Recent studies have suggested that weight gain may be an unwanted side effect of certain antidepressants, with the researchers highlighting the importance of full discussion about medical adherence with patients who are prescribed several common medications.
Through their research, which included 183 118 participants, the study authors found that people taking bupropion (brand name Wellbutrin) were the least likely to experience weight gain, while those taking escitalopram (Lexapro, Cipralex), paroxetine (Paxil, Seroxat), and duloxetine (Cymbalta) were the most likely to gain extra kilos.
The results were published in the Annals of Internal Medicine.
The observational cohort study, led by a team from Harvard Medical School, took place over two years and looked at the use of eight common antidepressants, with the researchers using electronic health record prescription data for information. They specifically focused on new users of antidepressant medications, and those who were prescribed one antidepressant drug.
The average age was 48, and participants with a recent history of cancer, pregnancy, or bariatric surgery were excluded.
Weight measurements at baseline, at six months, at one year, and after two years from starting antidepressant medication, were measured.
The primary outcome was to compare weight change after six months of antidepressant use to sertraline, a very commonly prescribed antidepressant.
Researchers also examined the weight changes at the one- and two-year marks, and estimated the likelihood of participants gaining at least 5% of their baseline weight.
Medical News Today reports that in their analysis, they were able to adjust for co-variates like prescriptions for medications that could also influence weight change, smoking status, and evidence of recent weight change.
Common meds
The most used medications among the participant group were sertraline (Zoloft), citalopram (Celexa), and bupropion. Adherence to antidepressant use was between 28% and 41% at six months, and decreased to 4% to 5% at two years.
Based on their estimation, researchers found that at the six-month point, compared with sertraline, bupropion was associated with less weight gain.
In contrast, escitalopram, duloxetine, paroxetine, venlafaxine (Effexor), and citalopram were associated with more weight gain. Fluoxetine (Prozac) was similar to sertraline when it came to this side effect.
Researchers also estimated that escitalopram, paroxetine,b and duloxetine each had an associated 10%-15% higher risk of gaining 5% of baseline weight or more.
Bupropion had an associated 15% reduced risk of gaining 5% of baseline weight or more.
At the one-year and two-year marks compared with sertraline, bupropion’s estimations for weight gain were still lower. Escitalopram was still associated with weight gain after one year but not after two years.
After two years, duloxetine and venlafaxine were associated with less weight gain than sertraline.
However, these estimates have a limited accuracy because of low medication adherence.
Overall, the results highlight the potential need for weight changes to be part of conversations regarding antidepressant prescriptions.
Erich Conrad, MD, FACLP, a professor of psychiatry at LSU Health New Orleans, and Behavioural Health Service Line director at the University Medical Centre in New Orleans, who was not involved in this research, said the finding supports what has largely been known from previous clinical trials.
“The large number of subjects in the study is impressive… this is a good reminder to take the possibility of weight gain into account when considering prescribing this group of medications, and to potentially utilise medications that are less likely to cause this side effect if it is clinically indicated and the best choice for the patient.”
How accurate are the study findings?
The research, nevertheless, faces certain limitations. First, the researchers lacked certain data that could have affected the results. For example, they did not have data on medication dispensing.
Participants also had low medication adherence. The authors also noted they had incomplete data on adherence and weight measures across time points, and acknowledged that they could have misclassified some participants as being non-adherent because of missing data.
There is also some risk for residual, baseline, and time-varying confounding.
Low medication adherence reduced the precision of later time point data because fewer participants were included. The research did not look at dose-response effects either.
In addition, the study was observational, meaning that it cannot prove cause, like that certain antidepressants cause weight gain or loss.
Again, while researchers sought to focus on first-time users of antidepressants, it is possible that some participants were not first-time users.
Almost 80% of participants were white, and 65% were female, which could influence the generalisability of the results.
In addition, about 15%–30% of participants had weight measurements exactly at the six-month, one-year, and two-year marks, and only 40% to 50% had weight measurements at one time point or more.
Finally, some participants were prescribed additional antidepressants over the follow-up time, which could have affected the results.
Study details
Medication-Induced Weight Change Across Common Antidepressant Treatments: A Target Trial Emulation Study
Joshua Petimar, Jessica Young, Jason Block et al.
Published in the Annals of Internal Medicine on 2 July 2024
Abstract
Background
Antidepressants are among the most commonly prescribed medications, but evidence on comparative weight change for specific first-line treatments is limited.
Objective
To compare weight change across common first-line antidepressant treatments by emulating a target trial.
Design
Observational cohort study over 24 months.
Setting
Electronic health record (EHR) data from 2010 to 2019 across eight US health systems.
Measurements
Prescription data determined initiation of treatment with sertraline, citalopram, escitalopram, fluoxetine, paroxetine, bupropion, duloxetine, or venlafaxine. The investigators estimated the population-level effects of initiating each treatment, relative to sertraline, on mean weight change (primary) and the probability of gaining at least 5% of baseline weight (secondary) 6 months after initiation. Inverse probability weighting of repeated outcome marginal structural models was used to account for baseline confounding and informative outcome measurement. In secondary analyses, the effects of initiating and adhering to each treatment protocol were estimated.
Results
Compared with that for sertraline, estimated 6-month weight gain was higher for escitalopram (difference, 0.41 kg [95% CI, 0.31 to 0.52 kg]), paroxetine (difference, 0.37 kg [CI, 0.20 to 0.54 kg]), duloxetine (difference, 0.34 kg [CI, 0.22 to 0.44 kg]), venlafaxine (difference, 0.17 kg [CI, 0.03 to 0.31 kg]), and citalopram (difference, 0.12 kg [CI, 0.02 to 0.23 kg]); similar for fluoxetine (difference, −0.07 kg [CI, −0.19 to 0.04 kg]); and lower for bupropion (difference, −0.22 kg [CI, −0.33 to −0.12 kg]). Escitalopram, paroxetine, and duloxetine were associated with 10% to 15% higher risk for gaining at least 5% of baseline weight, whereas bupropion was associated with 15% reduced risk. When the effects of initiation and adherence were estimated, associations were stronger but had wider CIs. Six-month adherence ranged from 28% (duloxetine) to 41% (bupropion).
Limitation
No data on medication dispensing, low medication adherence, incomplete data on adherence, and incomplete data on weight measures across time points.
Conclusion
Small differences in mean weight change were found between eight first-line antidepressants, with bupropion consistently showing the least weight gain, although adherence to medications over follow-up was low. Clinicians could consider potential weight gain when initiating antidepressant treatment.
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