Does escitalopram (Lexapro) cause weight gain?

Does escitalopram (Lexapro) cause weight gain?

Comment by InpharmD Researcher

Extensive data from primarily observational studies have determined escitalopram to be associated with weight gain. However, whether such weight increases are clinically significant is unknown. Additionally, some data have even reported weight loss with the initial use of escitalopram and weight regained with long-term use.

Background

A 2020 meta-review systematically searched network meta-analyses and meta-analyses of randomized controlled trials (RCTs), individual RCTs, and cohort studies reporting on 78 a priori selected adverse events in children and adolescents, of 80 psychotropic medications, including escitalopram. Data from a total of 337,686 children and adolescents were pooled for analysis. Based on data from 312 patients, the odds ratio of weight gain associated with escitalopram was determined to be 2.30 (95% confidence interval 1.01 to 5.25). However, this data was extracted from RCTs and was determined to be low quality. [1]

A review of short-term studies (≤ 12 weeks) found mean weight losses ≤ 0.5 kg with escitalopram, fluvoxamine, paroxetine, and venlafaxine, 0.5 to 1 kg with citalopram, duloxetine, fluoxetine, and sertraline, and 1.13 kg with bupropion. Mirtazapine increased weight by 1.74 kg. In long-term (≥ 4 months) studies, weight losses were 1.87 kg for bupropion, 0.31 kg for fluoxetine, and 0.12 kg for sertraline. The mean weight gain was 0.71 kg for duloxetine, 0.65 kg for escitalopram, 2.59 kg for mirtazapine, and 2.73 kg for paroxetine. For long-term studies, only changes in weight loss with bupropion and weight gain with paroxetine were significant. [2]

A 2018 random effect meta-analysis was conducted to evaluate the heterogeneity among antidepressants (SSRIs, SNRIs, TCAs, and others) for causing ≥ 5% weight gain. For escitalopram, the adjusted rate ratio (aRR) of weight gain was 1.23 (95% CI 1.17 to 1.29). When comparing relative frequencies of prescribing with the adjusted rate ratio, the frequency of use for escitalopram was 3.7%, which indicates that escitalopram is not a commonly-prescribed medication associated with weight gain. These findings are similar to other SSRIs except for citalopram which is significantly associated with ≥ 5% weight gain (aRR 1.26; 95% CI 1.23 to 1.28). Fluoxetine, amitriptyline, and citalopram appear to be correlated with weight gain, but there is potential for residual confounding. Furthermore, meta-analyses are typically conducted between separate clinical trials, but the represented data for the analysis is inadequately described. It is likely the meta-analysis is more of an analysis of their current patient population registered in the United Kingdom's general practice database. [3]

Literature Review

A search of the published medical literature revealed 2 studies investigating the researchable question:

Does escitalopram (Lexapro) cause weight gain?

Level of evidence

B - One high-quality study or multiple studies with limitations Read more→

Please see Tables 1-2 for your response.

Changes in body weight during pharmacological treatment of depression
Design	Multi-center, part-randomized, open-label study N= 630
Objective	To compare changes in body weight during treatment with different antidepressants
Study Groups	Escitalopram (n= 384) Nortriptyline (n= 246)
Inclusion Criteria	Adults, International Classification of Diseases 10th Revision (ICD-10)/Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) unipolar major depression of at least moderate severity, white European heritage
Exclusion Criteria	Personal or family history of bipolar disorder or schizophrenia and current substance dependence
Methods	Participants were randomized to receive either escitalopram or nortriptyline unless one of the drugs was contraindicated to the patient, in which case, they would receive the other drug. Escitalopram was started at 10 mg per day and could be increased as high as 30 mg per day while nortriptyline was initiated at 50 mg per day and could be increased up to 200 mg per day. Weight gain and weight loss were measured using the clinician-rated Udvalg for Kliniske Undersøgelser (UKU) Side-effect Rating Scale and the self-rated Antidepressant Side-Effect Check list (ASEC). Both scales record whether any adverse experience is present and whether it is considered likely to be linked to the medication in question.
Duration	Recruitment: July 2004 to December 2007 Follow-up: 26 weeks
Outcome Measures	Body Mass Index (BMI) at weeks 6, 8, 12, and 26.
Baseline Characteristics		Escitalopram (n= 384)	Nortriptyline (n= 246)	Total (N= 630)
	Age, years	Not disclosed	Not disclosed	42.8 ± 11.6
	Female, n	Not disclosed	Not disclosed	395
	Clinician-rated 10-item Montgomery–Asberg Depression Rating Scale (MADRS) Score	Not disclosed	Not disclosed	28.4 ± 6.6
	Randomly Allocated to the Respective Treatment Group, n	192 (50%)	157 (64%)	---
	BMI at Week 0	25.28 ± 4.65	26.15 ± 5.27	---
	Reported as mean ± standard deviation (SD) unless otherwise specified The included subjects did not differ from the remaining 181 participants (those that did not have BMI data) on sex, age, depression severity or BMI at baseline.
Results	Endpoint	Escitalopram (n= 384)	Nortriptyline (n= 246)
	BMI at weeks 6, 8, 12 and 26, n (mean ± SD) 6 8 12 26	286 (25.05 ± 4.76) 334 (25.33 ± 4.57) 302 (25.33 ± 4.60) 134 (24.72 ± 4.01)	179 (26.23 ± 4.68) 211 (26.26 ± 4.83) 168 (26.47 ± 5.02) 61 (26.83 ± 5.02)
	Escitalopram caused a non-significant average increase of 0.14 kg, or 0.05 on the BMI (95% confidence interval [CI] -0.001 to 0.10, p= 0.0541) at 26 weeks based on the best linear unbiased estimate adjusted for baseline differences in BMI. Among escitalopram-treated participants, a small weight gain was limited to those whose weight was in the normal range at baseline (BMI change 0.14, 95% CI 0.07–0.21, p< 0.001)
Adverse Events	Common Adverse Events: Weight gain (subjectively reported by 51.6% patients in nortriptyline group vs. 35.2% in escitalopram group; p < 0.0001), weight loss (subjectively reported by 11% patients in nortriptyline group vs. 13% in escitalopram group)
	Serious Adverse Events: Not disclosed
	Percentage that Discontinued due to Adverse Events: Not disclosed
Study Author Conclusions	Escitalopram was associated with little weight change in both men and women over up to 6 months of treatment. The non-significant result is consistent with escitalopram either being weight-neutral or causing a very small weight increase.
InpharmD Researcher Critique	The authors of this study pointed out that one limitation is the lack of placebo group, making it impossible to assess whether any changes in weight are pharmacologic or disease treatment/progression related. This study also enrolled only patients of white European parentage, restricting the generalizability of the results. Follow-up only lasted six months and many patients are treated for depression for longer time periods, so data regarding long-term weight change are not represented. Also, a large number of patients were missing BMI data, so many of the reported results and conclusions are based on estimates rather than actual real-world values.

References:

Uher R, Mors O, Hauser J, et al. Changes in body weight during pharmacological treatment of depression. Int J Neuropsychopharmacol. 2011;14(3):367-375. doi:10.1017/S1461145710000933

Weight gain and associated factors in patients using new antidepressant drugs
Design	Cross-sectional study N= 362
Objective	To examine weight gain and its association with clinical and sociodemographic characteristics in patients using newer antidepressants
Study Groups	Weight gain (n= 147) Without weight gain (n= 215) Escitalopram (n= 76)
Inclusion Criteria	Age 18 to 65 years, use of antidepressant drugs for 6 to 36 months, ability to definitively follow and describe weight changes from initiation of the antidepressant treatment to the assessment
Exclusion Criteria	Mental retardation; history of schizophrenia or related psychotic disorders or bipolar disorders; concomitant medical illnesses; history of any acute medical disease during the previous month; use of any medical drugs that could lead to weight gain or weight loss; weight loss due to psychiatric disorders before starting antidepressant treatment; use of any other psychotropic drugs at the same time as an antidepressant drug; combined antidepressant usage and any confusing reports by the patients about their weight changes during the treatment
Methods	Information regarding each patient's weight before and after the antidepressant treatment was recorded. Correlations between final weight and the dose and duration of each antidepressant in addition to independent factors associated with weight gain were analyzed.
Duration	N/A
Outcome Measures	Weight before and after treatment, correlation between final weight and dose and duration,
Baseline Characteristics		Weight gain (n= 147)	Without weight gain (n= 215)	p-value
	Age, years	38.53 ± 10.29	41.82 ± 12.71	0.009
	Female	127 (86.4%)	158 (73.5%)	0.004
	Weight at baseline, kg	64.03 ± 11.97	70.78 ± 12.74	0.000
	Body mass index (BMI), kg/m²	23.76 ± 4.24	26.01 ± 4.46	0.000
	Smoking	31 (21.1%)	51 (23.7%)	0.610
	Family history of diabetes	50 (34.0%)	63 (29.3%)	0.357
	Family history of obesity	47 (32.0%)	42 (19.5%)	0.009
	Duration of antidepressant, months	14.86 ± 10.05	13.36 ± 8.46	0.259
Results	Endpoint	Escitalopram (n= 76)
	Weight at baseline, kg Weight after treatment, kg p-value vs. baseline	68.14 ± 12.49 73.96 ± 12.51 0.000
	Weight gain	49 (64.5%)
	Weight gain ≥ 7%	37 (48.7%)
	Weight gain ≥ 20%	7 (9.2%)
	Dose, mg p-value for correlation with weight	16.86 ± 5.51 0.336
	Duration, months p-value for correlation with weight	12.75 ± 8.55 0.172
Adverse Events	N/A
Study Author Conclusions	The study results suggest that patients who take newer antidepressants might have significant problems related to body weight.
InpharmD Researcher Critique	The present study had several limitations as it is descriptive and cross-sectional, enrolled patients only attending psychiatric outpatient clinics, and did not examine in-depth psychiatric diagnoses and their effects on body weight.

References:

Uguz F, Sahingoz M, Gungor B, Aksoy F, Askin R. Weight gain and associated factors in patients using newer antidepressant drugs. Gen Hosp Psychiatry. 2015;37(1):46-48. doi:10.1016/j.genhosppsych.2014.10.011