective studies normally have several limitations having less
precise design and measurements.22 However, they allow us to
study certain aspects of clinical drugs, which generally are not
approached in prospective studies and can provide new perspectives
of the study.22 Prospective designs minimize errors in exposure
measurement.
The main drugs that are mentioned in this review are as follows:
‐ Antidepressants as Mirtazapine, serotonin‐noradrenaline reuptake
inhibitors (SNRIs) (Duloxetine, Venlafaxina), SSRIs (Citalopram,
Escitalopram, Fluoxetine, Paroxetine, Sertraline, Trazodone), TCAs
(Amitriptyline, Nortriptyline, Dosulepin), and Bupropion.
‐ Antipsychotics as FGAs (Haloperidol, Chlorpromazine, Perphena-
zine, Sulpiride, Chlorpromazine, Perphenazine, Trifluoperazine,
3
Periazine, Pimozide, Tioproperazin, Tioridazine and Zuclopentixol),
SGAs (Olanzapine, Clozapine, Risperidone, Aripiprazole, Quetiapine,
Ziprasidone, Paliperidone, Amisulpride), Valproate, and Lithium.
3.1 | Antidepressants
We found six out of seven articles related to antidepressant treatment
with good quality assessed by Newcastle‐Ottawa Quality Assessment
for Cohort studies. All of them were carried out both in women and in
men. In two studies,10,23 the number of women was more than double
the number of men, because a greater proportion of women are
affected by depression. Regarding the duration of the studies, we
identified studies of less than 5 years,23-26 and others with more than
10 years of follow‐up.10,27,28
Antidepressant therapy was reported to be associated with weight
gain (Table 1). Among the antidepressants studied, Mirtazapine, Flu-
oxetine, Citalopram, Escitalopram, Sertraline, Paroxetine, Trazodone,
Venlafaxine, and Duloxetine had a positive association with weight
gain. However, some studies evaluating TCAs23,24,27,28 did not show
association, but several studies with Bupropion23,25 showed weight
loss.23,25
Among the studies with a follow‐up higher than 10 years, Gafoor
et al reported that the risk of increasing weight by in more than 5%
was 21% higher in subjects treated with antidepressants vs subjects
that were not treated ) after 10 years of follow‐up (Table 1).10 during
the second (46% higher risk of ≥5% weight gain) and the third years
(48% higher risk of more than ≥5% weight gain) of treatment.10 Pat-
ten et al indicated a weight gain of +5.0 kg in individuals aged 18 to
65 taking any antidepressant medications, compared with individuals
affected by depression who were not taking the medication (+3.7 kg)
during 13 years of follow‐up.28 Another study found that SSRIs users
(mean age: 68.9 y) were associated with a weight gain of +1.2 kg and
with approximately +0.5 kg/m2 higher body mass index (BMI) com-
pared with non‐users in an 18‐year follow‐up study.27
4 ALONSO‐PEDRERO ET AL.

TABLE 1 Effect on weight gain of the studied antidepressant and antipsychotic drugs

Drug Reference Follow‐up n Dose Mean Weight Change P Value

Adult population
Any antidepressant used Patten et al28 12 y 14 117 Not reported +5.0 kg (95% CI, 4.3‐5.8) .01
24
SSRIs Shi et al 4.4 y 2334 Not reported +0.61 kg/y (SD 1.89) <.001
26 b
Kivimäki et al 4.8 y 9197 200‐400 daily doses +2.8 kg Not reported
Noordam et al27 18 y 7269 1.03 daily dosesa +4.2 kgb (in ≥90 d of treatment) .005
TCAs Shi et al24 4.4 y 2334 Not reported −0.01 kg/y (SD 1.32) .908
Kivimäki et a26 4.8 y 9197 200‐400 daily doses +2.7 kgb Not reported
Noordam et al 27
18 y 7269 0.52 daily doses a
+2.9 kg (in ≥90 d of treatment) .68
b

10
Escitalopram, Citalopram, Gafoor et al 10 y 314 449 Not reported >5% <.001
Fluoxetine, Sertraline,
Paroxetine, Dosulepin,
Amitriptyline,
Nortriptyline,
Duloxetine,
Venlafaxine,
Mirtazapine, and
Trazadone
Citalopram Arterburn et al25 2y 5932 Not reported +0.54 kgb .4
25 b
Paroxetine Arterburn et a 2y 5932 Not reported +0.36 kg .78
25 b
Sertraline Arterburn et al 2y 5932 Not reported +2.7 kg .02
Trazadone Arterburn et al25 2y 5932 Not reported +0.36 kgb .75
Duloxetine Arterburn et al 25
2y 5932 Not reported −0.45 kg b
.88
Mirtazapine Arterburn et al25 2y 5932 Not reported +5.3 kgb .12
Venlafaxine Arterburn et al 25
2y 5932 Not reported −0.9 kg b
.67
Bupropion Arterburn et al 25
2y 5932 Not reported Non‐smokers: −3.22 kg b
Non‐smokers: <.01
Smokers: +0.99 kgb Smokers: .33
Chlorpromazine, Yoon19 1y 111 275 mg/d of ce +6.6 kg (SD 8.5) <.001
Perphenazine,
Trifluoperazine, and
Sulpride
Olanzapine, Aripiprazole, Arterburn et al37 8y 4962 Not reported <7% Not reported
Risperidone, and
Quetiapine
Aripiprazole Nguyen et al13 4y 1915 Not reported +2.97% (SE 0.28) over 180 d <.001
42 b
Amisulpiride, Quetiapine, Tschoner et al 6 wk 28 Dose according to +0.47 kg n.s.
Risperidone, and standard dosage
Ziprasidone procedures
Risperidone Saddichha et al41 6 wk 99 4.4 ± 1.2 mg/d >7% <.001
Iqbal et al39 1y 124 2 mg/d −1.2 kgb Not reported
20 b
Tadger and Melamed 1y 100 Not reported +2.7 kg <.01
19
Yoon 1y 111 1‐5 mg/d +9.7 kg (SD 9.3) <.001
Olanzapine Iqbal et al39 1y 124 10 mg/d +18.1 kgb <.001
20 b
Tadger and Melamed 1y 100 Not reported +2.7 kg <.05
19
Yoon 1y 111 5‐30 mg/d +9.7 kg (SD 9.3) <.001
Saddichha et al41 6 wk 99 16.5 ± 4.6 mg/d >7% <.001
42 b
Tschoner et al 6 wk 28 Dose according to +2.59 kg <.01
standard dosage
procedures
Quetiapine Iqbal et al39 1y 124 200 mg/d +17.2 kgb <.001

(Continues)
ALONSO‐PEDRERO ET AL. 5

TABLE 1 (Continued)

Drug Reference Follow‐up n Dose Mean Weight Change P Value

Haloperidol Saddichha et al41 6 wk 99 13.4 ± 3.6 mg/d >7% <.001
Iqbal et al39 1y 124 10 mg/d +7.9 kgb <.001
Yoon19 1y 111 275 mg/d of ce +6.6 kg (SD 8.5) <.001
Trifluoperazine Iqbal et al39 1y 124 2 mg/d +13.7 kgb <.001
Neurodegenerative disease
Risperidone Zheng et al40 9 mo 85 1‐8‐1.1 mg/d +0.05 kg/wk (SE 0.06) .07
31 b
Mathys et al 1y 56 Not reported +0.8 kg Not reported
Olanzapine Zheng et al40 9 mo 99 5.5‐5.6 mg/d 0.05 kg/wk (SE 0.06) .032
Mathys et al31 1y 56 Not reported −1.7 kgb Not reported
40
Quetiapine Zheng et al 9 mo 94 56.5‐61.1 mg/d +0.05 kg/wk (SE 0.06) .019
Mathys et al31 1y 56 Not reported −2.1 kgb Not reported
Paediatric population
Risperidone Hrdlicka et al22 6 wk 109 2.7 mg/d +3.6 kg (SD 2.6) Not reported
Ronsley et al43 1y 130 Not reported +10.8 kgb <.001
33 b
Baeza et al 1y 117 2.55 mg/d +12.4 kg <.001
Cuerda et al35 1y 54 78.040 ce +10.9 kgb <.001
22
Olanzapine Hrdlicka et al 6 wk 109 15 mg/d +4.4 kg (SD 2.5) Not reported
33 b
Baeza et al 1y 117 9.42 mg/d +6.7 kg <.001
Cuerda et al35 1y 54 46.053 ce +10.9 kgb <.001
22
Clozapine Hrdlicka et al 6 wk 109 247.5 mg/d +2.1 kg (SD 4.0) Not reported
43 b
Quetiapine Ronsley et al 1y 130 Not reported +9.7 kg <.001
Baeza et al33 1y 117 389.1 mg/d +18.7 kgb <.001
35 b
Cuerda et al 1y 54 89.140 ce +10.9 kg <.001

Abbreviations: ce, chlorpromazine equivalents; CI, confidence interval; n.s., nonsignificant; SSRIs, selective serotonin reuptake inhibitors; TCAs, tricyclic
antidepressants.
a
Mean dose.
b
Standard deviation (SD) or standard error (SE) not reported.

Concerning SSRIs users, Blumenthal et al found that subjects
(mean age: 54.1 y) gained +0.48 kg per year vs non‐users and those
with a sedentary lifestyle gained +1.01 kg vs non‐users after a 4.4‐
year follow‐up study.23 This weight gain may be due to a higher
total energy intake in SSRIs users (9160 kJ/d) vs non‐users (8628
kJ/d).24 Interestingly, a greater weight gain was shown in those indi-
viduals with unhealthy habits, such as smoking, sedentary activity, or
Western dietary pattern24. Age was also an important factor in this
study because individuals under 50 years old were more likely to
gain weight after antidepressant treatment than individuals over 65
years.24 Similarly, Arterburn et al reported a weight gain of +2.67
kg in subjects (age: 18‐65 y) utilizing SSRIs compared with Fluoxe-
tine users (which was the reference treatment) after a 2‐year
follow‐up study.25

TABLE 2 Criteria for grading the internal validity of individual studies

Study Design According to

Newcastle‐Ottawa Quality
Assessment Form Criteria

Cohort studies Representativeness of the exposed cohort

Selection of the nonexposed cohort
Ascertainment of exposure
Demonstration that outcome of interest was not present at start of the study
Comparability of cohorts on the basis of the design or analysis controlled for confounders
Assessment of outcome
Follow up long enough for outcomes to occur
Adequacy of follow‐up cohorts
6 ALONSO‐PEDRERO
Regarding SRNIs, one10 out of three articles10,23,25 associated
them with weight gain. Duloxetine was not associated with weight
gain compared with Citalopram (which was the reference treatment)
23
in subjects aged from 18 to 64 years after a 1 year of follow‐up.
Arterburn et al found no association between SRNIs and weight gain
because they did not have enough individuals treated with Duloxetine,
Venlafaxine, and Mirtazapine to estimate 2 years of weight gain
25
changes. However, Gafoor et al reported that subjects (mean age:
51.5 y) using Venlafaxine and Duloxetine had a high risk of having a
5% weight gain (15% and 23%, respectively) after 10 years of
follow‐up.10
10,26 10,23,24,26-28
In regard to TCA treatment, two articles out of six
showed an association with weight gain (Table S2). Kivimäki et al
reported that individuals (15 to 64 y) treated with tricyclic drugs had
a 4.7% weight gain compared with non‐user subjects (2.4%) in a 5‐
year follow‐up study.26 In addition, Gafoor et al found that subjects
(mean age: 51.5 y) treated with tricyclic drug have a higher risk of
increasing 5% their weight vs non‐users (16%) after 10 years of
follow‐up.10 However, Nortriptyline Hydrochloride and Amitriptyline
users (aged from 18 to 65 y) showed lower weight gain than
Citalopram (SSRIs) (which was the reference drug) after a 1‐year
follow‐up study.23 Moreover, Shi et al24 and Noordam et al27 reported
no weight gain in subjects treated with TCAs for 4.4 and 18 years,
respectively. Taking these results into consideration, it suggests that
there is no association between TCAs and weight gain.
Two studies with Bupropion showed weight loss in subjects aged
from 18 to 65 years.23,25 Blumenthal et al found weight loss in sub-
23
jects treated with Bupropion who were followed for a year. A 2‐year
follow‐up study indicated that there was a weight loss of –7.1 lb (–
3.22 kg) in subjects taking Bupropion compared with Fluoxetine in
non‐smokers, while smokers that used Bupropion gained +2.2 lb
(+0.99 kg) compared with Fluoxetine (which was the reference
treatment).25
3.2 | Antipsychotics
We found 20 articles related to antipsychotics and adiposity. Double
the number of men than women participated in seven studies,29-35
and three studies were mainly conducted in women.13,36,37 We evalu-
ated 13 studies with less than 1‐year duration,20,22,30-33,35,38-43 and
seven with more than 1‐year follow‐up.13,19,29,34,36,37,44 We also report
two studies in individuals with degenerative diseases31,40 and seven in
19,22,33,35,36,43,44
paediatric population. Thirteen out of 20 studies had
good quality, four studies had fair quality, and three studies had poor
quality as assessed by Newcastle‐Ottawa Quality Scale (see Table S1).
FGA treatment was found to generate less weight gain than SGAs,
although some studies did not indicate differences between
them.20,30,28 Aripiprazole monotherapy, Risperidone, Olanzapine,
Clozapine, and Quetiapine were reported to have a positive
association with weight gain, both in children and in adults (see
TableS2).13,19,20,22,29-39,41-45 Lithium, Valproate, Trifluoperazine, Halo-
peridol, Chlorpromazine, Perphenazine, Sulpiride, Perfenazine,
ET AL.
Pimozide, Pipotiazine, Tiapride, Tioproperazine, Tioridazine,
and Zuclopentixol were associated with weight gain in adults (see
Table S1).30,35-37,43,40
3.2.1 | Adult population
Among studies with a follow‐up higher than 1 year, we found seven
articles. According to Arterburn et al, between 7% and 17% of an adult
sample (mean age: 48.5 y) showed a ≥7% weight gain while using
SGAs.37 Forty per cent of this weight gain occurred in adults with nor-
mal weight in the first year of follow‐up. The weight gain was +10 kg
after 8 years of SGA treatment.37 In this study, Olanzapine and Cloza-
pine showed the highest rate of ≥7% weight gain (17.0% cases).37 In
the same way, Risperidone was associated with a high risk of ≥7%
weight gain (11.4% users),37 and Clozapine seemed to be related to
a high risk of weight regain.37 However, Ziprasidone did not show sta-
tistically significant increases in weight gain in adults (7.7% of cases).37
Interestingly, Gebhardt et al reported some predictive parameters
for body weight gain under antipsychotic treatment including:
increased parental BMI, individuals' BMI at the premorbid stage (prior
to onset of the psychiatric disorder) and prior to FGA treatment,
female sex, younger age, and non‐smoking status.44 A higher acceler-
ation of BMI change was associated with a lower BMI prior to FGA
treatment in some individuals (mean age: 30.9 y) after a 5‐year
follow‐up study.44 The percentage of subjects with
overweight/obesity in this study increased from 10.8/6.3% to 36.9/
32.3% during the 5 years of follow‐up.44
Nguyen et al showed significant weight gain (3.4%) after 180 days
with Aripiprazole monotherapy.13 Nevertheless, no differences were
found in weight gain between individuals (mean age: 49 y) treated
with Aripiprazole monotherapy in combination with drugs with high
serotonergic activity (3.67%) and individuals treated with Aripiprazole
monotherapy in combination with drugs with low serotonergic activity
(Aripiprazole and Bupropion combination) (2.79%).13 Aripiprazole was
associated with a high risk of ≥7% weight gain both in adults (mean
age: 48.5 y) after 8 years of follow‐up (14.2%)37 and in children (mean
age: 7 y) after 4 years of follow‐up.34
We found 13 studies with less than 1 year of follow‐up. An
increased risk in weight gain was seen in SGA users (mean age: 54.2
y) compared with FGAs after a 1‐year follow‐up study (see Table 1,
n = 2130).30 However, there was a similar weight gain between FGA
and SGA users in a 1‐year follow‐up study, in which adults affected
by schizophrenia gained +6.6 ± 8.5 and + 9.7 ± 9.3 kg, respectively.19
An increase in body weight was shown in adults affected by schizo-
phrenia treated with Risperidone and Chlorpromazine after 1 year of
follow‐up (+69.6 ± 15.7 and + 71.7 ± 32.9 kg, respectively, n =
111).19 Additionally, they reported that Olanzapine showed a higher
weight gain (+14.3 ± 10.1 kg) compared with other antipsychotics
examined (see Table 1).19
Vandenberghe et al in a 1‐year follow‐up study reported age‐
dependent changes in BMI (decreasing with an increasing age).38 They
found that a 5% weight gain in subjects (mean age: 46 y) after 1 month
of treatment with SGAs was the best predictor for weight gain higher
ALONSO‐PEDRERO ET AL.
than 15% or 20% after 3 or 12 months of treatment, respectively.38 In
the same study, the prevalence of metabolic syndrome and obesity
was increased after 1 year of treatment (from 22% and 17% [baseline
38
measures] to 32% and 24%, respectively).
Olanzapine and Clozapine showed higher odds ratios for changes in
BMI and persistence among new users of antipsychotics (mean age:
54.2 y), as well as for Risperidone and Quetiapine after 1 year of
30
follow‐up.
Tadger and Melamed also found significant weight gain in indi-
viduals (mean age: 47.4 y) with persistent mental disorders treated
with Olanzapine (in inpatient rehabilitation and in day care units)
20
for 1 year of follow‐up. Moreover, BMI in individuals treated with
Olanzapine and Risperidone (SGAs) was higher than in those treated
with FGAs.20 In addition, individuals treated with Risperidone did
not show significant weight gain.20 They had a high rate of weight
constancy (avoiding further weight increase even where no weight
reduction has been attempted, 59%) and a low rate of an increased
in BMI (23%).20 Other studies with Risperidone did not show any
statistically significant increase in weight gain after either 1 or 8
37,39
years of treatment.
Saddichha et al performed a study in individuals (mean age: 26.6 y)
with first‐episode schizophrenia, evaluating Olanzapine, Risperidone,
Clozapine, and Haloperidol to identify any predictor related to weight
gain during a 6‐week treatment.41 Among all of them, Clozapine was
more likely to show weight gain in women with lower baseline
weights, young people, individuals treated with higher doses of Cloza-
pine, and subjects receiving this treatment for the first time.41 This
study also reported positive correlations between three parameters
(weight, waist circumference, and BMI) and the use of these antipsy-
41
chotics. When comparing users of Olanzapine, Haloperidol, and
Risperidone, the medication that showed the highest weight gain
(≥7% weight gain) was Olanzapine (77%), followed by Risperidone
(63%) and Haloperidol (22%).41 Another study showed a higher BMI
(+0.92 ± 0.97 kg/m2) in a group of 28 individuals (mean age: 34.2 y)
taking Olanzapine, Clozapine, Risperidone, Amisulpride, Quetiapine,
42
and Ziprasidone after 28 days.
Odds ratios associating changes in BMI were studied in Risperidone
and Quetiapine users (mean age: 54.2 y) after 1 year of follow‐up.30
According to Iqbal et al, weight gain showed an increased tendency
after a 1 year of follow‐up in Pakistani individuals treated with
several SGAs (aged about 34 y).39 The maximum weight gain in this
study was observed in individuals taking Olanzapine (29% of the sub-
jects), followed by Trifluoperazine (28%), Quetiapine (24%), and
39
Haloperidol (13%).
3.2.2 | Neurodegenerative diseases
As seen in Table 1, Mathys et al found that 8.92% of the individuals
aged from 70 to 85 years with dementia treated with SGAs gained
more than 7% of the baseline weight after 1 year.31 Total weight gain
was higher in the treatment group (+0.45 kg/mo) than in the placebo
31
group (−0.41 kg/mo). However, in the study, the overall weight
decreased by +1.3 kg, and 7.25% of the subjects worsened their lipid
7
profiles (50% of those ones were taking Risperidone, Quetiapine, and
Olanzapine).31
Four hundred twenty‐one individuals (mean age: 77 y) affected by
Alzheimer disease who were treated with SGAs (Olanzapine,
Quetiapine, and Risperidone) normally used to treat schizophrenia
showed metabolic abnormalities (weight gain, unfavourable change
in high density lipoprotein [HDL] cholesterol, and waist circumfer-
ence), mainly in female individuals after 9 months of treatment.40 A
decreased HDL cholesterol and an increased waist circumference
were associated with Olanzapine, whereas weight gain was associated
with Quetiapine and Risperidone treatment.40 The weight gain
reached by these individuals after 12 weeks of treatment was 1.4 lb
(+0.63 kg), 1.7 lb (+0.76 kg), and 1.2 lb (+0.54 kg) after Olanzapine,
Quetiapine, and Risperidone therapy, with a mean gain of +0.10 to
+0.14 lb (+0.045 to +0.063 kg) per week.40 The percentage of subjects
with weight gain was 10% in subjects treated for 12 weeks, 20% in
individuals treated from 12 to 24 weeks, and 17% in individuals with
treatment of longer than 24 weeks compared with individuals not
using SGAs.40
3.2.3 | Paediatric populations
Among the 20 studies associating weight gain and antipsychotics,
seven were carried out in children populations.22,33-36,43,44 Sixty‐one
adolescents (mean age: 16.3 y) treated with SGAs for 1 year had
increases in weight gain and waist circumference (+10.8 ± 6.2 kg and
+11.1 ± 5.0 cm, respectively).35 There was an increase in fat mass per-
centage while fat free mass decreased.35 Another study in 117 chil-
dren and adolescents from 2 to 20 years old (64.1 % male) treated
with SGAs (Risperidone, Quetiapine, and Olanzapine) showed an
increase in body weight, BMI, and BMI–standard deviation score
(BMI‐SDS) after 1 year of follow‐up (+5.8 ± 4.3 kg at 3 mo, +8.1 ±
6.1 kg at 6 mo, and +11.6 ± 7.0 kg at 1 y).33 Notably, children taking
Quetiapine gained a mean of +9.5 kg more than Risperidone users,
and +7.7 kg more than subjects treated with Olanzapine. Ronsley
et al indicated that children aged from 2 to 18 years taking
Risperidone and Quetiapine gained +10.8 and +9.7 kg, respectively,
after 1 year.43
An average of +3.6, +4.4, and +2.1 kg of weight gain was observed
in children (mean age: 15.8 y) taking Risperidone, Olanzapine, and Clo-
zapine, respectively, after 6 weeks of treatment.22 The same study
showed no weight gain differences in subjects treated with SGAs
(+3.4 kg) and FGAs (+2 kg).22
Panagiotopoulos et al in a paediatric population (mean age: 13.8
y) reported that the rate of overweight and obesity in the SGA‐
treated group during 2.5 years of treatment was more than double
compared with the SGA‐naive group (a person that may have
never received a particular drug), especially in subjects treated with
Olanzapine.36
Yoon et al reported that Quetiapine and Ziprasidone were not
associated with weight gain or an increased BMI‐SDS in children with
ASD during 4 years of treatment.34 However, Olanzapine was
8 ALONSO‐PEDRERO
associated with a higher rate of weight gain and a statistically signifi-
cant increase in BMI‐SDS when compared with other SGAs in the
same population after 4 years.34
4 | DISCUSSION
Analysis of the data from 27 cohort studies in 459 143 individuals
treated with several antidepressants and antipsychotics revealed
important findings. Of all the individuals receiving antidepressants and
antipsychotics in these studies, a high number of them increased their
body weight while taking these drugs. In our review, we found a direct
association between some antidepressants (Fluoxetine, Estitalopram,
Citalopram, Sertraline, Paroxetine, MirtazapineTrazodone, Venlafaxine,
and serotonin reuptake transporter antidepressants with a high level of
binding affinity [hSERT]) and antipsychotics (Aripiprazole, Risperidone,
Olanzapine, Clozapine, Paloperdione, Amisulpride, Quetiapine,
Ziprasidone, Lithium, Valproate, Trifluoperazine, Haloperidol,
Chlorpromazine, Perphernazine, Sulpiride, Perfenazine, Pimozide,
Pipotiazine, Tiapride, Tioproperazine, Tioridazine, and Zuclopentixol)
with body weight gain, excluding Bupropion. TCAs were doubtfully
associated with weight gain, because some articles revealed associa-
tion,10,26 but others did not.23,24,27 Only one study associated
10
Duloxetine (SNRIs) with weight gain, but the other studies did
not.23,25 Ziprasidone was not associated with increased body weight
in children,34 but only in adults.28,30,35,40 Risperidone was not associ-
ated with weight gain in two studies in adult subjects. 20,39 Quetiapine
was not associated with weight gain in two studies, one in adults 31
34
and another in children.
Several mechanisms may explain the weight gain caused by antide-
pressants and psychotropic drugs.11 The hypothalamic‐pituitary‐
adrenal axis may be activated by depressive disorders, leading to vis-
ceral fat deposition, inflammatory cytokine secretion and a cascade
of biological changes, which contributes to elevated blood pressure,
dyslipidemia, and impaired carbohydrate metabolism.46
Metabolic markers, such as adipokines, incretins, and neuropep-
tides, have been explored during SGAs treatment without a clear
answer about their pathophysiology. In adults, leptin and ghrelin seem
to increase after a SGAs treatment, whereas adiponectin decreased.
However, in studies with children, it was found that ghrelin and
adiponectin do not change and leptin levels increases.3 The bio-
markers of β‐cell hyperstimulation (C‐peptide and GIP) rise after an
antipsychotic treatment leading to insulin resistance and, therefore,
to diabetes. Some biomarkers of pro‐inflammatory status (Visfatin)
decreased.3 Several metabolic effects were associated with genetic
variants in pharmacodynamic receptor pathways or in energy homeo-
stasis regulating genes.6
There were several limitations for this review that should be con-
sidered, such as differences in the characteristics of subjects based
on age, sex, lifestyle factors, disease status, and initial body weight
and in the design of the studies concerning sample size, dose, and
duration of the treatment, among others. The age was a limitation
because at the age of 65 or older, individuals tend, on average, to lose
ET AL.
weight20,28 due to a reduction in mass muscle and demineralization.
Besides, weight gain found in adults (but not elderly adults) taking
SGAs was higher than the observed values in children.22 The risk of
being affected by mental disorders is higher in women. In this review,
the proportion of females with mental disorders was about 50%.
Moreover, as several studies suggest, women on average tend to gain
more weight than men.28,29,44 In addition, unhealthy habits, such as
smoking, sedentary lifestyle, alcohol, or unhealthy dietary habits may
also influence weight gain in individuals with these drugs prescribed.24
It should be taken into account that in some studies, the statistical
analysis was performed after adjustment for potential confounders
such as dietary intake or lifestyle factors, but others not, and they
are crucial for obesity development. For example, in a study, higher
energy intake was shown in antidepressant users vs non‐users.24
Meanwhile, diseases such as dementia are related to weight loss;
therefore, this may be a limitation in studies including elderly subjects
with dementia31. It should be emphasized that weight gain could be a
favourable side effect in underweight subjects with dementia. A lower
baseline BMI (below 18.5 kg/m2) is associated with a higher weight
gain after antipsychotic treatments.20,29,44 However, Gebhardt et al
found an increased speed, but not the final extent, in weight gain in
individuals with a lower baseline BMI before FGAs/SGAs or short pre-
treatment SGA individuals with a reduced baseline BMI.44 It seems
that this acceleration in BMI change to the short time period of the
study while during long‐term studies, the BMI change can be
explained by predisposition factors.44 Thus, a lower baseline BMI prior
to FGAs or SGAs may act as a predictor for an accelerated weight gain
in subjects by increasing food intake.44 Concerning to antidepressants,
a study found that individuals with normal weight at baseline might
become people with overweight or with obesity after treatment and
those who were overweight at the beginning of the study were more
likely to become people with obesity.10
We cannot exclude the possibility that psychiatric disorders rather
than the treatment were the reasons for changes in body weight. Indi-
viduals with schizophrenia may have lost weight during psychotic epi-
sodes prior to the initiation of drug treatment. Similarly, subjects with
depression can both lose or gain weight as a result of the disorder
itself. Therefore, weight gain could in theory reflect a return to the
normal weight of an individual who lost weight during a psychiatric
episode. Several studies were unable to examine lifestyle factors (diet,
physical activity, alcohol, drug abuse, and smoking status) that may
affect weight changes.37
The small sample size population (less than 100 subjects) included
in some articles does not allow a solid estimation of weight gain
induced by the studied drugs. Moreover, the different dosages used
in these studies should be taken with caution. The doses administered,
for example, of Olanzapine (from 10 to 15 mg/d) and Risperidone
(from 2 to 4 mg/d), in the study of Saddichha et al, were in the
established ranges. The dosage of Haloperidol was in the upper range
(mean dosage: 13.4 ± 3.6 mg) than the one that is commonly used
(from 1 to 15 mg/d).41 However, several studies did not show the dos-
age administered for each drug; therefore, this could be a limitation
because a high dose of any of these drugs mentioned in this review
ALONSO‐PEDRERO ET AL.
may lead to a greater weight gain. Another limitation of this review
was the duration of the treatment, because weight gain occurring in
subjects taking antidepressants or antipsychotics is gradual over
22
time. Moreover, during the second and the third years of treatment
in cohort studies, the risk of weight gain seemed to be substantially
higher compared with the complete follow‐up period.10 And it is
known that in long‐term studies, some participants are inevitably lost
to follow‐up.
The FDA considers a significant result to be body weight gain ≥7%
of baseline body weight. Therefore, according to these data,20 only a
few drugs (Quetiapine, Haloperidol, Risperidone, Olanzapine, and Clo-
zapine) are able to produce this significant increase in body weight.
However, most of the drugs increased body weight by 5% in treated
individuals. This therapy with antidepressants and antipsychotics is
appropriate for underweight individuals.26 As a higher energy intake
was found in antidepressant users compared to non‐users, this may
partially explain the increase in body weight.24 However, TCA users
did not show the same association with weight gain as SSRIs or SNRIs
users did.24 As the antidepressant associated with weight loss was
Bupropion (although this effect was limited to non‐smokers), it should
be the first‐line drug for individuals affected by overweight and obe-
sity, unless there is any contraindication.25 It is not known how this
drug reduces body weight, but it appears that it plays an important
role in the regulation of appetite, satiety, craving, and feeding
behaviour. 25
Aripiprazole was associated with weight gain. It acts at the 5‐HT2
as a partial agonist,13 and it is possible to act as an antagonist at the 5‐
HT2c causing weight gain when used in combination with other anti-
depressants with high serotonergic activity.13 However, when
Aripiprazole is used in combination with antidepressants with low
serotonergic activity, it may act as an agonist of the 5‐HT2c, causing
satiety and, therefore, diminishing weight gain.13 The results shown
by Nguyen et al with low serotonergic activity users are not signifi-
cant; this could be partiallyexplained by a high proportion of females
and individuals with obesity within the high serotonergic group.13
To summarize, we found an increased weight (≥5% of baseline
body weight) after therapy with antipsychotics and antidepressants.
Moreover, SGAs are more likely to produce weight gain in paediatric
population or young adults, but not in elderly subjects37,38. These data
show the importance of the prevention of obesity development, with
a correct indication of the treatment and the later supervision of indi-
viduals taking antidepressants and antipsychotics.30
5 | C O N CL U S I O N S
In conclusion, this systematic review found an association between
weight gain and antidepressants and antipsychotics therapy in individ-
uals affected by several mental disorders. Quetiapine, Haloperidol,
Trifluoperazine, Risperidone, Olanzapine, and Clozapine, which are
SGAs, increased the weight ≥7% from baseline in subjects under 65,
which is considered clinical relevant by the FDA. Moreover, antide-
pressants are shown to increase the risk of gaining weight over 5%.
9
Interestingly, Bupropion was found not to be associated with
weight gain.
Given that weight gain is an important health problem, there is a
high interest in the scientific community to find new drugs that do
not cause or even reduce weight gain. Further research, in large sam-
ple size studies over longer periods of time and a better characteriza-
tion of individuals (ie, lifestyle factors), is needed to verify this
association.
ACKNOWLEDGEMENT
L.A.‐P. acknowledges their fellowships from the Asociación de Amigos
de la Universidad de Navarra (ADA). This research work was supported
by grants from the CIBERobn (CB12/03/30002).
CONFLIC T OF INT E RE ST
No conflict of interest was declared.
ORCID
Lucia Alonso‐Pedrero https://orcid.org/0000-0003-2062-2758
Maira Bes‐Rastrollo https://orcid.org/0000-0002-9139-4206
Amelia Marti https://orcid.org/0000-0001-9832-7981
RE FE RE NC ES
1. Abajobir AA, Abate KH, Abbafati C, et al. Global, regional, and national
disability‐adjusted life‐years (DALYs) for 333 diseases and injuries and
healthy life expectancy (HALE) for 195 countries and territories, 1990–
2016: a systematic analysis for the Global Burden of Disease Study
2016. Lancet. 2017;390(10100):1260‐1344. https://doi.org/10.1016/
S0140‐6736(17)32130‐X
2. Consejo General de Colegios Oficiales de Farmacéuticos. Depresión.
Punto Farm. no 15. 2017;7:1‐49. https://doi.org/10.7458/SPP201577
3311
3. Pisano S, Coppola G, Catone G, et al. Differences in metabolic factors
between antipsychotic‐induced weight gain and non‐pharmacological
obesity in youths. Clin Drug Investig. 2018;38(5):457‐462. https://doi.
org/10.1007/s40261‐018‐0627‐3
4. WHO. World Health Day‐7 April 2017. World Health Day. Depression:
let's talk. 1‐year on.
5. Salvi V, Mencacci C, Barone‐Adesi F. H1‐histamine receptor affinity pre-
dicts weight gain with antidepressants. Eur Neuropsychopharmacol.
2016;26(10):1673‐1677. https://doi.org/10.1016/j.euroneuro.2016.
08.012
6. Delacrétaz A, Lagares Santos P, Saigi Morgui N, et al. Influence of poly-
genic risk scores on lipid levels and dyslipidemia in a psychiatric
population receiving weight gain‐inducing psychotropic drugs.
Pharmacogenet Genomics. 2017;27(12):464‐472. https://doi.org/
10.1097/FPC.0000000000000313
7. WHO|Cardiovascular diseases (CVDs). WHO (World Health
Organization).
8. Martin‐Rodriguez E, Guillen‐Grima F, Aubá E, Martí A, Brugos‐Larumbe
A. Relationship between body mass index and depression in women: a
7‐year prospective cohort study. The APNA study. Eur Psychiatry.
2016;32:55‐60. https://doi.org/10.1016/j.eurpsy.2015.11.003
9. Martin‐Rodriguez E, Guillen‐Grima F, Martí A, Brugos‐Larumbe A.
Comorbidity associated with obesity in a large population: the APNA
10
study. Obes Res Clin Pract. 2015;9(5):435‐447. https://doi.org/10.1016/
j.orcp.2015.04.003
10. Gafoor R, Booth HP, Gulliford MC. Antidepressant utilisation and inci-
dence of weight gain during 10 years' follow‐up: population based
cohort study. BMJ. 2018;361:1‐9. https://doi.org/10.1136/bmj.k1951
11. Abosi O, Lopes S, Schmitz S, Fiedorowicz JG. Cardiometabolic effects
of psychotropic medications. Horm Mol Biol Clin Investig. 2018;1‐15.
12. Sadock BJ, Sadock VA, Ruiz P. Kaplan and Sadock's Comprehensive Text-
book of Psychiatry. 9th ed. Philadelphia: (Wilkins LW&, ed.), Wolters
Kluwer; 2009.
13. Nguyen C, Novac A, Hazen J, Howard P, Tieu R, Bota RG. Weight gain
changes in patients with aripiprazole monotherapy compared with
aripiprazole–antidepressant polypharmacy in an outpatient sample. J
Psychopharmacol. 2017;32(4):423‐429. https://doi.org/10.1177/0269
881117742659
14. Nihalani N, Schwartz TL, Siddiqui UA, Megna JL. Weight gain, obesity,
and psychotropic prescribing. J Obes. 2010;2011:1‐9. https://doi.org/
10.1155/2011/893629
15. Uguz F, Sahingoz M, Gungor B, Aksoy F, Askin R. Weight gain and asso-
ciated factors in patients using newer antidepressant drugs. Gen Hosp
Psychiatry. 2015;37(1):46‐48. https://doi.org/10.1016/j.genhosppsych
.2014.10.011
16. Ballon JS, Pajvani UB, Mayer LE, et al. Pathophysiology of drug induced
weight and metabolic effects: findings from an RCT in healthy volun-
teers treated with olanzapine, iloperidone, or placebo. J
Psychopharmacol. 2018;32(5):533‐540. https://doi.org/10.1177/0269
881118754708
17. Choong E, Bondolfi G, Etter M, et al. Psychotropic drug‐induced weight
gain and other metabolic complications in a Swiss psychiatric popula-
tion. J Psychiatr Res. 2012;46(4):540‐548. https://doi.org/10.1016/j.
jpsychires.2012.01.014
18. Shamseer L, Moher D, Clarke M, et al. Preferred reporting items for
systematic review and meta‐analysis protocols (PRISMA‐P) 2015: Elab-
oration and explanation. BMJ. 2015;349(jan02 1):1‐25. https://doi.
org/10.1136/bmj.g7647
19. Yoon CK. Weight Gain and First‐Generation Antipsychotics. Experience
from a Developing Country. Vol 28.; 2008.
20. Tadger S, Melamed Y. Weight gain due to long term antipsychotic
treatment of persistent mental disorders. Psychiatr Danubia. 2008;
20:37‐41.
21. Wells G, Shea B, O'Connell D, et al. Newcastle‐Ottawa Quality Assess-
ment Form for Cohort Studies. Ottawa Hosp Res Inst. 2014;113:17‐18.
https://doi.org/10.2307/632432
22. Hrdlicka M, Zedkova I, Blatny M, Urbanek T. Weight gain associated
with atypical and typical antipsychotics during treatment of adolescent
schizophrenic psychoses: a retrospective study. Neuroendocrinol Lett.
2009;30:256‐261. doi: NEL300209A02 [pii]
23. Blumenthal SR, Castro VM, Clements CC, et al. An electronic health
records study of long‐term weight gain following antidepressant use.
JAMA Psychiatry. 2014;71(8):889‐896. https://doi.org/10.1001/
jamapsychiatry.2014.414
24. Shi Z, Atlantis E, Taylor AW, et al. SSRI antidepressant use potentiates
weight gain in the context of unhealthy lifestyles: results from a 4‐year
Australian follow‐up study. BMJ Open. 2017;7(8):e016224. https://doi.
org/10.1136/bmjopen‐2017‐016224
25. Arterburn D, Sofer T, Boudreau DM, et al. Long‐term weight change
after initiating second‐generation antidepressants. J Clin Med. 2016;5
(4). https://doi.org/10.3390/jcm5040048
ALONSO‐PEDRERO ET AL.
26. Kivimäki M, Hamer M, Batty D, et al. Antidepressant medication use,
weight gain, and risk of type 2 diabetes. Diabetes Care. 2010;33
(12):2611‐2616. https://doi.org/10.2337/dc10‐1187
27. Noordam R, Aarts N, Tiemeier H, Hofman A, Stricker BH, Visser LE. Sex‐
Specific association between antidepressant use and body weight in a
population‐based study in older adults. J Clin Psychiatry. 2015;76(06):
e745‐e751. https://doi.org/10.4088/JCP.13m08896
28. Patten SB, Williams JVA, Lavorato DH, Khaled S, Bulloch AGM.
Weight gain in relation to major depression and antidepressant medi-
cation use. J Affect Disord. 2011;134(1‐3):288‐293. https://doi.org/
10.1016/j.jad.2011.06.027
29. Sušilová L, Češková E, Hampel D, Sušil A, Šimůnek J. Changes in BMI in
hospitalized patients during treatment with antipsychotics, depending
on gender and other factors. Int J Psychiatry Clin Pract.
2017;21(2):112‐117. https://doi.org/10.1080/13651501.2017.129
1818
30. Monnelly EP, Fonda J, Gagnon DR, Chittamooru S, Lawler EV. Weight
gain on antipsychotic medication is associated with sustained use
among veterans with schizophrenia. J Clin Psychopharmacol.
2015;35(1):57‐62. https://doi.org/10.1097/JCP.0000000000000262
31. Mathys M, Blaszczyk A, Busti A. Incidence of abnormal metabolic
parameters and weight gain induced by atypical antipsychotics in
elderly patients with dementia. Consult Pharm. 2009;24(3):201‐209.
https://doi.org/10.4140/TCP.n.2009.201
32. Sicras‐Mainar A, Rejas Gutiérrez J, Navarro Artieda R, Blanca Tamayo
M. Impacto de la obesidad en la utilización de fármacos antipsicóticos
en población adulta atendida en varios centros de atención primaria.
Actas Españolas Psiquiatr. 2008;36:90‐93.
33. Baeza I, Vigo L, de la Serna E, et al. The effects of antipsychotics on
weight gain, weight‐related hormones and homocysteine in children
and adolescents: a 1‐year follow‐up study. Eur Child Adolesc Psychiatry.
2017;26(1):35‐46. https://doi.org/10.1007/s00787‐016‐0866‐x
34. Yoon Y, Wink LK, Pedapati EV, Horn PS, Erickson CA. Weight gain
effects of second‐generation antipsychotic treatment in autism spec-
trum disorder. J Child Adolesc Psychopharmacol. 2016;26(9):822‐827.
https://doi.org/10.1089/cap.2016.0049
35. Cuerda C, Merchan‐Naranjo J, Velasco C, et al. Influence of resting
energy expenditure on weight gain in adolescents taking second‐
generation antipsychotics. Clin Nutr. 2011;30(5):616‐623. https://doi.
org/10.1016/j.clnu.2011.03.007
36. Panagiotopoulos C, Ronsley R, Davidson J. Increased prevalence of
obesity and glucose antipsychotic medications. Can J Psychiatry/La
Rev Can Psychiatr. 2009;54(11):743‐749.
37. Arterburn D, Wood GC, Theis MK, et al. Antipsychotic medications
and extreme weight gain in two health systems. Obes Res Clin Pract.
2016;10(4):408‐423. https://doi.org/10.1016/j.orcp.2015.08.012
38. Vandenberghe F, Gholam‐Rezaee M, Saigí‐Morgui N, et al. Importance
of early weight changes to predict long‐term weight gain during psy-
chotropic drug treatment. J Clin Psychiatry. 2015;76(11):
e1417‐e1423. https://doi.org/10.4088/JCP.14m09358
39. Iqbal SP, Khan RAM, Ahmer S. Antipsychotic treatment and weight
gain: does risperidone behave differently in Pakistani psychiatric
patients? J Ayub Med Coll Abbottabad. 2011;23:66‐69.
40. Zheng L, Mack WJ, Dagerman KS, et al. Metabolic changes associated
with second‐generation antipsychotic use in Alzheimer's disease
patients: the CATIE‐AD Study. NIH Public Access.
2009;166(5):583‐590. https://doi.org/10.1176/appi.ajp.2008.0808
1218
41. Saddichha S, Ameen S, Akhtar S. Predictors of antipsychotic‐induced
weight gain in first‐episode psychosis: conclusions from a randomized,
double‐blind, controlled prospective study of olanzapine, risperidone,
ALONSO‐PEDRERO ET AL. 11

and haloperidol. J Clin Psychopharmacol. 2008;28(1):27‐31. https://doi. 46. Silverstein‐Metzler MG, Shively CA, Clarkson TB, et al. Sertraline
org/10.1097/jcp.0b013e3181602fe6 inhibits increases in body fat and carbohydrate dysregulation in adult
42. Tschoner A, Engl J, Rettenbacher M, et al. Effects of six second genera- female cynomolgu monkeys. HH Public Access. 2017;68:29‐38.
tion antipsychotics on body weight and metabolism risk assessment and https://doi.org/10.5588/ijtld.16.0716.Isoniazid
results from a prospective study. Pharmacopsychiatry. 2009;42(01):
29‐34. https://doi.org/10.1055/s‐0028‐1100425 SUPPORTING INFORMATION
43. Ronsley R, Nguyen D, Davidson J, Panagiotopoulos C. Increased risk of
Additional supporting information may be found online in the
obesity and metabolic dysregulation following 12 months of second‐
generation antipsychotic treatment in children: a prospective cohort Supporting Information section at the end of the article.
study. Can J Psychiatry. 2015;60(10):441‐450. https://doi.org/10.1177
/070674371506001005
44. Gebhardt S, Haberhausen M, Heinzel‐Gutenbrunner M, et al. Antipsy-
How to cite this article: Alonso‐Pedrero L, Bes‐Rastrollo M,
chotic‐induced body weight gain: predictors and a systematic
categorization of the long‐term weight course. J Psychiatr Res. Marti A. Effects of antidepressant and antipsychotic use
2009;43(6):620‐626. https://doi.org/10.1016/j.jpsychires.2008.11 on weight gain: A systematic review. Obesity Reviews.
.001 2019;1–11. https://doi.org/10.1111/obr.12934
45. Zheng W, Zhang Q, Cai D, et al. Combination of metformin and life-
style intervention for antipychotic‐related weight gain: a meta‐
analysis of randomized controlled trials. Pharmacopsychiatry. 2017.