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General Hospital Psychiatry 37 (2015) 46–48

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General Hospital Psychiatry


journal homepage: http://www.ghpjournal.com

Weight gain and associated factors in patients using newer


antidepressant drugs☆
Faruk Uguz, M.D. a,⁎, Mine Sahingoz, M.D. a, Buket Gungor, M.D. b, Fadime Aksoy, M.D. a, Rustem Askin, M.D. b
a
Department of Psychiatry, University of Necmettin Erbakan, Meram Faculty of Medicine, Konya, Turkey
b
Department of Psychiatry, Sevket Yilmaz Research and Training Hospital, Bursa, Turkey

a r t i c l e i n f o a b s t r a c t

Article history: Objective: The aim of the present study was to examine weight gain and its association with clinical and
Received 11 April 2014 sociodemographic characteristics in patients using newer antidepressants.
Revised 25 October 2014 Methods: The study had a cross-sectional design. A total of 362 consecutive psychiatric patients taking antide-
Accepted 27 October 2014 pressant drugs for 6 to 36 months were included in the study.
Results: The prevalence rate of weight gain was 55.2%; 40.6% of the patients had a weight gain of 7% or more
Keywords:
compared to the baseline. Overall, antidepressant use was significantly related to increased body weight. Specifi-
Antidepressants
Weight gain
cally, citalopram, escitalopram, sertraline, paroxetine, venlafaxine, duloxetine and mirtazapine, but not fluoxetine,
Body mass index were associated with significant weight gain. Multivariate logistic regression analysis indicated that lower educa-
tion status, lower body mass index at the onset of antidepressant use and family history of obesity were indepen-
dent predictors of weight gain ≥7% compared to the baseline.
Conclusions: The study results suggest that patients who take newer antidepressants might have significant
problems related to body weight.
© 2015 Elsevier Inc. All rights reserved.

1. Introduction among the SSRIs, paroxetine and citalopram, were found to be associated
with weight gain during medium- and long-term treatment [3]. Similarly,
Weight gain is an important problem that contributes to patient Dent et al. [4] reported that mirtazapine, paroxetine, amitriptyline,
noncompliance and can lead to medical comorbidity [1]. In the last two citalopram and escitalopram were associated with weight gain. However,
decades, there has been growing interest in the topic of psychotropic most of the available studies do not include data such as the rate of weight
medications and body weight. The relationship between new- gain and factors related to weight gain in patients taking antidepressants.
generation antipsychotics and weight gain has been well documented. Thus, the aim of the present study was to examine weight changes, the
However, compared with antipsychotics, interest in the effects of antide- rate of significant weight gain and factors associated with significant
pressant drugs, which are frequently used in the treatment of depression weight gain in these patients.
or anxiety disorders, on body weight is more limited in the literature.
The study data on the effects of antidepressants are based mostly on
clinical trials examining their efficacy and safety in the treatment of 2. Methods
psychiatric disorders. Previously, some authors have reported that, in
contrast to tricyclic antidepressants, selective serotonin reuptake inhibi- The current study was conducted among patients who were admitted
tors (SSRIs) were thought to induce weight loss rather than weight gain to the outpatient clinics of three hospitals. The sample included 362
[2]. A meta-analysis including clinical trials prior to 2009 suggested that consecutive patients who met the criteria of the present study. The inclu-
amitriptyline and mirtazapine were associated with significant increase sion criteria were (a) age18–65 years, (b) willingness to participate in the
in rate of weight gain in both acute and maintenance periods of the treat- study, (c) use of antidepressant drugs for 6–36 months and (d) ability to
ment. In contrast, none of the SSRIs, venlafaxine and duloxetine were definitively follow and describe weight changes from initiation of the
related to weight gain in the acute phase of treatment. Only two agents antidepressant treatment to the assessment. The exclusion criteria for
the study were (a) mental retardation; (b) history of schizophrenia or
related psychotic disorders or bipolar disorders; (c) concomitant medical
☆ Conflicts of interest and source of funding: The authors have no conflict of interest illnesses such as cardiopulmonary disease, neurological disease, metabolic
with any commercial or other associations in connection with the submitted paper. In disturbances, hematological or other carsinomas, endocrine abnormali-
addition, they have no source of funding. ties and inflammatory bowel diseases; (d) history of any acute medical
⁎ Corresponding author. Tel.: +90 332 223 6306.
E-mail addresses: farukuguz@gmail.com (F. Uguz), drpekalkan@hotmail.com
disease, such as an infectious disease, during the previous month;
(M. Sahingoz), buket.gungor@yahoo.com (B. Gungor), fadime_aksoy84@hotmail.com (e) use of any medical drugs that could lead to weight gain or weight
(F. Aksoy), rustemaskin@gmail.com (R. Askin). loss, such as corticosteroids, oral contraceptives, antihistamines and

http://dx.doi.org/10.1016/j.genhosppsych.2014.10.011
0163-8343/© 2015 Elsevier Inc. All rights reserved.
F. Uguz et al. / General Hospital Psychiatry 37 (2015) 46–48 47

antiepileptic drugs; (f) weight loss due to psychiatric disorders before Table 2
starting the antidepressant treatment; (g) use of any other psychotropic Sociodemographic and clinical features in patients with and without significant (7% or more)
weight gain
drugs at the same time as the antidepressant drug; (h) combined anti-
depressant usage and (i) any confusing reports by the patients about Patients with Patients without P value
their weight changes during the treatment. weight gain weight gain
n=147 n=215
Initially, the objectives and procedures of the study were explained to
all participants, and written informed consent forms were obtained. In ad- Age, mean±S.D., years 38.53±10.29 41.82±12.71 .009a
Education, mean±S.D., years 9.72±2.57 10.48±2.82 .007b
dition, the local Ethics Committee approved the study. A semistructured
Number of children, mean±S.D. 1.94±1.15 1.99±1.22 .698a
interview form developed by the investigators was used to determine Weight at baseline, mean±S.D., kg 64.03±11.97 70.78±12.74 .000a
sociodemographic features and use of antidepressant drugs. After the BMI at baseline, mean±S.D. 23.76±4.24 26.01±4.46 .000a
sociodemographic characteristics were obtained, information regarding Duration of antidepressant, 14.86±10.05 13.36±8.46 .259b
each patient’s weight before and after the antidepressant treatment was mean±S.D., months
Gender, n (%) .004c
recorded. Study data on the weight change, history of medical illnesses,
Female 127 (86.4) 158 (73.5)
use of medical drugs and family history of obesity and diabetes were Employment status, n (%) .908c
based on the patients’ reports. Unemployed 103 (70.1) 149 (69.3)
All statistical analyses were performed using SPSS (Statistical Package Family income level, n (%) .127d
Low (b$10,000/year) 27 (18.4) 34 (15.8)
for the Social Sciences), version 16.0, for Windows. Differences with
Moderate ($10,000–30,000/year) 103 (70.1) 139 (64.7)
regard to continuous variables, 3 or more×2 categorical variables and High (N$30,000/year) 17 (11.6) 42 (19.5)
2×2 categorical variables between the groups were analyzed with Marital status, n (%) .394c
t test, χ 2 test and Fisher’s Exact Test, respectively. The correlations be- Single 19 (12.9) 30 (14.0)
tween final weight and the dose and duration of each antidepressant Married 123 (83.7) 171 (79.5)
Widowed, divorced or separated 5 (3.4) 14 (6.5)
were analyzed with Pearson correlation test. To determine independent
Smoking, n (%) 31 (21.1) 51 (23.7) .610c
factors associated with weight gain, multivariate binary logistic regres- Family history of diabetes, n (%) 50 (34.0) 63 (29.3) .357c
sion analysis was used. All significant levels were two-tailed and set at Family history of obesity, n (%) 47 (32.0) 42 (19.5) .009c
the level of .05. a
t test.
b
Mann–Whitney U test.
c
3. Results Fisher’s Exact Test.
d
χ2 test.

The mean age of the sample (n=362) was 40.49±11.89 years.


Most subjects were women (n= 285, 78.7%), were married (n=294, 7.2% showed a weight gain of 20% or more. Table 1 presents the specific
81.2%), were unemployed (n=252, 69.6%) and had moderate economi- antidepressants and the variables related to body weight. Citalopram,
cal level (n=242, 66.9%). The mean duration of education was 10.17± escitalopram, sertraline, paroxetine, venlafaxine, duloxetine and
2.74 years. The proportion of patients who smoke was 22.7%. Of mirtazapine, but not fluoxetine, were associated with significant weight
the participants, 89 (24.6%) had a family history of obesity, and 113 gain. Patients receiving mirtazapine (76.5%), paroxetine (55.0%),
(31.2%) had a family history of diabetes mellitus. The most commonly venlafaxine (52.1%) and escitalopram (48.7%) gained 7% or more
used antidepressants were sertraline (n= 80, 22.1%) and paroxetine compared with the baseline weight. These proportions were 33.3%,
(n= 80, 22.1%) followed by escitalopram (n= 76, 21.0%), venlafaxine 31.6%, 20.0% and 6.9 % in patients taking duloxetine, citalopram, sertraline
(n= 49, 13.5%), fluoxetine (n= 29, 8.0%), citalopram (n= 19, 5.3%), and fluoxetine, respectively. In addition, patients receiving mirtazapine
mirtazapine (n=17, 4.7%) and duloxetine (n=12, 3.3%). (17.6%), venlafaxine (12.5%), citalopram (10.5%) and paroxetine (10.0%)
The results indicated that body weight increased with antidepressant reported a weight gain of 20% or more.
use in 55.2% of the patients (n=200), weight remained unchanged Statistical analysis indicated no significant differences in marital
in 40.5% (n=147) and a decrease in weight was observed in 4.1% status, employment status, economical level, smoking, family history of
(n=15). Of the 200 patients, 177 (48.8%) described an increase in appe- diabetes, number of children or duration of antidepressant treatment be-
tite, and 143 (39.5%) reported a craving for carbohydrates. The mean tween subjects with and without weight gain following the treatment.
weight gain was 4.97±6.16 kg, and the mean onset time of weight gain The subjects who gained weight were primarily female and younger,
following the administration of antidepressants was 2.28±1.99 months. with a family history of obesity, fewer years of education and lower
Weight gain was observed in 85.0% of the patients, with body weight body weight and body mass index (BMI) at the onset of antidepressant
increasing within the first 3 months following the initiation of antide- therapy (Table 2). We found no significant correlation between final
pressant use. weight and the dose and duration of each antidepressant (Table 3).
The mean body weight before and after the treatment was Multivariate logistic regression analysis indicated that fewer years
68.04±12.86 kg and 72.76±12.71 kg, respectively; the difference was of education [Wald χ 2= 12.23, S.E: 0.049, odds ratio (OR): 0.842,
statistically significant (P=.000). Of 362 patients, 147 (40.6%) showed P=.000], lower BMI at the onset of the antidepressant therapy (Wald
a weight gain of 7% or more compared to the baseline weight, and χ2=4.59, S.E: 0.062, OR: 0.876, P=.032) and a family history of obesity

Table 1
Weight changes following specific antidepressant treatment in the patients

Drug Weight at baseline Weight after treatment P value Patients with weight Weight gain of 7% Weight gain of 20%
gain, n (%) or more, n (%) or more, n (%)

Citalopram, n=19 69.26±13.34 74.78±9.92 .014 10 (52.6) 6 (31.6) 2 (10.5)


Fluoxetine, n=29 71.24±13.98 71.10±12.43 .893 4 (13.8) 2 (6.9) 0 (0)
Escitalopram, n=76 68.14±12.49 73.96±12.51 .000 49 (64.5) 37 (48.7) 7 (9.2)
Paroxetine, n=80 67.12±12.46 73.13±12.88 .000 59 (73.8) 44 (55.0) 8 (10.0)
Sertraline, n=80 69.75±12.87 72.01±12.82 .000 27 (33.8) 16 (20.0) 1 (1.2)
Venlafaxine, n=49 66.62±11.60 74.06±13.45 .000 31 (64.6) 25 (52.1) 6 (12.5)
Mirtazapine, n=17 56.88±11.96 67.29±9.51 .001 15 (88.2) 13 (76.5) 3 (17.6)
Duloxetine, n=12 73.83±13.14 76.75±13.55 .038 5 (41.7) 4 (33.3) 0 (0)
48 F. Uguz et al. / General Hospital Psychiatry 37 (2015) 46–48

Table 3
The mean dose and duration of each antidepressant and their correlations with final weight

Drug The mean dose, mg Correlations The mean duration, month Correlations
The final weight and dose The final weight and duration

r P r P

Citalopram, n=19 25.57±5.01 −0.205 .405 14.89±9.15 −0.031 .902


Fluoxetine, n=29 23.96±8.38 0.229 .232 12.20±873 −0.049 .801
Escitalopram, n=76 16.86±5.51 0.112 .336 12.75±8.55 0.158 .172
Paroxetine, n=80 23.43±7.77 0.116 .306 14.57±8.96 0.176 .119
Sertraline, n=80 81.56±39.12 0.011 .921 13.03±8.56 0.118 .298
Venlafaxine, n=49 126,56±49.30 0.176 .233 17.93±10.76 0.144 .328
Mirtazapine, n=17 29.11±11.21 −0.209 .422 13.47±9.74 0.200 .441
Duloxetine, n=12 57.50±8.66 −0.029 .939 12.08±7.60 −0.498 .105

(Wald χ2=12.33, S.E: 0.278, OR: 2.657, P=.000), but not gender (Wald duration of antidepressant use were risk factors for weight gain [9]. A
χ 2= 0.22, S.E: 0.384, OR: 0.833, P= .634), age (Wald χ 2= 0.59, S.E: longitudinal study carried out in Canada [6] reported that weight gain
0.011, OR: 0.992, P=.442) or body weight at the onset of the antidepres- was related to a lower BMI at baseline, the male gender and age under
sant treatment (Wald χ2=0.21, S.E: 0.023, OR: 0.646, P=.990), were in- 65 years. In our study, lower BMI at baseline, family history of obesity
dependent predictors of weight gain following usage of antidepressants. and lower educational level were independently associated with weight
gain following the use of antidepressants.
4. Discussion The present study has several limitations. First, the study was
conducted among patients attending psychiatric outpatient clinics;
This descriptive cross-sectional study suggests that sertraline, therefore, it might not be representative of all patients receiving antide-
paroxetine, citalopram, escitalopram, mirtazapine, venlafaxine and pressants. Second, the study design was cross-sectional and descriptive.
duloxetine are associated with significant weight gain. In contrast, it Third, we did not examine psychiatric diagnoses and their effects on
appears that fluoxetine does not have any effect on body weight. There body weight. For example, depression itself may be associated with
are some differences between the results of the current study and weight gain in adults [6]. In addition, we did not measure severity of
those of some previously published studies. Serretti et al. [3] reported depression both at baseline when patients started antidepressants and
that paroxetine and mirtazapine, but not the other newer antidepres- over time in this study. These factors are major limitations for the
sants, were associated with a greater risk of weight gain. They also present study. Finally, that our data on weight before and after antide-
reported that the mean weight difference during long-term treatment pressant medication, history of medical illnesses, and family history of
was 2.73 kg for paroxetine and 2.59 kg for mirtazapine. According to a obesity and diabetes mellitus were based on the patients’ report is
systematic review [4], venlafaxine, fluoxetine and sertraline have another major limitation.
minimal effects on weight gain. An analysis of 10 clinical studies by In conclusion, the results of this study suggest that most newer anti-
Wise et al. [5] indicated that long-term use of duloxetine (mean weight depressants are associated with increased body weight. In particular,
gain: 0.9 kg) and paroxetine (mean weight gain: 1.0 kg) was significantly patients with the risk factors described above should be followed with
associated with weight gain. The mean weight increase was higher in our respect to body weight changes. However, this topic needs further
sample than in these previous studies. However, the results of several control studies with a larger sample size.
other studies are relatively consistent with ours. Patten et al. [6] reported
that the mean body weight increased from 72.9 to 76.9 kg after 12 years. References
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