- Antidepressants are a common group of medications that help treat many mental health conditions.
- Doctors should consider potential side effects when prescribing specific antidepressants.
- A recent study highlighted weight changes associated with several antidepressants.
- Bupropion was associated with the least weight gain, while antidepressants such as escitalopram and paroxetine were associated with the greatest weight gain.
Every medication has potential risks and sometimes unpleasant side effects. Doctors must consider possible side effects and how these effects may affect outcomes, such as treatment compliance.
Antidepressants are a group of medications commonly used to treat chronic mental disorders, particularly major depression. Reports have suggested that some antidepressants can sometimes cause weight gain as a side effect.
A study recently published in the Annals of internal medicine examined weight changes associated with several common antidepressants.
In 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 participants taking escitalopram (Lexapro, Cipralex), paroxetine (Paxil, Seroxat), and duloxetine (Cymbalta) were the most likely to experience weight gain.
The findings highlight the importance of discussing antidepressant side effects and treatment adherence with people taking these medications.
This study is an observational cohort study that took place over 2 years. The researchers included 183,118 participants in their analysis and looked at the use of eight different common antidepressants.
They used prescription data from electronic medical records to collect information. They focused specifically on people who were new users of antidepressant medications and included only participants who had been prescribed only one antidepressant medication.
The average age of participants was 48 years. The researchers included participants aged 20 to 80 who had no history of antidepressant use. They excluded participants who had a recent history of cancer, pregnancy or bariatric surgery.
The researchers looked at weight measurements at baseline, 6 months, 1 year, and 2 years after starting antidepressant treatment.
The main outcome was to compare weight change after 6 months of antidepressant use with that of sertraline, a very commonly prescribed antidepressant. The researchers also looked at weight change after 1 and 2 years and estimated the likelihood that participants would regain at least 5% of their initial weight.
In their analysis, they were able to adjust for covariates such as medication prescriptions that might also influence weight change, smoking status, and evidence of recent weight change.
The study found that the most commonly used medications among the participant group were sertraline (Zoloft), citalopram (Celexa), and bupropion. Adherence to antidepressant medication ranged from 28% to 41% at 6 months, and declined to 4% to 5% at 2 years.
By their estimates, the researchers found that after 6 months, bupropion was associated with less weight gain than sertraline. In contrast, escitalopram, duloxetine, paroxetine, venlafaxine (Effexor), and citalopram were associated with greater weight gain. Fluoxetine (Prozac) was similar to sertraline with respect to this side effect.
The researchers also estimated that escitalopram, paroxetine, and duloxetine each had a 10 to 15 percent increased risk of gaining 5 percent of baseline weight or more.
Bupropion had a 15% reduced associated risk of gaining 5% of initial weight or more.
At 1 and 2 years, estimates of weight gain with bupropion were still lower than those with sertraline. Escitalopram was still associated with weight gain at 1 year, but not at 2 years. At 2 years, duloxetine and venlafaxine were associated with less weight gain than sertraline.
However, these estimates have limited precision due to low treatment adherence.
Overall, the results highlight the potential need to include weight changes in discussions regarding antidepressant prescribing.
Erich J. Conrad, MD, FACLP, professor of psychiatry at LSU Health New Orleans and director of the behavioral health service line at University Medical Center New Orleans, who was not involved in this research, commented on the study results at Today’s Medical News.
He told us that:
“The results of this study support what is already known from previous clinical trials and years of experience in prescribing these drugs. The large number of subjects in the study, more than 183,000, is impressive. I think it is a good reminder of the need to consider the possibility of weight gain when considering prescribing this group of drugs, and to possibly use drugs less likely to cause this side effect if clinically indicated and the best choice for the patient.”
This research does, however, have some limitations that may impact the results. First, the researchers lacked some data that could have impacted the results. For example, they did not have data on drug distribution.
Participants also had poor adherence to treatment. The study authors also noted that they had incomplete data on adherence and weight measurements over time.
They acknowledged that they may have misclassified some participants as non-adherent due to missing data. There is also a risk of residual confounding, both initial and time-varying.
Low treatment adherence reduced the precision of later data, as fewer participants were included. The study also did not examine dose-response effects.
Additionally, the study was observational, meaning it cannot prove cause, such as whether some antidepressants cause weight gain or loss.
Again, although the researchers sought to focus on new antidepressant users, it is possible that some participants were new to antidepressants. Nearly 80% of participants were white and 65% were women, which could affect the generalizability of the results.
Additionally, approximately 15–30% of participants had accurate weight measurements at 6 months, 1 year, and 2 years, and only 40–50% had weight measurements at any time point or more.
This could have impacted the study results. Finally, some participants were prescribed additional antidepressants during the follow-up period, which could have affected the results.
Aarohee Desai-Gupta, MBBS, MRCPsych, consultant psychiatrist, clinical director of holistic psychiatric clinic Atrom Mindcare, not involved in this study, expressed the opinion that “any direct clinical implications based on this research alone are minimal.”
“However,” she noted, “if some patients experience weight gain while taking an SSRI (selective serotonin reuptake inhibitor), consideration should be given to modifying the treatment to suit each individual’s specific circumstances and needs, keeping in mind the results of this research.”
Groups of antidepressants include selective serotonin reuptake inhibitors (SSRIs), serotonin/norepinephrine reuptake inhibitors (SNRIs), and tricyclic antidepressants (TCAs).
Dr. Alex Dimitriu, double board certified in psychiatry and sleep medicine and founder of Menlo Park Psychiatry & Sleep Medicine, who was not involved in the current study, offered more detailed information on antidepressants. MNT:
“Antidepressants are most commonly used for depression and anxiety, where they can significantly improve mood and energy while reducing negative thoughts, obsessive thoughts, and rumination. It is thought that antidepressants may also work by increasing levels of BDNF (brain-derived neurotrophic factor). BDNF is like a miracle herb for neurons, which often means it can help people change old thought patterns and be more open to new ideas and perspectives, which can be helpful.”
The researchers who conducted the current study noted that weight gain is a common side effect of antidepressants.
Overall, they wanted to learn more about weight changes linked to specific antidepressants and how these results compare to each other, in the hopes that these findings could help individuals receive better personalized care.