Antidepressant Therapy Linked to a 2% Weight Gain

 The use of antidepressants has been linked to a 2% weight gain in patients who used this treatment at any point during a 6-year follow-up, according to a Spanish study. The authors suggest that these findings should encourage weight control and metabolic monitoring in patients with depression who are being treated with medications.

The multicenter study, led by the Hospital del Mar Medical Research Institute in Barcelona, Spain, and published in Frontiers in Psychiatry, highlights the relationship between antidepressant use and weight gain.

The research used data from the REGICOR (REgistre GIroni del COR) study, which tracked participants in Australia and the Netherlands and revealed that 2% of the population on antidepressants gained weight, focusing on a large cohort of participants aged 16 years or older.

Depression affects approximately 280 million people globally and remains the most prevalent mental health disorder, with twice the incidence in women compared with men. Weight gain is a major reason for discontinuing treatment, and obesity is strongly linked to depression. Spain, along with Sweden and Portugal, is one of the leading countries in antidepressant consumption.

Camille Lassale, PhD, from the Hospital del Mar Medical Research Institute and the Barcelona Institute for Global Health, Barcelona, Spain, and one of the study’s authors, told Medscape’s Spanish edition: “Although it was already known that antidepressants could cause weight gain, this relationship had mostly been seen in short- to medium-term studies.” This study is innovative because it “analyzes the trajectories of antidepressant use over 6 years in an adult cohort in Spain.” The study also showed that both prolonged use and the initiation or discontinuation of treatment were associated with significant weight gain, independent of socioeconomic status, depression, or lifestyle.

Different Consumption Trajectories

Lassale highlighted: “This is a pioneering study in Spain regarding the longitudinal follow-up of weight in antidepressant users.” Similar studies in the United Kingdom, Finland, and Canada have shown associations between prolonged antidepressant use and weight gain, but this study is unique in examining various trajectories of consumption over time.

The study included 3127 adults (1701 women) from the REGICOR study, with an average age of 55.6 years, residing in northeastern Spain. Participants provided self-reported data at two points in time — initially and after a median of 6.3 years — on their antidepressant use, body weight, and height. Data on smoking, physical activity, diet quality, education, marital status, and depressive symptoms (evaluated with the Patient Health Questionnaire [PHQ-9]) were also collected during follow-up.

Only Repeated Use Tied to Obesity

The average weight gain after 6 years was 0.53 kg (1.01% of body weight), and 24.5% of participants gained more than 5% of their body weight.

Most participants (83.6%) did not report antidepressant use, 6.2% initiated use during follow-up, 5.1% discontinued use, and the remaining 5.1% used them at both timepoints. In multivariable analyses, compared to patients who never used antidepressants, all trajectories were associated with greater weight gain: 1.78% (0.57-2.98) for discontinued use, 2.08% (0.97-3.19) for new use during follow-up, and 1.98% (95% CI, 0.75-3.20) for repeated use.

Additionally, for participants without obesity at the start of the study (n = 2404), the odds ratio for developing obesity during follow-up was 2.06 (1.03-3.96) for repeated use but not statistically significant for the other three consumption patterns.

Different Consumption Trajectories

Lassale highlighted, “This is a pioneering study in Spain regarding the longitudinal follow-up of weight in antidepressant users.” Similar studies in the United Kingdom, Finland, and Canada have shown associations between prolonged antidepressant use and weight gain, “but this study is unique in examining various trajectories of consumption over time.”

The study included 3127 adults (1701 women) from the REGICOR study, with an average age of 55.6 years, residing in northeastern Spain. Participants provided self-reported data at two timepoints — initially and after a median of 6.3 years — on their antidepressant use, body weight, and height. Additional data on smoking, physical activity, diet quality, education, marital status, and depressive symptoms (evaluated using the PHQ-9) were also collected during follow-up.

Only Repeated Use Linked to Obesity

The average weight gain after 6 years was 0.53 kg (or 1.01% of body weight), and 24.5% of participants gained more than 5% of their body weight.

Most participants (83.6%) did not report using antidepressants, 6.2% initiated use during follow-up, 5.1% discontinued use, and the remaining 5.1% used them at both timepoints. In multivariable analyses, compared with patients who never used antidepressants, all consumption trajectories were associated with greater weight gain: 1.78% (95% CI, 0.57-2.98) for discontinued use, 2.08% (95% CI, 0.97-3.19) for new use during follow-up, and 1.98% (95% CI, 0.75-3.20) for repeated use.

Additionally, for participants without obesity at the start of the study (n = 2404), the odds ratio for developing obesity during follow-up was 2.06 (95% CI, 1.03-3.96) for repeated use, but it was not statistically significant for the other three consumption patterns.

“All individuals taking antidepressants had a higher likelihood of weight gain and developing obesity, with the risk increasing for those with continued use of these medications,” Lassale pointed out.

The study also examined the already-known bidirectional relationship between depression and obesity, as well as other contributing factors such as poor adherence to healthy diets and lack of physical activity. Despite these factors, the relationship between antidepressant use and weight gain remained independent of age, sex, socioeconomic status, lifestyle, and the presence or absence of depressive symptoms.

Higher Risk in Women, Young

Regarding the profile of patients most prone to gaining weight with antidepressant use, “data indicate that women, individuals under 55, and those with normal weight at the start of the study were more likely to experience it,” said Lassale.

As for which antidepressant class causes the most weight gain, Lassale explained: “Although this study didn’t analyze each type of antidepressant in detail, it is known that selective serotonin reuptake inhibitors and tricyclic antidepressants are more associated with weight gain. However, other studies have shown that some antidepressants, such as bupropion, can have a neutral effect or even promote weight loss.”

In a press release, Víctor Pérez, MD, PhD, head of the Psychiatry Department at Hospital del Mar, noted that “antidepressants are highly effective for treating certain prevalent mental health conditions. Their effect on weight is not universal, but some, like mirtazapine or paroxetine, can cause significant weight gain.” He added that “given the risk of patients discontinuing medication due to weight gain, we must consider alternatives to complement the treatment with these drugs.”

Necessary Weight Control

“Given the global obesity epidemic and the widespread use of antidepressants, weight management and metabolic monitoring should be encouraged and integrated into depression follow-up guidelines alongside antidepressant prescriptions,” the authors concluded. While confirming the effectiveness of antidepressants, Lassale emphasized “the importance of considering non-pharmacological alternatives in treating depression, such as psychotherapy and adopting healthy lifestyles, including exercise and diet changes, as these have been shown to help reduce anxiety and depression.”

Regarding the continuation of the study, Lassale outlined the following goals: “To analyze the specific impact of each class of antidepressants on weight gain” and “to evaluate the combined effect of antidepressants with other psychoactive drugs, such as antipsychotics,” and “to explore strategies to mitigate weight gain in patients on long-term treatment.”

Lassale disclosed no relevant financial conflicts of interest.

https://www.medscape.com/viewarticle/antidepressant-therapy-linked-2-weight-gain-2025a10007d3