The topic of weight gain and depression remains somewhat taboo. Still, we observe a rising trend in antidepressant use alongside increasing obesity rates. Furthermore, between 2019 and 2023, antidepressant prescriptions increased by 60% among young people, coinciding with a higher prevalence of childhood obesity. This makes the conversation essential.

First, antidepressants appear to be effective. According to the Obesity Action Coalition, in fact, 89% of individuals with depression report that medication improves their symptoms. Unfortunately, weight gain is the 3rd most commonly reported negative side effect behind withdrawal effects and sexual dysfunction. Weight gain has been reported by 65% of individuals on long-term antidepressant therapy, while only 15% of individuals on antidepressants reported weight-loss. That alone merits to be adressed.

Is it depression itself that leads to weight gain, or the treatment?

The debate remains complex and highly relevant. In general, untreated depression can also affect body weight, most often leading to weight loss due to reduced appetite. If a person becomes less physically active, weight gain may also occur. On the other hand, certain emotional disturbances can lead to food-based coping behaviors, which may increase body weight.

Carrying excess weight remains highly stigmatized in our society. Some believe that the correlation between antidepressant use and weight stems from the greater social challenges faced by individuals with obesity, which may increase the risk of depression. But the reverse also holds true. A large proportion of individuals wish to lose weight despite having a healthy body weight. Many thin individuals experience depression as well.

Antidepressants and Weight Gain: Understanding the Impact of Treatment on Metabolism

Antidepressants play an essential role in the treatment of mood disorders, including depression and anxiety. However, one of their most frequently reported side effects involves weight gain. Many individuals report noticeable changes in body weight after several months of treatment, which can influence both physical and psychological well-being.

Why can antidepressants lead to weight gain? Several mechanisms may explain why certain antidepressants contribute to weight changes:

Increased appetite

Some antidepressants influence neurotransmitters involved in appetite regulation, such as serotonin and dopamine. These effects may increase hunger signals or cravings, particularly for carbohydrate-rich and high-fat foods.

Metabolic changes

Certain medications may slow metabolic rate, meaning the body burns fewer calories at rest.

Water retention

Some antidepressants may cause fluid retention, temporarily increasing body weight.

Impact on physical activity

Some treatments may induce fatigue or a sensation of heaviness, which can reduce physical activity and promote a more sedentary lifestyle.

Indirect effects

In some individuals, depression itself may cause weight loss due to reduced appetite. Once treatment begins, appetite may normalize, which can be perceived as weight gain.

How much weight gain can be expected?

The general discourse is that these medications produce relatively small changes. But most studies look at a very small time window, sometimes even only 4-12 weeks prior to treament initiation. Most studies measure the risk of gaining 5% weight. That may look insignificant, but clinically, this can make a big difference:

Here is what that looks like in real life: If you weigh:

60 kg (132 lbs) → 5% = 3 kg (6.6 lbs)
70 kg (154 lbs) → 5% = 3.5 kg (7.7 lbs)
80 kg (176 lbs) → 5% = 4 kg (8.8 lbs)
90 kg (198 lbs) → 5% = 4.5 kg (9.9 lbs)

The long term impact

According to the Obesity Action Coalition, less than 12 months’ use of antidepressants does not appear to be associated with significant weight gain. But what happens long-term, with years and years of use?

The King’s study (1) published by the School of Population Health and Environmental Science, measured the impact of antidepressants on a more long-terme span. It revealed that the weight gain could accumulate enough to make a person shift to the overweight category.

Among people of normal weight, those taking antidepressants had a 29 % higher adjusted risk of moving into overweight or obesity than those not taking them. Among people already overweight, they had a 29 % higher risk of progressing to obesity compared to those not taking antidepressants.

In this study, participants with one or more years of treatment showed an increased risk of weight gain that was maintained during six years of follow-up. Adjusted rate ratios were 1.46 (1.43 to 1.49) in the second year of follow-up and 1.48 (1.45 to 1.51) in the third year. Adjusted rate ratios then declined; from year 7, there was no evidence for an increased risk of weight gain (probably since the metabolic adaptation had already occured). The most critical year appeared to be the second one. During the second year of treatment, the risk of one additional episode of ≥ 5% weight gain may be expected for every 27 (25 to 29) patients treated.

Tailoring the treatment to the individual

Different classes of antidepressants produce varying effects on body weight. If you or your patient are prone to weight gain, it is important to discuss the potential impact on the treatment on their weight. Here is a table summarizing what we know:

Antidepressants and Their Impact on Weight

Category	Examples of Medications	Mechanism of Action	Impact on Weight
Selective Serotonin Reuptake Inhibitors (SSRIs)	Fluoxetine, Paroxetine, Sertraline	Increase serotonin availability in the brain	Moderate (long-term tendency toward weight gain)
Serotonin–Norepinephrine Reuptake Inhibitors (SNRIs)	Venlafaxine, Duloxetine	Act on serotonin and norepinephrine	Low to moderate
Tricyclic Antidepressants (TCAs)	Amitriptyline, Clomipramine	Act on multiple neurotransmitters (serotonin, norepinephrine, histamine)	High (notably due to appetite stimulation)
Monoamine Oxidase Inhibitors (MAOIs)	Phenelzine, Tranylcypromine	Inhibit breakdown of serotonin and dopamine	Variable (may cause weight gain or loss)
Atypical Antidepressants	Mirtazapine, Trazodone	Sedative effects and appetite stimulation	High (especially mirtazapine)
Bupropion (Dopaminergic Antidepressant)	Bupropion	Acts on dopamine and norepinephrine	May promote weight loss

Sources:

(1)Gafoor, R, Utilisation and incidence of weight gain during 10 years’ follow-up: population based cohort study, BMJ 2018;  361. doi: https://doi.org/10.1136/bmj.k1951 (Published 23 May 2018)

Complementary readings:

Marx W, Manger SH, Blencowe M, et al. Clinical guidelines for the use of lifestyle-based mental health care in major depressive disorder: World Federation of Societies for Biological Psychiatry (WFSBP) and Australasian Society of Lifestyle Medicine (ASLM) taskforce. World J Biol Psychiatry 2023;24:333-86.

Bizzozero-Peroni B, Martínez-Vizcaíno V, Fernández-Rodríguez R, et al. The impact of the Mediterranean diet on alleviating depressive symptoms in adults: a systematic review and meta-analysis of randomized controlled trials. Nutr Rev 2024 Jan. 14 [Epub ahead of print]:nuad176. doi: 10.1093/nutrit/nuad176.

Jacka FN, O’Neil A, Opie R, et al. A randomised controlled trial of dietary improvement for adults with major depression (the “SMILES” trial) [published erratum in BMC Med 2018;16:236]. BMC Med 2017;15:23.