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In a new study, researchers have looked at which antidepressants were associated with the most weight gain. Image credit: Michela Ravasio/Stocksy.
  • Antidepressants are a common group of medications that help treat several mental health conditions.
  • Doctors need to consider potential side effects when prescribing specific antidepressants.
  • A recent study highlighted the weight changes associated with several antidepressants.
  • Buproprion was associated with the least amount of weight gain, while antidepressants like escitalopram and paroxetine were associated with the most weight gain.

Every medication carries potential risks and sometimes unpleasant side effects. Doctors must consider possible side effects and how these effects may impact outcomes like medication adherence.

Antidepressants are a group of medications commonly used to treat chronic mental health conditions, particularly major depression. Reports have suggested that certain antidepressants can sometimes have weight gain as a side effect.

A study recently published in the Annals of Internal Medicine examined weight changes related to several common antidepressants.

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 participants taking escitalopram (Lexapro, Cipralex), paroxetine (Paxil, Seroxat), and duloxetine (Cymbalta) were the most likely to experience weight gain.

The results highlight the importance of discussing antidepressant side effects and medication adherence with individuals taking these medications.

This study was an observational cohort study that took place over 2 years. Researchers included 183,118 participants in their analysis and looked at the use of eight different common antidepressants.

They used electronic health record prescription data to help collect information. They specifically focused on people who were new users of antidepressant medications and only included participants who were prescribed one antidepressant medication.

The average age of participants was 48. Researchers included participants between the ages of 20 and 80 who did not have a previous history of antidepressant use. They excluded participants who had a recent history of cancer, pregnancy, or bariatric surgery.

Researchers looked at weight measurements at baseline, at 6 months, at 1 year, and after 2 years from starting antidepressant medication.

The primary outcome was to compare weight change after 6 months of antidepressant use to sertraline, a very commonly prescribed antidepressant. Researchers also examined the weight changes at the 1- and 2-year marks, and estimated the likelihood of participants gaining at least 5% of their baseline weight.

In their analysis, they were able to adjust for covariates like prescriptions for medications that could also influence weight change, smoking status, and evidence of recent weight change.

The study found that 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 6 months, and decreased to 4% to 5% at 2 years.

Based on their estimation, researchers found that at the 6-month point, compared to 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, 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 1-year and 2-year marks compared to sertraline, bupropion’s estimations for weight gain were still lower. Escitalopram was still associated with weight gain after 1 year but not after 2 years. After 2 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 J. Conrad, MD, FACLP, a professor of psychiatry at LSU Health New Orleans, and Behavioral Health Service Line director at the University Medical Center in New Orleans, not involved in this research, commented on the study findings to Medical News Today.

He told us that:

“The finding in this study supports what has largely been known from previous clinical trials and with years of experience with prescribing these medications. The large number of subjects in the study, over 183,000, is impressive. I think it is a good reminder to take the possibility of weight gain into account when considering prescribing this group of medications, and to potentially utilize medications that are less likely to cause this side effect if it is clinically indicated and the best choice for the patient.”

This research, nevertheless, faces certain limitations that may have impacted the findings. First, the researchers lacked certain data that could have impacted the results. For example, they did not have data on medication dispensing.

Participants also had low medication adherence. The study authors also noted they had incomplete data on adherence and weight measures across time points.

They acknowledged that they could have misclassified some participants as being nonadherent 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 generalizability of the results.

In addition, about 15–30% of participants had weight measurements exactly at the 6-month, 1-year, and 2-year marks, and only 40% to 50% had weight measurements at one time point or more.

This could have impacted the study results. Finally, some participants were prescribed additional antidepressants over the follow-up time, which could have affected the results.

Aarohee Desai-Gupta, MBBS, MRCPsych, a consultant psychiatrist, clinical director of Atrom Mindcare Holistic Psychiatric Clinic, not involved in this study, expressed the opinion that any “direct clinical implications based on this research alone are minimal.”

“However,” she noted, “if individual patients do experience weight gain with an SSRI [serotonin reuptake inhibitor], thought should be given to altering the treatment to tailor to the individuals specific circumstances and requirements, with the findings of this research in mind.”

Antidepressants are a medication group that doctors may prescribe to assist with treating depression. However, antidepressants can also help treat obsessive-compulsive disorder (OCD), anxiety-related conditions like panic disorder, and post-traumatic stress disorder (PTSD).

Groups of antidepressants include selective serotonin reuptake inhibitors (SSRIs), serotonin/norepinephrine reuptake inhibitors (SNRIs), and tricyclic antidepressants (TCAs).

Alex Dimitriu, MD, 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 further insight into antidepressants to MNT:

“The most common uses of antidepressants are for depression and anxiety, where they can significantly boost mood, energy while reducing negative thoughts, obsessive thoughts, and rumination. It is believed that antidepressants may also work by increasing levels of BDNF — brain-derived neurotrophic factor. BDNF is like miracle grow for neurons, which often means it can help people change old patterns of thinking, and be more open to new ideas, 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 were interested in learn more about weight changes related to certain antidepressants and how these results compare to each other, in the hope that these findings might help individuals receive better personalized care.